Propionibacter

Nahrung, 2000 Apr, 44(2), 102 - 6
Isolation and characterization of proline iminopeptidase from Propionibacterium freudenreichii ATCC 9614; Stepaniak L; A dimeric, 90 kDa subunit intracellular proline iminopeptidase from Propionibacterium freudenreichii ATCC 9614 was purified to homogeneity by chromatography on hydroxyapatite, Sephacryl 200, Phenyl Superose and Mono Q . The enzyme was specific on Pro-p-nitroanilide and Pro-X dipeptides . It hydrolyzed 2 fragments of hormone oligopeptides with an N-terminal proline: bradykinin, f2-7 and substance P, f4-11 . A number of oligopeptides containing 5-11 amino acids residues and proline at the penultimate position from N-terminus or other internal position were not hydrolyzed . The enzyme was most active at pH 7-7.5 and at 37-40 degrees C but it retained 9% of maximal activity at pH 5.5 and >12% of maximal activity at 10 or 60 degrees C . The enzyme was inhibited strongly by the serine protease inhibitor 3,4-dichloroisocoumarin, and stimulated markedly by 1 mol/l of NaCl . The results indicate that the enzyme may lead to the accumulation of proline from dipeptides and oligopeptides during the ripening of cheese.

Appl Environ Microbiol, 2000 May, 66(5), 2012 - 20
Interactions between pyruvate and lactate metabolism in Propionibacterium freudenreichii subsp . shermanii: in vivo (13)C nuclear magnetic resonance studies; Deborde C et al.; In vivo (13)C nuclear magnetic resonance spectroscopy was used to elucidate the pathways and the regulation of pyruvate metabolism and pyruvate-lactate cometabolism noninvasively in living-cell suspensions of Propionibacterium freudenreichii subsp . shermanii . The most important result of this work concerns the modification of fluxes of pyruvate metabolism induced by the presence of lactate . Pyruvate was temporarily converted to lactate and alanine; the flux to acetate synthesis was maintained, but the flux to propionate synthesis was increased; and the reverse flux of the first part of the Wood-Werkman cycle, up to acetate synthesis, was decreased . Pyruvate was consumed at apparent initial rates of 148 and 90 micromol . min(-1) . g(-1) (cell dry weight) when it was the sole substrate or cometabolized with lactate, respectively . Lactate was consumed at an apparent initial rate of 157 micromol . min(-1) . g(-1) when it was cometabolized with pyruvate . P . shermanii used several pathways, namely, the Wood-Werkman cycle, synthesis of acetate and CO(2), succinate synthesis, gluconeogenesis, the tricarboxylic acid cycle, and alanine synthesis, to manage its pyruvate pool sharply . In both types of experiments, acetate synthesis and the Wood-Werkman cycle were the metabolic pathways used most.

Biochemistry, 2000 Apr 4, 39(13), 3666 - 70
Evaluation of biosynthetic pathways to delta-aminolevulinic acid in Propionibacterium shermanii based on biosynthesis of vitamin B12 from D-{1-13C}glucose; Iida K et al.; Analysis of the (13)C nuclear magnetic resonance (NMR) spectrum of (13)C-labeled vitamin B(12) biosynthesized from D-{1-(13)C}glucose by Propionibacterium shermanii provided evidence suggesting that delta-aminolevulinic acid (ALA) incorporated in the (13)C-labeled vitamin B(12) may have been synthesized via both the Shemin pathway and the C5 pathway under anaerobic conditions in the ratio of 1 < {(ratio of ALA biosynthesis from the Shemin pathway)/(that from the C5 pathway)} < 1.8 . The D-ribose moiety of vitamin B(12) was labeled with (13)C at R-1, R-3, and R-5 . The aminopropanol moiety of vitamin B(12) was labeled on Pr-1 and Pr-2, but not Pr-3.

Hepatology, 2000 Mar, 31(3), 633 - 40
Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage; Guebre-Xabier M et al.; Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure . The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers that have been sensitized to endotoxin damage by Propionibacterium acnes infection . The latter induces interleukin (IL)-12 and -18, causing a selective reduction of CD4+NK T cells, diminished IL-4 production, deficient production of T-helper type 2 (Th-2) cytokines (e.g., IL-10), and excessive production of Th-1 cytokines (e.g., interferon gamma {IFN-gamma}) . Liver and spleen lymphocyte populations and hepatic cytokine production were compared in genetically obese, ob/ob mice (a model for obesity-related fatty liver) and lean mice . Obese mice have a selective reduction of hepatic CD4+NK T cells . Serum IL-18 is also increased basally, and the hepatic mRNA levels of IL-18 and -12 are greater after endotoxin challenge . Thus, up-regulation of IL-18 and IL-12 in fatty livers may reduce hepatic CD4+NK T cells . In addition, mononuclear cells from fatty livers have decreased expression of the adhesion molecule, leukocyte factor antigen-1 (LFA-1), which is necessary for the hepatic accumulation of CD4+NK T cells . Consistent with reduced numbers of hepatic CD4+NK T cells, mononuclear cells from fatty livers produce less IL-4 . Furthermore, after endotoxin treatment, hepatic induction of IL-10 is inhibited, while that of IFN-gamma is enhanced . Thus, fatty livers have inherent immunologic alterations that may predispose them to damage from endotoxin and other insults that induce a proinflammatory cytokine response.

Biochemistry, 2000 Mar 14, 39(10), 2509 - 16
High resolution solution structure of the 1.3S subunit of transcarboxylase from Propionibacterium shermanii; Reddy DV et al.; Transcarboxylase (TC) from Propionibacterium shermanii, a biotin-dependent enzyme, catalyzes the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate to form propionyl-CoA and oxalacetate . Within the multi-subunit enzyme complex, the 1.3S subunit functions as the carboxyl group carrier and also binds the other two subunits to assist in the overall assembly of the enzyme . The 1.3S subunit is a 123 amino acid polypeptide (12.6 kDa) to which biotin is covalently attached at Lys 89 . The three-dimensional solution structure of the full-length holo-1.3S subunit of TC has been solved by multidimensional heteronuclear NMR spectroscopy . The C-terminal half of the protein (51-123) is folded into a compact all-beta-domain comprising of two four-stranded antiparallel beta-sheets connected by short loops and turns . The fold exhibits a high 2-fold internal symmetry and is similar to that of the biotin carboxyl carrier protein (BCCP) of acetyl-CoA carboxylase, but lacks an extension that has been termed "protruding thumb" in BCCP . The first 50 residues, which have been shown to be involved in intersubunit interactions in the intact enzyme, appear to be disordered in the isolated 1.3S subunit . The molecular surface of the folded domain has two distinct surfaces: one side is highly charged, while the other comprises mainly hydrophobic, highly conserved residues.

Am Fam Physician, 2000 Jan 15, 61(2), 357 - 66
Topical therapy for acne; Russell JJ; Acne is a common problem in adolescents and young adults . The disorder is caused by abnormal desquamation of follicular epithelium that results in obstruction of the pilosebaceous canal . This obstruction leads to the formation of comedones, which can become inflamed because of overgrowth of Propionibacterium acnes . Topical retinoids such as tretinoin or adapalene are effective in many patients with comedonal acne . Patients with inflammatory lesions benefit from treatment with benzoyl peroxide, azelaic acid or topical antibiotics . Frequently, the use of comedonal and antibacterial agents is required.

Curr Med Res Opin, 1999, 15(4), 298 - 9
Metronidazole, its bioactive metabolites and acne; Bannatyne RM; Metronidazole's activity has been established in both acneiform rosacea and acne vulgaris . Recent research indicating that the breakdown products of several antibiotics, including metronidazole, may have considerably greater activity than the parent compound, prompted a re-examination of the susceptibility of Propionibacterium acnes, the organism involved in the fundamental pathogenesis of acne vulgaris . Although the organism was marginally more sensitive to the hydroxy derivative, MIC levels were still outside the readily attainable therapeutic range . The beneficial effects of metronidazole in acne vulgaris are attributable to its anti-inflammatory activities rather than its antibacterial ones.

Neurol Neurochir Pol, 1999 Jul-Aug, 33(4), 797 - 805
{The evaluation of the use of antineoplaston AS2-1 treatment in subacute sclerosing panencephalitis}; Sobczyk W et al.; A follow-up study was carried out of 16 SSPE patients two years after completion of 6-month treatment with Antineoplaston . The study was based on an inquiry sent to the families of the patients and on control examinations at the clinic . In the period of follow-up 6 patients died, all had the downhill type of disease course and their mean survival was 18 months . Out of the remaining 10 patients 4 are in stationary condition and the remaining ones had minimal worsening . A more detailed clinical analysis showed that half the patients were in contact with and general orientation in the environment, but impairment of motor functions made difficult in most cases self-care and self-dependent functioning . All patients had evident changes in brain MRI . The survival time of the patients has been as yet from 2.5 to 5.5 years (mean 3.9 years) . The results of the treatment with Antineoplaston AS2-1 + isoprinosine are comparable with those observed during isoprinosine alone treatment but significantly worse than those after administration of Propionibacterium granulosum with isoprinosine . This suggests that Antineoplaston AS2-1 fails to modify importantly the natural course of SSPE.

Zentralbl Bakteriol, 1999 Oct, 289(4), 445 - 56
In-vitro and in-vivo efficacy of zinc acetate against propionibacteria alone and in combination with erythromycin; Fluhr JW et al.; Some studies have been published about the in vitro activity of zinc acetate (ZA), erythromycin (E) and their combination (ZA/E) against Propionibacterium spp., especially erythromycin resistant strains . The efficacy of topical ZA/E combination has been reported as well, but a comparison to ZA monotherapy is missing . Therefore, the MIC values of ZA, E and the ZA/E combination were determined for 15 erythromycin-resistant and 12 erythromycin-sensitive Propionibacterium strains using the agar dilution method and the checkerboard technique . Furthermore, the antimicrobial efficacy of ZA (1.2%) vs . the ZA/E (1.2%/4%) combination in an alcoholic solution was tested in a 7-day treatment administered to 32 acne patients . The MIC 100 for ZA was 1024 micrograms ZA/ml for both, erythromycin resistant and erythromycin sensitive Propionibacterium strains . The ZA, as well as the ZA/E solution showed efficacy reducing both the Propionibacterium spp., and the Micrococcaceae in the sebaceous gland infundibula of acne patients . There was no significant difference between the two treatments . As the MIC 100 of ZA/E was equal to the MIC 100 of ZA, the decrease of the erythromycin MIC of the ZA/E combination in erythromycin-resistant strains may be partly attributed to the addition of ZA to E . The in vivo antibacterial efficacy on 32 acne patients supports the hypothesis that the antibacterial effect of ZA/E in short-term treatment can be mostly attributed to ZA.

Ophthalmology, 1999 Dec, 106(12), 2395 - 401
Treatment strategies for postoperative Propionibacterium acnes endophthalmitis; Aldave AJ et al.; PURPOSE: Propionibacterium acnes endophthalmitis after cataract extraction and posterior chamber intraocular lens (IOL) implantation is characterized by a chronic indolent course, frequently associated with recurrence after standard endophthalmitis treatment . This study was designed to evaluate the efficacy of various therapeutic methods in the treatment of primary and recurrent episodes of postoperative P . acnes endophthalmitis . DESIGN: Retrospective, noncomparative case series . PARTICIPANTS: Twenty-five patients treated at Wills Eye Hospital for P . acnes endophthalmitis . METHODS: The authors retrospectively reviewed the clinical charts and microbiology files of all patients treated at Wills Eye Hospital between January 1991 and April 1998 with culture-proven P . acnes endophthalmitis after cataract extraction and posterior chamber IOL implantation . MAIN OUTCOME MEASURES: Results of cultures and microbiologic examinations, efficacy of various treatment methods in the prevention of recurrent inflammatory episodes, and final visual outcome . RESULTS: Twenty-five patients who met inclusion criteria were identified; initial therapy consisted of 1 of the following: intraocular antibiotic (IOAB) injections alone (2 patients); IOAB combined with pars plana vitrectomy (PPV) (10 patients); IOAB and PPV combined with partial capsulectomy (9 patients); and IOAB, PPV, total capsulectomy, and IOL exchange (4 patients) . Nearly half of the patients (10 of 21, or 48%) initially treated with IOAB alone (1 of 2), IOAB and PPV (5 of 10), and IOAB combined with PPV and partial capsulectomy (4 of 9) required further therapeutic interventions for recurrent disease . Retreatment with IOAB alone or combined with PPV and partial capsulectomy in these patients failed to eradicate the infection in three (75%) of four patients . None of the patients (0 of 4) treated initially with total capsulectomy and IOL exchange required additional surgical intervention . Furthermore, none of the patients (0 of 13) who underwent total capsulectomy with IOL removal or exchange or IOL exchange alone as an initial, secondary, or tertiary treatment required further intervention . CONCLUSION: In the authors' series, approximately half of the patients with P . acnes endophthalmitis were treated successfully initially with nonsurgical or limited surgical intervention . All patients treated with total capsulectomy and IOL exchange or removal, either as an initial treatment or for recurrent disease, were cured . Removal of the entire capsular bag and the IOL may be performed as a definitive initial therapy and should be performed for recurrent inflammation.

Nat Biotechnol, 1999 Dec, 17(12), 1175 - 8
cobA, a red fluorescent transcriptional reporter for Escherichia coli, yeast, and mammalian cells; Wildt S et al.; We demonstrate the use of Propionibacterium freudenreichii uroporphyrinogen III methyltransferase (cobA) as a reporter of gene expression in Escherichia coli, fission yeast, and mammalian cells . Overexpression of cobA in cells resulted in bright red fluorescence that was visualized with standard fluorescence microscopy and fluorescence-activated cell sorting analysis at the single-cell level . As with green fluorescent protein (GFP), no addition of exogenous substrate was required . When expressed in Chinese hamster ovary cells from a bicistronic transcript, cobA and GFP gave rise to fluorescence signals of similar intensity . The bright red fluorescence generated by the cobA reporter promises a better signal-to-noise ratio than blue and green fluorescent reporter systems, as autofluorescence and light scattering of cells, media, and materials are reduced in the red wavelengths.

J Neurosurg, 1999 Dec, 91(6), 1041 - 4
Glioblastoma multiforme at the site of metal splinter injury: a coincidence? Case report; Sabel M et al.; The authors report the case of a man who had suffered a penetrating metal splinter injury to the left frontal lobe at 18 years of age . Thirty-seven years later the patient developed a left-sided frontal tumor at the precise site of the meningocerebral scar and posttraumatic defect . Histological examination confirmed a glioblastoma multiforme adjacent to the dural scar and metal splinters . In addition, a chronic abscess from which Propionibacterium acnes was isolated was found within the glioma tissue . The temporal and local association of metal splinter injury with chronic abscess, scar formation, and malignant glioma is highly suggestive of a causal relationship between trauma and the development of a malignant brain tumor.

Ophthalmology, 1999 Nov, 106(11), 2106 - 8
Use of agar in ophthalmic pathology: a technique to improve the handling and diagnosis of temporal artery biopsies, subfoveal membranes, lens capsules, and other ocular tissues; LoRusso FJ et al.; DESIGN: Prospective laboratory methodology study . PURPOSE: Certain tissues, by virtue of their shape and extreme thinness or pliability, are difficult to position correctly during routine paraffin embedding to provide the optimal orientation for histopathologic studies . Biopsy specimens from temporal arteries must be sampled at different points along the length of the artery . Other tissues such as subfoveal neovascular membranes and fragments of lens capsule lack the thickness and rigidity to be positioned on edge to yield cross-sectional views . The authors' technique improves the orientation and thereby maximizes the histologic information obtained from such specimens . METHODS AND MATERIALS: From January 1, 1990, to April 30, 1999, the authors studied 500 consecutive temporal artery biopsy specimens and 200 successive subfoveal neovascular membranes . RESULTS: Cutting a 20-mm cylindrical fragment of temporal artery at 1- to 1.5-mm intervals yielded approximately 13 to 20 cross-sections along the length of the artery . When the specimens were positioned together and embedded in agar, the pathologist could easily study multiple cross-sections of the artery . Additionally, using the agar technique, the authors were able to obtain cross-sections of other specimens submitted, such as subfoveal neovascular membranes, and studied each of the different layers to evaluate the disease process . By the same method, the authors placed small fragments of lens capsule with underlying cortex on edge and readily identified short, gram-positive coccobacilli consistent with Propionibacterium acnes endophthalmitis . CONCLUSION: The agar technique can greatly improve the quality of diagnostic information gleaned from temporal artery biopsy specimens and other small tissue samples.

Schweiz Med Wochenschr, 1999 Oct 16, 129(41), 1496 - 503
{Acne and its treatment possibilities}; Boni R et al.; Acne is a multifactorial disease affecting the pilosebaceous follicles . It is a treatable condition for which the aims of therapy are to reduce social isolation and to prevent or minimise scarring . Propionibacterium acnes is an anaerobic bacterium strongly implicated in the pathogenesis of acne . A gradual increase in the resistance of P . acnes to many antibiotics has been documented in the last decade, and there is thus a growing need to use either appropriate antibiotics or even change the therapeutic strategy in favour of other regimens, i.e . isotretinoin, antiandrogens . A treatment guide is presented and the side-effects of these regimens are discussed.

Dig Dis Sci, 1999 Oct, 44(10), 1975 - 84
Experimental liver injury induced by Propionibacterium acnes and lipopolysaccharide in macrophage colony stimulating factor-deficient osteopetrotic (op/op) mice; Nishioji K et al.; To clarify the involvement of growth and differentiation of liver macrophages mediated by macrophage colony-stimulating factor (M-CSF) in the liver injury induced by Propionibacterium acnes (P . acnes) and lipopolysaccharide (LPS), we used M-CSF-deficient osteopetrotic (op/op) mice . Seven days after injection of P . acnes, granulomas as well as the numbers of Thy-1.2-, Mac-1-, and ERMP-20-positive cells and F4/80-positive areas in the liver were significantly reduced in the op/op mice compared to the normal littermates . After injection of LPS, serum levels of alanine aminotransferase as well as concentrations of IL-1beta and TNF-alpha in the serum and liver were significantly lower in the op/op mice than in the normal littermates, whereas the concentrations of IL-1beta and TNF-alpha in the spleen were similar in op/op mice and normal littermates . These results suggest that M-CSF plays a partial but highly significant role in the development of liver injury induced by P . acnes and LPS via an intrahepatic increase of primed macrophages including those in granulomas, in response to P . acnes, which produce proinflammatory cytokines such as IL-1beta and TNF-alpha.

Schweiz Med Wochenschr, 1999 Oct 9, 129(40), 1456 - 60
{Spondylodiscitis due to Propionibacterium acnes . Case report and review of the literature}; Hammann C et al.; Propionibacterium acnes, a gram positive anaerobic organism, is a component of normal skin flora . It can exceptionally be a source of osteoarticular infection (osteitis, arthritis, spondylodiscitis) . We report a case of Propionibacterium acnes spondylodiscitis following lumbar puncture . This observation should alert the clinician to the fact that Propionibacterium acnes may rarely cause spondylodiscitis and lumbar pain, and should be considered a causative agent of bone infections after local procedures.

J Am Acad Dermatol, 1999 Nov, 41(5 Pt 1), 710 - 6
Digital fluorescence photography can assess the suppressive effect of benzoyl peroxide on Propionibacterium acnes; Pagnoni A et al.; BACKGROUND: Porphyrins produced by Propionibacterium acnes exhibit an orange-red fluorescence under UVA light . The amount of fluorescence can be estimated by digital fluorescence photography . OBJECTIVE: We thought that digital fluorescence photography would be a quicker and simpler method than bacteriologic culture to demonstrate depopulation of P acnes in sebaceous follicles . We used benzoyl peroxide to bring about rapid suppression of P acnes . METHODS: Benzoyl peroxide 10% was applied twice daily for 7 days to the faces of 9 subjects . Five subjects were untreated controls . Digital fluorescence photographs of cheek and nose, and scrub samples for quantitative recovery of P acnes from the cheek were taken at baseline, day 3, day 7 (end of treatment), and day 16 (regression phase) . RESULTS: The effect of benzoyl peroxide against P acnes was clearly demonstrated both by culture and by fluorescence photography after only 3 days . Image analysis of porphyrin fluorescence correlated well with the decrease in P acnes density from scrub cultures . No further decrease was observed at day 7 (end of therapy) . Ten days later there was a return to baseline values, although in some subjects these remained lower . CONCLUSION: Digital fluorescence photography is a reliable, fast, and easy screening technique to demonstrate the suppressive effect of topical antibacterial agents on P acnes.

Immunity, 1999 Sep, 11(3), 359 - 67
Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice; Tsutsui H et al.; IL-18, produced as a biologically inactive precursor, is processed by caspase-1 in LPS-activated macrophages . Here, we investigated caspase-1-independent processing of IL-18 in Fas ligand (FasL)-stimulated macrophages and its involvement in liver injury . Administration of Propionibacterium acnes (P . acnes) upregulated functional Fas expression on macrophages in an IFNgamma-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with FasL . This was also the case for caspase-1-deficient mice . Administration of recombinant soluble FasL (rFasL) after P . acnes priming induced comparable elevation of serum IL-18 in parallel with elevated serum liver enzyme levels . However, liver injury was not induced in IL-18-deficient mice after rFasL administration . These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury.

Life Sci, 1999, 65(13), 1359 - 71
Gallium nitrate suppresses the production of nitric oxide and liver damage in a murine model of LPS-induced septic shock; Krecic-Shepard ME et al.; The efficacy of gallium (Ga) nitrate was examined in a murine model of sepsis . Male Balb/c mice (6-8 weeks) were randomized into 3 groups: 1) vehicle-treated controls 2) mice with sepsis induced by treatment with 0.3 mg i.v . of Propionibacterium acnes followed one week later by 0.01 microg lipopolysaccharide (LPS) and 10 mg of D-galactosamine (GalN) 3) mice with sepsis injected with 45 mg/kg s.c . of gallium nitrate (calculated as elemental Ga) 24 hours prior to LPS/GalN . Two hours after LPS/GalN or vehicle, plasma concentrations of tumor necrosis factor (TNF-alpha) in groups 1, 2 and 3 were 54+/-31 (n=6), 21,390+/-5139 (n=4), and 21,909+/-943 (n=5) pg/ml, respectively . After 6 hours, plasma concentrations of gamma interferon (IFN-gamma) were <10 (n=8), 4771+/-1078 (n=6), and 1622+/-531 (n=15) pg/ml, respectively, and of nitrate/nitrite (products of nitric oxide) were 64+/-8 (n=7), 146+/-18 (n=8), and 57+/-8 (n=15) microM . At 18 hours, serum chemistries were; SGOT 171+/-46 (n=13), 10,986+/-3062 (n=7), and 1078+/-549 (n=8) IU/L; SGPT 165+/-59, 17,214+/-4340, and 2088+/-1097 IU/L; and total bilirubin 0.2+/-0.0, 0.9+/-0.4, and 0.2+/-0.0 mg/dl for groups 1, 2, and 3 respectively . Blinded histologic evaluation of livers at 18 hours revealed inflammatory infiltrate scores (x {range}, 0=none, 1=minimal, 2=mild, 3=moderate, and 4=severe) of 0.1 {0-1} (n=8), 3.0 {2-4} (n=15), and 2.0 {0-3} (n=10), and necrosis scores of 0.0, 2.8 {0-4}, and 0.9 {0-4} . Although Ga did not affect production of TNF-alpha, it ameliorated hepatocellular injury and protected against necrosis . Based on this model of sepsis, Ga may have a role in treating the human disease.

J Biomed Sci, 1999 Sep-Oct, 6(5), 349 - 56
Propionibacterium acnes induces acute TNFalpha-mediated apoptosis of hepatocytes followed by inflammatory T-cell-mediated granulomatous hepatitis in mice; Chen YL et al.; The CD3+/TCRalphabeta+ T-cell-mediated hepatic inflammation induced by Propionibacterium acnes could be divided into an acute and a chronic phase . The acute phase occurred within 72 h after injection and displayed hepatic apoptosis . Anti-TNFalpha antibody inhibited both the P . acnes-induced hepatic apoptosis and lymphocyte infiltration seen in this phase, indicating the involvement of this cytokine . Thereafter, a chronic phase was manifested from days 7 to 14 after injection . It was characterized as granulomatous inflammation admixed with apoptosis of infiltrating lymphocytes and some hepatocytes . Immunohistochemical staining showed that the infiltrating lymphocytes displayed TNFalpha, TNF type I receptor and a variety of cytokines including IL-1beta, IL-4, IL-6, IL-10, IFNgamma or IL-12 . Interestingly, in naive mice, the arteries in the liver constitutively expressed IFNgamma . Its expression appeared to be substantially increased at 48 h, decreased at 72 h, and increased again on day 14 after P . acnes injection . Furthermore, Fas or FasL was only detected on the lymphocytes within the granuloma . We conclude that P . acnes can induce a TNFalpha-mediated acute hepatic apoptosis which subsequently progress to a T-cell-mediated granulomatous hepatitis with increased expression of multiple cytokines and Fas/FasL.

Ophthalmology, 1999 Sep, 106(9), 1665 - 70
Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis; Clark WL et al.; PURPOSE: To report the treatment strategies and visual acuity outcomes of chronic postoperative endophthalmitis caused by Propionibacterium acnes . DESIGN: Retrospective noncomparative case series . PARTICIPANTS: All patients presenting 8 or more weeks after cataract surgery with intraocular inflammation caused by culture-proven P . acnes infection and treated at two institutions from 1974 through 1996 were included . METHODS: Patients underwent three different initial treatment strategies . The study did not have a defined treatment protocol, but all patients received intraocular antibiotics . Patients were not randomly assigned to the various treatment strategies . MAIN OUTCOME MEASURES: Final visual acuity and effectiveness of various treatment procedures either as initial or follow-up therapy were assessed . RESULTS: Using the 3 initial strategies, 36 patients were treated: (1) intraocular antibiotic injection alone (IOAB; n = 12); (2) pars plana vitrectomy and IOAB injection (PPV; n = 10); and (3) PPV with subtotal capsulectomy and IOAB injection (PPV-PC; n = 14) . The number of patients with recurrent or persistent inflammation after one of the three initial treatment strategies were as follows: (1) IOAB alone, 12 (100%); (2) PPV, 5 (50%); and (3) PPV-PC, 2 (14%) . None of the patients that underwent subsequent PPV, total capsular bag removal, IOAB injection, and either intraocular lens (IOL) exchange or removal had persistent or recurrent intraocular inflammation . Overall, final visual acuity was 20/40 or better in 18 patients (50%), and a total of 28 patients (78%) retained 20/400 or better vision . The mean follow-up after the last treatment was 2.9 years . CONCLUSIONS: In this series of chronic P . acnes endophthalmitis, initial treatment with IOAB injection alone or vitrectomy without capsulectomy was associated with high rates of recurrent or persistent intraocular inflammation . Pars plana vitrectomy, partial capsulectomy, and IOAB injection without IOL exchange was usually successful on long-term follow-up . In patients with recurrent intraocular inflammation, pars plana vitrectomy, total capsular bag removal, IOAB injection, and IOL exchange or removal was a uniformly successful strategy . In contrast to other types of postoperative endophthalmitis, IOL exchange can be considered in these patients after total capsular bag removal.

Dermatology, 1999, 199 Suppl 1, 29 - 31
Antibacterial activity of retinaldehyde against Propionibacterium acnes; Pechere M et al.; BACKGROUND: Retinaldehyde has been shown to exert antibacterial activity in vitro . AIM: This study evaluates the effect of retinaldehyde on Propionibacterium acnes both in vivo and in vitro . METHODS: Microbial minimal inhibitory concentrations (MICs) of retinaldehyde and retinoic acid were determined on reference strains of P . acnes . In vivo activity of daily topical application of 0.05% retinaldehyde on the P . acnes density was evaluated after application in a single-blind randomised study . RESULTS: MICs of retinaldehyde were 4 mg/l for P . acnes No . CIP179 and CIP53119 and 8 mg/l for P . acnes No . CIP53117 . In contrast, the MICs of retinoic acid were superior to 128 mg/l for these three strains . In vivo, retinaldehyde-treated areas displayed a significant decrease in counts of viable P . acnes as compared with the untreated areas with a median decrease of 10(2) log P . acnes/cm(2) after 2 weeks of daily application . Vehicle alone had no effect . CONCLUSION: The MIC of retinaldehyde against P . acnes suggests a direct antibacterial activity . Daily topical application of 0.05% retinaldehyde is associated with a clear reduction of the P . acnes density.

Appl Environ Microbiol, 1999 Sep, 65(9), 4241 - 4
Genus- and species-specific PCR-based detection of dairy propionibacteria in environmental samples by using primers targeted to the genes encoding 16S rRNA; Rossi F et al.; PCR assays with primers targeted to the genes encoding 16S rRNA were developed for detection of dairy propionibacteria . Propionibacterium thoenii specific oligonucleotide PT3 was selected after partial resequencing . Tests allowed the detection of less than 10 cells per reaction from milk and cheese and 10(2) cells per reaction from forage and soil.

Cutis, 1999 Aug, 64(2), 116 - 8
Recalcitrant acne vulgaris secondary to a dental abscess; Boyd AS et al.; This case report describes a middle-aged man with acne that was recalcitrant to numerous medications, including three courses of isotretinoin . His condition cleared after an infected tooth was removed and recurred when another tooth became carious . Acne vulgaris is associated with several immunologic responses including the production of antibodies against Propionibacterium acnes, the gram-positive bacteria found in acne lesions . We believe that the presence of our patient's dental infections provoked a follicular inflammatory response resulting in his recalcitrant acne.

Inflamm Res, 1999 Jul, 48(7), 380 - 5
Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis; Taguchi I et al.; OBJECTIVE AND DESIGN: To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P . acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis . MATERIAL: Male BALB/c mice were used . Macrophages/Kupffer cells isolated from P . acnes-primed murine liver were used for the in vitro study . TREATMENT: Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p . o.) . Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice . METHOD: Plasma TNFalpha estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study . The LPS-induced production of TNFalpha in vitro from the cultured macrophage/Kupffer cells was determined by ELISA . RESULTS: Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them . Both agents attenuated the LPS-induced release of TNFalpha in vivo, and suppressed the TNFalpha production from the cultured macrophage/Kupffer cells . CONCLUSIONS: These results suggest that rolipram and dbcAMP have potential to inhibit TNFalpha production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P . acnes/LPS hepatitis model.

Zhonghua Yan Ke Za Zhi, 1997 Jan, 33(1), 45 - 8
{An analysis of the cause of misdiagnosis with ocular opportunistic infection}; He Y et al.; OBJECTIVE: To evaluate the causes of misdiagnosis with ocular opportunistic infection . METHOD: The causes of misdiagnosis on 4 cases (6 eyes) with ocular opportunistic infection were analyzed . RESULTS: Acanthoamoeba keratitis was misdiagnosed as herpes simplex keratitis and fungal keratitis in 1 case (1 eye) . Propionibacterium acne endophthalmitis was misdiagnosed as exogenous fungal keratitis in 1 case (1 eye) . Endogenous fungal endophthalmitis was misdiagnosed as metastatic choroid cancer from lung in 1 case (2 eyes) . Cytomegalovirus retinitis was misdiagnosed as endogenous fungal endophthalmitis in 1 case (2 eyes) . CONCLUSION: If common therapies are of no effect with some ocular infections and the causative organisms responsible for the infection could not be found out after repeated tests, the rare ocular opportunistic infection should be considered . Special examinations (such as acanthoamoeba culture, anaerobic culture, fungus blood culture, cytomegalovirus serological assays, etc.) should be made for a definite diagnosis.

Postgrad Med J, 1999 Jun, 75(884), 328 - 31
Acne: a review of immunologic and microbiologic factors; Burkhart CG et al.; Acne vulgaris is a self-limiting skin disorder seen primarily in adolescents, whose aetiology appears to be multifactorial . The four main aetiological factors are hypercornification of the pilosebaceous duct, increased sebum production, colonization with Propionibacterium acnes, and subsequently the production of inflammation . Considerable investigation has addressed the immunologic reaction to extracellular products produced by the acne-causing organism, P acnes . The immunologic response involves both humoral and cell-mediated pathways . Further research should clarify the role of complement, cytotoxins, and neutrophils in this acne-forming response.

Antimicrob Agents Chemother, 1999 Aug, 43(8), 2027 - 31
Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology; Credito KL et al.; Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria . Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2) . Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml . Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin . Clindamycin was active (MIC </= 2.0 microg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 microg/ml . Amoxicillin-clavulanate had MICs of </=1.0 microg/ml, while metronidazole was active (MICs, 0.03 to 2.0 microg/ml) against all except Propionibacterium acnes . After 48 h at twice the MIC, telithromycin was bactericidal (>/=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains . After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred . Lower rates of killing were seen at earlier times . Similar kill kinetics relative to the MIC were seen with other macrolides . After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively . After 24 h, 90% killing of 10 strains occurred at the MIC . The kinetics of clindamycin were similar to those of pristinamycin . After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains . At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.

Pneumologie, 1999 Apr, 53(4), 216 - 8
{Thoracic actinomycosis--a case report}; Enders M et al.; BACKGROUND: Actinomycosis is caused by a variety of gram-positive anaerobic or microaerophilic rods belonging to the genus Actinomyces or Propionibacterium . The production of suppurative abscesses or granulomas that eventually develop draining sinuses are hallmarks of the disease . We describe the case of a 55 year old smoker who presented himself 4 months ago with right thoracic pain and an unproductive cough . He developed a warm, red mass in the lower part of the right thorax . We performed an ultrasound guided needle aspiration and the pathologic examination revealed typical sulfur granules and masses of neutrophils in the aspirate . After surgical resection of the abscess and under high-dose therapy with penicillin G the further course of disease was uneventful . CONCLUSIONS: Although uncommon, thoracic actinomycosis should always taken into account in the differential diagnosis of chronic inflammatory processes that involve the pulmonary parenchyma or pleural space.

Lancet, 1999 Jul 10, 354(9173), 120 - 3
Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis; Ishige I et al.; BACKGROUND: The causes of sarcoidosis are not known . The DNA of Mycobacterium tuberculosis has been detected in some sarcoid lesions . In Japan, Propionibacterium acnes has been isolated from such lesions, but whether this indigenous bacterium is related to the disease is unclear . We used PCR to estimate the number of genomes of these bacteria in sarcoid lesions, to identify any link between sarcoidosis and these two bacterial species . METHODS: We examined formalin-fixed and paraffin-embedded sections of biopsy and surgical samples from lymph nodes of 15 patients with sarcoidosis, 15 patients with tuberculosis, and 15 patients with gastric cancer (controls) . Quantitative PCR was done to amplify segments of 16 S ribosomal RNA of P . acnes and P . granulosum and of insertion sequence 6110 of M . tuberculosis . PCR products were identified and the quantities of the products were estimated in terms of the fluorescence of oligonucleotide reporter probes . The numbers of bacterial genomes in samples were estimated from standard curves of serially diluted bacterial DNA . FINDINGS: Genomes of M . tuberculosis were found in samples from all 15 patients with tuberculosis, from three patients with sarcoidosis, and in one control sample . Genomes of P . acnes were found in 12 of the 15 patients with sarcoidosis, in two tuberculosis patients, and three controls . The difference in the estimated number of P . acnes genomes between individuals with and without sarcoidosis was similar to that in the number of M . tuberculosis between people with and without tuberculosis . There were 5x10(5) P . acnes genomes in sarcoidosis and 3x10(6) M . tuberculosis genomes in tuberculosis, respectively, on average per microg of total DNA . The three patients with sarcoidosis but without P . acnes all had P . granulosum DNA in their biopsy samples; the number of genomes of the bacterium was 5x10(5) . INTERPRETATION: These findings suggest that propionibacteria had resided or proliferated ectopically in the sarcoid lesions, whether there was a connection with the disease or not . Propionibacteria are a more likely cause than mycobacteria of sarcoidosis.

Dermatology, 1999, 198(3), 273 - 7
Antibacterial efficacy of benzoyl peroxide in phospholipid liposomes . A vehicle-controlled, comparative study in patients with papulopustular acne; Fluhr JW et al.; BACKGROUND: Literature reports indicate that phospholipid liposomes facilitate the accumulation of active agents in the infundibulum . OBJECTIVE: The study hypothesis of an improved antibacterial efficacy of benzoyl peroxide (BPO) in phospholipid liposomes was tested in comparison with a commercial and a pharmacopoeial BPO preparation . METHODS: The infundibular bacterial samples were obtained with the Permabond technique from 20 acne patients who had been treated with the test substances (vehicle-controlled) for 2 weeks twice per day in a single-blinded, comparative study on the upper back . RESULTS: A significant antibacterial effect in the infundibula (Propionibacteria and Micrococcaceae, both: p < 0.001) for a BPO phospholipid liposome formulation could be demonstrated . In comparison to the other significantly efficacious BPO formulations which were also tested (commercial product and pharmacopoeial formulation), the BPO phospholipid liposome formulation showed a significantly greater antibacterial efficacy for Propionibacteria and Micrococcaceae (both: p < 0.01) . CONCLUSION: A BPO formulation in phospholipid liposomes may represent an improvement of the conventional external BPO treatment of acne.

Rapid Commun Mass Spectrom, 1999, 13(12), 1197 - 200
A rapid and reliable method for NO quantification and 15NO/14NO determination using isotope ratio mass spectrometry: an application for the detection of NO synthesis in propionibacteria; Avice JC et al.; For the last decade, numerous studies have focused on the positive or toxic effects of nitric oxide (NO) in procaryotic and eucaryotic cells . This gas has fundamental roles in neurotransmission, vasodilatation, cytotoxicity, and intestinal motility . The ability to produce NO by intestinal microflora or probiotic bacteria is unknown . In this preliminary study, we present a rapid and reproducible procedure for NO quantification and 15NO/14NO determination (based on the reaction between nitrite and acidic potassium iodide) by isotope ratio mass spectrometry . Using this method, we have demonstrated for the first time in vitro production of NO by a dietary bacterium (Propionibacterium acidipropionici, Pa 1) under anaerobic culture conditions . Using different sources of nitrogen, we have clearly shown that propionibacteria can synthesize NO from reduction of nitrate or nitrite . In our experimental conditions, NO synthase was not involved in NO production by propionibacteria.

Intern Med, 1999 Apr, 38(4), 355 - 8
Localized pericarditis with calcifications mimicking a pericardial tumor; Iseki H et al.; A 62-year-old man was admitted with increasing palpitations . Radiography of the chest demonstrated a calcified mass . Magnetic resonance imaging revealed compression of the right ventricle by a tumor . At the time of cardiac catheterization, the coronary arteries were found not to supply blood flow of the mass, and no dip-and-plateau pattern was seen in the right ventricular pressure measurements . At the time of surgery, the mass was found to be a focal calcified thickening of the pericardium containing only pus . The thickening resembled an oval pericardial tumor . Microbiologic examination of the pus revealed Propionibacterium acnes.

Neurosurgery, 1999 May, 44(5), 1138 - 41
Propionibacterium as a cause of postneurosurgical infection in patients with dural allografts: report of three cases; Jallo GI et al.; OBJECTIVE AND IMPORTANCE: Although Propionibacterium acnes is a common inhabitant of human skin, it is an uncommon pathogen in postoperative infections . We report three cases of postoperative wound infection/osteomyelitis caused by P . acnes . CLINICAL PRESENTATION: Three patients underwent craniotomy for a supratentorial meningioma and had a dural allograft at the time of closure . The patients presented several weeks after surgery with clinical evidence of a wound infection . INTERVENTION: All patients were diagnosed with P . acnes infection and treated for this pathogen with appropriate antibiotics . The bone flap was removed in two patients . After antibiotic therapy, all patients demonstrated no further evidence of infection . CONCLUSION: To our knowledge, this is the first published report of P . acnes infection in patients with a dural substitute . The source of infection cannot be confidently ascertained; however, two patients had strains of P . acnes from one brand of graft, which were indistinguishable by pulsed field gel electrophoresis typing.

Eur J Biochem, 1999 May, 262(1), 117 - 27
Manipulating the coordination mumber of the ferric iron within the cambialistic superoxide dismutase of Propionibacterium shermanii by changing the pH-value A crystallographic analysis; Schmidt M; The structure of the Propionibacterium freudenreichii subspecies shermanii superoxide dismutase (SOD) was determined at various pH values . As a comparison, the structure of the fluoride coordinated SOD was solved . The SOD crystallizes at pH 6.1 in the space group C2221 with two subunits, A and B, in the asymmetric unit . An increase of the pH value changes the cell parameters slightly but not the symmetry of the crystals . The overall structure of the SOD remains a compact tetrameter and is comparable to that at pH 6.1 no matter whether the pH increases or fluoride is added . At values above pH 7.4, an additional hydroxide ion can bind to the active center . Its position is similar to the binding site of the fluoride . The coordination number changes from five to six if the pH increases or fluoride is added . The binding behavior of the hydroxide ion is different for subunit A and B . Structures at different pH-values are comparable with models derived by spectroscopic methods . The influence of temperature on the binding properties of the hydroxide ion was investigated using analysis of an X-ray structure solved at pH 8.1 and 140 K . Compared to the structure at room temperature, the structural changes are observable but remain small . The consequences of hydroxide binding to the iron are discussed.

Int Immunol, 1999 Mar, 11(3), 471 - 80
IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxin shock; Sakao Y et al.; IL-18 is an IL-1-related cytokine which shares biological functions with IL-12 . These include the activation of NK cells, induction of IFN-gamma production and Th1 cell differentiation . In this study we analyzed the effect of IL-18 deficiency on lipopolysaccharide (LPS)-induced liver injury and endotoxin shock in Propionibacterium acnes-primed mice . P . acnes-primed IL-18-deficient (IL-18KO) mice showed resistance to LPS-induced liver injury . Unexpectedly, P . acnes-primed IL-18KO mice were highly susceptible to LPS-induced endotoxin shock . Serum level of tumor necrosis factor (TNF)-alpha were markedly elevated (approximately 10-fold higher) within 1.5 h after LPS challenge in IL-18KO mice as compared with wild-type mice . Anti-TNF-alpha antibody administration to IL-18KO mice was significantly protective against endotoxin-induced lethality . P . acnes-primed IL-18KO macrophages produced approximately 6-fold more TNF-alpha protein than did P . acnes-primed wild-type control macrophages . Taken together, these findings demonstrate that IL-18 is responsible for the progression of endotoxin-induced liver injury as well as down-regulation of endotoxin-induced TNF-alpha production in P . acnes-primed mice.

Rev Med Liege, 1999 Feb, 54(2), 100 - 4
{Bacterial resistance during anti-acne antibiotic therapy . How to limit the risk}; Pierard GE et al.; The treatment of moderate to severe acne often relies on antibiotherapy in order to eradicate as much as possible microorganisms such as Propionibacterium spp colonizing the sebaceous follicles . In recent years, bacterial resistances against specific antibiotics have emerged . Both the antibiotic and its administration modalities must be considered in order to control the risk . With regard to this conundrum, minocycline is a medication of choice among the diverse anti-acneic therapies.

Int J Dermatol, 1999 Mar, 38(3), 200 - 3
Propionibacterium acnes: interaction with complement and development of an enzyme-linked immunoassay for the detection of antibody; Burkhart CG et al.; OBJECTIVE: To characterize the immune response to Propionibacterium acnes in acne patients . DESIGN: Comparison of serologic responses in acne and normal patients using counterimmunoelectrophoresis for antibody and an enzyme-linked immunosorbent assay (ELISA) to detect immunoglobulin G (IgG) antibody . SETTING: The serum of acne and nonacne patients from the Dermatology Clinic at the Medical College of Ohio was utilized for analysis . RESULTS: Using counterimmunoelectrophoresis, antibody was detected in 13 of 20 acne patients . The antigen was detectable as an anion in the barbital buffer at pH 8.2, strongly suggesting a carbohydrate component . By ELISA, the antibody proved to be IgG, and the bacteria and its water-soluble fractions were capable of fixing complement . CONCLUSIONS: The primary instigator of inflammation in acne vulgaris is an immunologic reaction to extracellular products of P . acnes . The immunologic response involves both humoral and cell-mediated pathways . The antibodies to P . acnes have not been characterized fully, although they are largely of the IgG class . We have further characterized the dominant antigen to have a carbohydrate component.

J Leukoc Biol, 1999 Apr, 65(4), 482 - 91
Functional roles of MCP-1 in Propionibacterium acnes-induced, T cell-mediated pulmonary granulomatosis in rabbits; Ichiyasu H et al.; The immunological manifestation of granuloma formations in humans largely depends on the delayed-type hypersensitivity response . We investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated pulmonary granulomatosis . Intravenous injection of Propionibacterium acnes (P . acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas . Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before the granuloma formation reached the peak (on days 1 and 3 after challenge, respectively) . Chemotactic activities toward monocytes and T cells in BALF were inhibited by anti-MCP-1 IgG by 80 and 36%, respectively . The phenotypic analysis of the migrating T cells revealed that activated and memory T cells rather than naive cells were preferentially attracted to the BALF . Administration of anti-MCP-1 antiserum inhibited the development of granuloma formation in both size and number, the numbers of infiltrating leukocytes in BALF, the expression of adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells in BALF, and the production of TNF-alpha in the lung . Anti-MCP-1 resulted in a trend toward decreased level of IL-1beta in the lung . The inhibition of the production of these cytokines appeared to be induced indirectly through the inhibition of the recruitment of macrophages that produce these cytokines . The results suggest important roles of MCP-1 in the development of granuloma formation in this model through the attraction and activation of specific types of cells.

Biotechnol Prog, 1999 Mar-Apr, 15(2), 201 - 7
Metabolic pathway of Propionibacterium growing with oxygen: enzymes, 13C NMR analysis, and its application for vitamin B12 production with periodic fermentation; Ye K et al.; The metabolic pathway of Propionibacterium grown under an aerobic condition is still not clear so far . In this work, cell growth, organic acid formation, vitamin B12 synthesis, and enzyme activities were determined in different aerobic cultivation systems . It was found that the propionate, which is accumulated during anaerobic cultivation, was completely decomposed when the cultivation was shifted to an aerobic condition . Moreover, pyruvate was formed in accordance with the decomposition of the propionate . Besides, more acetate was produced and a large amount of malate was formed during the aerobic cultivation . Such phenomena could be repeatedly observed in a periodic cultivation in which the dissolved oxygen concentration was alternatively controlled at 0 or 1 ppm . Enzyme analysis indicates that the regulation of organic acid formation depends on which molecule, i.e., oxygen or fumarate, serves as an electron acceptor in the respiratory chain reactions . No tricarboxylic acid cycle was found to exist in this species grown under an aerobic condition . It is evident that the randomizing pathway worked in a reversed direction in the presence of oxygen, through which the propionate is oxidized to pyruvate . The 13C NMR spectral analysis confirmed this observation.

Int J Dermatol, 1999 Feb, 38(2), 128 - 30
Acne neonatorum: a study of 22 cases; Katsambas AD et al.; BACKGROUND: Acne is not uncommon in the neonatal period . Acne neonatorum is characterized by a mainly facial eruption of inflammatory and noninflammatory lesions . It is most commonly mild and transient . Hyperactivity of sebaceous glands, stimulated by neonatal androgens, has been implicated as the underlying pathogenetic mechanism . MATERIALS AND METHODS: All patients diagnosed with acne neonatorum in "A . Sygros" Hospital, Athens, Greece, during the years 1993-1996, were evaluated clinically and epidemiologically . Histologic examination and smears for Propionibacterium acnes and Pityrosporum ovale were performed in selected cases . RESULTS: Of the 22 patients studied, 18 were male (81.8%) and 4 were female . The mean age at onset was 3 weeks and the mean duration of the disease was 4 months . Papules and pustules were the most frequent types of lesions (72.7%), followed by comedones only (22.7%) . The cheeks were the most common site of predilection (81.8%) . A family history of acne was reported in only three patients . Histologic examination showed hyperplastic sebaceous glands with keratin-plugged orifices . Smears for P . ovale were negative . CONCLUSIONS: Our findings are consistent with previous experience, although inflammatory lesions were encountered more often than previously reported . Hereditary factors did not seem to play a significant role in our series . Topical treatment hastened the resolution of this self-limited condition . Recalcitrant cases warrant investigation for underlying androgen excess.

J Exp Med, 1999 Apr 5, 189(7), 1129 - 38
Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1 responses in IL-1 receptor-associated kinase (IRAK)-deficient mice; Kanakaraj P et al.; Interleukin (IL)-18 is functionally similar to IL-12 in mediating T helper cell type 1 (Th1) response and natural killer (NK) cell activity but is related to IL-1 in protein structure and signaling, including recruitment of IL-1 receptor-associated kinase (IRAK) to the receptor and activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-kappaB . The role of IRAK in IL-18-induced responses was studied in IRAK-deficient mice . Significant defects in JNK induction and partial impairment in NF-kappaB activation were found in IRAK-deficient Th1 cells, resulting in a dramatic decrease in interferon (IFN)-gamma mRNA expression . In vivo Th1 response to Propionibacterium acnes and lipopolysaccharide in IFN-gamma production and induction of NK cytotoxicity by IL-18 were severely impaired in IRAK-deficient mice . IFN-gamma production by activated NK cells in an acute murine cytomegalovirus infection was significantly reduced despite normal induction of NK cytotoxicity . These results demonstrate that IRAK plays an important role in IL-18-induced signaling and function.

Biotechnol Bioeng, 1998 Feb 20, 57(4), 454 - 61
Propionic acid production by extractive fermentation . I . Solvent considerations; Gu Z et al.; Solvent selection for extractive fermentation for propionic acid was conducted with three systems: Alamine 304-1 (trilaurylamine) in 2-octanol, 1-dodecanol, and Witcohol 85 NF (oleyl alcohol) . Among them, the solvent containing 2-octanol exhibited the highest partition coefficient in acid extraction, but it was also toxic to propionibacteria . The most solvent-resistant strain among five strains of the microorganism was selected . Solvent toxicity was eliminated via two strategies: entrapment of dissolved toxic solvent in the culture growth medium with vegetable oils such as corn, olive, or soybean oils; or replacement of the toxic 2-octanol with nontoxic Witcohol 85 NF . The complete recovery of acids from the Alamine 304-1/Witcohol 85 NF was also realized with vacuum distillation .

Zentralbl Bakteriol, 1999 Feb, 289(1), 53 - 61
In Vitro activity of 6 antimicrobials against propionibacteria isolates from untreated acne papulopustulosa; Fluhr JW et al.; In the present study, MIC values of 6 antibiotics were determined for 70 Propionibacterium acnes and 13 P.granulosum strains from 71 untreated acne patients using the agar dilution method . The interpretation of in vitro results is difficult because there are only poor data about the concentrations of antibiotics achievable in the sebaceous gland infundibulum . Based on breakpoint concentrations according to DIN 58,944, no resistance was found against chlortetracycline, doxycycline, minocycline, and chloramphenicol . In contrast, 11% of the P.acnes and 31% of the P.granulosum strains were not susceptible in vitro to erythromycin at a breakpoint concentration of 4 micrograms/ml . The present study shows that these strains are not suppressed even at higher erythromycin concentrations up to 256 micrograms/ml . Data from the literature reporting ineffective treatment of patients carrying erythromycin-resistant P.acnes strains may be explained by our study . Concerning clindamycin, resistance was found in only 6.8% of P.acnes and in 0% of the P.granulosum strains . Since sensitivity was seen in 100% of the strains already at a concentration of 16 micrograms/ml, a therapeutic effect may be possible.

Am J Kidney Dis . 1999 Feb;33(2):E6.
Peritoneal dialysis-associated peritonitis caused by Propionibacteria species; Castillo AA et al.; There are an increasing number of reports about unusual causes of peritonitis in peritoneal dialysis (PD) patients . The Propionibacteria species is a microorganism that is a normal skin flora . Under the presence of certain risk factors, it may produce serious infections . Patients at risk of having Propionibacteria sp infections have malignancy, diabetes mellitus, foreign bodies, or immunodeficiency . We describe a PD-associated peritonitis in a 51-year-old woman that was caused by Propionibacteria sp . This patient's risk factors for developing Propionibacteria sp peritonitis include a history of CREST syndrome, malignancy of the breast, and recent catheter surgery . To our knowledge, this is the first case of a PD-associated peritonitis caused by Propionibacteria sp reported in the literature.

Eur J Dermatol, 1999 Jan-Feb, 9(1), 25 - 8
Antimicrobial susceptibility of Propionibacterium acnes isolated from acne vulgaris; Kurokawa I et al.; Systemic and topical antimicrobial treatment for acne vulgaris remains the mainstay method of therapy in Japan . Strains of Propionibacterium acnes (P . acnes) resistant to erythromycin (EM), clindamycin (CLDM), tetracycline (TC), doxycycline (DOXY) and minocycline (MINO) have been reported . The aim of the present study was to examine the antimicrobial susceptibility to 10 currently used antimicrobial agents of 50 strains of P . acnes isolated from acne lesions and identified using a Rap ID ANA II panel . Minimum inhibitory concentrations (MIC) were determined by the agar dilution method according to the criteria of the Japan Society of Chemotherapy . EM, ampicillin (ABPC), and CLDM were the most potent drugs, followed by MINO, nadifloxacin (NDFX), cephalexin (CEX), DOXY, ofloxacin (OFLX), and TC . In terms of the MIC80, EM and ABPC were the most potent, followed by CLDM, NDFX, MINO, CEX, DOXY, OFLX, TC and gentamycin (GM) . Although most of the strains used were susceptible to the antimicrobial agents tested, strains of P . acnes resistant (MIC 12.5 mug/ml) to EM (4%), CLDM (4%), DOXY (2%) and TC (2%) were observed . In this study, no strains of P . acnes resistant to MINO were seen, suggesting that oral MINO is the most useful treatment for acne vulgaris with minimal risk of bacterial resistance.

J Immunol, 1999 Jan 15, 162(2), 1049 - 55
Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium acnes-primed IFN-gamma-deficient mice by a concomitant reduction of TNF-alpha, IL-12, and IL-18 production; Tsuji H et al.; The present study was designed to investigate the role of IFN-gamma in LPS-induced liver injury following priming with Propionibacterium acnes . At 1 week after priming BALB/c mice with P . acnes, a large number of macrophages (Mphi) and lymphocytes predominantly infiltrated the portal area, resulting in the intrahepatic formation of granulomas consisting of epithelioid and lymphoid cells . In comparison, in IFN-gamma gene-disrupted BALB/c mice (IFN-gamma knockout mice), the number of infiltrated Mphi was decreased, with a significant reduction in the number and size of granulomas . Subsequent elicitation with a low dose of LPS induced massive hepatic necrosis in wild-type BALB/c mice, with a marked increase in the serum levels of TNF-alpha, IL-12, and IL-18 and subsequently of alanine transferase . In contrast, IFN-gamma knockout mice developed scattered focal necrosis of the liver with significantly lower levels of serum alanine transferase as well as drastic decreases in TNF-alpha, IL-12, and IL-18 production . The administration of an anti-IFN-gamma neutralizing mAb at the eliciting phase significantly alleviated liver injury and reduced serum IL-12 and IL-18 levels . Thus, endogenously produced IFN-gamma is involved in the pathogenesis of this liver injury model by regulating Mphi infiltration and granuloma formation in the priming phase as well as cytokine production in the eliciting phase.

J Appl Microbiol, 1998 Dec, 85(6), 956 - 64
Identification and clustering of dairy propionibacteria by RAPD-PCR and CGE-REA methods; Rossi F et al.; A total of 67 classical propionic acid bacteria (PAB) strains, 10 of which were from type culture collections and 57 from milk, typical Italian cheeses, acid whey and feed flour of different regions, were analysed by Randomly Amplified Polymorphic DNA (RAPD-PCR) and by Conventional Gel Electrophoresis Restriction Endonuclease Analysis (CGE-REA) . The genotypic traits achieved using RAPD-PCR with three primers (OPL-01, OPL-02 and OPL-05) and SmaI CGE-REA patterns were compared by numerical analysis and allowed a clear distinction of four clusters corresponding to the currently described species of classical propionibacteria according to type and reference strains positions . No discrepancies exist in species recognition between the two methods; 36 isolates were identified as Propionibacterium freudenreichii, 15 as P . jensenii, four as P . acidipropionici and two as P . thoenii . Many differences, however, were observed in intraspecific clustering . Numerical comparison of RAPD-PCR profiles appeared to be a suitable method for highlighting the presence of particular phenotypic characters, while intraspecific differentiation obtained by CGE-REA analysis allowed association of strains at high similarity levels on the basis of their geographical origin.

J Dermatol, 1998 Nov, 25(11), 697 - 702
A clinical, microbiological, and histopathologic study of trichostasis spinulosa; Chung TA et al.; Trichostasis spinulosa (TSS) is a relatively common follicular disorder that can occur on the face and trunk, especially in the interscapular area . Its cause remains unclear . We examined clinically 30 patients with TSS and follicular materials extracted from each patient were examined microscopically . Bacterial culture and skin biopsy were done in 12 and 10 patients, respectively . Periodic acid Schiff (PAS) and Brown-Brenn Gram stain were used for detection of pityrosporum (malassezia) and bacteria . The interscapular area (14/30), nose (8/30), and cheek (4/30) were common sites of TSS . Pityrosporum and bacteria in the extracted follicular material were found at the rates of 82.6% and 73.3%, respectively . In histologic examination, follicular hyperkeratosis and numerous vellus hairs enveloped within keratotic sheath were common features . Pityrosporum and bacteria were found at the rate of 70% in biopsied specimens on PAS and Brown-Brenn Gram stain . In bacterial culture, Propionibacterium acne was most commonly identified in 75% (9 out of 12 patients) . Pityrosporum and bacteria, especially Propionibacterium acne, were commonly found in the extracted follicular material and biopsied specimens . Thus, they may be related to the induction of follicular hyperkeratosis with retention of vellus hairs, and we suggest that these microorganisms may be one of the possible etiologic factors of TSS.

Yao Xue Xue Bao, 1996, 31(9), 662 - 5
{Effect of matrine on mouse hepatitis and tumor necrosis factor production induced by Propionibacterium acnes/lipopolysaccharides}; Hu ZL et al.; The effect of matrine (Mat) on lipopolysaccharides (LPS)-induced fatal hepatitis and tumor necrosis factor (TNF) production in Propionibacterium acnes (PA)-primed mice were studied . Mice were injected i.p . LPS (10 micrograms/mouse) 7 d after i.p . PA (0.5 ml/mouse) to induce fatal hepatitis . After i.p . LPS, serum TNF activity rose to 1657 +/- 406 kU.L-1 at 1.5 h and ALT activity increased up to 1,496 +/- 890 U.L-1 at 5 h . Six of 8 mice died within 5 h and the massive hemorrhagic necrosis of the liver was observed in all mice . Administration of Mat (10, 50 mg.kg-1, i.p., bid x 3 d) before the LPS injection markedly reduced the elevation of serum TNF and ALT activity in a dose-dependent manner, and diminished the mortality induced by LPS . Liver congestion and necrosis induced by LPS in PA-primed mice were ameliorated markedly by Mat pretreatment . Mat (62.5-250 mg.L-1) inhibited LPS-induced TNF release from PA-primed mouse peritoneal macrophage in vitro in a concentration-dependent manner . These results seggest that Mat protected PA-primed mice from the development of fatal hepatitis induced by LPS due to inhibition of TNF production.

Ann Acad Med Stetin, 1998, 44, 65 - 85
{Skin reactions to antigens of propionibacterium acnes in patients with acne vulgaris treated with autovaccine}; Zaluga E; One of the most common diseases of the skin is acne . The etiology and pathogenesis of acne, in spite of the advancement of medical knowledge, remain unknown and the effects of treatment unsatisfactory . The mechanism of the beneficial effects of immunotherapy in some cases of acne, including autovaccines prepared from the bacterial strains of the patient, also awaits explanation . The present work was aimed at elucidating the influence of autovaccine on some parameters of specific humoral and cellular response against the same strains of Propionibacterium acnes that were isolated from the patient to prepare the autovaccine . These parameters were evaluated in vivo on the basis of early and delayed skin reactions and in vitro using respective laboratory tests . By analysing the influence of autovaccine on the immunological status it was hoped to shed some light on the immunological aspects of acne . An improvement after autovaccine was noted in 47.6% of patients . At the same time it was observed that the results of the present treatment with autovaccine were much better in patients who were previously treated for acne with Acnevac or autovaccine than in other patients . One may therefore conclude that repeated immunotherapy in acne is advantageous in terms of results . The frequency of early skin reactions against the Propionibacterium acnes of the patient and against standard strains, the level of serum IgE antibodies in patients with acne of various intensity and the release of histamine in the presence of Propionibacterium acnes from basophils of patients with positive early skin reactions all stand against the role of early-type hypersensitivity and anaphilactoid phenomena linked with the structural antigens of the patient's strains of Propionibacterium acnes in the pathogenesis of acne (Tab . 1, Fig . 1) . Reactions reflecting delayed-type hypersensitivity against the patient's strains of Propionibacterium acnes were observed more frequently than early-type reactions and more frequently than against standard strains (Tab . 2) . Clinical improvement was particularly evident in patients in whom the intensity of the reactions decreased after treatment . This was accompanied by higher titres of specific antibodies against structural antigens of Propionibacterium acnes (Tab . 3) and a greater inhibition of migration of mononuclear cells in the presence of these bacteria or a nonspecific mitogen (PHA) . It was concluded that specific antibodies generated by the autovaccine and directed against the strain of Propionibacterium acnes of the patient may reduce the intensity of delayed-type reactions in some cases of acne, as previously reported for tularemia and tuberculosis . Final unequivocal conclusions as to the pathogenesis of acne and mechanism of the effects of autovaccine could not be drawn . However, the present results form an encouraging basis for further research in this field.

Presse Med, 1998 Nov 21, 27(36), 1839 - 41
{Propionibacterium acnes infectious endocarditis}; Durupt S et al.; BACKGROUND: Propionibacterium acnes, a Gram positive microaerophilic bacteria is considered to have a low level of virulence . Nevertheless, it can be associated with infective endocarditis . We report 2 cases and a review of the literature . CASE REPORTS: The first man developed an acute prosthetic valve infective endocarditis and died . The second case was also a prosthetic valve infective endocarditis in a patient who developed infectious spondylitis . DISCUSSION: P . acnes is an uncommon causal agent in infective endocarditis and appears to have a predilectio for prosthetic valves . A prior history of skin infection is rare . P . acnes grow quite slowly, often requiring 7 to 14 days for identification . All isolates of P . acnes from blood or valve do not necessarily mean contamination.

Syst Appl Microbiol, 1998 Aug, 21(3), 419 - 28
Identification of classical Propionibacterium species using 16S rDNA-restriction fragment length polymorphisms; Riedel KH et al.; The phenotypic identification of the classical propionibacteria is essentially still problematic and alternative techniques for the identification of the various species are required . A rapid and sensitive technique for the routine identification of the classical propionibacteria, based on the amplification of 16S rRNA genes using the polymerase chain reaction and the subsequent restriction endonuclease digestion of the PCR products, was previously described . Although this technique enabled differentiation between the various classical species examined it was only evaluated on a limited number of type and reference strains . During this study, the taxonomic relationship between 135 Propionibacterium strains from diverse ecological niches, representing four classical species was investigated using this PCR/RFLP technique . Visual differentiation between the classical Propionibacterium was possible after restriction endonuclease digestion of the PCR products obtained using primers 16sP1-16sP4 and 16sP3-16sP4 with the restriction endonucleases HaeIII, AluI and HpaIII, respectively . With the exception of strains independently identified as "P . rubrum" and "P . sanguineum", the results of this study confirm the consolidation of the "old" species into the various classical species as they currently exist . It was therefore concluded that the PCR/RFLP protocol is suitable for the rapid and routine identification of the classical propionibacteria.

J Clin Invest, 1998 Dec 1, 102(11), 1933 - 41
Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice; Yoneyama H et al.; Thymus and activation-regulated chemokine (TARC) is a recently identified lymphocyte-directed CC chemokine which specifically chemoattracts T helper type 2 CD4(+) T cells in human . To establish the pathophysiological roles of TARC in vivo, we investigated whether a monoclonal antibody (mAb) against TARC could inhibit the induction of hepatic lesions in murine model using Propionibacterium acnes and lipopolysaccharide (LPS) . P . acnes-induced intrahepatic granuloma formation in the priming phase is essential to the subsequent liver injury elicited by a low dose of LPS . The priming phase appears to be dominated by Th1 type immune responses determined by the profile of chemokine and chemokine receptor expression . TARC was selectively produced by granuloma-forming cells, and CC chemokine receptor 4 (CCR4)-expressing CD4(+) T cells migrated into the liver after LPS administration . In vivo injection of anti-TARC mAb just before LPS administration protected the mice from acute lethal liver damage, which was accompanied by a significant reduction of both CCR4 mRNA expression and IL-4 production by liver-infiltrating CD4(+) T cells . Moreover, both TNF-alpha and Fas ligand expressions in the liver were decreased by anti-TARC treatment . These results suggest that recruitment of IL-4-producing CCR4(+) CD4(+) T cells by granuloma-derived TARC into the liver parenchyma may be a key cause of massive liver injury after systemic LPS administration.

Protein Sci, 1998 Oct, 7(10), 2156 - 63
Structural characterization of the entire 1.3S subunit of transcarboxylase from Propionibacterium shermanii; Reddy DV et al.; Transcarboxylase (TC) from Propionibacterium shermanii, a biotin-dependent enzyme, catalyzes the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate in two partial reactions . Within the multisubunit enzyme complex, the 1.3S subunit functions as the carboxyl group carrier . The 1.3S is a 123-amino acid polypeptide (12.6 kDa), to which biotin is covalently attached at Lys 89 . We have expressed 1.3S in Escherichia coli with uniform 15N labeling . The backbone structure and dynamics of the protein have been characterized in aqueous solution by three-dimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy . The secondary structure elements in the protein were identified based on NOE information, secondary chemical shifts, homonuclear 3J(HNHalpha) coupling constants, and amide proton exchange data . The protein contains a predominantly disordered N-terminal half, while the C-terminal half is folded into a compact domain comprising eight beta-strands connected by short loops and turns . The topology of the C-terminal domain is consistent with the fold found in both carboxyl carrier and lipoyl domains, to which this domain has approximately 26-30% sequence similarity.

J Gastroenterol Hepatol, 1998 Sep, 13 Suppl, S51 - 4
Effect of FK506 on the activation state of hepatic macrophages in Propionibacterium acnes-treated rats; Toshima K et al.; Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes . In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506 . The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats . When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-gamma-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-gamma were significantly increased compared with normal rats . Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen . FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-alpha production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats . It is suggested that a cytokine network through interferon-gamma-inducing factor, interferon-gamma and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network . FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.

Mikrobiologiia, 1998 Jul-Aug, 67(4), 527 - 31
{Isolation and purification of a protective protein from Propionibacterium freudenreichii subsp . Shermanii}; Zinchenko AA et al.; A protein responsible for the protective and reactivating activities of two active fractions (AF1 and AF2) of the cells of Propionibacterium freudenreichii subsp . shermanii was isolated . The active fraction AF1 was obtained by fractional precipitation of the cell-free extract of propionic acid bacteria between 20 and 40% ammonium sulfate saturation, whereas fraction AF2 was precipitated between 60 and 80% saturation . Further fractionation of AF1 and AF2 by gel filtration on Sephacryl S-200 and by ion-exchange chromatography on DEAE-Sepharose yielded seven active subfractions, as revealed by testing for their protective activity on UV-inactivated cells of Escherichia coli . Analysis of subfraction AF2-2.5 by SDS-electrophoresis and HPLC showed that it contained an apparently homogeneous protein with a molecular mass of 44 +/- 2 kDa . The concentrational dependence of the protective activity of this protein was derived . Peptides of subfractions AF2-2.1 and AF2-2.2 with molecular masses lower than 15 kDa also exhibited protective activity.

Arthritis Rheum, 1998 Oct, 41(10), 1889 - 93
Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis; Schaeverbeke T et al.; This report describes the case of a patient with a 14-month course of severe oligoarthritis associated with acne . Pure cultures of Propionibacterium acnes were isolated from synovial tissue and synovial fluid specimens collected from the same joint after a 4-month interval . After 2 months of treatment with roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal antiinflammatory drug (NSAID), followed by 4 months of treatment with azithromycin 1 gm/week and an NSAID, the synovitis persisted . Cultures of skin lesions and synovial fluid at this time were negative . Although P acnes has previously been isolated from bone specimens obtained from patients with osteitis associated with acne, this is the first report of the isolation of this microorganism from the synovial tissue of a patient with arthritis associated with acne . Our findings raise the question of the role of P acnes in the pathogenesis of arthritis associated with acne.

J Immunol Methods, 1998 Aug 1, 217(1-2), 97 - 102
Establishment of the cells useful for murine interleukin-18 bioassay by introducing murine interleukin-18 receptor cDNA into human myelomonocytic KG-1 cells; Taniguchi M et al.; We genetically engineered human myelomonocytic KG-I cells by introducing cDNA of murine interleukin-18 receptor (MuIL-18R) and established human cells which were capable of responding to MuIL-18 . These cells expressed larger number of MuIL-18R (> 13,000 sites/cell) than intrinsic human IL-18 receptor (HuIL-18R) (< 2,500 sites/cell) . And the cells responded to MuIL-18 as well as to HuIL-18 in a dose-dependent manner, and produced large amounts of interferon-gamma (IFN-gamma) . We could estimate the amount of murine IL-18 based on the amounts of IFN-gamma produced by these cells . The stoichiometry was observed up to 150 ng/ml of MuIL-18 . By using these cells, a large amount of MuIL-18 (448 +/- 89.2 ng/ml) was detected in sera of Propionibacterium acnes (P . acnes)/lipopolysaccharide (LPS)-treated endotoxic mice (the same conditions in which IL-18 was first identified) . These cells provide us with a useful tool for determining the bioactivity of MuIL-18.

Yao Xue Xue Bao, 1996, 31(8), 577 - 80
{Effect of silymarin on mouse liver damage, production and activity of tumor necrosis factor}; Zhang JP et al.; Tumor necrosis factor (TNF) has been well-characterized as a prominent mediator in the development of liver injury . Effects of silymarin (SB) on mouse liver damage, TNF production and activity were studied . Pretreatment with SB (25-50 mg.kg-1, i.p., bid x 3 d) before the lipopolysaccharides (LPS) injection markedly alleviated liver injury and diminished LPS-induced TNF production in Propionibacterium acnes (PA)-primed mice . SB (12.5-50 micrograms.ml-1) significantly inhibited LPS-induced TNF release from mouse peritoneal macrophage in a concentration-dependent manner . SB(12.5-100 micrograms.ml-1) was also shown to markedly reduce TNF cytotoxicity on human hepatic cell line GSG-7701 and mouse fibroblastic cell line L929 cells concentration-dependently . These results suggest that inhibition of TNF production and its actions may be involved in the mechanism of protective action of SB on liver damage.

Biochemistry, 1998 Oct 13, 37(41), 14386 - 93
Stabilization of radical intermediates by an active-site tyrosine residue in methylmalonyl-CoA mutase; Thoma NH et al.; The adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the reversible rearrangement of methylmalonyl-CoA into succinyl-CoA by a free-radical mechanism . The recently solved X-ray crystal structure of methylmalonyl-CoA mutase from Propionibacterium shermanii has shown that tyrosine 89 is an active-site residue involved in substrate binding . The role of tyrosine 89, a conserved residue among methylmalonyl-CoA mutases, has been investigated by using site-directed mutagenesis to replace this residue with phenylalanine . The crystal structure of the Tyr89Phe mutant was determined to 2.2 A resolution and was found to be essentially superimposable on that of wild-type . Mutant and wild-type enzyme have very similar KM values, but kcat for the Tyr89Phe mutant is 580-fold lower than for wild-type . The rate of release of tritium from 5'-{3H}adenosylcobalamin during the enzymatic reaction and its rate of appearance in substrate and product were measured . The tritium released was found to partition unequally between methylmalonyl-CoA and succinyl-CoA, in a ratio of 40:60 when the reaction was initiated by addition of methylmalonyl-CoA and in a ratio of 10:90 when the reaction was initiated by addition of succinyl-CoA . The overall release of tritium was four times faster when succinyl-CoA was used as substrate . The tritium isotope effect on the enzyme catalyzed hydrogen transfer, measured with methylmalonyl-CoA as a substrate, was kH/kT = 30, which is within the expected range for a full primary kinetic tritium isotope effect . The different partitioning of tritium, dependent upon which substrate was used, and the normal value for the kinetic tritium isotope effect contrast markedly with the behavior of wild-type mutase . It appears that the loss of a single interaction involving the hydroxyl group of tyrosine 89 both affects the stability of radical intermediates and decreases the rate of interconversion of the substrate- and product-derived radicals.

Anal Biochem, 1978 Dec, 91(2), 557 - 65
A rapid, enzymatic assay for the measurement of inorganic pyrophosphate in animal tissues; Cook GA et al.; A simple, rapid enzymatic assay for the determination of inorganic pyrophosphate in tissue and plasma has been developed using the enzyme pyrophosphate--fructose-6-phosphate 1-phosphotransferase (EC 2.7.1.90) which was purified from extracts of Propionibacterium shermanii . The enzyme phosphorylates fructose-6-phosphate to produce fructose-1,6-bisphosphate using inorganic pyrophosphate as the phosphate donor . The utilization of inorganic pyrophosphate is measured by coupling the production of fructose-1,6-bisphosphate with the oxidation of NADH using fructose-bisphosphate aldolase (EC 4.1.2.13), triosephosphate isomerase (EC 5.3.1.1), and glycerol-3-phosphate dehydrogenase (NAD+)(EC 1.1.1.8) . The assay is completed in less than 5 min and is not affected by any of the components of tissue or plasma extracts . The recovery of pyrophosphate added to frozen tissue powder was 97 +/- 1% (n = 4) . In this assay the change in absorbance is linearly related to the concentration of inorganic pyrophosphate over the curvette concentration range of 0.1 microM to 0.1 mM.

Med J Aust, 1998 Sep 7, 169(5), 259 - 61
Systematic review of Propionibacterium acnes resistance to systemic antibiotics; Cooper AJ; OBJECTIVE: To document changes in the prevalence of resistance of Propionibacterium acnes to antibiotics used for treating acne . DATA SOURCES: MEDLINE and EMBASE were searched for publications on P . acnes resistance to systemic antibiotics . The search strategy mapped "acne" or "acne vulgaris" with the terms "antibiotic resistance" or "drug resistance, microbial" . Only papers published in English during 1976 to 1997 were included in the search . STUDY SELECTION: 53 publications met the search criteria . The search output was refined by selecting papers that specifically addressed P . acnes resistance patterns . Additional studies (not included in the search output) were identified from review articles and references of the retrieved articles . Twelve articles were reviewed . DATA EXTRACTION: Data on the prevalence of antibiotic-resistant propionibacteria, the incidence of individual resistance phenotypes, mixed resistance, and correlation between poor therapeutic response and resistant propionibacteria were extracted . DATA SYNTHESIS: Research since 1978 has suggested an association between poor therapeutic response and antibiotic-resistant propionibacteria . The overall incidence of P . acnes antibiotic resistance has increased from 20% in 1978 to 62% in 1996 . Resistance to specific antibiotics varied and was most commonly reported with erythromycin and clindamycin, tetracycline and doxcycline, and trimethoprim . Resistance to minocycline is rare . CONCLUSIONS: In many patients with acne, continued treatment with antibiotics can be inappropriate or ineffective . It is important to recognise therapeutic failure and alter treatment accordingly . The use of long-term rotational antibiotics is outdated and will only exacerbate antibiotic resistance.

Curr Opin Pediatr, 1998 Aug, 10(4), 381 - 6
Update on acne; DeGroot HE et al.; Acne is a common condition seen routinely by both primary care physicians and dermatologists . Most patients have no underlying pathology and respond to traditional treatment; others, however, require more individualized evaluation and aggressive therapy . New information regarding the pathogenesis and treatment of acne is now available . This update discusses the proper evaluation of early childhood acne, the emergence of Propionibacterium acnes resistance, and the rare but serious side effects occasionally seen with minocycline . Advances in the topical treatment of acne, the use of oral contraceptives in acne, and the use and efficacy of isotretinoin are also addressed.

Am J Physiol, 1998 Oct, 275(4 Pt 2), R1049 - 57
Mechanism of suppressed neutrophil mobilization in a mouse model for binge drinking: role of glucocorticoids; Vinson RB et al.; The goals of this study were to determine if suppression of neutrophil accumulation and TNF-alpha production in the peritoneal cavity occurs in mice exposed to a chemical stressor {ethanol (EtOH)}, to evaluate the role of EtOH-induced increases in endogenous glucocorticoids in any such suppression, and to determine if decreased tumor necrosis factor-alpha (TNF-alpha) production is responsible for decreases in neutrophil accumulation in EtOH-treated mice . An inflammatory response induced in the peritoneal cavity of mice by administration of heat-killed Propionibacterium acnes (P . acnes) was suppressed by a single dose of EtOH given 1 h before administration of the bacteria, as indicated by decreased accumulation of neutrophils in the peritoneal cavity . The concentration of TNF-alpha in the peritoneal cavity was also decreased by EtOH, but exogenous TNF-alpha did not prevent the suppression of neutrophil accumulation . The glucocorticoid antagonist RU-486 did not prevent the suppression of neutrophil accumulation in mice treated with EtOH, but RU-486 did block suppression of neutrophil accumulation caused by administration of exogenous corticosterone . The suppression of neutrophil accumulation caused by exogenous corticosterone was less than produced by EtOH . These observations suggest that the increase in endogenous corticosterone induced by EtOH may explain some of the suppression of neutrophil accumulation, but other neuroendocrine mediators (or EtOH per se) are sufficient to cause the full suppressive effect when the action of corticosterone is blocked by RU-486 . The results also demonstrate that EtOH decreases TNF-alpha production, but this is not the mechanism by which neutrophil accumulation is decreased in this model.

Childs Nerv Syst, 1998 Aug, 14(8), 378 - 80
Propionibacterium {correction of Proprionibacterium} acnes infections of cerebrospinal fluid shunts; Thompson TP et al.; Ventricular cerebrospinal fluid shunt infections with Propionibacterium acnes are generally low-grade, indolent infections . Typical presentations include gradual shunt malfunction, nausea, headache, malaise, and infrequently, fever . In all, 489 shunt procedures performed between January 1992 and December 1995, and in 15 of these cases P . acnes was subsequently cultured from reservoir taps or an intraoperative culture which was obtained when the existing shunt components were revised . Six of these, representing 14.6% of shunt infections, were considered to be true P . acnes shunt infections, as they were associated with either CSF leukocytosis or the identification of gram-positive rods by gram stain . The others were considered to be probable contaminants . Detailed analysis of all 15 of these cases revealed that no patient had positive CSF cultures after removal of the infected shunt and the initiation of antibiotics . Given the benign characteristics of P . acnes shunt infections, the broad sensitivity to antibiotics, and the rapid sterilization of the cerebrospinal fluid, it may be possible to treat such cases with short-term perioperative antibiotics and replacement of the shunt components, in place of prolonged external ventricular drainage and antibiotics . This would have eliminated 8 operative procedures and reduced the estimated length of stay by 77 patient-days in these 15 children.

Syst Appl Microbiol, 1998 Mar, 21(1), 135 - 43
Isolation and characterisation of obligately anaerobic, lipolytic bacteria from the rumen of red deer; Jarvis GN et al.; Two Gram-positive, obligately anaerobic, lipolytic bacteria, isolates LIP4 and LIP5, were obtained from the rumen contents of juvenile red deer . These mesophilic bacterial strains were capable of hydrolysing the neutral lipids, tallow, tripalmitin and oliver oil, into their constituent free long-chain fatty acid and glycerol moieties . The latter compound was dissimilated by both isolates, with isolate LIP4 producing propionate as the predominant product, while isolate LIP5 produced acetate, ethanol and succinate . The lactate-utilising isolate LIP4 grew on a limited range of saccharide substrates including glucose, fructose and ribose, and exhibited an unusual cell wall structure and morphology . The isolate LIP5 grew upon a wider range of saccharides, but was unable to use lactate as a substrate . Based upon phenotypic and 16S rRNA gene sequence analyses, isolate LIP4 clusters with species in the genus Propionibacterium, while isolate LIP5 is a member of clostridial cluster XIVa.

Cesk Slov Oftalmol, 1998 Jul, 54(4), 250 - 6
{Chronic postoperative endophthalmitis caused by Propionibacterium acnes}; Kocur I et al.; There is a report of three cases of chronic postoperative endophthalmitis following cataract operations . In two patients there was proven Propionibacterium acnes . There is presented a technique to obtain specimens for microbiological examination and an overview of clinical experience in treatment of the mentioned less common types of endophthalmitis . Early surgical treatment as well as intraocular injection of vancomycin can help to restore a good visual acuity despite of longlasting inflammation.

J Food Prot, 1998 Feb, 61(2), 211 - 6
Response of cultures of Propionibacterium to acid and low pH: tolerance and inhibition; Rehberger JL et al.; Seventeen Propionibacterium strains were tested for acid production and final pH achieved on glucose, fructose, or maltose as the primary carbon source . On average, strains of Propionibacterium acidipropionici produced more acid and reached lower final pH values than did strains of the other species . Three strains of P . acidipropionici, one Propionibacterium jensenii, and two Propionibacterium thoenii strains were tested further for the ability to survive and/or grow at low pH with lactic, hydrochloric, or propionic acid as acidulant . The organic acids were more inhibitory than hydrochloric acid; propionic acid was most inhibitory . In all cases, the P . jensenii and P . thoenii strains initiated growth and survived at lower pH values than did the p . acidipropionici stains . The ability to produce large amounts of acid or achieve low final pH values did not coincide with the ability to initiate growth or survive in low-pH conditions . Strains could not initiate growth below pH 5.0, but cultures started at neutral pH reached final pH values of less than 4.4 . At neutral pH, strains could grow in the presence of increased lactate concentrations (up to 180 mM) or propionate concentrations (150 mM) that were inhibitory at acid pH . attempts to isolate variants able to initiate growth below pH 5.0 were unsuccessful.

Syst Appl Microbiol, 1998 Jun, 21(2), 251 - 9
Classification and identification of propionibacteria based on ribosomal RNA genes and PCR; Dasen G et al.; A rapid method was developed to differentiate the genus Propionibacterium from other genera by using a modified multiplex-PCR (MPCR) approach . Three 16S rRNA-targeted oligonucleotide primers were designed to amplify simultaneously two DNA-fragments in the MPCR assay . The universal primer pair bak11w and bak4 (corresponding to the E . coli 16S rRNA positions 8-25 and 1522-1540, respectively) was used in combination with the primer pair bak4 and gd1 (5'-TGCTTTCGATACGGGTTGAC-3') . The later sequence corresponding to a 16S rRNA motif that is unique for the genus Propionibacterium . Propionibacteria were identified by the amplification of a Propionibacterium-genus specific 900-bp fragment whereas MPCR with DNA from other bacteria generated only a DNA fragment of 1500 bp in amplifications with the two universal primers . The whole procedure including cell lysis, MPCR amplification and analysis can be performed within 1 day, detection limits are at approximately 10(3) cfu propionibacteria (or 35 pg DNA) . In addition, the taxonomic situation of the genus Propionibacterium was reexamined using a cycle sequencing strategy . Based on the 16S rDNA, a phylogenetic tree of all the Propionibacterium type strains was reconstructed.

Ophthalmologe, 1998 Jun, 95(6), 438 - 41
{Bacterial colonization of conjunctiva with Propionibacterium acnes before and after polyvidon iodine administration before intraocular interventions}; Binder C et al.; BACKGROUND: Propionibacterium acnes has been described as a causative agent of postoperative endophthalmitis . This gram-positive, immotile, non-spore-forming bacterium is highly pleomorphic and grows under conditions of low to no oxygen concentration . It is commonly found on the skin at the openings of sebaceous glands and on hairs . A near-symptomless postoperative endophthalmitis occurs particularly when Propionibacteria are enclosed in the capsular bag . We investigated to what extent the number of P . acnes in the conjunctival sac can be reduced by preoperative disinfection with polyvidone iodine (1%) . PATIENTS AND METHODS: A total of 261 patients with intrabulbar surgery had two conjuctival swabs taken: the first immediately prior to preoperative preparation in the operating theatre, following in-patient application of antibiotic eye drops (Polymyxin-B-sulfat, Neomycinsulfat and Gramicidin in combination); the second swab was taken after disinfection with polyvidone iodine before opening the conjunctiva . RESULTS: Of the 261 swabs, 60 (23%) taken prior to polyvidone iodine application were positive for Propinibacterium acnes . Following polyvidone iodine treatment, a further 5 (1.9%) remained culture-positive . After disinfection, 55 (92%) of the 60 positive swabs for Propionibacterium acnes remained culture-negative . CONCLUSIONS: We concluded that a significant reduction of P . acnes can be achieved by preoperative application of polyvidone iodine (1%) (P < 0.001).

Antimicrob Agents Chemother, 1998 Jul, 42(7), 1702 - 5
16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium; Ross JI et al.; A genetic basis for tetracycline resistance in cutaneous propionibacteria was suggested by comparing the nucleotide sequences of the 16S rRNA genes from 16 susceptible and 21 resistant clinical isolates and 6 laboratory-selected tetracycline-resistant mutants of a susceptible strain . Fifteen clinical isolates resistant to tetracycline were found to have cytosine instead of guanine at a position cognate with Escherichia coli 16S rRNA base 1058 in a region important for peptide chain termination and translational accuracy known as helix 34 . Cytosine at base 1058 was not detected in the laboratory mutants or the tetracycline-susceptible strains . The apparent mutation was recreated by site-directed mutagenesis in the cloned E . coli ribosomal operon, rrnB, encoded by pKK3535.E . coli strains carrying the mutant plasmid were more resistant to tetracycline than those carrying the wild-type plasmid both in MIC determinations and when grown in tetracycline-containing liquid medium . These data are consistent with a role for the single 16S rRNA base mutation in clinical tetracycline resistance in cutaneous propionibacteria.

Vet Immunol Immunopathol, 1998 Jun 12, 63(4), 303 - 15
Immunologic function in horses after non-specific immunostimulant administration; Flaminio MJ et al.; Inactivated Propionibacterium acnes is a biologic response modifier for treatment of non-specific respiratory disease in horses . The objectives of this investigation were to determine alterations in phagocytic activity, phenotypic expression of lymphocyte subpopulations and lymphokine-activated killing cell response in healthy young horses . Samples were collected on day 0, 7 and 14 of the investigation . Blood samples were obtained via jugular venipuncture and pulmonary leukocytes were recovered via bronchoalveolar lavage (BAL) . Commercially available P . acnes (Eqstim) was administered intravenously on days 7, 9 and 11 of the investigation . Fever was observed on days 8 and 10, indicating immune reaction . Total peripheral blood white cell count was increased (P < 0.05) on day 14 after P . acnes administration compared to values on days 0 and 7 . Total BAL fluid cell count decreased (P < 0.01) on day 14 compared to values on days 0 and 7, which was characterized by a decrease in total lymphocyte (P < 0.01) and macrophage (P < 0.01) counts . The proportion of lymphocytes in BAL fluid decreased (P < 0.005) on day 14 compared to values on days 0 and 7, and the proportion of macrophages increased (P < 0.005) on day 14 compared to values on days 0 and 7 . P . acnes administration increased the total (P < 0.05) and proportional (P < 0.05) counts of CD4+ T lymphocytes in peripheral blood . Bronchoalveolar lavage fluid proportion of CD4+ (P < 0.05), CD5+ (P < 0.001) and MHC II (P < 0.05) lymphocytes increased on day 14 after P . acnes administration compared to values on days 0 and 7 . Nonopsonized phagocytic activity in peripheral blood increased (P < 0.0005) on day 14 after P . acnes administration compared to values on days 0 and 7 . Lymphokine-activated killing cell activity in peripheral blood and BAL fluid leukocytes was enhanced (P < 0.005) on day 14 after P . acnes administration compared to values on days 0 and 7 . Serum IgG and IgM concentrations were within laboratory reference values and were not altered by administration of P . acnes . This investigation demonstrated immunostimulant and immunomodulatory properties of P . acnes, characterized by increased CD4+ T lymphocyte expression and LAK activity in peripheral blood and BAL fluid, increased nonopsonized phagocytosis in peripheral blood leukocytes and decreased pulmonary cellularity.

Structure, 1998 Jun 15, 6(6), 711 - 20
Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism; Mancia F et al.; BACKGROUND: Methylmalonyl CoA mutase catalyses the interconversion of succinyl CoA and methylmalonyl CoA via a free radical mechanism . The enzyme belongs to a family of enzymes that catalyse intramolecular rearrangement reactions in which a group and a hydrogen atom on adjacent carbons are exchanged . These enzymes use the cofactor adenosylcobalamin (coenzyme B12) which breaks to form an adenosyl radical, thus initiating the reaction . Determination of the structure of substrate-free methylmalonyl CoA mutase was initiated to provide further insight into the mechanism of radical formation . RESULTS: We report here two structures of methylmalonyl CoA mutase from Propionibacterium shermanii . The first structure is of the enzyme in a nonproductive complex with CoA at 2.5 A resolution . This structure serves as a model for the substrate-free conformation of the enzyme, as it is very similar to the second much poorer 2.7 A resolution structure derived from a truly substrate-free crystal . The true substrate-free structure also shows the adenosyl group bound to the cobalt atom . Comparison of this structure with that of the previously reported complex of the enzyme with a substrate analogue shows that major conformational changes occur upon substrate binding . The substrate-binding site of the enzyme is located within a (beta alpha)8 TIM-barrel domain . In the absence of substrate, this TIM-barrel domain is split apart and the active site is accessible to solvent . When substrate binds, the barrel closes up with the substrate along its axis and the active site becomes completely buried . CONCLUSIONS: The closure of the active-site cavity upon substrate binding displaces the adenosyl group of the cofactor from the central cobalt atom into the active-site cavity . This triggers the formation of the free radical that initiates the rearrangement reaction . The TIM-barrel domain is substantially different from all others yet reported: in its unliganded form it is broken open, exposing the small hydrophilic sidechains which fill the centre . The typical barrel structure is only formed when substrate is bound.

Dtsch Tierarztl Wochenschr, 1998 May, 105(5), 186 - 90
Adjuvant properties of killed Propionibacterium avidum KP-40 in vaccination of dogs against canine parvovirosis; Siwicki AK et al.; Immunomodulating and adjuvant properties of Propionibacterium avidum KP-40 (PA), a potent stimulator of the macrophage-monocyte system and inducer of endogenous interferon, were tested in healthy dogs and in dogs vaccinated against canine parvovirosis (CPV) . A single subcutaneous injection of PA (0.5 mg/kg b . m.) was administered either 10 days before or simultaneously with CPV immunization . The immunomodulating properties of PA were expressed by enhancement of phagocytic and bactericidal activities of blood leukocytes, accompanied by elevated serum levels of interferon-gamma and interleukin-1 and higher Con-A-induced transformation rates of lymphocytes . Titres of CPV antibodies were significantly (p < 0.01) higher in dogs vaccinated and treated with PA either 10 days prior to or simultaneously with immunization . It is concluded that PA may be applied as a potent and safe adjuvant in vaccination of small animals and additionally, it provides enhancement of non-specific antibacterial and antiviral resistance of the organism.

Biotechnol Prog, 1998 May-Jun, 14(3), 457 - 65
Extractive fermentation for enhanced propionic acid production from lactose by Propionibacterium acidipropionici; Jin Z et al.; An extractive fermentation process using an amine extractant and a hollow-fiber membrane extractor to selectively remove propionic acid from the fermentation broth was developed to produce propionate from lactose . Compared to the conventional batch fermentation, the extractive fermentation had a much higher productivity ( approximately 1 g/(L.h) or 5-fold increase), higher propionate yield (up to 0.66 g/g or more than 20% increase), higher final product concentration (75 g/L or higher), and higher product purity ( approximately 90%) . Meanwhile, acetate and succinate productions in the extractive fermentation were significantly reduced . The improved fermentation performance can be attributed to the reduced product inhibition and a possible metabolic pathway shift to favor more propionic but less acetic and succinic acid production . The process was stable and gave consistent long-term performance over the 1 . 5-month period studied . The effects of propionate concentration, pH, and amine content in the solvent on the extractive fermentation were also studied and are discussed in this paper.

Biochem J, 1998 Apr 15, 331 ( Pt 2), 403 - 7
pH-dependent inhibition by azide and fluoride of the iron superoxide dismutase from Propionibacterium shermanii; Meier B et al.; The iron-containing superoxide dismutase from Propionibacterium shermanii shows, in contrast with other iron superoxide dismutases, only a minor inhibition by azide or fluoride (10-100 mM) of up to 23% at pH 7.8 . The activity of the protein with Mn bound to the active site was not diminished under the same conditions . The binding constant between azide and the Fe3+ ion was determined as approx . 2 mM and for fluoride approx . 2.3 mM; they are so far comparable to those known for other iron superoxide dismutases . This seems to be a discrepancy because all other iron superoxide dismutases so far known are described as being inhibited by 50-70% by 10 mM azide . However, towards lower pH there was a drastically increased inhibition by both anions . At pH 6.8 about 80% inhibition was exhibited by azide or fluoride at a concentration of 10 mM or higher . In contrast, on increasing the pH, azide or fluoride still bound to the Fe3+ at the active site but their inhibition capacity decreased . This observation implies that both anions bind to the metal at a position that is empty at low pH, whereas at higher pH water or a negatively charged hydroxyl anion is bound . It is likely that the superoxide anion binds to the same position and has to replace the sixth ligand, leading to a diminished catalytic activity of the superoxide dismutase owing to steric and/or electrostatic inhibition of the ligand.

Biochem Biophys Res Commun, 1998 May 29, 246(3), 731 - 5
Contribution of CD14 to endotoxin-induced liver injury may depend on types of macrophage activation in rats; Toshima K et al.; Activated Kupffer cells and hepatic macrophages can produce massive liver necrosis through microcirculatory disturbance due to sinusoidal fibrin deposition . This mechanism is involved in the development of liver injury after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes (P.acnes) or undergoing 70% liver resection . The significance of CD14, a receptor for lipopolysaccharide and its binding protein, was evaluated in both models in relation to the activation mechanisms of Kupffer cells and hepatic macrophages . Northern blot analysis revealed that CD14 mRNA expression was increased in the liver of rats following P.acnes administration . In these rats, hepatic macrophages immediately after isolation showed marked increased of CD14 mRNA expression compared to Kupffer cells from normal rats . In contrast, CD14 mRNA expression was minimal in partially resected liver . Interleukin (IL)-18 and IL-2 mRNA expression in the liver and interferon (IFN)-gamma mRNA expression in the spleen were significantly increased in P.acnes-treated rats compared to normal rats, while these increases were absent in partially hepatectomized rats . Thus, CD14 expressed on hepatic macrophages after activation through a cytokine network of IL-18, IFN-gamma, and IL-2 may contribute to endotoxin-induced liver injury in P.acnes-treated rats . In contrast, in partially hepatectomized rats, this network may not operate during Kupffer cell activation, and the liver injury might develop through endotoxin receptors other than CD14 on the cells.

Jpn J Antibiot, 1998 Feb, 51(2), 130 - 6
{Fundamental studies on antibacterial activity of clindamycin against Propionibacterium acnes}; Komagata Y et al.; Antibacterial activity of clindamycin against Propionibacterium acnes (P . acnes) was evaluated in comparison with nadifloxacin in vitro . Using a burned-infected mouse model, topical application of 1% gel form of clindamycin phosphate on P . acnes was also evaluated in in vivo . (1) The MIC of clindamycin measured by agar dilution method was 0.02 microgram/ml, and this value was smaller than that of nadifloxacin (0.3 microgram/ml) . (2) At concentrations on 1-, 2- and 4- times the MIC clindamycin demonstrated bacteriostatic activity on P . acnes and showed bactericidal activity at 5-times the MIC . Nadifloxacin showed bacteriostatic activity at one half the MIC and bactericidal activity at the MIC . (3) Against acquired resistant strains of P . acnes, the highest concentrations of clindamycin and nadifloxacin that did not inhibit growth of the organism increased 5-fold higher than those against sensitive strain during 25 successive cultures in vitro . Therefore, the resistance of P . acnes was found to be emerged at almost the same ratio against both agents . (4) The chemotherapeutic effects of 1% gel form of clindamycin phosphate and 1% cream of nadifloxacin were evaluated for given subcutaneously to infected P . acnes at the burned site in mice . The topical application of either agents showed a significant reduction of number of bacteria and this result predicted clinical efficacy of topical application of clindamycin.

Arzneimittelforschung, 1998 Feb, 48(2), 188 - 96
Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol and pale sulfonated shale oil . Multicentre, randomized, vehicle-controlled, double-blind study on 91 acne patients with acne papulopustulosa (Plewig and Kligman's grade II-III); Fluhr JW et al.; In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence could be provided of a significant reduction of the propionibacteria as well as a subosuppressive effect (squalene reduction) under a combination of 1% chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the alcoholic vehicle (1-2 ml twice daily) . Likewise, monotherapy with chloramphenicol resulted in a significant reduction in bacteria compared to the vehicle . The combination therapy was superior to the monotherapy with regard to the sebosuppressive effects . Based on a kinetics test carried out for a total of 2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled out . The chloramphenicol serum level was between < 5.0 microgram/l to 180 microgram/l (average 25 micogram/l) . This is important because with systemic application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l (25,000 microgram 1) . None of the blood count and serum parameters were pathologically changed in a clinically relevant way before and after the therapy . An induction of resistance against chloramphenicol in the propionibacteria could be excluded . No adverse events and side effects occurred . The topical therapy of acne papulopustulosa with chloramphenicol as a monosubstance or in combination with pale sulfonated shale oil represents an effective and safe local antibiotic treatment possibility.

Dermatology, 1998, 196(1), 135 - 9
Systemic antibiotics for acne; Meynadier J et al.; Antibiotic therapy for acne is very common . Antibiotics are frequently used in acne, either systemically or topically . Systemic antibiotics are indicated as treatment of moderate and quite severe acne or if acne is considered as very serious by the patient for psychological or social reasons . Results are very often excellent, but failure is possible; in this case using another treatment, especially isotretinoin, is necessary . A few antibiotics are useful: tetracyclines (tetracycline, doxycycline, minocycline, lymecycline), erythromycin, co-trimoxazole and trimethoprim . Their side effects are reviewed . During pregnancy the best antibiotic is erythromycin . For the nursing mother it is generally said that tetracyclines are contraindicated but the risks if they exist are certainly slight . The mechanism of action of systemic antibiotics for acne is not perfectly clear as it is not only antimicrobial: they diminish chemotaxis of polymorphonuclear leukocytes, modify the complement pathways and inhibit the polymorphonuclear leukocyte chemotactic factor and the lipase production in Propionibacterium acnes.

Dermatology, 1998, 196(1), 130 - 4
An overview of topical antibiotics for acne treatment; Toyoda M et al.; Topical use of antibiotics is currently a widely accepted effective and safe treatment for acne . A review of the articles published in the past 30 years revealed that topical application of antibiotics such as erythromycin, clindamycin or tetracycline showed clinical effectiveness for mild to moderate inflammatory acne, especially when they are combined with zinc, tretinoin or benzoyl peroxide, while they showed little influence on noninflammatory acne . The main mechanism of action of topical antibiotics for acne treatment is inhibition of inflammation caused by bacteria rather than a direct bactericidal effect . The adverse reactions of topical antibiotics are mostly minor and negligible, while special attention should be given to the risk of development of resistant strains of Propionibacterium acnes . The development of new antibiotics is promising and will provide a wider range of therapeutic options for refractory cases.

Dermatology, 1998, 196(1), 119 - 25
Topical drug treatment in acne; Gollnick H et al.; The main part of acne treatment uses the topical route . More than 50% of acne patients belong to the group presenting with acne comedonica and papulopustulosa . Whenever small nodes or scarring occur, systemic comedication is indicated, however . Topical treatment affects at least three of the four main pathogenetic factors responsible for the development of acne, i.e . hyperseborrhea, hyperkeratosis, microbial colonization and inflammation . The agents currently available influence at least one of these factors but often have additional properties . Those which act in a comedolytic and anticomedogenic manner are the retinoids tretinoin, isotretinoin, adapalene and tazarotene and azelaic acid as well, some of the retinoids having additional anti-inflammatory potency . Azelaic acid has strong antibacterial potency without inducing bacterial resistance similar to benzoyl peroxide . Unfortunately, bacterial resistances are beginning to emerge as a significant problem . Propionibacterium acnes resistance to the commonly used erythromycin can also be transferred to clindamycin, whereas no resistance has been reported to nadifloxacin so far . Today, more and more evidence comes up that topical antiandrogenic agents will soon be available to treat the important factor seborrhea, because patients with marked hyperseborrhea frequently relapse . Finally, liposome encapsulation of agents including phospholipids can enhance penetration and efficacy but, particularly with regard to retinoids, can lead to higher absorption and adverse drug reactions.

Dermatology, 1998, 196(1), 82 - 5
The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation; Akamatsu H et al.; The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation . Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics . Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils . The drug is known to have no significant effect on the growth of Propionibacterium acnes . The proportion of linoleic acid is markedly decreased in acne comedones . Linoleic acid significantly suppressed ROS generated by neutrophils . The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation . These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.

Dermatology, 1998, 196(1), 80 - 1
Inflammatory acne represents hypersensitivity to Propionibacterium acnes; Webster GF; Hypersensitivity to P . acnes may account for the great variation in acne severity . Alternative explanations such as hyperandrogenism fail to account for disease severity in large numbers of patients.

Dermatology, 1998, 196(1), 55 - 8
Propionibacterium acnes colonization in acne and nonacne; Leyden JJ et al.; Propionibacterium acnes is a number of the resident bacterial flora and resides in sebaceous follicles . Age-related and body-dependent quantitative differences exist, indicating the role of sebum as an important ecological factor for P . acnes . Acne patients demonstrate marked increases in this organism which generates inflammation through a variety of mechanisms.

J Bacteriol, 1998 Apr, 180(8), 2137 - 43
PPi-dependent phosphofructokinase from Thermoproteus tenax, an archaeal descendant of an ancient line in phosphofructokinase evolution; Siebers B et al.; Flux into the glycolytic pathway of most cells is controlled via allosteric regulation of the irreversible, committing step catalyzed by ATP-dependent phosphofructokinase (PFK) (ATP-PFK; EC 2.7.1.11), the key enzyme of glycolysis . In some organisms, the step is catalyzed by PPi-dependent PFK (PPi-PFK; EC 2.7.1.90), which uses PPi instead of ATP as the phosphoryl donor, conserving ATP and rendering the reaction reversible under physiological conditions . We have determined the enzymic properties of PPi-PFK from the anaerobic, hyperthermophilic archaeon Thermoproteus tenax, purified the enzyme to homogeneity, and sequenced the gene . The approximately 100-kDa PPi-PFK from T . tenax consists of 37-kDa subunits; is not regulated by classical effectors of ATP-PFKs such as ATP, ADP, fructose 2,6-bisphosphate, or metabolic intermediates; and shares 20 to 50% sequence identity with known PFK enzymes . Phylogenetic analyses of biochemically characterized PFKs grouped the enzymes into three monophyletic clusters: PFK group I represents only classical ATP-PFKs from Bacteria and Eucarya; PFK group II contains only PPi-PFKs from the genus Propionibacterium, plants, and amitochondriate protists; whereas group III consists of PFKs with either cosubstrate specificity, i.e., the PPi-dependent enzymes from T . tenax and Amycolatopsis methanolica and the ATP-PFK from Streptomyces coelicolor . Comparative analyses of the pattern of conserved active-site residues strongly suggest that the group III PFKs originally bound PPi as a cosubstrate.

J Bacteriol, 1998 Apr, 180(8), 2014 - 20
Expression and regulation of the sodF gene encoding iron- and zinc-containing superoxide dismutase in Streptomyces coelicolor Müller; Kim EJ et al.; Streptomyces coelicolor Muller contains two superoxide dismutases (SODs), nickel-containing (NiSOD) and iron- and zinc-containing SOD (FeZnSOD) . The sodF gene encoding FeZnSOD was isolated by using PCR primers corresponding to the N-terminal peptide sequence of the purified FeZnSOD and a C-terminal region conserved among known FeSODs and MnSODs . The deduced amino acid sequence exhibited highest similarity to Mn- and FeSODs from Propionibacterium shermanii and Mycobacterium spp . The transcription start site of the sodF gene was determined by primer extension . When the sodF gene was cloned in pIJ702 and introduced into Streptomyces lividans TK24, it produced at least 30 times more FeZnSOD than the control cells . We disrupted the sodF gene in S . lividans TK24 and found that the disruptant did not produce any FeZnSOD enzyme activity but produced more NiSOD . The expression of the cloned sodF gene in TK24 cells was repressed significantly by Ni, consistent with the regulation pattern in nonoverproducing cells . This finding suggests that the cloned sodF gene contains the cis-acting elements necessary for Ni regulation . When the sodF mRNA in S . coelicolor Muller cells was analyzed by S1 mapping of both 5' and 3' ends, we found that Ni caused a reduction in the level of monocistronic sodF transcripts . Ni did not affect the stability of sodF mRNA, indicating that it regulates transcription . S . lividans TK24 cells overproducing FeZnSOD became more resistant to oxidants such as menadione and lawsone than the control cells, suggesting the protective role of FeZnSOD . However, the sodF disruptant survived as well as the wild-type strain in the presence of these oxidants, suggesting the complementing role of NiSOD increased in the disruptant.

Clin Exp Dermatol, 1997 Sep, 22(5), 211 - 5
Investigation of the mechanism of action of 2% fusidic acid lotion in the treatment of acne vulgaris; Sommer S et al.; We describe the results of a single-centre, double-blind, vehicle-controlled, parallel group study on the quantitative effects of 2% fusidic acid lotion (Fucidin lotion) in facial acne vulgaris . The trial was completed by 52 patients aged 15-25 years with mild to moderate acne who had been randomized to either Fucidin Lotion (n = 25) or its base (n = 27) . Primary outcome measures included colony counts of Propionibacterium acnes and micrococcaceae and measurements of skin surface lipid free fatty acids and sebum excretion rate . Clinical assessment was based on the acne grade, count of inflamed and non-inflamed lesions and evidence of a primary irritant dermatitis . There was a variable but gradual reduction in lesion counts with the maximum improvement at 12 weeks for inflamed lesions, where the reduction was 19.9% for fusidic acid and 24.7% for the placebo . The non-inflamed lesions decreased by 10.8% in the fusidic acid group and increased by 15.9% in the placebo group; this difference was not statistically significant . Although the fusidic acid reduced the micrococcaceae count by 1 log cycle, inferring adequate compliance, there was no reduction in the counts of P . acnes, surface free fatty acids or sebum excretion rate . This study has failed to explain the mechanism of action of topical fusidic acid.

J Biol Chem, 1998 Mar 13, 273(11), 6508 - 17
Cloning, sequencing, expression, and insertional inactivation of the gene for the large subunit of the coenzyme B12-dependent isobutyryl-CoA mutase from Streptomyces cinnamonensis; Zerbe-Burkhardt K et al.; Purification of the coenzyme B12-dependent isobutyryl-CoA mutase (ICM) from Streptomyces cinnamonensis gave a protein of approximately 65 kDa by SDS-polyacrylamide gel electrophoresis, whose gene icmA was cloned using sequences derived from tryptic peptide fragments . The gene encodes a protein of 566 residues (62, 487 Da), with 43-44% sequence identity to the large subunit of methylmalonyl-CoA mutase (MCM) from S . cinnamonensis and Propionibacterium shermanii . Targeted disruption of the icmA gene yielded an S . cinnamonensis mutant devoid of ICM activity . The IcmA protein is approximately 160 residues shorter than the large subunit of the bacterial MCMs, corresponding to a loss of the entire C-terminal coenzyme B12 binding domain . The sequence of the (beta/alpha)8-barrel comprising residues A1-A400 in P . shermanii MCM is highly conserved in IcmA . The protein was produced in Streptomyces lividans and Escherichia coli with an N-terminal His6 tag (His6-IcmA), but after purification His6-IcmA showed no ICM activity . In the presence of coenzyme B12, protein from S . lividans and S . cinnamonensis of approximately 17 kDa by SDS-polyacrylamide gel electrophoresis could be selectively eluted with His6-IcmA from a Ni2+ affinity column . After purification, this small subunit showed no ICM activity but gave active enzyme when recombined with coenzyme B12 and IcmA or His6-IcmA.

Rev Rhum Engl Ed, 1998 Jan, 65(1), 68 - 71
Two cases of discitis due to Propionibacterium acnes; Crouzet J et al.; We report two cases of discitis due to Propionibacterium acnes and review previously published cases of bone and joint infections in which this organism was recovered as a pure culture . P . acnes is an anaerobic organism usually considered a normal inhabitant of the skin but capable of producing a variety of infections including discitis, osteitis, arthritis, and chest wall osteitis . Most patients were immunocompetent . A few infections occurred spontaneously, whereas others were secondary to a break in the skin or to implantation of foreign material into the body for instance during internal fixation of a fracture or arthroplasty . Cases of P . acnes chest wall infection have been reported in patients with palmoplantar pustulosis or chronic or multifocal osteitis, supporting a role for P . acnes in SAPHO syndrome.

J Gastroenterol Hepatol, 1997 Dec, 12(12), 887 - 92
All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats; Motomura K et al.; All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages . The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats . All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure . Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134+/-119 IU/L and 72.7%) compared with the control group (713+/-411 IU/L and 18.2%; P< 0.05) . Histological findings supported these results . These effects may be due to suppression of tumour necrosis factor-alpha (TNF-alpha) and superoxide anions produced by activated macrophages . Serum levels of TNF-alpha 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5+/-7.0 ng/mL) as compared with the control group (105.2+/-39.3 ng/mL; P< 0.05) . Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages . These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.

Rev Esp Cardiol, 1997 Dec, 50(12), 906 - 8
{Acute endocarditis of the native aortic valve caused by Propionibacterium acnes}; Caballero Gueto J et al.; Propionibacterium acnes is often considered to be a contaminant but it has also been found to be the principal pathogen in serious infections . P . acnes is a rare cause of infective endocarditis . It has been suggested that aortic root abscesses are caused by bacteria that are particularly virulent . The strongest risk factor for serious infections by this bacteria is the presence of foreign bodies . A case is presented in which endocarditis of a native aortic valve caused by P . acnes was associated with an aortic root abscess . Transesophageal echocardiography is particularly helpful in the diagnosis of this severe complication of infective endocarditis . The literature for P . acnes endocarditis is reviewed.

Protein Eng, 1997 Sep, 10(9), 1067 - 70
Effect of Lys175 mutation on structure function properties of Propionibacterium shermanii superoxide dismutase; Gabbianelli R et al.; The role of electrostatic factors in the enzyme-substrate encounter process of manganese and iron containing superoxide dismutases has been studied in the enzyme from Propionibacterium shermanii by chemical neutralization of lysine residues and site-directed mutagenesis of the highly conserved residue Lys175 . Lysine residues have been neutralized by carbamoylation and Lys175 has been selectively replaced by isoleucine and arginine . Catalytic measurements show a dramatic decrease of the activity in the chemically modified enzyme . Electrostatic potential calculations evidence in the modified enzyme a large contraction of the positive potential areas which surround the active sites in the native enzyme, indicating that electrostatic factors are critical in the enzyme-substrate encounter process of Mn- and Fe-superoxide dismutases . The activity drastically decreases also in Lys175-->Ile but not in the Lys175-->Arg mutant . Brownian dynamics simulations indicate that the decrease of activity in the Lys175-->Ile mutant cannot be due only to a decrease of the enzyme-substrate association rate, suggesting that Lys175 plays a relevant role also in the structural stabilization of the active site.

Zh Mikrobiol Epidemiol Immunobiol, 1995 Jul-Aug, (4), 3 - 5
{Bacterial contamination of human blood in the early period after sudden death}; Men'shikov DD et al.; The bacterial contamination of blood and its components was studied in 517 corpses during the first 2-4 hours after sudden death . Investigations were made with the use of anaerobic cultivation techniques, modern identification methods by means of test systems and gas-liquid chromatography . As revealed in this study, in 14.1% of the corpses different bacteria, belonging to the representatives of normal human microflora, were detected in the blood . More than a half of the isolates were represented by Propionibacterium (P . acnes and P . granulosum) . The endogenous way of contamination from the lymph of the hepatic duct seems to be most probable.

FEMS Immunol Med Microbiol, 1997 Nov, 19(3), 247 - 53
Fibronectin binding by Propionibacterium acnes; Yu JL et al.; Strains of Propionibacterium acnes, isolated from different kinds of orthopaedic and biomaterial-associated infections and from skin flora were shown to express binding of soluble as well as immobilized fibronectin . Among these 7 strains isolated from orthopaedic infections, 2 from breast prostheses, and 9 skin isolates, 2, 2, and 5 strains respectively bound immobilized fibronectin . The fibronectin binding was sensitive to protease and heat treatment, and was inhibited by a cell surface extract from one of the binding strains . In SDS-PAGE and autoradiography of cell surface extracts, a band corresponding to a MW of about 80 kD reacted with fibronectin and the 150 kD fragment of fibronectin . Binding to fibronectin and the 150 kD fragment of fibronectin could be inhibited with heparin . We thus present a first Fn binding protein of P . acnes, a surface exposed protein of 80 kD . None of the strains bound soluble collagen, and only one strain expressed weak binding of vitronectin and bone sialoprotein II.

Pediatr Dermatol, 1997 Nov-Dec, 14(6), 480 - 8
Current options for the topical treatment of acne vulgaris; Weiss JS; The etiopathogenesis of acne vulgaris, a common disorder of youth and adolescence, includes four primary processes: hyperkeratinization (plugging) of the pilosebacous follicles, increased testosterone levels, bacterial colonization with Propionibacterium acnes, and inflammation . No single agent has yet been developed that addresses all of these factors . Combination regimens, therefore, which usually include an antibiotic and an agent to reduce follicular plugging, have become the mainstay of treatment . Despite a relative dearth of new treatments for almost a decade, recent research has produced a number of new significant oral and topical agents . Azelaic acid, a naturally occurring dicarboxylic acid analogue, has shown promise, and a group of retinoids that include adapalene, tazarotene, and reformulations of tretinoin represent new and forthcoming agents for topical treatment of acne vulgaris . Some studies indicate that several of these agents are associated with less skin irritation than previous formulations while they retain potent comedolytic activity . Adapalene also possesses significant anti-inflammatory activity.

Yale J Biol Med, 1996 Nov-Dec, 69(6), 477 - 82
Severe infections caused by Propionibacterium acnes: an underestimated pathogen in late postoperative infections; Jakab E et al.; Propionibacterium acnes belongs to the cutaneous flora of humans and is rarely considered a pathogen in human diseases . It is a frequent contaminant in blood cultures; however, in some patients it has been identified as the causative agent of life-threatening infections . Within the last years we have observed an abrupt increase in severe P . acnes infections which prompted us to study in detail the clinical and microbiological features, risk factors, and outcomes of these cases . In a retrospective review of microbiological records of 905 Propionibacterium isolates from a five-year period (1990-95), 70 were identified from 20 patients with clinical and microbiological evidence of a P . acnes infection . The clinical syndromes included endocarditis (7 patients), post-craniotomy infections (6 patients), arthritis and spondylodiscitis (4 patients), endophthalmitis (2 patients) and pansinusitis (1 patient) . The predominant predisposing conditions were previous surgery preceding the infection from 2 weeks to 4 years and implantation of foreign bodies such as prosthetic heart valves, intraocular lenses and ventriculo-peritoneal shunts . Therapy consisted of intravenous antibiotics in all cases and surgical procedures to remove infected tissue in eighteen patients . The outcome was favorable in sixteen patients (80 percent) who had a complete recovery . These data confirm the pathogenic potential of P . acnes in late post-surgical infections, in particular after implantation of a foreign body, and suggest a combined therapeutic approach with intravenous antibiotics and surgical removal of the infected tissue.

Clin Neurol Neurosurg, 1997 Oct, 99 Suppl 2, S221 - 4
The relationship between moyamoya disease and bacterial infection; Yamada H et al.; To examine the relationship between Moyamoya disease and bacterial infections, authors studied the serum of 85 cases of Moyamoya disease and the influence of Propionibacterium acnes (P . acnes) infection on intracranial arteries in rats . The serum levels of P . acnes antibody, IgM, transferrin (Tf), alpha 2-macroglobulin (alpha 2M) were significantly higher in Moyamoya disease than in normal volunteers . Moyamoya-like changes of the intracranial internal carotid arteries were histopathologically demonstrated in P . acnes infectious rats . These findings suggest that P . acnes and immunological factors might play a role in the pathogenesis of Moyamoya disease.

Int J Sports Med, 1997 Aug, 18(6), 483 - 8
Effects of exercise on the macrophage MHC II response to inflammation; Woods JA et al.; The purpose of this investigation was to determine the effects of different doses of exercise on the ability of Propionibacterium acnes (P . acnes) to induce major histocompatibility complex (MHC) II antigen expression on macrophages (M phi's) . Pathogen-free male Balb/c mice were exercised on a treadmill moderately (MOD, 15-17 m/min, 5% grade, 30 min/day) or exhaustively (EXH, 15-40m/min, 5% grade, 2-4hr/day) for a period of 7 days during P . acnes-induced inflammation . A control group (CON) consisted of animals exposed to the treadmill environment and handling . Sub-optimal (0.03 mg/g b.wt., i.p.) and optimal (0.08 mg/g b.wt.) doses of P . acnes were used to increase M phi MHC II expression . Animals were sacrified on Day 7 and M phi's were harvested by peritoneal lavage . Direct immunofluorescent staining was performed by incubating peritoneal exudate cells (10{6}) with an FITC-labeled anti-mouse MHC II (I-A{d}) antibody . Basal expression of MHC II was not affected by exercise . There were no significant differences among the groups in the percentage of M phi's expressing MHC II at any dose of P . acnes . However, EXH significantly (p < 0.05) suppressed the expression (mean fluorescent intensity, MFI) of MHC II when compared to MOD (37.1+/-1.95 {mean+/-sem} vs 49.1+/-2.15, p < 0.05) at the suboptimal P . acnes dosage . At the optimal P . acnes dose, both MOD and EXH significantly suppressed (27+/-1.6, 25+/-2.2 and 41.5+/-3.2, for EXH, MOD, and CON, respectively, p<0.0001) P . acnes-induced M phi MHC II MFI . Plasma corticosterone was highly (r=-0.71, p = 0.001) inversely correlated with M phi MHC II expression . However, exercise failed to affect P . acnes-induced production of interferon-gamma . These data suggest that, dependent on the degree of stimulation, exercise can negatively affect M phi expression of MHC II, an effect that may be detrimental to the M phi's ability to present antigen to T lymphocytes.

Bioelectromagnetics, 1997, 18(7), 506 - 13
Magnetic field effects on coenzyme B12-dependent enzymes: validation of ethanolamine ammonia lyase results and extension to human methylmalonyl CoA mutase; Taoka S et al.; Enzymes with radical-pair intermediates have been considered as a likely target for purported magnetic field effects in humans . The bacterial enzyme ethanolamine ammonia lyase and the human enzyme methylmalonyl-CoA mutase catalyze coenzyme B12-dependent rearrangement reactions . A common step in the mechanism of these two enzymes is postulated to be homolysis of the cobalt-carbon bond of the cofactor to generate a spin-correlated radical pair consisting of the 5'-deoxyadenosyl radical and cob(II)alamin {Ado . Cbl(II)} . Thus, the reactions catalyzed by these enzymes are expected to be sensitive to an applied magnetic field according to the same principles that control radical pair chemical reactions . The magnetic field effect on ethanolamine ammonia lyase reported previously has been corroborated independently in one of the authors' laboratory . However, neither the human nor the bacterial mutase from Propionibacterium shermanii exhibits a magnetic field effect that could be greater than about 15%, considering the error limit imposed by the uncertainty of the coupled assay . Our studies suggest that putative magnetic field effects on physiological processes are not likely to be mediated by methylmalonyl-CoA mutase.

J Immunol, 1997 Oct 15, 159(8), 3961 - 7
IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice; Tsutsui H et al.; When LPS is administered to heat-killed Propionibacterium acnes-primed BALB/c nude mice, they develop endotoxin-induced liver injury . As previously reported, this liver injury can be prevented by treatment with an Ab against IL-18, a novel cytokine with the ability to induce IFN-gamma production and up-regulate functional Fas ligand (FasL) expression . To identify the pathologic role of IL-18 in this liver injury, we investigated the hepatic cytokine network and FasL induction after LPS challenge . After LPS challenge to BALB/c nude mice, their livers expressed IL-12 mRNA, followed by the induction of IFN-gamma and FasL mRNA and then by the late elevation of TNF-alpha mRNA, but stably expressed IL-18 mRNA . The TNF-alpha induction curve had two peaks . The first peak was the result of the direct reaction to LPS, and the late peak might have been induced, since P . acnes-elicited Kupffer cells showed one-peak TNF-alpha kinetics in response to LPS stimulation in vitro . LPS-activated P . acnes-elicited Kupffer cells secreted both IL-12 and IL-18, as determined by ELISA and bioassay, respectively . The in vivo administration of anti-IL-18 just before an LPS challenge suppressed not only the induction of IFN-gamma and the late TNF-alpha elevation, but also the FasL induction, resulting in the total prevention of liver injury, whereas such an anti-IL-12 treatment did not . Anti-IFN-gamma treatment reduced the late increase in TNF-alpha, but not FasL, resulting in a partial prevention of the liver injury . The administration of anti-TNF-alpha just before elevation of the late TNF-alpha peak also markedly, but incompletely, suppressed the LPS-induced liver injury . These data suggested that IL-18 activates both TNF-alpha- and FasL-mediated hepatocytotoxic pathways in endotoxin-induced liver injury.

Clin Exp Dermatol, 1997 Mar, 22(2), 72 - 6
Comparison of serum antibiotic levels in acne patients receiving the standard or a modified release formulation of minocycline hydrochloride; Gardner KJ et al.; Serum levels of minocycline hydrochloride were determined by bioassay in a total of 223 acne patients (123 male, 100 female) receiving either the recommended dose (100mg/day) or a high dose (200mg/day) of the standard preparation (101 patients) of a modified release formulation (132 patients) . Sera were collected within 6 h of the morning dose 7-10 days after the start of treatment . Mean minocycline serum levels were consistently higher in females than in males, irrespective of dose or formulation . The differences only reached statistical significance (P < 0.05, Student's t-test) in the case of the standard preparation at a dose of 50 mg, b.d . Serum levels were increased significantly in both sexes at the higher dosage of each formulation (P < 0.01) but there was no significant difference between formulations at either dosage . Variation in serum concentrations was not accounted for by variation in body mass . Serum levels above the modal minimum inhibitory concentration (MIC) of minocycline for fully sensitive strains of Propionibacterium acnes I (0.125 micrograms/mL) were recorded in all patients . In contrast, serum levels equal to or greater than the modal MIC of minocycline for resistant propionibacteria (2 micrograms/mL) were recorded in only 17.9% of patients on the low dose standard preparation compared with 55.6% on the high dose standard preparation (P < 0.001, chi 2) . Even in females on the high-dose modified release formulation, 32.2% had serum levels below the modal MIC of minocycline for resistant strains . We conclude that, in terms of achievable serum levels over a short time period, there is no advantage of the modified release formulation over the standard preparation of minocycline . Whichever formulation is used, dose manipulation may be necessary to achieve maximum therapeutic benefit, especially in those individuals who are colonized by propionibacteria with reduced sensitivity to minocycline.

J Dairy Sci, 1997 Sep, 80(9), 1959 - 64
Isolation and structural identification of bifidogenic growth stimulator produced by Propionibacterium freudenreichii; Mori H et al.; A bifidogenic growth stimulator produced by Propionibacterium freudenreichii was purified, and its chemical structure was determined . We obtained 7.1 mg of a bifidogenic growth stimulator from 1738 g of lyophilized P . freudenreichii cells by silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC . The mass of the bifidogenic growth stimulator was 217.037 (C11H7NO4) as determined by high resolution mass spectrometry . Various experimental analyses indicated that the chemical structure of the bifidogenic growth stimulator was 2-amino-3-carboxy-1,4-naphthoquinone.

Dermatology, 1997, 195 Suppl 1, 4 - 9; discussion 38-40
Does oral isotretinoin prevent Propionibacterium acnes resistance?
Coates P, Adams CA, Cunliffe WJ, McGinley KT, Eady EA, Leyden JJ, Ravenscroft J, Vyakrnam S, Vowels B.
Oral and topical antibiotics play a major role in acne therapy . Physicians base treatment choices on personal perceptions of efficacy, cost-effectiveness or risk-benefit ratios and rarely take bacterial resistance into account . Propionibacterium acnes isolates resistant to one or more anti-acne antibiotics have been reported in Europe, the USA, Japan and New Zealand . Therapeutic failure on some but not all antibiotic regimens is an increasing management problem . In Leeds, UK, resistant strains are found in 60% of acne patients and 50% of close contacts . Recommendations for the use of antibiotics in acne therapy to help prevent the emergence of resistance in P . acnes include the implementation of antibiotic usage policies and the encouragement of improved prescribing habits . Strategies to reduce the resistant P . acnes population are necessary . This paper reports preliminary data demonstrating that oral isotretinoin (Roaccutane/Accutane) significantly reduces total numbers of resistant P . acnes on the skin of all patients.

FEBS Lett, 1997 Sep 1, 414(1), 122 - 4
Comparative stability studies on the iron and manganese forms of the cambialistic superoxide dismutase from Propionibacterium shermanii; Meier B et al.; The superoxide dismutase of Propionibacterium shermanii shows similar activity with iron and manganese bound at the active site of the protein . On the other hand, the iron form, in comparison to the manganese form, exhibits higher stability towards thermal- and pH-dependent inactivation . Upon inactivation the metal ions are released from the active site . Thus, in comparison to the manganese form, a higher stability of the iron-protein complex might be the triggering reason for this behavior.

Arch Biochem Biophys, 1997 Sep 1, 345(1), 156 - 9
Effect of Val 73 --> Trp mutation on the reaction of "cambialistic" superoxide dismutase from Propionibacterium shermanii with hydrogen peroxide; Gabbianelli R et al.; The H2O2 inactivation of the "cambialistic" superoxide dismutases from Propionibacterium shermanii, which is active with either iron or manganese at the active site, has been studied in the native and Val 73 --> Trp mutant enzymes . The wild-type iron-containing form of this enzyme is much more resistant to treatment with H2O2 with respect to the other metal-specific Fe superoxide dismutase isoenzymes . After incubation with high amounts of H2O2 the enzyme maintains more than 40% of the initial activity . The activity of the Val 73 --> Trp mutant drastically decreases to less than 5% of the initial activity after incubation with hydrogen peroxide . Amino acid analysis of the H2O2-treated mutant enzyme evidenced the loss of the Trp 73 residue which is shown to play a critical role in the stabilization of the monomer fold of the enzyme . On the other hand, the manganese-containing wild-type and mutant enzymes were completely resistant toward H2O2 demonstrating the specific role of iron in the inactivation process.

Eur J Med Res, 1997 Aug 28, 2(8), 321 - 34
Advances and perspectives in acne therapy; Jansen T et al.; Acne is one of the most common diseases in dermatology . It is of considerable esthetic significance, which explains the mental stress in affected patients . Although acne almost always heals spontaneously in early adulthood, treatment measures can shorten the course, reduce the severity of the disease, and avoid complications such as scarring . Treatment has changed substantially in recent years . In accordance with pathogenic principles, effective treatment is possible . In most patients, a combination of drugs aimed at correcting abnormal keratinization and reducing the proliferation of Propionibacterium acnes is sufficient to control the disease . For more severely affected patients with no response to this approach, therapy to suppress sebum production is indicated . Of all therapeutic modalities available, only oral isotretinoin alters the natural course of the disease . In acne inversa, surgical management should be undertaken as early as possible.

J Glaucoma, 1997 Aug, 6(4), 201 - 2
Propionibacterium endophthalmitis following Molteno tube repositioning; Fanous MM et al.; PURPOSE: We describe an aphakic patient who developed recurrent Propionibacterium acnes endophthalmitis after Molteno tube revision . PATIENT AND METHOD: The patient presented with a red painful right eye, decreased vision, and a hypopyon . A moderate anterior chamber reaction and mild vitritis were present . Two weeks earlier, the patient had undergone Molteno tube repositioning . A diagnosis of P . acnes endophthalmitis was made after positive culture of anterior chamber needle aspirate . RESULTS: Initially the patient was treated with repeated intraocular vancomycin injections, to which the eye "responded poorly." Temporary clearance of the infection was achieved after placement of the tube in the subconjunctival space . The patient required explantation of the implant to achieve complete resolution of the infection . CONCLUSION: Tube reinsertion into the anterior chamber resulted in recurrence of the infection . The evaluation of alternative therapies of aqueous tube shunt-related endophthalmitis would require a large case-controlled series of patients.

Infection, 1997 Jul-Aug, 25(4), 247 - 9
Culture and biological activity of Propionibacterium acnes; Schlecht S et al.; Administration of killed Propionibacterium acnes to experimental animals leads to the development of hypersensitivity to the lethal and cytokine-inducing effects of endotoxin . This sensitizing property of P . acnes is not always expressed by different bacterial preparations . Its expression depends very much on the conditions employed for the cultivation of this microorganism . The present study investigates which culturing conditions result in P . acnes preparations with optimal sensitizing properties . The composition of the medium, the culturing time and temperature as well as the type of cultivation (in minifermentor or stationary culture) were all varied for this purpose . The resulting bacterial preparations were killed at 65 degrees C for 1 h and tested for sensitizing activity . The results show that stationary cultures of P . acnes grown at 37 degrees C for 4 to 5 days in the appropriate medium produce biologically active preparations with satisfactory sensitizing activity.

Int J Syst Bacteriol, 1997 Jul, 47(3), 825 - 31
Propionibacterium cyclohexanicum sp . nov., a new acid-tolerant omega-cyclohexyl fatty acid-containing propionibacterium isolated from spoiled orange juice; Kusano K et al.; A non-spore-forming, coryneform bacterium, strain TA-12T, was isolated from spoiled off-flavor orange juice . Growth of this organism occurs at pH 3.2 to 7.5, and optimum growth occurs at pH values between 5.5 and 6.5 . This organism produces lactic acid, propionic acid, and acetic acid from glucose . It is catalase negative . The cells are heat resistant and can withstand a temperature of 90 degrees C for 10 min . The DNA G + C content is 66.8 mol% . This strain has as MK-9(H4) respiratory quinone system and contains meso-diaminopimelic acid in its cell wall, and omega-cyclohexyl undecanoic acid is the major cellular fatty acid . The results of a phylogenetic analysis of the 168 rRNA gene of this organism indicated that its highest level of homology is its level of homology with the representative of the classical propionibacteria, Propionibacterium freudenreichii (97.1%) . Strain TA-12T is phenotypically similar to P . freudenreichii, but it produces a large amount of lactic acid and has a distinct fatty acid composition, acid tolerance, and heat resistance, which differentiate it from P . freudenreichii and other propionic acid-producing bacteria . On the basis of these findings we propose the name Propionibacterium cyclohexanicum sp . nov . for this organism . The type strain is TA-12 (= IAM 14535 = NRIC 0247).

J Immunol, 1997 Jul 1, 159(1), 97 - 106
Propionibacterium acnes treatment diminishes CD4+ NK1.1+ T cells but induces type I T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells; Matsui K et al.; LPS injection into normal mice does not induce liver injury, while the same treatment of Propionibacterium acnes-primed mice induces severe liver injury, indicating that P . acnes treatment renders the mice susceptible to LPS . Since IFN-gamma sensitizes macrophages to LPS, we investigated the mechanism of induction and activation of IFN-gamma-producing (type 1) T cells by P . acnes . Twenty percent of liver lymphocytes of C57BL/6 mice are CD4+ NK1.1+ T cells that promptly produce IL-4 in response to anti-CD3 in vitro . However, P . acnes treatment diminished these lymphocytes . Therefore, liver lymphocytes from P . acnes-primed mice showed reduced IL-4 production . Furthermore, P . acnes treatment induced CD4- type 1 T cells in the liver . Isolated P . acnes-elicited Kupffer cells produced IL-12 and to a lesser degree IL-18 in vitro . Injection of anti-IL-12 Ab totally abrogated these actions of P . acnes, while injection of anti-IL-18 Ab caused only partial abrogation . Thus, administration of P . acnes diminished CD4+ NK1.1+ T cells, but induced type 1 T cells in the liver by induction of IL-12 and IL-18 production . Injection of IL-12 (approximately 1,000 ng) dose dependently diminished CD4+ NK1.1+ T cells, but induced type 1 T cells . In contrast, injection of IL-18 (approximately 1,000 ng) failed, although injection of a much larger dose of IL-18 (10,000 ng) or IL-18 (approximately 1,000 ng) with suboptimal doses of IL-12 (1-100 ng) diminished CD4+ NK1.1+ T cells in a dose-dependent manner . Thus, P . acnes treatment renders the mice highly susceptible to LPS by induction and activation of type 1 T cells.

Br J Pharmacol, 1997 Jun, 121(3), 540 - 6
Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo; Lewis EJ et al.; 1 . Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-{(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl}-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively) . The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively) . 2 . Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM) . 3 . Ro 32-3555 was well absorbed in rats when administered orally . Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1 . 4 . Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.) . 5 . Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes . 6 . Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

Clin Immunol Immunopathol, 1997 Jun, 83(3), 302 - 9
Experimental hepatitis in neonatally thymectomized mice: transfer of disease and the role of T cells; Kamiyasu M et al.; Using neonatally A/J thymectomized mice, we have produced chronic hepatitis by administration of sublethal doses of Propionibacterium acnes and lipopolysaccharide (LPS) . Our goal in this unique model was to evaluate the effector cell population required to generate chronic hepatitis by transferring spleen cells or splenic subpopulations derived from donor thymectomized mice with chronic hepatitis into congenic recipient nonimmunized thymectomized or sham-thymectomized animals . Several key observations were made regarding the ability to induce and to transfer disease . First, an inflammatory liver injury in neonatally thymectomized (NTx) mice was readily generated using sublethal doses of P . acnes and LPS . Second, the lesions were persistent and associated with the production of autoantibodies to liver-specific lipoprotein and anti-nuclear antibodies . Third, these features were not found in comparably injected nonthymectomized control A/J mice . Fourth, the same liver injury was transferred to neonatally thymectomized but otherwise naive mice by the transfer of donor spleen cells from affected mice previously induced to develop experimental hepatitis . Fifth, the transfer of this liver injury could not be achieved using T-cell-depleted spleen cells . Deletion of CD4+ T cells or CD8+ T cells by sensitized spleen cells resulted in suppression of the transferred liver injury . In contrast, transfer of nylon wool adherent splenic T cells induced severe hepatitis . These data suggest that the chronic liver injury induced in NTx mice by administration of P . acnes and LPS involves a breakdown in tolerance accompanied by the appearance of autoantibodies and that nylon wool adherent CD4+ and CD8+ T cells play important roles in the modulation of liver injury.

J Infect, 1997 May, 34(3), 269 - 71
Failure of intravenous antibiotic therapy of multiple temporal brain abscesses due to Propionibacterium acnes requiring temporal lobectomy; Senneville E et al.; Propionibacterium acnes is a common skin colonizer . Its involvement in brain abscesses is generally described as a complication of neurosurgical intervention . Propionibacterium acnes is susceptible to antibiotics used as treatment of anaerobic infections, except for the 5-nitroimidazoles . Surgical excision or drainage of a simple abscess combined with a long course of antibiotics is considered the treatment of choice . A case of a patient with multiple brain abscesses located in the right temporal lobe that occurred after the manipulation of an abscess of the right upper maxillary is reported . The patient did not improve despite a prolonged course of high-dose intravenous penicillin plus thiamphenicol and cure was finally obtained after the excision of the right temporal lobe . Culture of the purulent material and the shell of the abscesses yielded P . acnes which was sensitive to all the antibiotics administered to the patient up to the intervention . The temporal lobectomy was followed by a 6-month course of ofloxacin . One year after the intervention, the patient remained apyretic without any other abscess on cranial computed tomography scan.

Microbiology, 1997 May, 143 ( Pt 5), 1745 - 55
Propionibacterium acnes, a resident of lipid-rich human skin, produces a 33 kDa extracellular lipase encoded by gehA; Miskin JE et al.; Five independent clones of the Propionibacterium acnes P-37 lipase gene (gehA) were obtained in Escherichia coli, and the gene was localized to a 2.75 kb Xhol fragment by subcloning . The five clones were shown to contain the same gene by Southern blotting with a DIG-labelled probe to gehA . The nucleotide sequence of gehA was determined, and shown to contain a single ORF of 1017 kb, encoding a protein of 339 amino acids . The predicted molecular mass was 36 kDa . A 33 kDa (PAGE) radiolabelled polypeptide was detected from E . coli minicell preparations harbouring gehA, which could correspond to GehA after cleavage of the putative 26 amino acid residue signal peptide . gehA was overexpressed in E . coli under the control of the bacteriophage T7 promoter, and the corresponding polypeptide was found to be present in insoluble aggregates . Active lipase was produced when the overexpressing strain was incubated at a reduced temperature in the presence of sucrose . Purification of lipase from P . acnes culture supernatant fluids confirmed the production of a 33 kDa (PAGE) lipase.

Antimicrob Agents Chemother, 1997 May, 41(5), 1162 - 5
Clinical resistance to erythromycin and clindamycin in cutaneous propionibacteria isolated from acne patients is associated with mutations in 23S rRNA; Ross JI et al.; The genetic basis of erythromycin resistance in cutaneous propionibacteria was determined by comparing the nucleotide sequences of the peptidyl transferase region in the 23S rRNAs from 9 susceptible and 26 resistant clinical isolates as well as 4 laboratory-selected erythromycin-resistant mutants of a susceptible strain . In 13 isolates and the 4 laboratory mutants, cross-resistance to macrolides, lincosamides, and B-type streptogramins was associated with an A-->G transition at a position cognate with Escherichia coli 23S rRNA base 2058 . These strains were resistant to > or = 512 microg of erythromycin per ml . Two other mutations were identified, an A-->G transition at base 2059 in seven strains, associated with high-level resistance to all macrolides, and a G-->A transition at base 2057 in six strains, associated with low-level resistance to erythromycin . These mutations correspond to three of four phenotypic classes previously identified by using MIC determinations.

Infect Immun, 1997 May, 65(5), 1892 - 8
Tumor necrosis factor receptor p55 is essential for intrahepatic granuloma formation and hepatocellular apoptosis in a murine model of bacterium-induced fulminant hepatitis; Tsuji H et al.; Accumulating evidence implicates tumor necrosis factor (TNF) and Fas systems in liver injury, although the interaction between these two systems remains to be investigated . In this study, we examined Propionibacterium acnes-primed TNF receptor p55-deficient (TNFRp55-/-) or Fas-deficient MRL/MpJ Lpr/Lpr mice challenged with lipopolysaccharide (LPS) . Priming with P . acnes caused mononuclear cell infiltration into the hepatic lobules and granuloma formation in the livers of TNFRp55 wild-type mice . Subsequent LPS challenge caused massive liver injury and a marked increase in transaminase levels, leading to acute lethality in control wild-type mice . In contrast, the same treatment caused few pathological changes in livers of TNFRp55-/- mice, and all animals survived . P . acnes and subsequent LPS challenge induced granuloma formation and apoptotic changes, respectively, in livers of MRL/MpJ Lpr/Lpr mice . However, liver injury was 50% of that in control MRL/MpJ +/+ mice, suggesting some role of the Fas-Fas ligand system in this liver injury model . On the other hand, an agonistic anti-Fas antibody caused massive apoptosis and hemorrhagic changes of the liver without any priming with P . acnes, leading to death in both TNFRp55-/- and control wild-type mice . These results suggest that TNFRp55 but not Fas was involved in P . acnes-induced granuloma formation as well as subsequent LPS-induced liver injury and that TNFRp55 and Fas independently induced apoptosis of hepatocytes in vivo.

J Periodontol, 1997 Apr, 68(4), 369 - 74
Exocellular phospholipase C activity from a Propionibacterium acnes strain isolated from a periodontal pocket; Bulkacz J et al.; The culture supernatant of a strain of Propionibacterium acnes was investigated for its phospholipase (PL) activity . The microorganism was isolated from a periodontal pocket of a patient with periodontal disease . Supernatants from cultures of this microorganism were used as a source to obtain enzymes . Proteins from the supernatants were concentrated, and their enzymatic activity was partially purified through molecular sieving . The procedure yielded two peaks of activity . This activity was shown to hydrolyze phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) and was effective in a pH range of 5 to 9, with an optimal activity at pH 7.0 . Divalent cations were not required for activity of the enzymes . Analysis of the products obtained from the hydrolysis of PC labeled in the choline, phosphoryl, or acyl moieties and PE containing labeled oleic acid indicated that the supernatants' activity was mostly phospholipase C (PL-C) . Phospholipase C can act synergistically with other factors to produce tissue damage, and hence may contribute to the pathogenesis of periodontal disease.

Liver, 1997 Apr, 17(2), 107 - 14
Preventive effect of cyclosporin A on experimentally induced acute liver injury in rats; Wasaki S et al.; We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat-killed Propionibacterium acnes (P . acnes) and subsequent injection of lipopolysaccharide (LPS) . Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor-alpha (TNF-alpha) production, without changing the TNF-alpha mRNA level in the liver, and plasma interferon-gamma (IFN-gamma), following LPS injection in this model . Twenty-four-hour mortality was also markedly improved, from 100% in the P . acnes plus LPS group to 0% in the CsA-pretreated group . Although direct addition of CsA to isolated hepatic macrophages from P . acnes-pretreated rats did not prevent the production of TNF-alpha and active oxygen species, isolated hepatic macrophages from P . acnes plus CsA-pretreated rats significantly reduced their production in response to the addition of LPS . These results suggest that CsA protects against P . acnes plus LPS-induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN-gamma levels.

Int J Syst Bacteriol, 1997 Apr, 47(2), 278 - 83
Friedmanniella antarctica gen . nov., sp . nov., an LL-diaminopimelic acid-containing actinomycete from Antarctic sandstone; Schumann P et al.; A gram-positive, aerobic, slowly growing actinomycete was isolated from antarctic sandstone . Packets of spherical cells of this organism form clusters . The diagnostic diamino acid of the peptidoglycan is LL-diaminopimelic acid with glycine in position 1 of the peptide subunit . The major menaquinone is MK-9(H4), and the main cellular fatty acids are 12- and 13-methyltetradecanoic acids . Only a few organic compounds are metabolized . The DNA base composition is 73 mol% G + C . A 16S ribosomal DNA sequence comparison showed that this isolate is a phylogenetic neighbor of the propionibacteria and related taxa . Its closest relative is Microlunatus phosphovorus . Morphological, physiological, and genotypic characteristics support the description of a new genus and new species, Friedmanniella antarctica gen . nov., sp . nov . The type strain is strain AA-1042 (= DSM 11053).

Nat Med, 1997 Apr, 3(4), 409 - 13
Essential roles of the Fas ligand in the development of hepatitis; Kondo T et al.; The Fas ligand (FasL) is expressed in activated T cells and induces apoptosis in Fas-bearing cells . A cytotoxic T lymphocyte (CTL) clone specific for hepatitis B surface antigen (HBsAg) causes an acute liver disease in HBsAg transgenic mice . Here we observed that the CTL clone killed hepatocytes expressing HBsAg in a Fas-dependent manner . Administration of the soluble form of Fas into HBsAg transgenic mice prevented the CTL-induced liver disease . In the second model, mice were primed with Propionibacterium acnes . A subsequent challenge with lipopolysaccharide (LPS) killed the mice by inducing liver injury . Neutralization of FasL rescued the mice from LPS-induced mortality, and Fas-null mice were resistant to LPS-induced mortality . These results suggest that FasL has an essential role in the development of hepatitis.

Ocul Immunol Inflamm, 1997 Mar, 5(1), 67 - 8
Chronic Propionibacterium acnes endophthalmitis as a cause of intermediate uveitis; Ormerod LD et al.; Although the pathogenesis in most cases of intermediate uveitis is unknown, a small minority of cases is associated with a variety of specific inflammatory etiologies: sarcoidosis; multiple sclerosis; Lyme disease; syphilis; ocular lymphoma; and as a rare manifestation of Behcet's disease and AIDS . A 61-year-old woman developed pars planitis after cataract surgery . A vitrectomy was performed after ten months when a white capsular plaque and an hypopyon developed . Propionibacterium acnes was isolated . The intermediate uveitis was not controlled until later removal of the intraocular lens and capsular remnants . Chronic propionibacterial endophthalmitis may be a cause of intermediate uveitis.

Zentralbl Bakteriol, 1997 Feb, 285(3), 445 - 9
Protection and therapy of experimental herpesvirus infections in mice with immunomodulating Propionibacterium avidum KP-40 and/or acyclovir; Kobus M et al.; Protection and therapy of NMRI mice with experimental herpes virus (HSV-1) encephalitis were investigated using heat-killed, lyophilized Propionibacterium avidum KP-40 (PA) and/or the herpes-specific antiviral substance acyclovir (ACL) as immunomodifier . Poly I:C as a potent macrophage activator was used as a reference compound for PA . Survival of experimental HSV-1 infections during 18 days following the inoculation of viruses was used for the evaluation of the effects of immunotherapy . The applied model of HSV-1 infection resulted in a mortality of about 87% of NMRI mice at 7-16 days following the inoculation of the virus . Treatment with ACL or Poly I:C at the day of HSV-1 infection resulted in a lowering of the mortality rate to about 40% (p < 0.05) . PA applied 4 days before HSV-1 infection lowered the mortality rate to 27%, while treatment 2 days after infection was less effective and the mortality rate reached 44%, although still being significantly lower (p < 0.01) than in untreated controls . A combined treatment with ACL and PA on the day of HSV-1 infection protected 93% of animals against the development of clinically detectable herpesvirus encephalitis.

Science, 1997 Jan 10, 275(5297), 206 - 9
Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme; Gu Y et al.; The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine . ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export . Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form . Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide . The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

Enferm Infecc Microbiol Clin, 1997 Jan, 15(1), 24 - 7
{Propionibacterium acnes infection in patients with CSF shunts}; Bordes A et al.; BACKGROUND AND METHODS: Propionibacterium acnes is a common inhabitant of human skin rarely associated with clinical disease . However it has been recognized as a cause of shunt and postneurosurgical infections . From January 1992 to June 1995, 5,947 cerebrospinal fluid (CSF) samples were cultured in our laboratory . We carried out a clinical-epidemiological study in patients where P . acnes was isolated from CSF . RESULTS: P, acnes was isolated from 11 CSF samples which corresponded to 7 episodes of shunt infection in 6 patients . Five were men; the mean age was 28.5 years . The mean time of onset of infection after the last shunt manipulation was 104 weeks . All of them presented symptomatology associated with infection . All episodes but one, where P . acnes was considered to be a contaminant, were treated with systemic and intraventricular antibiotic therapy and complete shunt removal . Four patients made an uneventful recovery and two patients died due to causes not directly related with the infection . CONCLUSIONS: P . acnes is frequently isolated in patients with shunt infections . Its isolation must be seriously considered not viewed as a contaminant without an exhaustive investigation.

J Submicrosc Cytol Pathol, 1997 Jan, 29(1), 125 - 33
Immunohistochemical and ultrastructural analyses of in situ activation of hepatic stellate cells around Propionibacterium acnes-induced granulomas in the rat liver; Tsuji N et al.; Stellate cells embrace the hepatic sinusoids as pericytes . To demonstrate their activation in juxta-sinusoidal location, we induced hepatic granulomatous inflammation, which did not accompany liver injury nor fibrosis, by administrating a low dose (10 mg/kg b.w.) of heat-killed Propionibacterium acnes into rats . Macrophages and lymphocytes migrated out of the sinusoid and made compact granulomas in the space of Disse . Stellate cells which faced on the granulomas were closely attached to the sinusoidal endothelial cells and extended projections into the spaces between the constituent mononuclear cells of granulomas . They did not migrate into granulomas nor displayed mitosis . Immunohistochemically, stellate cells around the granulomas expressed alpha-smooth muscle actin (alpha-SMA), whereas those in the non-granulomatous regions did not . Small deposits of type III collagen were found at the periphery of granulomas . Biochemical analysis showed an increased amount of alpha-SMA protein and type III collagen mRNA in the granuloma-bearing liver . Transforming growth factor-beta and platelet-derived growth factor were detected within the granulomas . The present study has revealed that stellate cells are activated in situ by extrasinusoidal macrophages in a paracrine manner without being detached from the sinusoidal wall.

Ophthalmologica, 1997, 211 Suppl 1, 62 - 7
Preoperative disinfection of the conjunctival sac in cataract surgery; Hara J et al.; Conjunctival cultures were obtained from 488 patients undergoing cataract extraction . Bacterial isolation rates from the lids and conjunctiva were 84.6 and 36.7, respectively . Propionibacterium acnes was the only anaerobic organism identified . A significantly lower incidence of P . acnes was observed in the eyes after preoperative conjunctival irrigation using povidone-iodine solution (9%) compared with those using benzetonium chloride solution (30%) . Topical use of ofloxacin and cefmenoxime for 1 or 2 days preoperatively, and irrigation of the conjunctival sac with a 16-fold-diluted povidone-iodine solution for at least 30 s immediately prior to cataract surgery are recommended.

Rev Rhum Engl Ed, 1997 Jan, 64(1), 54 - 6
Propionibacterium avidum sacroiliitis and osteomyelitis; Estoppey O et al.; The anaerobic Gram-positive bacterium Propionibacterium avidum is a common inhabitant of the skin with low pathogenicity . We report a case of P . avidum sacroilitis, psoas abscess and osteomyelitis in a 67-year-old male who had recently undergone surgical repair of an inguinal hernia . The organism was recovered from blood cultures, a bone biopsy specimen and specimens from the abscess . The spectrum of bone and joint infections caused by Propionibacterium is discussed . Infection by Propionibacterium spp . should be considered in patients with bone and joint infections.

Proc Natl Acad Sci U S A, 1996 Dec 10, 93(25), 14320 - 2
Biosynthesis of vitamin B12: concerning the identity of the two-carbon fragment eliminated during anaerobic formation of cobyrinic acid; Wang J et al.; It has been proved that, during anaerobic biosynthesis of the corrin macrocycle, the two-carbon fragment excised from the precursor, precorrin-3, is acetaldehyde, which originates from C-20 and its attached methyl group . This apparently contradictory finding is rationalized in terms of the subsequent enzymatic oxidation of acetaldehyde to acetic acid, which was previously regarded as the volatile fragment released by the action of the biosynthetic enzymes of Propionibacterium shermanii . The observation that acetaldehyde (rather than acetic acid) is extruded during anaerobic B12 synthesis is in full accord with the structure of factor IV, a new intermediate on the pathway.

Proc Natl Acad Sci U S A, 1996 Dec 10, 93(25), 14316 - 9
Biosynthesis of vitamin B12: factor IV, a new intermediate in the anaerobic pathway; Scott AI et al.; The structure of a novel tetradehydrocorrin, factor IV, isolated from Propionibacterium shermanii has been established by multidimensional NMR spectroscopy . Incorporation of radiolabeled factor IV into cobyrinic acid established the biointermediacy of this cobalt complex, whose structure has implications for the mechanisms of the anaerobic pathway to B12.

J Dermatol, 1996 Dec, 23(12), 871 - 5
Activity of eleven kampo formulations and eight kampo crude drugs against Propionibacterium acnes isolated from acne patients: retrospective evaluation in 1990 and 1995; Higaki S et al.; We reviewed the susceptibility of Propionibacterium acnes to eleven Kampo formulations and to eight Kampo crude drugs that had been studied by examining their minimum inhibitory concentrations (MIC) in 1990 and 1995 . P . acnes strains were most sensitive to Oren-gedoku-to (OGT) among these Kampo formulations . Coptidis Rhizoma (CR) and Phellodendri Cortex (PC) inhibited the growth of P . acnes significantly among the eight Kampo crude drugs examined . The patterns of distribution of MIC of Kampo formulations and Kampo crude drugs to P . acnes in this study were almost the same as in our previous report in 1990 . No significant increases in MIC of Kampo formulations and Kampo crude drugs to P . acnes were observed . We speculated that Kampo crude drugs such as CR and PC, were better than minocycline or erythromycin from the point of view of a progressive increase in MIC to P . acnes . CR and PC, which were each an ingredient of OGT, might contain some components with strong antibacterial activity to P . acnes.

J Int Med Res, 1996 Nov-Dec, 24(6), 473 - 7
Sensitivity of Propionibacterium acnes isolated from acne patients: comparative study of antimicrobial agents; Nishijima S et al.; The antimicrobial susceptibility of Propionibacterium acnes isolated before and after treatment of acne patients was measured . The four female and three male acne patients were treated with an oral acne medication, roxithromycin or minocycline, and/or a topical acne medication, nadifloxacin cream or clindamycin hydrochloride lotion for 1-8 weeks . The isolated strains were tested for their susceptibility to the antimicrobial action of: nadifloxacin, ofloxacin, erythromycin, clindamycin hydrochloride, tetracycline hydrochloride, minocycline, doxycycline, ampicillin, cephalexin and gentamycin . No resistant strains of P . acnes were observed.

FEBS Lett, 1996 Sep 30, 394(2), 126 - 8
The masked cysteine residues in methylmalonyl-CoA mutase from Propionibacterium shermanii are essential for catalytic activity; Roy I; Two masked cysteine residues have been reported in methylmalonyl-CoA mutase from Propionibacterium shermanii, Cys-535 in the alpha-subunit and Cys-517 in the beta-subunit, which are revealed only after reduction of the denatured enzyme with dithiothreitol . It has been postulated that these residues are involved in disulphide linkages to unknown thiols of low M(r) . These two masked cysteine residues have been changed to an alanine, individually . Both the mutants, C535alphaA and C517betaA, were inactive . This shows that both these residues are essential for catalytic activity.

Biochemistry, 1996 Sep 10, 35(36), 11791 - 6
Tritium isotope effects in adenosylcobalamin-dependent methylmalonyl-CoA mutase; Meier TW et al.; Methylmalonyl-CoA mutase from Propionibacterium shermanii is an adenosylcobalamin-dependent enzyme which catalyzes the reversible isomerization of methylmalonyl-CoA and succinyl-CoA . The rate of tritium loss from 5'-{3H}adenosylcobalamin during the enzymic reaction and the relative rates of tritium appearance in substrate and product were examined . Upon the addition of methylmalonyl-CoA to a solution of holoenzyme, tritium was completely released from the cofactor within about 500 ms . No tritium was found either bound to the enzyme or released into the water . The radioactivity was found in methylmalonyl-CoA and succinyl-CoA in a constant ratio of 1 to 3, which did not change during the first 300 ms of the reaction . Upon the addition of succinyl-CoA to a solution of holoenzyme, tritium was released at essentially the same rate, and the radioactivity was found in methylmalonyl-CoA and succinyl-CoA in the identical constant ratio of 1 to 3 . The tritium isotope effect on the enzyme-catalyzed hydrogen transfer, measured using 14C-labeled methylmalonyl-CoA as substrate, was kH/kT = 4.9 . This low value shows that hydrogen transfer is only partly rate limiting and that at least one subsequent slow step, such as product release, contributes substantially to the overall reaction velocity . The identical partitioning of tritium, regardless of the substrate used, shows that the rearrangement of the substrate radical into the product radical is not rate limiting . The very low tritium isotope effect and the fact that all the tritium is found bound either to the CoA esters or to the cofactor make it very unlikely that a protein radical is an intermediate in the methylmalonyl-CoA mutase-catalyzed rearrangement.

Protein Sci, 1996 Sep, 5(9), 1922 - 7
Homology modeling of human methylmalonyl-CoA mutase: a structural basis for point mutations causing methylmalonic aciduria; Thoma NH et al.; Point mutations in the human gene encoding coenzyme B12 (adenosylcobalamin)-dependent methylmalonyl-CoA mutase give rise to an inherited disorder of propionic acid metabolism termed mut methylmalonic aciduria . Almost all such mutations alter amino acids in the homodimeric human enzyme that are identical to residues in the catalytic alpha-subunit of the heterodimeric methylmalonyl-CoA mutase from the bacterium Propionibacterium shermanii, to which the mature human enzyme shows an overall 65% sequence identity . To explore how specific mutations might cause the observed clinical phenotype, 12 known mutations were mapped onto a three-dimensional homology model of the subunit of the human enzyme, generated using the program MODELLER on the basis of the recently published 2.0 A X-ray crystal structure of the P . shermanii methylmalonyl-CoA mutase . Eight mutations are found in the C-terminal B12-binding domain, of which 4 (G623R, G626C, G630E, G703R) are in direct contact with the corrin and are clustered around the histidine ligand (H627) provided by the protein to coordinate the cobalt atom of the B12 cofactor . Introduction of a side chain, particularly one that is charged, at any of these positions is expected to disrupt the flavodoxin-like fold and severely impair its binding of B12 . Mutation at either of two other highly conserved glycine residues in this domain (G648D, G717V) also disrupts critical elements in the fold as would the introduction of an additional positive charge in the mutation H678R . Mutation of an arginine in a solvent-exposed loop to a hydrophobic residue (R694W) is also pathogenic . The remaining mutations have been mapped to the N-terminal region of the mutase, two of which introduce a buried, uncompensated charge, either near the subunit interface (A377E), or near the narrow channel through which acyl-CoA esters gain access to the active site (W105R) . The extreme N-terminus of methylmalonyl-CoA mutase is predicted to make extensive contacts with the other subunit, and a mutant in this region (R93H) may prevent the correct assembly of the dimer.

Vaccine, 1996 Aug, 14(12), 1167 - 73
Oral administration of a bacterial immunomodulator enhances the immune response to cholera toxin; Flo J et al.; Attempts to achieve IgA responses in the intestine by oral immunization with non replicating antigens have been characterized by ineffective responses of short duration unless long term dosages are administered . Cholera toxin (CT) is an exception in that it is able to produce a high secretory and systemic immune response . We study the effects of a bacterial immunomodulator {3 x 10(10) Propionibacterium granulosum ml-1 and lipopolysaccharide (LPS) 5 mg ml-1} on the immune response to CT orally administered to Wistar rats . The immunomodulator was orally administered as follows: in schedule 1 during 7 days prior to the first dose of CT; and in schedule 2, 2 days before, together, and 3 days after the first dose of CT . Schedules 1 and 2 were effective in increasing the specific IgA in the intestinal fluid and specific IgG in serum (P < 0.001) when compared to controls . Besides, schedule 2 was more effective than schedule 1 when the levels of specific IgG in serum or specific IgA in intestinal fluid was measured (P < 0.05) . Total IgA in the intestinal fluid was increased in rats receiving the immunomodulator (P < 0.01) . However, the ratio of specific IgA per total IgA was higher in rats receiving treatment 1 or 2 when compared to controls (P < 0.01) . The number of antitoxin antibody producing cells was not increased in the Peyer patches, but a significant increase was observed in the mesenteric lymph nodes and spleen when compared to controls (P < 0.05) . The administration of LPS alone produced an increase in the antitoxin immune response when compared to controls, but it was lower than those produced by the administration of the immunomodulator . These results indicate that this immunomodulator is an effective adjuvant of the mucosal and systemic immune response to CT . The mechanisms of action possibly involve nonespecific and specific modulations of the immune response.

Zentralbl Bakteriol, 1996 Aug, 284(4), 501 - 15
Sub-species discrimination, using pyrolysis mass spectrometry and self-organising neural networks, of Propionibacterium acnes isolated from normal human skin; Goodacre R et al.; Curie-point pyrolysis mass spectra were obtained from 30 Propionibacterium acnes strains isolated from the foreheads of six healthy humans . Multivariate analyses and Kohonen artificial neural networks (KANNs), employing unsupervised learning, were used successfully to discriminate between the P.acnes isolates from different individual hosts . The classification of the isolates by KANNs was compared with the more classical multivariate techniques of canonical variates analysis and hierarchical cluster analysis and found to give similar groupings . The combination of pyrolysis mass spectrometry with these numerical methods also showed that more than one strain of P.acnes had been isolated from three of the human hosts.

Clin Rheumatol, 1996 Jul, 15(4), 399 - 402
Infection of a total knee joint prosthesis by peptostreptococcus micros and propionibacterium acnes in an elderly RA patient: implant salvage with longterm antibiotics and needle aspiration/irrigation; Stoll T et al.; We describe the favourable long-term outcome after late total knee joint prosthesis infection in an elderly RA patient . Peptostreptococcus micros and Propionibacterium acnes were cultured from the synovial fluid, and the finding of a coexistent abscess at the root of a wisdom tooth suggested a dental origin to the joint infection . Long-term antibiotics in conjunction with aspiration/irrigation resulted in salvage of the implant and an excellent functional outcome.

Zentralbl Bakteriol, 1996 Jul, 284(2-3), 367 - 71
Influence of Propionibacterium avidum KP-40 on the cellular immune system after intensive sport activity; Pottkamper M et al.; Intensive sport activities resulted in temporary downregulation of defined immune functions . To check its influence on the cellular immune system, 15 male professional ice hockey players of a German first league club were observed and a decrease of lymphocyte subset counts and activities was found after anaerobic exercise . To stabilize cellular immune functions, the players were orally treated with Propionibacterium avidum KP-40 (10 mg per administration; twice a day; 7 days), a well documented bacterial immunmodifier . After administration of Propionibacterium avidum KP-40, lymphocyte counts and activities after anaerobic exercise resembled normal values . For some subjects, defined lymphocyte subset counts and activities even exceeded normal values.

J Rheumatol, 1996 Jul, 23(7), 1302 - 4
Propionibacterium acnes isolated from sternal osteitis in a patient with SAPHO syndrome; Kotilainen P et al.; A woman presented with palmar pustulosis and deep chest pain in association with osteitic lesions in the lower part of the sternum . Propionibacterium acnes was isolated and grew in pure culture from 6 surgically obtained bone specimens . The patient received clindamycin treatment for 6 months . Synovitis in both her wrists persisted and, based on a clinical suspicion of seronegative rheumatoid arthritis, she was treated with intramuscular gold and methotrexate with no apparent benefit . Subsequently, she was diagnosed with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteomyelitis) . Our patient provides further data on the potential association between P . acnes and SAPHO syndrome.

J Am Acad Dermatol, 1996 Jul, 35(1), 58 - 63
Fluorescence photography in the evaluation of acne; Lucchina LC et al.; BACKGROUND: Quantification of acne remains a challenge . It may be difficult to identify lesions by standard flash photography . Previous studies have shown that foci of light in fluorescence photographs correspond to high protoporphyrin IX production by Propionibacterium acnes in open comedones, follicles, and inflammatory lesions . OBJECTIVE: Our purpose was to study the utility of fluorescence photography for evaluation of acne . METHODS: Forty subjects with mild to moderate acne vulgaris were randomly selected to apply either clindamycin 1% topical solution or vehicle twice daily . Counts of acne lesions and flash and fluorescence photographs were obtained at baseline, and at 4, 8, and 12 weeks . RESULTS: At 12 weeks, the treatment group had a larger percentage change in open comedones, less fluorescence in all areas assessed, and a larger percent decrease in fluorescence than the vehicle group . CONCLUSION: Fluorescence photography appears to be a useful tool to chart the course of acne treatment.

Biochem Biophys Res Commun, 1996 Jun 25, 223(3), 578 - 82
Singlet oxygen (1 delta g) generation from coproporphyrin in Propionibacterium acnes on irradiation; Arakane K et al.; Although singlet oxygen has been postulated to be a highly reactive and toxic intermediate, there has been no evidence of considerable generation of singlet oxygen in vivo level except for special cases . In this work, we firstly measured the near-infrared emission spectra corresponding to the O2(1 delta g) --> O2(3 epsilon g-) transition of singlet oxygen of cutaneous Propionibacterium acnes (P . acnes) porphyrin under laser excitation . A comparison of the singlet oxygen production of coproporphyrin, which is produced predominantly from P . acnes, with that of other photosensitizers revealed coproporphyrin to be a highly efficient singlet oxygen generator under ultraviolet light A irradiation on the skin . These results suggest that singlet oxygen can be generated on the skin surface from P . acnes porphyrin under ultraviolet irradiation and induce serious damage to the skin.

Br J Neurosurg, 1996 Jun, 10(3), 321 - 3
Postoperative subdural empyema caused by Propionibacterium acnes--a report of two cases; Critchley G et al.; Two patients with postoperative subdural empyema following burr hole evacuation of chronic subdural haematoma are reported, both caused by Propionibacterium acnes . The need to consider this diagnosis in patients developing recurrent symptoms after surgical drainage of chronic subdural haematoma is emphasized.

J Bacteriol, 1996 Jun, 178(11), 3049 - 58
Biotinylation in vivo as a sensitive indicator of protein secretion and membrane protein insertion; Jander G et al.; Escherichia coli biotin ligase is a cytoplasmic protein which specifically biotinylates the biotin-accepting domains from a variety of organisms . This in vivo biotinylation can be used as a sensitive signal to study protein secretion and membrane protein insertion . When the biotin-accepting domain from the 1.3S subunit of Propionibacterium shermanii transcarboxylase (PSBT) is translationally fused to the periplasmic proteins alkaline phosphatase and maltose-binding protein, there is little or no biotinylation of PSBT in wild-type E . coli . Inhibition of SecA with sodium azide and mutations in SecB, SecD, and SecF, all of which slow down protein secretion, result in biotinylation of PSBT . When PSBT is fused to the E . coli inner membrane protein MalF, it acts as a topological marker: fusions to cytoplasmic domains of MalF are biotinylated, and fusions to periplasmic domains are generally not biotinylated . If SecA is inhibited by sodium azide or if the SecE in the cell is depleted, then the insertion of the MalF second periplasmic domain is slowed down enough that PSBT fusions in this part of the protein become biotinylated . Compared with other protein fusions that have been used to study protein translocation, PSBT fusions have the advantage that they can be used to study the rate of the insertion process.

Biochemistry, 1996 May 28, 35(21), 6777 - 85
Initial rate and equilibrium isotope exchange studies on the ATP-dependent activity of polyphosphate Glucokinase from Propionibacterium shermanii; Kowalczyk TH et al.; Polyphosphate glucokinase {EC 2.7.1.63} catalyzes the phosphorylation of glucose using either inorganic polyphosphate {poly(P)} or ATP as the phosphoryl donor . Both activities purified from Propionibacterium shermanii are the functional properties of a single enzyme with separate binding sites for the two phosphoryl donor substrates . The enzyme was found to utilize poly(P) much more efficiently than it does ATP, with a kcat/Kpoly(P) to kcat/KATP ratio of 2800 . The catalytic constant for poly(P) is about 2-fold higher than for ATP . Other nucleotides like GTP and dATP also served as substrates with good efficiencies . The ATP-dependent reaction was analyzed using steady-state kinetics and isotopic exchange kinetics at chemical equilibrium . Intersecting initial velocity patterns for both glucose and ATP indicate sequential addition of substrates . Product inhibition studies resulted in two competitive and two noncompetitive patterns, which is characteristic of a Theorell-Chance mechanism or a random mechanism with two dead-end complexes . Results of isotope exchange experiments, however, rule out a Theorell-Chance mechanism, as well as a truly random mechanism . They are not consistent with a partially random mechanism (although a kinetically compulsory order of substrate binding is not excluded), where glucose is preferentially bound to free enzyme before ATP, and ADP is preferentially released as the first product, followed by glucose 6-phosphate . Dead-end inhibition analysis confirms this order of substrate binding . Competitive inhibition of ADP vs ATP is explained as resulting primarily from binding as a dead-end inhibitor (E.Glc.ADP) and not as a product . Another weaker abortive complex, E.ATP.G6P, is also formed . The chemical transformation or the release of ADP is the rate-limiting step in ATP utilization.

Structure, 1996 May 15, 4(5), 505 - 12
The reactivity of B12 cofactors: the proteins make a difference; Ludwig ML et al.; Determination of the structure of intact methylmalonyl-CoA mutase from Propionibacterium shermanii, and comparisons with the structure of the cobalamin-binding fragment of methionine synthase from Escherichia coli, afford a first glimpse at the similarities and distinctions between the two principal classes of B12-dependent enzymes: the mutases and the methyltransferases.

J Dermatol, 1996 May, 23(5), 310 - 4
Anti-lipase activity of Kampo formulations, coptidis rhizoma and its alkaloids against Propionibacterium acnes; Higaki S et al.; Anti-lipase activity of Kampo formulations, Coptidis Rhizoma (CR), and its alkaloids against Propionibacterium acnes were examined in vitro . The amounts of propionic and butyric acids in the medium were measured as growth and lipase activity of P . acnes, respectively . In tributyrin-PYG medium with each concentration of Kampo formulation, CR, or the alkaloids added, the production of propionic acid was suppressed remarkably more than that of butyric acid . The suppression of production of these acids by CR was higher than that of the alkaloids . Furthermore, no lipase-negative colonies were found on the medium to which Kampo formulations were added . From these observations, we concluded that not only Kampo formulations and CR, but also their alkaloids, showed suppression of growth of P . acnes, which reduced anti-lipase activity . Furthermore, it was suggested that Kampo formulations and Kampo crude drugs with anti-lipase activity to P . acnes should be synergistic when their ingredients are combined.

Int J Cancer, 1996 Apr 10, 66(2), 209 - 13
Purification, characterization and anti-tumor activity of a new cytokine, histiocyte-secreted-factor (HSF); Satomi N et al.; Purification of cytokines was carried out while monitoring their in vivo anti-tumor activity and in vitro cytotoxic activities . As a result, purified new cytokines were obtained from culture supernatant of a histiocytic cell line from rabbit serum . Briefly, a new cytokine (HSF, histiocyte-secreted-factor) was purified from the culture of supernatant of the histiocytic cell line (TYH) which we established from the peripheral blood of a malignant-lymphoma patient . The purified samples exhibited suppressive effects on tumor growth but no necrotizing activity towards transplanted murine tumors . The substance displayed no cytotoxic activity against L cells (mouse fibroblast cells) . The molecular weight of human HSF was about 42 kDa as estimated by SDS-PAGE . Amino-acid sequencing of the purified HSFD from the culture supernatant was performed, but the N-terminal was blocked . Next, a new cytokine was purified from rabbit serum stimulated with Propionibacterium acnes and elicited with lipopolysaccharide . The rabbit HSF was isolated by the same procedures as those used for the human HSF purification steps . Amino-acid sequencing was carried out after enzyme digestion . Three parts of the amino-acid sequence of the rabbit HSF were determined as LPPGLLAPMRQLRS-, NLEXFTNGMEQHYAQL-, NPAENQAHELPNQLN- . A computer-based homology search demonstrated that these sequences were novel . The molecular weight of HSF as determined using anti-peptide antibodies revealed the following values: human HSF, 41 and 46 kDa; rabbit HSF, 35, 42 and 55 kDa.

Microbiology, 1996 Apr, 142 ( Pt 4), 955 - 61
Degradation of host protease inhibitors and activation of plasminogen by proteolytic enzymes from Porphyromonas gingivalis and Treponema denticola; Grenier D; Bacterial proteases may participate in the pathogenesis of periodontal diseases through their action on host proteins . In the present study, the ability of selected periodontopathogens, as well as two proteases isolated from Porphyromonas gingivalis and Treponema denticola, to degrade host protease inhibitors was evaluated . The activation of human plasminogen by the two bacterial proteases was also investigated . Proteolytic breakdown of host protease inhibitors (alpha-1-antitrypsin, antichymotrypsin, alpha 2-macroglobulin, antithrombin III, antiplasmin and cystatin C) was evaluated by SDS-PAGE . The 80 kDa trypsin-like protease of P . gingivalis completely digested the six protease inhibitors under investigation, whereas the 95 kDa chymotrypsin-like protease of T . denticola was slightly less active, more particularly on alpha 2-macroglobulin and cystatin C . When whole cells from a number of oral bacterial species were tested, the most significant degradation was obtained with P . gingivalis, T . denticola, Prevotella intermedia, Prevotella nigrescens and Capnocytophaga spp . Peptostreptococcus micros and Propionibacterium acnes had only some degradative activity on selected inhibitors, whereas three bacterial species, Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Fusobacterium nucleatum, had no effect on the protease inhibitors . The 80 kDa protease of P . gingivalis demonstrated strong plasminogen activation, whereas no such activity was associated with the 95 kDa protease of T . denticola . This study indicates the high potential of some periodontal pathogens to destroy protease inhibitors and activate plasminogen . This may result in an uncontrolled degradation of periodontal tissues and a rapid progression of the disease.

Biol Pharm Bull, 1996 Apr, 19(4), 567 - 72
Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries; Hase K et al.; Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the water extract of the seed of Celosia argentea, was investigated using chemical and immunological liver injury models . Celosian inhibited the elevation of serum enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))-induced liver injuries in rat . In addition, the hepatoprotective effect of celosian was also observed in this model of liver injury by histopathological findings . Moreover, celosian suppressed rises in GPT or mortality on fulminant hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or Propionibacterium acnes/LPS in mice . These findings suggested that celosian is an active component in protection against chemical and immunological hepatitis and the activity was found to be a dose dependent . Celosian showed a concentration dependent inhibitory effect on lipid peroxide (LPO) generation in vitro . Though celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha), it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver injury in D-galactosamine sensitized mice.

J Clin Microbiol, 1996 Apr, 34(4), 1024 - 6
Susceptibility testing of Propionibacterium acnes comparing agar dilution with E test; Smith MA et al.; Propionibacterium acnes has been identified as a significant agent of nosocomial infections, including endophthalmitis . Data concerning susceptibility of P . acnes to newer beta-lactam antibiotics and fluoroquinolones are limited . Recent reports suggest that quinolones have activity against these organisms sufficient to warrant further study . We undertook a study to select appropriate antimicrobial agents for use in a rabbit model of P . acnes endophthalmitis . We compared the antibiotic susceptibilities of P . acnes by using the National Committee for Clinical Laboratory Standards method of agar dilution with the E test . Thirteen clinical isolates obtained from eye specimens and three American Type Culture Collection control strains were tested against 14 antibiotics . All the clinical isolates were susceptible by both methods to piperacillin, piperacillin-tazobactam, ampicillin-sulbactam, ticarcillin-clavulanate, cefotaxime, cefotetan, ceftriaxone, cefoxitin, and imipenem in addition to clindamycin but were resistant to metronidazole . The clinical P . acnes isolates also displayed high-level susceptibility to ciprofloxacin, sparfloxacin, and ofloxacin . Almost all the P . acnes strains demonstrated E-test MICs within 2 dilutions of the MICs observed by the agar dilution method . Those few strains for which discrepancies were noted exhibited E-test susceptibilities three- to fivefold dilutions lower than the agar dilution method susceptibilities but only with ampicillin-sulbactam, ticarcillin-clavulanate, and/or clindamycin . On the basis of our study, all of clinical eye isolates were susceptible to these newer antimicrobial agents and the two methods demonstrated similar susceptibility patterns.

Int Immunol, 1996 Apr, 8(4), 569 - 76
A pivotal role of IL-12 in Th1-dependent mouse liver injury; Tanaka Y et al.; Intravenous injection of Propionibacterium acnes and lipopolysaccharide (LPS) with a 7 day interval caused CD4+ T cell-dependent severe liver injury in the C57BL/6 (H-2b) mouse strain . In contrast, BALB/c (H-2d) mice were resistant to P . acnes and LPS-induced liver injury . The different susceptibilities of the two mouse strains to liver injury appeared to be closely correlated with their different abilities to produce IFN-gamma after P . acnes priming . Namely, the sensitive C57BL/6 mouse strain produced a significant level of IFN-gamma 7-10 days after P . acnes injection, whereas no significant amount of serum IFN-gamma was detected in the resistant BALB/c mouse strain . The important role of IFN-gamma in liver injury was demonstrated from the finding that in vivo administration of anti-IFN-gamma mAb abrogated P . acnes and LPS-induced liver injury in C57BL/6 mice . Moreover, it was demonstrated that in vivo administration of recombinant IL-12, a key cytokine for the induction of IFN-gamma, into mice induced P . acnes and LPS-induced liver injury in the resistant BALB/c mouse strain . Conversely, in vivo administration of anti-IL-12 mAb blocked the development of liver injury in the sensitive C57BL/6 mouse strain . Moreover, it was demonstrated that the failure of the induction of liver injury in BALB/c mice appeared to be derived from the lack of expression of IL-12 at the local site of liver in P . acnes-primed mice . These results strongly indicated that endogenous IL-12, which stimulates Th1-dominant cellular immunity and IFN-gamma production, may be an essential cytokine on the course of T cell-dependent liver injury.

Structure, 1996 Mar 15, 4(3), 339 - 50
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution; Mancia F et al.; BACKGROUND . The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta heterodimer of 150 kDa, is a member of a class of enzymes that uses coenzyme B12 (adenosylcobalamin) as a cofactor . The enzyme induces the formation of an adenosyl radical from the cofactor . This radical then initiates a free-radical rearrangement of its substrate, succinyl-CoA, to methylmalonyl-CoA . RESULTS . Reported here is the crystal structure at 2 A resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in complex with coenzyme B12 and with the partial substrate desulpho-CoA (lacking the succinyl group and the sulphur atom of the substrate) . The coenzyme is bound by a domain which shares a similar fold to those of flavodoxin and the B12-binding domain of methylcobalamin-dependent methionine synthase . The cobalt atom is coordinated, via a long bond, to a histidine from the protein . The partial substrate is bound along the axis of a (beta/alpha)8 TIM barrel domain . CONCLUSIONS . The histidine-cobalt distance is very long (2.5 A compared with 1.95-2.2 A in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the metal-carbon bond of the cofactor and favour the formation of the initial radical species . The active site is deeply buried, and the only access to it is through a narrow tunnel along the axis of the TIM barrel domain.

Appl Microbiol Biotechnol, 1996 Feb, 44(6), 710 - 6
Fed-batch fermentation with and without on-line extraction for propionic and acetic acid production by Propionibacterium acidipropionici; Ozadali F et al.; Fed-batch propionic and acetic acid fermentations were performed in semi-defined laboratory medium and in corn steep liquor with Propionibacterium acidipropionici strain P9 . On average, over four experiments, 34.5 milligrams propionic acid and 12.8 milligrams acetic acid were obtained in about 146 h in laboratory medium with 79 milligrams glucose added over five feeding periods . The highest concentration of propionic acid, 45 milligrams, was obtained when the glucose concentration was not allowed to drop to zero . In corn steep liquor 35 milligrams propionic acid and 11 milligrams acetic acid were produced in 108 h from 59.4 milligrams total lactic acid provided as seven feedings of corn steep liquor . Extractive fed-batch fermentations were conducted in semi-defined medium using either flat-sheet-supported liquid membranes or hollow-fiber membrane extraction to remove organic acids from the culture medium . As operated during the course of the fermentation, these systems extracted 25% and 22% of the acetic acid and 36.5% and 44.5% of the propionic acid, respectively, produced in the fermentation . Total amounts of acids produced were about the same as in comparable nonextractive fermentations: 30-37 milligrams propionic acid and 13 milligrams acetic acid were produced in 150 h . Limitations on acid production can be attributed to limited substrate feed, not to failure of the extraction system.

Vet Parasitol, 1996 Feb, 61(3-4), 201 - 10
Effect of silica treatment on resistance to Babesia rodhaini infection in immunized mice; Saeki H et al.; The effect of silica treatment on the course of Babesia rodhaini infection was investigated in ICR mice pretreated with either a mixture of B . rodhaini parasitized red blood cell hemolysation-sonication (S) antigen and Propionibacterium acnes bacterin or P . acnes bacterin alone and not subjected to immunization . In the normal mice (non-immunized), the mean survival time was decreased by approximately 1 day when 5 mg per mouse of silica were intraperitoneally inoculated at 5 h before infection . In immunization with S antigen and P . acnes bacterin, all mice survived regardless of the dose of silica (15-25 mg per mouse) treatment . In contrast, in immunization with P . acnes bacterin alone, 3/10, 4/10 and 1/10 mice died of B . rodhaini, when inoculated with 15 mg per mouse, 20 mg per mouse and 25 mg per mouse of silica treatment 5 h before infection, respectively . These results suggest that peritoneal macrophages (M luminal diameter of), especially when activated non-specifically by P . acnes bacterin, play an important role in inhibiting multiplication of organisms at the early stage of infection and the mice immunized with S antigen were ready to quickly acquire an enhanced solid specific protection even if the function of M luminal diameter of was damaged by a high dose of silica treatment.

J Leukoc Biol, 1996 Feb, 59(2), 145 - 51
Novel insight into molecular mechanism of endotoxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kappaB and regulation of cytokine production/action through beta2 integrin in vivo; Mukaida N et al.; Lipopolysaccharide (LPS), a constituent of gram-negative bacteria cell wall, plays an essential role in the pathogenesis of septic shock by generating endogenous mediators such as cytokines, nitrous oxide, superoxide anions, and lipid mediators . In vitro, LPS induces the transcription of a set of genes involved in inflammatory reactions by activating several types of transcription factors, particularly nuclear factor-kappaB (NF-kappaB) . An analysis of NF-kappaB activation using a cell-free system demonstated that two pathways converge to activate NF-kappaB; one is staurosporine-sensitive, the other is staurosporine-insensitive and tyrosine kinase-dependent . Furthermore, the latter pathway culminates in IkappaBalpha phosphorylation at serine/threonine residues in its carboxyl-terminal acidic region with dissociation of IkappaBalpha from NF-kappaB, thereby activating NF-kappaB . The requirement for the phosphorylation at this site was confirmed by the specific inhibition of NF-kappaB activation in a cell-free system by the synthetic peptide corresponding to this site . The in vivo administration of an anti-CD18 antibody prevented elevation of plasma tumor necrosis factor (TNF) levels and acute lethality induced by injection of a low dose of LPS into Propionibacterium acnes-primed rabbits or by the administration of a single high dose of LPS into animals . Anti-CD18 also prevented acute lethality induced by one of the main mediators of endotoxin shock, TNF-alpha . Furthermore, an antibody to a ligand for CD18, intercellular adhesion molecule-1, also prevented TNF-induced shock as well as endotoxin shock in rabbits . These observations suggest that the interaction between leukoytes and endothelium through beta2- integrin adhesion molecules may be of primary importance in mediating LPS signals in vivo.

Hepatology, 1996 Feb, 23(2), 320 - 8
Role of adhesion molecules in the development of massive hepatic necrosis in rats; Mochida S et al.; Massive hepatic necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids . Immunohistochemical hepatic expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen 1 alpha (LFA-1 alpha) and the effect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats . There were increased stains of ICAM-1 in endothelial cells and LFA-1 alpha in macrophages in the hepatic sinusoids in Propionibacterium acnes-pretreated rats compared with normal rats . Such stains were further increased soon after endotoxin administration, followed by development of hepatic necrosis . Monoclonal antibodies against both adhesion molecules significantly attenuated the extent of liver injury compared with controls, without affecting the infiltration and activation of hepatic macrophages . Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activation, attenuated the extent of liver injury . Thus, adhesion between endothelial cells and activated macrophages in the hepatic sinusoids via ICAM-1 and LFA-1 alpha is essential for the initiation of massive hepatic necrosis of this type . Contribution of neutrophils seems less likely.

Eur Arch Psychiatry Clin Neurosci, 1996, 246(2), 108 - 9
Propionibacterium acnes in the cortex of patients with Alzheimer's disease; Kornhuber HH; Propionibacterium acnes was found in the cortex of three patients with Alzheimer's disease and in one frontal cortex of an elderly patient with cardiovascular risk factors and hypoxia due to a large glioblastoma of the right frontal lobe with severely increased intracranial pressure . Propionibacterium acnes is an atypical anaerobic bacterium which is sensitive to cephalosporins, but insensitive to metronidazole . It is concluded that a capillary microangiopathy (in consequence of old age and cardiovascular risk factors such as high blood pressure) leads to cortical hypoxia and reduced resistance of the cortical immune system . Prevention by dietary regimes counteracting microangiopathy and treatment with cephalosporins are recommended.

Neoplasma, 1996, 43(4), 235 - 8
Bloodstream infections due to anaerobic bacteria in cancer patients: epidemiology, etiology, risk factors, clinical presentation and outcome of anaerobic bacteremia; Spanik S et al.; Thirty one bacteremic episodes (BE) in 31 patients due to anaerobic bacteremia (AB) in 979 BE among 9986 admissions at a 360 beds National Cancer Institute within last 6 years were analyzed for time distribution, risk factors, clinical presentation and outcome . Overall incidence of AB was 3.6%, but the proportion to other groups of microorganisms is decreasing . 73% were Bacteroides fragilis, 10.8% Peptostreptococci and Propionibacteria and 5.4% Clostridia . The most common risk factor for AB was prior surgery, solid tumor as underlying disease, prophylaxis with quinolones and previous therapy with third generation cephalosporines . 48.4% of AB were polymicrobial . Infected wound was the most common source of infection in 38.7% of our cancer patients . Six patients (19.4%) presented septic shock, and 45.2% died, but only in 22.6% death was related to bacteremia . Comparing the groups of AB due to B . fragilis (BF) to non-Bacteroides spp . (NB)AB, infection-associated mortality was higher in BFAB in comparison to NBAB . Other risk factors such as hematologic malignancies, previous prophylaxis with quinolones, prior surgery and prior therapy with broad spectrum antimicrobials, were more frequently associated with BFAB.

Wiad Parazytol, 1996, 42(1), 45 - 56
Propionibacterium granulosum activities in rats during the muscle phase of Trichinella spiralis invasion; Moskwa B; Immune response of Wistar rats, infected with 4000 L1 T . spiralis and treated with P . granulosum during the muscle phase of nematode invasion were measured . The increase of spleen mass was observed in all groups infected and exposed to P . granulosum . Intraperitoneal injection of bacteria results in higher level of T lymphocytes and activated neutrophils . The level of inhibition of macrophages migration was depended on relation to the time and doses of injection . In non-specific stimulated animals there were not statistically significant changes in the level of specific IgG1 antibodies determined by ELISA, against the crude extract of infective larvae of T . spiralis . The reduction of intensity of nematode invasion during the muscle phase was not observed in rats after P . granulosum treatment.

Eur Biophys J, 1996, 24(4), 243 - 50
EXAFS investigation of the active site of iron superoxide dismutase of Escherichia coli and Propionibacterium shermanii; Scherk C et al.; The local structure of the iron site in ferric superoxide dismutase from P . shermanii was analyzed by X-ray absorption spectroscopy . The metal-ligand cluster of the enzyme is found to be similar to the crystallographically investigated ferric superoxide dismutase from E . coli . At pH 6.4 the enzyme is five-fold coordinated with three histidines, an aspartate and a water molecule . The average bond lengths between the metal and the histidines are about 2.10 A, between metal and aspartate they are about 1.86 A and between metal and water 1.96 A . With an increase in pH a change in the coordination number from five to six is observed both in pre-edge peak and EXAFS spectra analysis . However, the bond lengths of the ligands do not change dramatically, they are conserved for the aspartate and increase slightly to 2.13 A for the average metal-histidine distance at pH 9.3 . The observation of the increase in coordination number is correlated with a decrease in enzymatic activity which occurs in the high pH range . The zinc EXAFS spectra of P . shermanii superoxide dismutase have shown that zinc can be incorporated in the active center instead of the iron.

Cutis, 1996 Jan, 57(1 Suppl), 8 - 12
An overview of acne and its treatment; Thiboutot DM; The pathophysiology of acne vulgaris results from the interplay of follicular hyperkeratinization, the presence of Propionibacterium acnes bacteria in the follicular canal, and sebum production . Several anti-acne agents are currently available that affect one or more of these pathogenic factors and are effective against one or more acne lesion types . The only currently available agent that is directly effective against comedones is tretinoin . Agents effective against inflammatory lesions include tretinoin, benzoyl peroxide, and topical and systemic antibiotics . Agents effective against nodules and cysts include oral antibiotics and isotretinoin . However, the successful utilization of the available agents and techniques is highly dependent on an accurate and thorough assessment of each patient's needs and concerns, followed by the implementation of an individualized treatment program that has been clearly communicated to the patient . Such a program may employ several different anti-acne agents and adjunctive treatments such as comedo extraction or intralesional injection.

Cutis, 1996 Jan, 57(1 Suppl), 20 - 35
Efficacy and safety of topical azelaic acid (20 percent cream): an overview of results from European clinical trials and experimental reports; Graupe K et al.; Azelaic acid cream (20 percent) is a new topical treatment for acne with an additional therapeutic potential in rosacea and hyperpigmentation disorders . Azelaic acid (AzA; HOOC-(CH2)7-COOH) is a naturally occurring compound that interferes with acne pathogenesis by virtue of its antikeratinizing, antibacterial, and anti-inflammatory properties . Vehicle-controlled studies have verified that AzA exercises a significant and clinically relevant effect on both non-inflammatory and inflammatory acne lesions . Comparisons with clinically proven therapies have shown that 20 percent AzA cream is an effective monotherapy in mild to moderate forms of acne, with an overall efficacy comparable to that of tretinoin (0.05 percent), benzoyl peroxide (5 percent), and topical erythromycin (2 percent) . In the treatment of moderate to severe acne, 20 percent AzA cream may be favorably combined with minocycline (90 percent good and excellent results), and may contribute towards reducing recurrences following discontinuation of systemic therapy (maintenance therapy with AzA cream) . Particular advantages of AzA therapy include its favorable safety and side effect profile . It is non-teratogenic, is not associated with systemic adverse events or photodynamic reactions, exhibits excellent local tolerability, and does not induce resistance in Propionibacterium acnes.

J Immunol, 1995 Dec 15, 155(12), 5743 - 9
IL-10 is involved in the protective effect of dibutyryl cyclic adenosine monophosphate on endotoxin-induced inflammatory liver injury; Arai T et al.; The effects of exogenous cAMP, dibutyryl cAMP (DBcAMP) on LPS-induced liver injury were examined in mice made hypersensitive to LPS by treatment with i.v . injection of Propionibacterium acnes . In vivo administration of DBcAMP significantly protected P . acnes-treated mice from LPS-induced liver injury, including apoptosis of hepatocytes . DBcAMP significantly increased circulating IL-10 level in correlation with suppression of the TNF-alpha level after LPS challenge in P . acnes-treated mice . Treatment with anti-IL-10 mAb abrogated the protective effect of DBcAMP on LPS-induced liver injury . Similar to in vivo findings, addition to DBcAMP to in vitro culture of liver adherent cells from P . acnes-treated mice enhanced IL-10 synthesis after LPS stimulation . These results suggest that the increment in IL-10 production by liver adherent cells is involved in the protective effect of DBcAMP on LPS-induced inflammatory liver injury.

Eur J Pharmacol, 1995 Dec 7, 293(4), 439 - 45
Kinetics of nitric oxide synthase induction by Propionibacterium avidum and lipopolysaccharide; Dhouib M et al.; Conditions for the induction of rat liver Ca2(+)-independent nitric oxide synthase were determined with killed Propionibacterium avidum, and compared with lipopolysaccharide endotoxin . Similar maximal induction was obtained intraperitoneally with the two types of inducers but killed Propionibacterium avidum gave a long-lasting induction while lipopolysaccharide displayed a rapid and short response . Moreover, the induction resulting from an intravenous administration of killed Propionibacterium avidum reached 60 times that of the control whereas lipopolysaccharide treatment induced a 24-fold stimulation only . It is noteworthy that with the first inducer the nitric oxide activity was stable with time whereas with the second one it dropped after 8 h . Whatever the route of administration of killed Propionibacterium avidum, some huge vacuolated Kupffer cells were found in the liver whose parenchyma was almost normal . Numerous monocytes, and unaltered Kupffer cells, were observed . Kupffer cells were identified to be responsible for the uptake of killed Propionibacterium avidum.

Res Commun Mol Pathol Pharmacol, 1995 Dec, 90(3), 373 - 87
Rapid formation of multicellular spheroids composed of Propionibacterium acnes pretreated adult rat liver cells by rotary culture and their immunological properties; Ueno K et al.; An experimental acute liver injury model can be produced by the injection of bacterial lipopolysaccharide (LPS) into Propionibacterium acnes (P . acnes) pretreated rats . The massive liver cell necrosis is estimated by elevation of serum transaminase activities . In this study, we produced this necrosis in an in vitro model by using primary co-cultured rat liver cells . A novel method for the preparation of spheroids consisting of P . acnes pretreated parenchymal and nonparenchymal liver cells has been successfully developed quickly by the rotary culture system within 24 hr although it takes 7 days to form the spheroid using a collagen-conjugated thermo-responsive polymer such as a cell substratum . Clear elevations of transaminase activities, TNF-alpha and CINC-1/gro/KC leaked from these spheroids into the medium caused by the exposure of 10 microgram/ml LPS for 48 hr were observed . These results suggest that this rotary co-culture system of rat liver cells is a useful model as an alternative to animal tests for fulminant hepatitis.

J Chemother, 1995 Dec, 7(6), 515 - 8
The in vitro activity of trospectomycin against anaerobic bacteria; Chisari G et al.; The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp . (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccharolytica (7 strains), Mobiluncus spp . (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp . (25 strains) and Propionibacterium spp . (7 strains) . The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H2, 10% CO2, 80% N2 . All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates . In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp . (MIC 90 = 0.5 mg/l).

J Photochem Photobiol B, 1995 Dec, 31(3), 125 - 31
Intracellular pH changes induced in Propionibacterium acnes by UVA radiation and blue light; Futsaether CM et al.; The intracellular pH changes induced in the Gram-positive skin bacterium Propionibacterium acnes by blue light and UVA radiation were studied . Two methods (31P nuclear magnetic resonance (NRM) spectroscopy and fluorescence spectroscopy using a pH-sensitive fluoroprobe (2',7'-bis-(2-carboxyethyl)-5-(and -6-)-carboxyfluorescein)) were used to determine the intracellular pH . The pH changes induced by irradiation were found to be a function of cell survival . These changes as a function of cell survival followed the same pattern for blue light and UVA radiation . A reduction of the pH gradient across the cell membrane (inside alkaline) was found for lethal doses (less than 15% survival) . This reduction corresponded to a decrease in intracellular pH and may indicate a proton influx . An increase in the pH gradient, which corresponded to an increase in the intracellular pH, was observed for sublethal doses . This increase appears to be reversible . Thus two separate mechanisms, which appear to be the same in UVA and blue light regions, may be responsible for the irradiation-induced pH alterations.

Infect Immun, 1995 Dec, 63(12), 4812 - 7
Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin beta 2 with concomitant reduction of cytokine production; Ikeda N et al.; Acute lethality was induced in rabbits by the sequential injection of Propionibacterium acnes and lipopolysaccharide (LPS) . P . acnes induced the infiltration of inflammatory cells into the liver lobules during the early phase, and LPS in the late phase caused death in association with pathological changes mimicking hepatocellular necrosis or degeneration around infiltrated mononuclear cells and fibrin deposition in the liver, lung, and kidney, suggestive of a systemic Schwartzman-like reaction . These pathological changes were accompanied by the elevation of plasma tumor necrosis factor (TNF) and interleukin-8 (IL-8) levels . A neutralizing antibody to a leukocyte adhesion molecule, integrin beta 2 (CD18), administered at the time of LPS challenge, prevented reduced the elevation of plasma TNF and IL-8 levels . An anti-TNF alpha antibody but not an anti-IL-8 mediator in this model . These results indicate that CD18 is critically involved in vivo in activating leukocytes to produce cytokines in response to LPS.

Cell Immunol, 1995 Dec, 166(2), 275 - 85
Adhesion molecules on intermediate TCR cells . II . Hepatoprotective effects of hyaluronic acid on acute liver injury; Nakayama M et al.; The liver is a major organ wherein extrathymic T cells and NK cells exist in mice . Due to their unique properties, i.e., extrathymic T cells are TCR (or CD3)-intermediate+ IL-2R beta+ (herein termed intermediate TCR cells) and NK cells are TCR(-)IL-2R beta+, they are easily distinguished from the other lymphocyte subsets by using mAbs in conjunction with immunofluorescence tests . They were recently found to express a higher level of CD44 antigen, which is a ligand for hyaluronic acid, than that of another T cell subset (i.e., thymus-derived T cells or bright TCR cells) . Since an intravenous administration of hyaluronic acid was also found to reduce the number of intermediate TCR cells and NK cells in the liver, we examined whether hyaluronic acid had a hepatoprotective effect on acute liver injury . Such injury was induced by LPS injection in mice pretreated with Propionibacterium acnes 1 week earlier . When a single dose of hyaluronic acid was given to these mice 12 hr before LPS injection, a prominent hepatoprotective effect was observed in terms of decreases of mortality (up to 50%), lymphocyte infiltration of the liver, serum transaminase levels, and tissue damage . At this time, liver mononuclear cells isolated from the treated mice showed decreased levels of cytokine production such as TNF and IL-1 . These results reveal that intermediate TCR cells and NK cells in the liver actually adhere the sinusoid walls by means of an interaction of CD44 molecules and hyaluronic acid even in the case of acute liver injury . It suggests a possible therapeutic effect of the administration of hyaluronic acid in acute liver injury by eliminating the effector cells and cytokine-producing cells from the liver.

Biochem Biophys Res Commun, 1995 Nov 22, 216(3), 841 - 7
Metal uptake of recombinant cambialistic superoxide dismutase from Propionibacterium shermanii is affected by growth conditions of host Escherichia coli cells; Gabbianelli R et al.; We constructed the complete nucleotide sequence coding for the cambialistic superoxide dismutase from Propionibacterium shermanii by ligation of a synthetic linker to a polymerase chain reaction amplification product obtained using degenerate primers . We set up an expression system yielding large amounts of recombinant superoxide dismutase in the cytoplasm of Escherichia coli and purified the enzyme from cells grown in a complex medium . The physicochemical properties of the recombinant enzyme were identical to those of the natural protein . Under anaerobic conditions the enzyme produced in an iron-supplemented medium incorporated iron as metal cofactor, while the enzyme purified from cells grown under aerobic conditions contained a variable amount of iron and manganese depending on metal availability . Functional equivalence of the two metals in this superoxide dismutase variant was indicated by independence of enzyme activity from Fe/Mn ratio.

Nature, 1995 Nov 2, 378(6552), 88 - 91
Cloning of a new cytokine that induces IFN-gamma production by T cells; Okamura H et al.; The mechanism underlying the differentiation of CD4+ T cells into functionally distinct subsets (Th1 and Th2) is incompletely understood, and hitherto unidentified cytokines may be required for the functional maturation of these cells . Here we report the cloning of a recently identified IFN-gamma-inducing factor (IGIF) that augments natural killer (NK) activity in spleen cells . The gene encodes a precursor protein of 192 amino acids and a mature protein of 157 amino acids, which have no obvious similarities to any peptide in the databases . Messenger RNAs for IGIF and interleukin-12 (IL-12) are readily detected in Kupffer cells and activated macrophages . Recombinant IGIF induces IFN-gamma more potently than does IL-12, apparently through a separate pathway . Administration of anti-IGIF antibodies prevents liver damage in mice inoculated with Propionibacterium acnes and challenged with lipopolysaccharide, which induces toxic shock . IGIF may be involved in the development of Th1 cells and also in mechanisms of tissue injury in inflammatory reactions.

Biochemistry, 1995 Oct 31, 34(43), 14125 - 30
Structural and electronic similarity but functional difference in methylmalonyl-CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin; Calafat AM et al.; The cofactor analog 2',5'-dideoxyadenosylcobalamin (ddAdoCbl) differs from the natural cofactor coenzyme B12 {5'-deoxyadenosylcobalamin (dAdoCbl)} by lacking only one oxygen atom . The 1H and 13C NMR spectra of ddAdoCbl have been assigned unambiguously by homonuclear and heteronuclear 2D NMR techniques . The 1H, 13C, and 31P chemical shift values for ddAdoCbl were compared with those of another organocobalamin, namely dAdoCbl . This assessment shows that the analog is very similar both electronically and structurally to the natural cofactor . The effectiveness of ddAdoCbl as a cofactor for both the human and Propionibacterium shermanii methylmalonyl-CoA mutases was compared with that of the natural cofactor . ddAdoCbl was found to be a competitive inhibitor with respect to dAdoCbl . Similar binding affinities to both enzymes were found for both the ddAdoCbl analog and the natural cofactor . However, in the presence of ddAdoCbl, the rate of conversion of methylmalonyl-CoA to succinyl-CoA was only 1-2% of that seen with the natural cofactor . There were no changes with time in the visible absorption spectrum of the bound cofactor analog in the presence of substrate, suggesting that the Co-C bond was not cleaved . The CD (circular dichroism) spectra of dAdoCbl and ddAdoCbl are very similar, consistent with the NMR results . The CD spectral changes upon binding to P . shermanii methylmalonyl-CoA mutase are large compared to those reported on the binding of dAdoCbl to ethanolamine ammonia lyase . Furthermore, the CD spectra of both enzyme-bound cobalamins are very similar, suggesting that similar changes in the conformation or structure in these cobalamins occur on binding to the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver, 1995 Oct, 15(5), 253 - 9
Functional differences between activated and normal rat liver macrophages: LPS uptake capacity by flow cytometric analysis in contrast with TNF-alpha release; Kayano K et al.; Activated liver macrophages are considered to play an important role in the development of liver injuries . Functional differences between activated and normal rat liver macrophages were investigated . In addition, from the therapeutic point of view, the effects of prostaglandin E1, prostaglandin I2 and E3330 ((2E)-3-{5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)}-2-nonyl-2-propenoic acid) on the functions of liver macrophages were also determined . Rat liver macrophages were primed by Propionibacterium acnes and activated by a small dose of lipopolysaccharide . Lipopolysaccharide uptake capacity was evaluated quantitatively by flow cytometric analysis . Tumor necrosis factor-alpha activities were measured by bioassay . There were no significant differences in lipopolysaccharide uptake capacity between activated and normal liver macrophages, while activated liver macrophages had a significantly (P < 0.01) higher capacity in the release of tumor necrosis factor-alpha . Prostaglandin E1 and E3330 inhibited tumor necrosis factor-alpha release without suppressing lipopolysaccharide uptake capacity . In this study we have clarified the functional differences between activated and normal liver macrophages . The beneficial effects of prostaglandin E1 and E3330 on the functions of liver macrophages were also demonstrated.

Can J Cardiol, 1995 Oct, 11(9), 785 - 7
Propionibacterium acnes endocarditis; Huynh TT et al.; Propionibacterium acnes endocarditis is a rare disease . A case of prosthetic valve endocarditis involving P acnes complicated by multiple mycotic aneurysms is reported . A brief review of the literature is presented.

Infect Immun, 1995 Oct, 63(10), 3966 - 72
A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock; Okamura H et al.; Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice . In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved . An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P . acnes and subsequently challenged with lipopolysaccharide . Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it . Its molecular mass was 18 to 19 kDa, and its pI was 4.9 . The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases . The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa . Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract . In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells . Thus, several of its biological activities were apparently similar to those of interleukin-12 . These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P . acnes treatment . This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P . acnes-treated mice.

Biochem J, 1995 Sep 15, 310 ( Pt 3), 945 - 50
Kinetic and spectroscopic studies on a superoxide dismutase from Propionibacterium shermanii that is active with iron or manganese: pH-dependence; Meier B et al.; Kinetic studies were performed on the superoxide dismutases isolated from the anaerobic bacterium Propionibacterium shermanii as active enzymes with either iron or manganese, which were naturally incorporated into the same molecule depending on the metal supply . Both the Fe- and Mn- forms showed decreasing activity with increasing pH . This suggests the protonation of some groups near the metal, possibly a metal-bound water molecule . Thus the kinetic behaviour of this superoxide dismutase is much more dependent on the protein structure than on the metal incorporated into the active site . The secondary structures of both forms were not influenced by variations in pH, whereas the EPR spectra of the Fe-superoxide dismutase changed as a function of pH . The EPR spectra apparently consist of two overlapping species . Steady-state experiments proved that all iron-containing species show catalytic activity, but the species predominating in the alkaline pH range displays a lower reaction rate . The Michaelis constant and maximal turnover number for the Fe-superoxide dismutase were determined polarographically as Km = 0.54 mmol/l and Vmax . = 2000 mol.s-1 at pH 9.5 . These data indicate that, in anaerobic bacteria under physiological conditions, the superoxide dismutase is not saturable with O2- . and the catalytic activity is similar to that of metal-specific Fe- or Mn-superoxide dismutases from aerobic organisms.

Anticancer Res, 1995 Sep-Oct, 15(5B), 2363 - 8
Immunostimulation by propionibacteria--effects on immune status and antineoplastic treatment; Isenberg J et al.; Experimental studies were performed to investigate further the effects of immunotherapy with Propionibacterium avidum KP-40 on thymocyte proliferation, maturation and emigration in BALB/c-mice . Thymus weight and thymocyte counts, especially cells presenting the immature or cytotoxic/suppressor phenotype were significantly increased . Due to enhanced emigration, peripheral blood lymphocyte and monocyte counts as well as expression of activation markers were significantly upregulated . The antimetastatic effect of Propionibacterium avidum KP-40 was demonstrated in BALB/c-mice, where RAW 117-H10 lymphosarcoma liver colonization was significantly reduced after immunostimulation . Clinical investigations proved that surgical treatment of colorectal carcinoma induced an evident decrease of peripheral blood lymphocytes as compared with preoperative counts . However, single preoperative Propionibacterium avidum KP-40 administration induced a considerable increase of peripheral white blood cell counts, especially lymphocytes . Clinical effects of preoperative immunostimulation by Propionibacterium granulosum KP-45 were investigated in a prospective randomized trial in colorectal carcinoma patients . Positive effects on survival time, local tumor recurrence and distant metastasis could be demonstrated in stages I and II, whereas no advantage of immunotherapy was found in advanced stages III and IV . A recent prospective randomized clinical trial was initiated on the quality of life of colorectal carcinoma patients . Three months after surgical treatment negative effects could not be determined after immunotherapy . Quality of life even proved to be better in patients with abdominoperineal resection as compared to non Propionibacterium avidum KP-40 treated control patients.

J Am Acad Dermatol, 1995 Aug, 33(2 Pt 1), 247 - 53
Inflammation in acne vulgaris; Webster GF; Recent findings suggest that an overly vigorous immune response to Propionibacterium acnes may be the fundamental problem in patients with inflammatory acne . These data and evidence for the antiinflammatory effects of acne medications are reviewed.

Infect Immun, 1995 Aug, 63(8), 3158 - 65
Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne; Vowels BR et al.; Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne . This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients . Both Propionibacterium acnes and supernatants obtained from 72-h P . acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay . There was no significant difference between acne and non-acne subjects . Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination . P . acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells . Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction . The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane . Incubation of P . acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity . The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity . Heating of the P . acnes supernatant to 65 degrees C also had no effect on the activity . Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.

Mol Biochem Parasitol, 1995 Jul, 73(1-2), 43 - 51
Kinetic mechanism of pyrophosphate-dependent phosphofructokinase from Giardia lamblia; Phillips NF et al.; The steady-state kinetics of the reaction catalyzed by inorganic-pyrophosphate-dependent D-fructose-6-phosphate 1-phosphotransferase from Giardia lamblia have been investigated . The reactants for the forward and reverse reactions were the Mg-chelated complexes of pyrophosphate (PPi) and Pi . Uncomplexed ligands were not substrates . In the direction of phosphorylation of fructose-6-phosphate (F6P), initial velocity double-reciprocal plots for both PPi and F6P were intersecting suggesting sequential addition of substrates . Similarly, intersecting patterns were observed in the reverse reaction with either Pi or fructose-1,6-bisphosphate (FBP) as the variable substrate . Although the catalytic constants for the forward and reverse reactions were found to be identical (83 s-1), the kcat/Km for PPi is about two orders of magnitude higher than the kcat/Km for Pi, indicating that PPi is utilized much more efficiently than Pi . Product inhibition of Pi is competitive vs . PPi and noncompetitive vs . F6P, when the fixed substrate is subsaturating . Product inhibition by FBP was found to be noncompetitive with either Pi or F6P as the variable substrate . These results are consistent with a sequential ordered Bi Bi mechanism with PPi adding first and Pi dissociating last . In the reverse reaction, however, PPi and F6P were found to be noncompetitive with either Pi or FBP . Dead-end inhibition analysis with fructose 2,6-bisphosphate, a competitive substrate analog of FBP, gave uncompetitive inhibition with respect to Pi, indicating that fructose 2,6-bisphosphate (and hence FBP) binds after Pi . This kinetic mechanism is different from that observed with the enzyme from Propionibacterium freudenreichii, Entamoeba histolytica or Mung bean, which were concluded to be rapid equilibrium random mechanism.

J Hosp Infect, 1995 Jul, 30(3), 229 - 32
Surgical wound infections due to Propionibacterium acnes: a study of 10 cases; Esteban J et al.; Ten cases of surgical wound infection in which Propionibacterium acnes was probably the aetiologic agent were reviewed; in five the organism was isolated in pure culture . Six patients underwent a neurosurgical procedure . The average time for development of infection was 17.5 days (range 1-30 days) . All patients were cured by surgical drainage and, in nine cases, with appropriate antimicrobial therapy . In conclusion, P . acnes must be considered as a cause of surgical wound infections especially after neurosurgery.

Appl Environ Microbiol, 1995 Jul, 61(7), 2572 - 6
Occurrence of Propionibacterium freudenreichii bacteriophages in swiss cheese; Gautier M et al.; We isolated bacteriophages active against Propionibacterium freudenreichii from 16 of 32 swiss cheese samples . Bacteriophage concentrations ranged from 14 to 7 x 10(5) PFU/g, depending on the sample and the sensitive strain used for detection . Only a few strains, 8 of the 44 strains of P . freudenreichii in our collection, were sensitive . We observed that multiplication of bacteriophages occurred in the cheese loaf during multiplication of propionibacteria in a warm curing room, but it seems that these bacteriophages have no adverse effect on the development of the propionic flora . We also found that sensitive cells, originating from either the starter or the cheese-making milk, were present at a high level (10(9) CFU/g) in the cheese.

J Leukoc Biol, 1995 Jul, 58(1), 90 - 8
Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice; Fujioka N et al.; Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra . A sensitive and specific ELISA against mouse IL-1ra was also established . In Propionibacterium acnes-induced liver injury, P . acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6 . However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels . Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P . acnes and eliciting phase by LPS challenge . Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P . acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.

J Immunol Methods, 1995 May 11, 182(1), 21 - 8
Establishment of a T cell-dependent nude mouse liver injury model induced by Propionibacterium acnes and LPS; Tanaka Y et al.; Normal ICR mice developed severe liver injury when they were given intravenous injections of Propionibacterium acnes and lipopolysaccharide (LPS) with a 7 day interval . In contrast, T cell-deficient ICR nude mice were resistant to P . acnes and LPS-induced liver injury . However, athymic ICR nude mice, which were treated with cell transfer of normal ICR mouse spleen cells (10(8) cells) or ICR mouse nylon-wool passed splenic T-enriched cells (over 10(7) cells), showed severe liver injury as assessed by elevation of serum transaminase activities . Histological analyses also demonstrated that the transferred cells migrated into the liver of nude mice to induce liver injury . However, depletion of both CD4+ T cells and CD8+ T cells from transferred cell populations caused a marked decrease in the elevation of serum transaminase, indicating the actual involvement of T cells in liver injury . Moreover, in vivo administration of anti-LFA-1 mAb blocked P . acnes and LPS-induced liver injury in nude mice following T cell transfer . Thus, this model will provide a new strategy to investigate T cell-dependent cell-cell interaction during the induction of liver damage.

Rinsho Shinkeigaku, 1995 May, 35(5), 526 - 30
{Hypertrophic cranial pachymeningitis with propionibacterium acnes detected by dural biopsy}; Nishioka R et al.; A 30-year-old woman experienced recurrent dull headache and frequent partial motor seizure (Jacksonian type) that marched from right fingers . This motor seizure was uncontrollable with ordinary anticonvulsant therapy . Cerebrospinal fluid showed mild pleocytosis . Cranial CT examination was unremarkable, but MRI revealed thickened dural lesion on the left fronto-parietal site, giving diagnosis of hypertrophic cranial pachymeningitis . Dural biopsy showed nonspecific chronic granulomatous state without specific granuloma such as tuberculosis nor sarcoidosis . Anaerobic culture revealed Propionibacterium acnes, a rare causative agent of meningitis . We conclude that it is important to follow a case of unknown cause pachymeningitis carefully with MRI, and in some cases, is required a dural biopsy to make a diagnosis before steroid therapy.

J Biol Chem, 1995 Apr 21, 270(16), 9295 - 300
Evidence from electron paramagnetic resonance spectroscopy of the participation of radical intermediates in the reaction catalyzed by methylmalonyl-coenzyme A mutase; Padmakumar R et al.; Recombinant methylmalonyl-coenzyme A (CoA) mutase from Propionibacterium shermanii has been purified 20-fold to near homogeneity in a highly active form . Neither the apoenzyme (the form in which the enzyme is isolated) nor the holoenzyme (reconstituted with the cofactor, adenosylcobalamin) has an electron paramagnetic resonance (EPR) spectrum associated with it . However, the addition of either the substrate, methylmalonyl-CoA, or the product, succinyl-CoA, results in the appearance of a transient EPR signal . The signal has hyperfine features that indicate coupling of the unpaired electron to the cobalt nucleus . In the presence of {CD3}methylmalonyl-CoA, an EPR signal is also seen and is similar to that obtained in the presence of protiated substrate . Power saturation studies reveal the presence of two components, a slow relaxing species (with an apparent g value of 2.11) and a fast relaxing species (with an apparent g value of 2.14) that can be partially resolved at low temperature and high power . The EPR-active intermediate is observed under catalytic conditions and is approximately midway in its resonance position between a free radical and cob(II)alamin . It is postulated to represent an exchange-coupled cob(II)alamin .. . free radical pair . The signal bears close resemblance to those observed with partially dehydrated polycrystalline adenosylcobalamin following laser photolysis (Ghanekar, V.D., Lin, R.J., Coffman, R.E., and Blakley, R.L . (1981) Biochem . Biophys . Res . Commun . 101, 215-221) and with the adenosylcobalamin-dependent ribonucleotide reductase under freeze-quench conditions (Orme-Johnson, W.H., Beinert, H., and Blakley, R.L . (1974) J . Biol . Chem . 249, 2338-2343) . When cob(II)alamin is generated under noncatalytic conditions (i.e . in the presence of propionyl-CoA or by electrochemical reduction of enzyme-bound hydroxocob-(III)alamin), a different EPR signal is observed with g = 2.26 and g = 2.00, typical of base-on cob(II)alamin.

Experientia, 1995 Apr 15, 51(4), 368 - 9
(E)-3-tridecen-2-one, an antibiotic from the interdigital glands of black-tailed deer Odocoileus hemionus columbianus; Wood WF et al.; (E)-3-tridecen-2-one, the major volatile component of interdigital gland extracts from the black-tailed deer, Odocoileus hemionus columbianus, inhibited the growth of gram-positive bacteria and fungi . The bacteria, Propionibacterium acnes, and the fungi, Trichophyton mentagrophytes had a minimum inhibitory concentration (MIC) of 12.5 micrograms/mL and 25 micrograms/mL, respectively.

Biochem J, 1995 Apr 1, 307 ( Pt 1), 143 - 9
Cloning, sequencing and expression of the pyrophosphate-dependent phosphofructo-1-kinase from Naegleria fowleri; Wessberg KL et al.; The cDNA for the PPi-dependent phosphofructo-1-kinase has been cloned and sequenced from a cDNA library prepared from the free-living amoeba Naegleria fowleri . The coding sequence of the cDNA consists of 1311 bases which translates into 437 amino acids with a molecular mass of 48095 Da . Comparison of the sequence with those of the previously described sequences of PPi-dependent phosphofructokinases from Propionibacterium freudenreichii and potato tuber revealed amino acid identities of 23 and 28% respectively and high conservation in those regions assumed to be part of the active site . The reading frame was cloned into an expression vector, which was transformed into Escherichia coli . Extracts of the transformed cells contained PPi-dependent phosphofructokinase activity that could be purified to homogeneity . The activity was lost on incubation with the chaotropic agent, KSCN, and recovered by subsequent incubation with AMP . These properties are consistent with those described by Mertens, De Jonckheere and Van Schaftingen {Biochem . J . (1993) 292, 797-803} for the enzyme prepared from Naegleria and support the idea that the cloned cDNA coded for the complete native enzyme . No nucleotide-binding motif or evidence for a nucleotide-binding site characteristic of the ATP-dependent phosphofructokinases could be found within the primary structure.

Antibiot Khimioter, 1995 Apr, 40(4), 25 - 9
{Comparative in vitro activity of ampicillin, cefoperazone and their combinations with sulbactam, as well as that of other antibiotics against anaerobic organisms}; Rezvan SP et al.; Susceptibility of 180 strains of anaerobic organisms to ampicillin, cefoperazone and their combinations with sulbactam, as well as that to cefoxitin, imipenem and metronidazole was studied with the method of serial microdilutions . 100 per cent of the strains was susceptible to the ampicillin + cefoperazone combination . Only 1 strain of Bacteroides fragilis was resistant to imipenem . 73.4 and 57.8 per cent of the B . fragilis strains were susceptible to cefoxitin and cefoperazone respectively . No resistance to metronidazole was detected . 100 per cent of the strains belonging to Bacteroides spp . fragilis (gr.) and Prevotella spp . was resistant to all the antibiotics except ampicillin . Gram-positive anaerobic cocci were susceptible to all the antibiotics . The strains of Actinomyces spp . and Propionibacterium acnes were resistant to metronidazole . Only 48.7 per cent the Actinomyces strains was susceptible to cefoxitin.

Diagn Microbiol Infect Dis, 1995 Apr, 21(4), 187 - 90
Minimum bactericidal concentrations of Propionibacterium acnes isolates from cases of chronic endophthalmitis; Hall GS et al.; Six isolates of Propionibacterium acnes recovered from cases of chronic infectious endophthalmitis following extracapsular cataract extraction were tested for antibiotic susceptibility . All isolates were susceptible to penicillin, cefazolin, and vancomycin with a macrobroth dilution method . Minimum bactericidal concentrations testing at 72 h revealed that six of six isolates were killed by < or = 1.0 micrograms of vancomycin/ml, one of six isolates by < or = 1.0 micrograms of penicillin/ml, and zero of six isolates by < or = 1.0 micrograms cefazolin/ml.

Arch Int Pharmacodyn Ther, 1995 Mar-Apr, 329(2), 319 - 30
Hepatoprotective effect of SY-640, a novel acetamide derivative, on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice; Tanaka Y et al.; The hepatoprotective effect of SY-640 on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice and its protective mechanism were examined . Oral administration of SY-640, 150 mg/kg once daily for 7 days, significantly inhibited Propionibacterium acnes and lipopolysaccharide-induced liver injury, but a single administration was without effect . Liver-infiltrating cells (T-lymphocytes and macrophages) play an important role in Propionibacterium and lipopolysaccharide-induced liver injury and express a higher level of leukocyte function-associated antigen-1 . SY-640 inhibited the number of liver-infiltrating cells and attenuated the increased expression of leukocyte function-associated antigen-1 on these cells . Tumor necrosis factor-alpha mediated Propionibacterium acnes and lipopolysaccharide-induced liver injury, and SY-640 inhibited the elevation of the serum tumor necrosis factor-alpha concentration after injection of lipopolysaccharide in Propionibacterium acnes-primed mice . The putative effects of SY-640 are inhibitory effects on infiltration into the liver and on activation of T-lymphocytes and macrophages after Propionibacterium acnes-priming, and attenuation of expression of cell adhesion molecules such as leukocyte function-associated antigen-1 . The immunological effect of SY-640 is likely to be closely related to the inhibition of Propionibacterium and lipopolysaccharide-induced liver injury.

Presse Med, 1995 Feb 18, 24(7), 338 - 40
{Current status of the SAPHO syndrome}; Kahn MF; In 1987, our group proposed the acronym SAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) to identify a clinical entity with characteristic manifestations formerly described under a wide variety of names . Since our first description, several new points have been recognized . For example it has been demonstrated that the skin lesions are not necessarily concomitant with osteoarticular manifestations sometimes separated by a long time interval . There are also several arguments suggesting a relationship with spondyloarthropathy . In addition, pseudo-tumoral fibrosis of anterior thoracic lesions which may lead to venous compression have been observed . It is difficult to determine the frequency of SAPHO . Most of the cases reported were observed in western Europe or Japan . Now that the concept has been accepted by our British colleagues, the number of cases reported has increased steadily, perhaps suggesting a reason for the apparently low frequency in the United States . The pathogenesis is still unknown . There is some evidence however that Propionibacterium acnes infection may be involved, at least in some cases, but formal proof is still lacking . Treating patients with SAPHO thus remains a question of debate . Non-steroid antiinflammatory agents are currently the treatment of choice although certain authors have tried colchicine and sulfasalazine or methotrexate with little success . There remains a good deal of work to be done before we thoroughly understand the SAPHO syndrome but we can nevertheless assure our patients that this strange bone disease is neither a tumour nor an infection and is never severely invalidating.

Br J Dermatol, 1995 Feb, 132(2), 204 - 8
The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora; Bojar RA et al.; A 28-day treatment regimen was undertaken by 12 volunteers, in which 5% (w/v) benzoyl peroxide (BP) in an aqueous gel was applied daily to the entire face . Clinical efficacy of the treatment was assessed after 2, 4, 9, 14 and 28 days, and the surface and follicular microbial populations were enumerated using established techniques . Viable counts were obtained for propionibacteria and Micrococcaceae . Mean numbers of propionibacteria recovered from the skin surface and follicular casts were significantly reduced after 2 days' treatment (P < 0.01), and the population was maintained at a significantly lower level throughout the study (P < 0.01), with mean values approaching the lower detection limit of the assay . Significant reductions in the surface and follicular Micrococcaceae were observed after 2 days' treatment, and at all subsequent visits (P < 0.05) . After 2 days' treatment, only slight reductions in mean acne grade and mean inflamed lesion count were observed . However, at all subsequent visits the mean acne grade was significantly reduced (P < 0.05) compared with T0 . The mean non-inflamed lesion count was lower than the pretreatment level at all visits, although the results were variable . The results indicate that significant reductions in surface and follicular microorganisms may be obtained after 48 h treatment with BP . Therefore, the non-specific antibacterial action of BP may be utilized in short intervening courses to reduce the carriage of antibiotic-resistant micro-organisms and thus improve the long-term efficacy of antibiotic acne treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

J Gastroenterol, 1995 Feb, 30(1), 48 - 54
Expression of hepatocyte growth factor and transforming growth factor beta 1 mRNA in P . acnes and lipopolysaccharide-treated rats; Masuhara M; Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, triggers hepatocyte regeneration after partial hepatectomy and acute liver cell necrosis induced by chemicals . In contrast, transforming growth factor beta 1 inhibits hepatocyte proliferation in vitro and suppresses liver regeneration in vivo . We assessed the expression of HGF and TGF beta 1 mRNA in an endotoxin-related hepatic cell necrosis model . Intravenous injection of Gram-negative lipopolysaccharide (LPS) into rats previously given heat-killed Propionibacterium acnes induced endotoxin-related hepatic cell necrosis . In this model, serum ALT began to rise to more than 100IU as early as 3 h after LPS injection, reaching 300IU 12h after injection . HGF mRNA levels in the liver did not increase significantly until 5h after LPS injection; at 12h, they had increased about threefold compared with controls . TGF beta 1 mRNA expression increased threefold after P . acnes treatment alone and increased further after LPS injection . In the spleen, HGF mRNA levels increased within 3h, but in the lung no increase in HGF mRNA was observed . Early elevation of liver TGF beta 1 mRNA levels and delayed elevation of HGF mRNA levels, with low expression of HGF in the lung, may play a role in the pathogenesis of endotoxin-related hepatic necrosis.

Planta Med, 1995 Feb, 61(1), 50 - 3
Preventive effect of taraxasteryl acetate from Inula britannica subsp . japonica on experimental hepatitis in vivo; Iijima K et al.; The survival rate for acute hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS) was increased when a hot water extract from the flowers of Inula britannica L . subsp . japonica Kitam . was injected into the experimental hepatitis mice, and anti-hepatitis substances could be extracted with CHCl3 . The CHCl3 extract from I.britannica was fractionated and anti-hepatitis fractions IB-3-2 and IB-3-3 were obtained . IB-3-3 had the most potent anti-hepatitis activity among the fractions but further purification of the active compound was not achieved because of the low yield . IB-3-2 contained only one substance which was identified to be taraxasteryl acetate by 1H- and 13C-NMR and MS . Taraxasteryl acetate showed potent preventive activity against acute hepatic failure induced by P.acnes and LPS in a dose-dependent manner, however deacetylation and modification of the olefinic bonds significantly decreased the anti-hepatitis activity of taraxasteryl acetate . Taraxasteryl acetate also inhibited the increment of plasma transaminase on acute hepatic failure induced by carbon tetrachloride (CCl4) or D-galactosamine . From a histological study it appeared that degeneration and necrosis, which were observed in the liver from CCl4 mice, were not found in the liver cells from taraxasteryl acetate treated mice . These results indicates that taraxasteryl acetate shows preventive effects on experimental hepatitis caused by either immunologically induced injuries or hepatotoxic chemicals.

Biochim Biophys Acta, 1995 Jan 25, 1260(2), 215 - 7
Cloning and sequencing a putative pyrophosphate-dependent phosphofructokinase gene from Entamoeba histolytica; Huang M et al.; Pyrophosphate-dependent phosphofructokinase (PPi-PFK) gene from Entamoeba histolytica was cloned from its genomic library and sequenced . The open reading frame has 1149 bp and codes for a protein of 41.5 kDa . The deduced amino acid sequence of E . histolytica PPi-PFK has 25 to 28% identity to the PPi-PFKs from Propionibacterium freudenreichii, Naegleria fowleri and potato . The amino acid residues known to contribute to the active site of PPi-PFK from P . freudenreichii are conserved.

Arch Biochem Biophys, 1995 Jan 10, 316(1), 541 - 6
{Omega-(adenosin-5'-O-yl)alkyl}cobalamins mimicking the posthomolysis intermediate of coenzyme B12-dependent rearrangements: kinetic investigations on methylmalonyl-CoA mutase; Poppe L et al.; Coenzyme-B12 analogues carrying oligomethylene chains (C3-C7) inserted between the central Co atom and the 5'-O atom of the adenosine moiety mimicking the putative posthomolysis intermediate in coenzyme B12-dependent rearrangements were synthesized and examined for their effects on methylmalonyl-CoA mutase from Propionibacterium shermanii . All analogues proved to be inhibitors of methylmalonyl-CoA mutase and in all cases competitive inhibition with respect to coenzyme B12 was found . Inhibition constants (Ki) were determined by two independent methods and showed in both cases the predicted trend: the Ki values versus chain length had minima at the C6 analogue in which the distance is about 10 A between the central Co atom and the 5'carbon of the adenosine, assuming a zig-zag chain conformation . This is the postulated distance between the Co and 5'-methylene paramagnetic centers generated in the methylmalonyl-CoA-coenzyme B12 complex after homolytic cleavage of the Co-C bond.

J Dermatol, 1995 Jan, 22(1), 4 - 9
The correlation of Kampo formulations and their ingredients on anti-bacterial activities against Propionibacterium acnes; Higaki S et al.; The correlation between the susceptibilities of Propionibacterium acnes strains to two Kampo formulations and these to their ingredients (Kampo crude drugs) was examined . Two out of 19 Kampo crude drugs, Coptidis Rhizoma (CR) and Phellodendri Cortex (PC), inhibited the growth of P . acnes significantly . The patterns of distribution of the minimal inhibitory concentrations of Keigai-rengyo-to (KRT) and of Seijo-bofu-to (SBT) were almost the same as those of the Kampo crude drugs, except CR and PC . Furthermore, no correlations between MICs of Kampo formulations and those of their ingredients against P . acnes were found . This might be due to mutual inhibition or to differences in anti-bacterial mechanisms between the two Kampo formulations and their ingredients . The Kampo formulations, composed of CR, PC and a few other kinds of Kampo crude drugs, might be more susceptible against P . acnes, since higher concentrations of the effective ingredients can be achieved.

Life Sci, 1995, 56(23-24), 2065 - 72
Anandamide inhibits macrophage-mediated killing of tumor necrosis factor-sensitive cells; Cabral GA et al.; Anandamide (arachidonoylethanolamide) was shown to inhibit macrophage-mediated killing of tumor necrosis factor-sensitive murine L929 fibroblasts . Scanning electron microscopy (SEM) demonstrated that L929 cells, co-cultured with Propionibacterium acnes (P . acnes)-activated peritoneal macrophages from mice treated with vehicle, were either disrupted or had surface abnormalities and numerous punctate lesions . In contrast, L929 cells co-cultured with macrophages from mice receiving P . acnes in concert with Anandamide (20 mg/kg-80 mg/kg) or the exogenous cannabinoid delta-9-tetrahydrocannabinol (THC; 80 mg/kg) did not exhibit ultrastructural abnormalities . Cytotoxicity assays were performed in parallel with SEM in order to determine whether ultrastructural observations correlated with target cell killing as measured by release of radiolabel from L929 target cells . P . acnes-activated macrophages from vehicle-treated mice elicited 41% specific release of radiolabel from {51Cr}-labeled L929 cells . In contrast, macrophages from animals treated with P . acnes and with 20, 40, or 80 mg/kg Anandamide exhibited 38%, 25%, or 28% specific release of radiolabel, respectively . Similarly, macrophages from animals treated with P . acnes and with 80 mg/kg THC exhibited 21% specific release of radiolabel . In vitro cytotoxicity studies using radiolabeled L929 target cells and conditioned medium from RAW264.7 murine macrophage-like cells allowed for determination of the time interval over which Anandamide exerted its inhibitory effect . Maximal inhibition of target cell killing occurred when conditioned medium was obtained from macrophages exposed to Anandamide for 1 hr prior to activation . In contrast, conditioned medium from THC-treated macrophages exerted its maximal inhibition of target cell killing when obtained from RAW264.7 cells pretreated for 24hr-48hr prior to activation . These results indicate that Anandamide and THC exert a similar inhibition of killing of TNF-sensitive target cells . However, the time interval over which these two substances elicit their suppressive effect differs.

Res Microbiol, 1995 Jan, 146(1), 51 - 8
Reclassification of "Propionibacterium rubrum" as P . jensenii; de Carvalho AF et al.; The taxonomic relationship of strains previously designated as "Propionibacterium rubrum" to P . thoenii and P . jensenii was investigated by use of 16S ribosomal RNA sequence comparison, biochemical characteristics and DNA hybridization . A total of 46 strains representing the species P . jensenii and P . thoenii and the former species "P . rubrum" and also including 21 reference strains and 25 strains isolated from dairy sources were studied . The 16S rRNA sequence of strain "P . rubrum" CNRZ 85 (= ATCC 4871) was found to be almost identical to that of the type strain of P . jensenii . DNA hybridization data indicated that "P . rubrum" should belong to the species P . jensenii rather than P . thoenii, as formerly proposed . The "P . rubrum" strains should then be reclassified as a beta-haemolytic biovar of P . jensenii . The genomic species P . jensenii and P . thoenii could be differentiated by biochemical characteristics such as the production of acid from myo-inositol and starch.

Zentralbl Bakteriol, 1995 Jan, 282(1), 86 - 91
Influence of propionibacterium avidum KP-40 on the proliferation, maturation, emigration and activity of thymocytes and monocytes; Ko HL et al.; Inactivated cells of Propionibacterium avidum KP-40 could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after intraperitoneal administration of the optimal immunomodulating dosage (1 mg per mouse) . The increase in thymus weight and thymocyte numbers per mg organ weight was most pronounced and statistically significant 10 days after P . avidum KP-40 administration . Determinations of lymphatic subsets revealed a considerable up-regulation of mature cells expressing helper/inducer (L3T4+) or cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells presenting both L3T4+/Lyt-2+ antigens . Obviously, P . avidum KP-40 administration accelerated murine thymocyte proliferation and maturation . Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) and monocytes (PBM) revealed statistically significant increases after P . avidum KP-40 administration with peak values after 6-10 days . The determination of activated PBL (expressing interleukin-2 receptors) or PBM (expressing MAC-3 antigens) proved that P . avidum KP-40 induced a potent immunostimulation since counts of these cells were significantly enhanced after P . avidum KP-40 treatment.

APMIS, 1995 Jan, 103(1), 45 - 53
MUM-4, a monoclonal antibody reacting with resident peritoneal mouse macrophages; Agger R et al.; A new rat monoclonal antibody, MUM-4, which recognizes a murine antigen/epitope that is absent on monocytes, strongly expressed on resident peritoneal macrophages and almost completely absent from peritoneal macrophages 4 days after an intraperitoneal injection of thioglycollate or heat-killed Propionibacterium acnes organisms, is described . Immunocytochemistry and flow cytometry have been used to characterize the specificity of the antibody . MUM-4 did not react with blood granulocytes, peritoneal exudate granulocytes, lymphocytes from blood or peritoneum, isolated spleen dendritic cells, or veiled cells from the thoracic duct of mesenteric lymphadenectomized mice . The MUM-4 antibody reacted with resident peritoneal macrophages from all the mouse strains studied . MUM-4 appears to represent a new specificity . The MUM-4 antibody is of the rat IgG2c isotype and exhibits complement-mediated cytotoxicity with rabbit complement . The staining achieved with MUM-4 by FACS or immunocytochemical methods is intense on most resident peritoneal macrophages and the antibody should be a valuable addition to the panel of monoclonal antibodies available for studies on mouse macrophages.

Jpn J Physiol, 1995, 45(4), 553 - 60
Effect of exercise on endotoxin shock with special reference to changes in concentration of cytokines; Ishizashi H et al.; The effects of exercise on susceptibility to endotoxin shock and the serum levels of interleukin-1 (IL-1) and interleukin-6 (IL-6) were studied in mice primed with Propionibacterium acnes (P . acnes, 1.0 mg) . Endotoxin shock was induced by injection of lipopolysaccharide (LPS, 0.2 mg) 7d after the priming injection of P . acnes . The exercise-loaded mice performed voluntary exercise for 120 min on a running-wheel and LPS was injected into the tail vein immediately after the end of exercise . Two of the nine animals in the exercised group survived, whereas all the mice in the control group died . The mean survival time after LPS injection in the exercised group (10.75 +/- 4.51 h) was significantly longer than that in the control group (3.3 +/- 1.34h) . The serum concentrations of IL-1 (2,883 +/- 1,542 U/ml) and IL-6 (966 +/- 619 ng/ml) in the exercised group, sampled 2h after LPS challenge, were significantly lower than those in the control group (6,571 +/- 2,766 U/ml and 2,428 +/- 1,228 ng/ml, respectively) . It is suggested that the exercise-induced inhibition of endotoxin shock may be caused, at least partly, by the decreased production of IL-1 and IL-6.

Biochem J, 1994 Dec 15, 304 ( Pt 3), 803 - 8
Regulation of an in vivo metal-exchangeable superoxide dismutase from Propionibacterium shermanii exhibiting activity with different metal cofactors; Sehn AP et al.; The anaerobic, but aerotolerant Propionibacterium freudenreichii sp . shermanii contains a single superoxide dismutase {EC 1.15.1.1.} exhibiting comparable activity with iron or manganese as metal cofactor . The formation of superoxide dismutase is not depending on the supplementation of iron or manganese to the culture medium . Even in the absence of these metals the protein is built in comparable amounts . Bacteria grown in the absence of iron and manganese synthesize a superoxide dismutase with very low activity which had incorporated copper . If the medium was also depleted of copper, cobalt was incorporated, leading to an enzymically inactive form . In the absence of cobalt an enzymically inactive superoxide dismutase was built with unknown metal contents . Upon aeration the amount of superoxide dismutase activity increased continuously up to 9 h, due to a de novo synthesis of the protein . This superoxide dismutase had incorporated iron into the active centre . The superoxide dismutase of Propionibacterium shermanii is able to form a much wider variety of complexes with trace metal ions in vivo than previously recognized, leading to the hypothesis that the original function of these proteins was the binding of cytoplasmic trace metals present in excess.

J Clin Microbiol, 1994 Dec, 32(12), 3043 - 5
Propionibacterium acnes as a cause of aggressive aortic valve endocarditis and importance of tissue grinding: case report and review; Gunthard H et al.; A case of prosthetic valve endocarditis with Propionibacterium acnes is described . The diagnosis was documented by histology and isolation of P . acnes from both blood and anulus tissue . Grinding of the tissue, which was first omitted to avoid contamination, was indispensable for cultivating the agent . The literature for P . acnes endocarditis is reviewed.

Int J Oral Maxillofac Surg, 1994 Dec, 23(6 Pt 1), 359 - 62
Chronic sclerosing osteomyelitis of the mandible in monozygotic twins; Ylikontiola L et al.; Identical female twins with chronic sclerosing osteomyelitis of the mandible are presented . The diagnoses of both at the age of 12 years were based on typical history, and on clinical, radiographic, and histologic findings . High concentrations of IgA and IgG were detected in the serum of both patients, but deviations were not observed in other immunologic variables . The normally commensal organism, Propionibacterium acnes grew from a bone biopsy specimen from the mandible of one twin . No oral focus of the disease was confirmed in either case . We suggest that hereditary factors must have played a role in the pathogenesis of these cases of chronic osteomyelitis.

J Appl Bacteriol, 1994 Nov, 77(5), 583 - 90
The microaerophily and photosensitivity of Propionibacterium acnes; Gribbon EM et al.; The effect of oxygen on the in vitro propagation of Propionibacterium acnes was investigated under defined culture conditions . This micro-organism is the predominant bacterial resident within the pilosebaceous follicles of sebum-rich areas of human skin . The organism was grown in continuous culture in defined synthetic medium with glucose as the main carbon-energy source at various air saturation concentrations and in the presence and absence of light . Steady state continuous cultures were achieved at very low oxygen tensions in the presence of light, and at higher levels of oxygen when non-illuminated . Culture biomass yields were higher than those of anaerobic cultures . Bacterial cells were inactivated in the presence of light at high oxygen concentrations because of photosensitization reactions involving excess oxygen and microbial porphyrin species.

Br J Dermatol, 1994 Nov, 131(5), 649 - 54
Variation in comedonal antibiotic concentrations following application of topical tetracycline for acne vulgaris; Gardner KJ et al.; A miniaturized sensitive bioassay was used to detect tetracycline in open comedones following topical twice daily application of 0.22% tetracycline hydrochloride for a minimum of 4 weeks to the facial skin of patients with mild to moderate acne . The lower limit of detection was 4.8 +/- 0.8 ng per comedone or per 10 microliters . Using this method, 111 of 155 open comedones from 15 patients were found to contain a detectable amount of tetracycline, ranging from 1.8 to 156.9 ng per comedone, and between 4.5 and 1140.1 ng per mg comedonal material . There was a significant effect of comedone weight on tetracycline content, with smaller comedones containing proportionately more tetracycline . The Spearman rank correlation coefficient was -0.5619 (P < 0.001) . All 111 comedones in which tetracycline was detected contained sufficient drug to inhibit fully antibiotic-sensitive propionibacteria . However, conditions favourable to the selection and overgrowth of highly tetracycline-resistant strains (MIC > or = 32 micrograms/ml) prevailed in at least 18.7% (29 of 155) of the comedones tested.

FEMS Microbiol Lett, 1994 Nov 1, 123(3), 325 - 9
A simple method for differentiation of Propionibacterium acnes and Propionibacterium propionicum; Mordarska H et al.; TLC glycolipid profiles of several culture collection and clinical strains of Propionibacterium acnes and Propionibacterium propionicum were examined . The former were characterized by weak orcinol-positive minor glycolipids of type g, while the others had mainly strong orcinol-positive major glycolipids of type G . The simple and rapid small scale procedure seemed to be useful for differentiation of these phenotypically similar and genotypically closely related species irrespective of their serotypes.

Res Microbiol, 1994 Nov-Dec, 145(9), 667 - 76
Identification of diary Propionibacterium species by rRNA gene restriction patterns; de Carvalho AF et al.; A total of 78 strains of dairy propionibacteria, 4 reference strains of Propionibacterium and 8 related bacteria were characterized by ribosomal ribonucleic acid (rRNA) gene restriction patterns (ribotyping) . The patterns were obtained after cleavage of total DNA with either BamHI or ClaI restriction endonucleases and hybridization of fragments with acetylaminofluorene-labelled 16 + 23S rRNA from Escherichia coli . The four different species of dairy propionibacteria, P . freudenreichii, P . jensenii, P . thoenii and P . acidipropionici, gave different restriction patterns with species-specific fragments . Moreover, ribotyping allowed the differentiation of P . freudenreichii subsp . freudenreichii from P . freudenreichii subsp . shermanii . The patterns of dairy propionibacteria were different from those of closely related bacteria and other bacteria used in the dairy industry.

Zentralbl Bakteriol, 1994 Nov, 281(4), 491 - 4
Combined immunomodulation (Propionibacterium avidum KP-40) and lectin blocking (D-galactose) prevents liver tumor colonization in BALB/c-mice; Pulverer G et al.; The protective effect of combined treatment (immunomodulation with Propionibacterium avidum KP-40; liver lectin blocking by D-galactose administration) on the liver colonization of RAW 117-H10 lymphosarcoma was investigated in BALB/c-mice . Both, immunomodulation with P . avidum KP-40 as well as liver lectin blocking by D-galactose treatment significantly decreased the number of liver tumor colonies in this experimental model . However, the combination of P . avidum KP-40 and D-galactose obviously proved to be superior to each monotherapy since the liver colonization by RAW 117-H 10 lymphosarcoma could be completely inhibited.

Appl Microbiol Biotechnol, 1994 Oct, 42(1), 22 - 7
Propionic acid production by immobilized cells of a propionate-tolerant strain of Propionibacterium acidipropionici; Paik HD et al.; Cells of the propionate-tolerant strain Propionibacterium acidipropionici P200910, immobilized in calcium alginate beads, were tested for propionic and acetic acid production both in a semidefined laboratory medium and in corn steep liquor in batch, fed-batch, and continuous fermentation . Cell density was about 9.8 x 10(9) cells/g (wet weight) of beads, and beads were added to the medium at 0.1 g (wet weight) beads/ml . Beads could be reused for several consecutive batch fermentations; propionic acid production in the tenth cycle was about 50%-70% of that in the first cycle . In batch culture complete substrate consumption (glucose in semidefined medium, lactate in corn steep liquor) and maximum acid production were seen within 36 h, and acid yields from the substrate were higher than in free-cell fermentations . Fed-batch fermentations were incubated up to 250 h . Maximum propionic acid concentrations obtained were 45.6 g/l in corn steep liquor and 57 g/l in semidefined medium; this is the highest concentration achieved to date in our laboratory . Maximum acetic acid concentrations were 17 g/l and 12 g/l, respectively . In continuous fermentation of semide-fined medium, dilution rates up to 0.31 h-1 could be used, which gave higher volumetric productivities (0.96 g l-1 h-1 for propionic acid and 0.26 g l-1 h-1 for acetic acid) than we have obtained with free cells . Corn steep liquor shows promise as an inexpensive medium for production of both acids by immobilized cells of propionibacteria.

Arch Biochem Biophys, 1994 Sep, 313(2), 296 - 303
Reactions of hydrogen peroxide with superoxide dismutase from Propionibacterium shermanii--an enzyme which is equally active with iron or manganese--are independent of the prosthetic metal; Meier B et al.; Propionibacterium shermanii contains a single constitutive superoxide dismutase (SOD) which is active with either iron or manganese incorporated in the same protein moiety . Copper and cobalt can also be incorporated by the bacteria in the active center of the SOD under conditions of metal deficiency, but in this case the enzyme is enzymatically inactive . In contrast to other bacterial SODs, the Fe-SOD of P . shermanii remains highly resistant to inactivation by hydrogen peroxide, as does Mn-SOD . Both SOD types cannot be distinguished by their inactivation patterns . Incubation with hydrogen peroxide results in a concentration- and time-dependent decrease in tryptophan fluorescence, independent of the metal present in the active center . Moreover, the Fe-SOD shows a time-dependent decrease in spin concentration after addition of hydrogen peroxide, which reflects alterations in the environment of the metal rather than a reduction of Fe3+ to Fe2+ . No obvious correlations exist, however, between these effects and the enzymatic activity of the enzyme . The resistance of the SODs from P . shermanii to inactivation by hydrogen peroxide seems to be caused by the fact that a tryptophan residue near the metal-chelating histidine-75--which is present in all Fe-SODs being rapidly inactivated by this agent--is exchanged for valine.

Eur J Clin Microbiol Infect Dis, 1994 Sep, 13(9), 747 - 9
Bronchopneumonia caused by Propionibacterium acnes; Claeys G et al.; Propionibacterium acnes was identified as the pathogen in a case of subacute lung infection by examination of an open lung biopsy specimen . The patient was a 65-year-old male with exacerbation of chronic lung disease . The organism was isolated in pure culture and was present in large numbers on Gram stain . Histological examination demonstrated active interstitial fibrosis; macrophages laden with Propionibacterium acnes antigen were revealed using a peroxidase-antiperoxidase stain . This is the first report of subacute infection of pulmonary tissue due to this organism.

Clin Pediatr (Phila), 1994 Aug, 33(8), 485 - 90
Infection caused by Propionibacterium in children; Brook I; Three hundred eighty-six isolates of Propionibacterium sp . were recovered from 2,003 specimens studied for the identification of anaerobic bacteria in children during a 15-year period . Three hundred forty-three (89%) of these were Propionibacterium acnes . A total of 50 (13%) Propionibacterium isolates identified from 45 patients were considered to cause infection . Clinically significant infections caused by Propionibacterium sp . were associated with bacteremia in 10 children; ear infection in eight; abscesses in seven; adenitis and central nervous system infection in five each; burns in four; wounds in three; tumors and bone in two each; and cysts, eye, sinus, and mastoid in one each . Predisposing or underlying conditions were present in 33 children (73%) . These included the presence of a foreign body (17), immunodeficiency (six), malignancy (five), diabetes (five), previous surgery (four), and steroid therapy (two) . Antimicrobial therapy was given to 41 (91%) children . Surgical drainage was concomitantly performed in 22 (49%) . Four patients died . This study highlights the importance of Propionibacterium sp . as an unusual, but potentially important, pathogen in children.

FEBS Lett, 1994 Jul 18, 348(3), 283 - 6
In vivo incorporation of cobalt into Propionibacterium shermanii superoxide dismutase; Meier B et al.; Propionibacterium shermanii, an aerotolerant anaerobic bacterium, has already been shown to incorporate, depending on the metal supplementation to the medium, either iron or manganese or copper into the same superoxide dismutase protein . The in vivo incorporation of cobalt in the same superoxide dismutase was obtained in an iron-, manganese- and copper-depleted medium . The protein was isolated and characterized by NMR which offers the possibility to identify the amino acid residues at the active site exploiting isotropically shifted proton resonance.

Spine, 1994 Jul 15, 19(14), 1598 - 605
Treatment of adolescent idiopathic scoliosis using Texas Scottish Rite Hospital instrumentation; Richards BS et al.; STUDY DESIGN . To determine the effectiveness of posterior TSRH instrumentation for the treatment of idiopathic scoliosis, 103 patients with a 2-year minimum followup were retrospectively studied . METHODS . Patients who underwent operations between October 1988 and April 1991 were evaluated for curve correction, spinal balance, and complications . Age at surgery averaged 14.3 years . Follow-up averaged 2.5 years . RESULTS . Thoracic curve correction averaged 65% in those with King Type III/IV curves and 54% in those with Type II curves . With follow-up, correction loss averaged approximately 13% for each group . Lumbar curve correction after instrumentation in Type I and II curves averaged 48% postop but lost approximately 20% with follow-up . Trunk balance improved 77% toward midline after surgery in those with Type III/IV curves . Improvement in trunk balance was less impressive in patients with Type II curves, particularly after selective thoracic fusions . Thoracic sagittal contour improved 43% for hypokyphotic (< 20 degrees) patients but, in the remainder, no significant radiographic change was evident . No neurologic complications occurred . Delayed deep infections developed in ten patients (10%) between 11 and 45 months postoperative . Cultures eventually grew Propionibacterium acnes, staph epidermidis, or staph coagulase negative in eight patients . Two patients had pseudarthroses . CONCLUSIONS . Frontal and sagittal thoracic curve correction can be satisfactorily obtained using TSRH instrumentation . Continued efforts are being made to improve lumbar hook patterns and technique to achieve and maintain better lumbar curve correction.

Int J Syst Bacteriol, 1994 Jul, 44(3), 579 - 82
Transfer of Propionibacterium innocuum Pitcher and Collins 1991 to Propioniferax gen . nov . as Propioniferax innocua comb . nov; Yokota A et al.; 16S ribosomal DNA analysis indicates that Propionibacterium innocuum is a phylogenetic neighbor of Luteococcus japonicus and that this pair of organisms branches intermediately between the genus Propionibacterium on the one side and the genera Aeromicrobium and Nocardioides on the other side . Phenotypically, strains of P . innocuum differ from species of Propionibacterium by exhibiting aerobic growth and possessing arabinose in the cell wall, they differ from species of Aeromicrobium and Nocardioides by the formation of propionic acid, and they differ from species of Luteococcus in morphology . Consequently, P . innocuum should not be classified with authentic Propionibacterium species, and the transfer of P . innocuum Pitcher and Collins 1991 to a new genus, Propioniferax, as Propioniferax innocua gen . nov., comb . nov . is proposed.

Am J Hum Genet, 1994 Jul, 55(1), 51 - 8
Mutations participating in interallelic complementation in propionic acidemia; Gravel RA et al.; Deficiency of propionyl-CoA carboxylase (PCC; alpha 4 beta 4) results in the rare, autosomal recessive disease propionic acidemia . Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA (alpha-subunit) and PCCB (beta-subunit) genes, respectively . The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect interallelic complementation between certain mutations of the PCCB gene . In this study, we have identified the mutations in two pccB, one pccC, and two pccBC cell lines and have deduced those alleles participating in interallelic complementation . One pccB line was a compound heterozygote of Pro228Leu and Asn536Asp . The latter mutation was also detected in a noncomplementing pccBC line . This leaves Pro228Leu responsible for complementation in the pccB cells . The second pccB line contained an insertional duplication, dupKICK140-143, and a splice mutation IVS + 1 G-->T, located after Lys466 . We suggest that the dupKICK mutation is the complementing allele, since the second allele is incompatible with normal splicing . The pccC line studied was homozygous for Arg410Trp, which is necessarily the complementing allele in that line . For a second pccC line, we previously had proposed that delta Ile408 was the complementing allele . We now show that its second allele, "Ins.Del," a 14-bp deletion replaced by a 12-bp insertion beginning at codon 407, fails to complement in homozygous form . We conclude that the interallelic complementation results from mutations in domains that can interact between beta-subunits in the PCC heteromer to restore enzymatic function . On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, we suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site.

Am Fam Physician, 1994 Jul, 50(1), 89 - 96, 99-100
Management of acne vulgaris; Nguyen QH et al.; Acne vulgaris can affect both adolescents and adults . The pathogenesis of acne is multifactorial and involves overproduction of sebum, an abnormal follicular keratinization process, proliferation of Propionibacterium acnes, and hormonal and immunologic factors . Clinical manifestations of acne range from noninflammatory comedones to inflammatory papules, pustules and cysts . Current therapy allows the physician to select a variety of topical and/or systemic antibiotics, retinoids, and hormone agents aimed at specific pathogenic factors . Most treatment regimens require several weeks of consistent use to be effective . Sound patient education, a strong therapeutic alliance and modification of lifestyle factors are powerful adjuncts to medical management.

Mikrobiologiia, 1994 Jul-Aug, 63(4), 630 - 6
{Reactivation of UV inactivated Escherichia coli cell extracts of propionic acid bacteria: fractionation of the extract}; Vorob'eva LI et al.; Cell free extract from Propionibacterium shermanii VKM-101 partially reactivates Escherichia coli AB 1157 irradiated by UV light . Fractionation of extract followed by the estimation of protective effect of fractions showed that this effect is linked to two fractions of soluble proteins . The fraction of cell walls, ribosomes and nucleic acids were poorly effective . Two active protein fractions (I-20-40% (NH4)SO4 and II-60-80% (NH4)2SO4) were separated by HPLC chromatography into 7 and 8 subfractions respectively . The activity was localised in subfraction N4 (fraction I) and N5.6 (fraction II).

Arch Biochem Biophys, 1994 Jul, 312(1), 135 - 41
Role of vascular nitric oxide synthase in endotoxin shock of Propionibacterium acnes-sensitized rats; Kida T et al.; The sensitivity of animals to endotoxin differs significantly between species . Thus, factors that determine the susceptibility to endotoxin may play important roles in the pathogenesis of septic shock . In order to determine the mechanism responsible for susceptibility to endotoxin, the effect of lipopolysaccharide (LPS) on the circulatory status of Propionibacterium acnes (PA)-sensitized rats was studied . Following the intravenous administration of a low dose of LPS, the arterial blood pressure of PA-treated rats, but not of normal animals, progressively decreased; the PA-sensitized animals died of circulatory shock within 7 h of LPS administration . N omega-nitro-L-arginine (NA) reduced the depressor effect of LPS by an L-arginine-inhibitable mechanism . Administration of LPS markedly increased the level of the inducible type of nitric oxide (NO) synthase in various tissues, including the aorta, of PA-treated rats but not of control animals . LPS also increased plasma levels of nitrate plus nitrite and aortic levels of cGMP . Dexamethasone inhibited the de novo synthesis of NO synthase in the aorta and other tissues and reduced the depressor effect of LPS . These and other findings suggest that induction of nitric oxide synthase in resistant arteries might underlie the pathogenesis of LPS-induced hypotension in PA-sensitized animals and the mechanism responsible for the susceptibility to endotoxin.

J Biol Chem, 1994 Jun 3, 269(22), 15553 - 7
Identification of basic residues involved in substrate binding and catalysis by pyrophosphate-dependent phosphofructokinase from Propionibacterium freudenreichii; Xu J et al.; Despite overall low identity of sequence between ATP- and PPi-dependent phosphofructo-1-kinases (PFK), an alignment permits the tentative identification of catalytically important residues in PPi-dependent PFK . Seven basic residues of the PPi-dependent PFK of Propionibacterium freudenreichii, Arg-310, Lys-315, Arg-326, Arg-186, Arg-78, Arg-90, and Lys-148 were chosen on the basis of this alignment for site-directed mutagenesis to neutral residues . Mutants R186A, K315A, and R326A had substantial increases of 43-, 389- and 678-fold, respectively, in Km for fructose 6-phosphate relative to wild-type enzyme and relatively small effects on kcat . The modest kinetic effects of mutations at Arg-78, Arg-90, and Arg-310 were not considered to indicate important roles for these residues . On the other hand, mutant K148M had a Km for PPi that was increased by 132-fold and kcat lowered by a factor of 490 . Cho and Cook (Cho, Y.-K., and Cook, P.F . (1988) Biochemistry 28, 4155-4160) concluded on the basis of kinetic and chemical modification data that the enzyme utilizes a proton shuttle mechanism and that two lysines are involved in substrate binding . The present data along with our previous data on mutant D151A support a double proton shuttle mechanism involving Asp-151 and Lys-148 with Lys-148, Arg-326, Lys-315, and perhaps Arg-186 being important for substrate binding.

JAMA, 1994 Jun 1, 271(21), 1662 - 3
Dermatology; Dover JS et al.; An increasing number of patients with antibiotic-resistant propionibacteria have been described . Extensive sunbathing, even after sunscreen application, may facilitate development of skin cancers by suppressing natural immunity to these atypical growths.

Can J Microbiol, 1994 Jun, 40(6), 439 - 45
Using fura-2 to measure intracellular free calcium in Propionibacterium acnes; Futsaether CM et al.; The fluorescent probe fura-2 was used to measure the intracellular free calcium concentration {Ca2+}i in the Gram-positive skin bacterium Propionbacterium acnes . Three methods for loading the probe into P . acnes were used . Two consisted of using the membrane permeable acetoxymethyl ester of fura-2, fura-2/AM, whereas in the third method, fura-2 was loaded directly into the bacteria by means of an acid shock procedure . One method using fura-2/AM was found to be satisfactory . In this case, a statistical experimental design (2(4-1)IV) was used to devise a suitable loading procedure . {Ca2+}i of P . acnes was dependent upon the external calcium concentration . At low external concentrations (0.2 < {Ca2+}o < 5 muM), {Ca2+}i was 135 +/- 13 nM (n = 20) . An increase in {Ca2+}o to 1mM resulted in an increase in {Ca2+}i to approximately 280 +/- 40 nM whereas in a Ca-free solution ({Ca2+}o < 5 nM), {Ca2+}i decreased to a lower resting value of 70 +/- 7 nM . The time constants for calcium regulation upon step changes in the external concentration were of the order of 10 min . Intracellular alkalinization induced by changes in the external pH (pHo) resulted in an increase in {Ca2+}i when {Ca2+}o was in the range 0.2-5 muM . {Ca2+}i was approximately constant in the range pHo 5.5-7.7 but increased when pHo > 8.0 . This increase was partially reversed when pHo was again lowered to below 8.0 . In a Ca-free solution, little or no increase in {Ca2+}i was observed when pHo > 8.0.

Nippon Rinsho, 1994 Jun, 52(6), 1492 - 7
{Sarcoidosis and Propionibacterium acnes}; Nakata Y et al.; Propionibacterium acnes (P . acnes) was isolated in high rates and in high concentrations from lymph nodes in patients with sarcoidosis . However, the precise mechanism of granuloma formation and immunomodulation by P . acnes has not been elucidated yet . In patients with sarcoidosis, it was found that the high levels of interleukin-2 released from alveolar lymphocytes as well as interleukin-1, tumor necrosis factor and interleukin-6 released from alveolar macrophages were stimulated by P . acnes . These cytokines (mainly IL-2), released by P . acnes in large quantities, play a major role in the compartmentalization of the T-cell population in the lung and lead to the formation of alveolitis and granuloma in the lung parenchyma of patients with sarcoidosis.

Int J Food Microbiol, 1994 Jun, 22(4), 257 - 67
Propionibacterium species diversity in Leerdammer cheese; Britz TJ et al.; Thirteen 'classical' Propionibacterium strains, isolated from Leerdammer cheese samples, using three different media were characterized phenotypically . The phenotypic data of 74 tests, conducted on 27 propionibacteria, including four type, 10 reference strains and the 13 cheese isolates were analysed by numerical taxonomical techniques, using the simple matching coefficient and single linkage cluster analysis . All the strains were grouped in four major clusters, with a final linkage at the 81% S-level . The clusters were equated with the 'classical' P . acidipropionici, P . freudenreichii, P . jensenii and P . thoenii species . The species were identified by relating them to specific type strains and by comparison of phenotypic characteristics . Differential characteristics of each cluster were determined . Strains of P . acidipropionici, P . freudenreichii and P . jensenii, but no P . thoenii strains were isolated from the Leerdammer cheese samples . No 'cutaneous' propionibacteria were isolated . The largest cluster, representing 46% of the cheese isolates was equated with P . jensenii . Various red/brown pigmented strains, which could be identified as the old 'P . rubrum' species were isolated from the cheese . These strains were, however, phenotypically identified as P . jensenii and also grouped in the P . jensenii cluster.

Curr Eye Res, 1994 Jun, 13(6), 465 - 6
Growth curve for Propionibacterium acnes; Hall GS et al.; We established growth curves for Propionibacterium acnes isolates recovered from eyes with chronic postoperative endophthalmitis . The growth curve plotted the average of the duplicate bacterial concentration against time . The generation time for P . acnes calculated from the growth curves was approximately 5.1 hours . The growth of P . acnes is slower than other anaerobic bacteria . This may account for its delayed appearance in culture of ocular specimens . It may also explain treatment failure if the concentration of an antibiotic injected into the vitreous does not remain at an effective level during the critical replicative phase of the organism.

Appl Microbiol Biotechnol, 1994 Jun, 41(4), 378 - 83
Microbial production of propionic acid and vitamin B12 using molasses or sugar; Quesada-Chanto A et al.; With a cell concentration of 125 g dry biomass l-1 and a dilution rate of 0.1 h-1, Propionibacterium acidipropionici produces 30 g propionic acid l-1 from sugar with a productivity of 3 g l-1 h-1 . The yield of propionic acid is approx . 0.36-0.45 g propionic acid g-1 sucrose and is independent of the dilution rate and cell concentration . Acetic acid is an unwanted by-product in the production of propionic acid . The concentration of acetic acid only increases slightly when the cell concentration is increased . A two-stage fermentation process was developed for the conversion of sugar or molasses of various types to propionic acid and vitamin B12 . By fermentation of blackstrap molasses (from sugar beet and sugar cane) in the first fermentation stage 17.7 g propionic acid l-1 with a yield of 0.5 g propionic acid g-1 carbohydrate was produced with a dilution rate of 0.25 h-1 . In the second stage 49 mg vitamin B12 1-1 was produced at a dilution rate of 0.03 h-1.

Anticancer Res, 1994 May-Jun, 14(3B), 1399 - 404
Preoperative immunostimulation by Propionibacterium granulosum KP-45 in colorectal cancer; Isenberg J et al.; In order to improve the perioperative resistance to the spread of cancer during operation the effect of preoperative stimulation of the immunesystem by Propionibacterium granulosum KP-45 was investigated in patients with colorectal carcinoma . In a prospective randomized trial 101 patients were allocated to either treatment (n = 51) or control (n = 50) . In the treatment 10 mg of Propioni bacteria were administered intravenously between the seventh and third day prior to surgical treatment . At the time of operation 21 tumours were classified as stage I (treatment n = 12, control n = 9), 22 as stage II (treatment n = 10, control n = 2) . Postoperatively wound infections requiring treatment were more prevalent in the control group (n = 4) than in the treated group (n = 0) . All patients were subsequently followed up for 76 months . For stage I carcinoma the survival rates, excluding perioperative deaths, were 91% in the treated and 63% in the control group respectively . One case of tumour metastasis was seen in the control group . For stage II carcinoma the survival rate was 90% for the treated group with distant spread in 1 case and 45% in the control group where the rate of recurrence was 55% . For stages III and IV there was no statistically significant difference in survival between the treated and the control groups.

J Appl Physiol, 1994 May, 76(5), 2177 - 85
Effects of exercise on macrophage activation for antitumor cytotoxicity; Woods JA et al.; Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important . We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat-inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-gamma, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals . Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18-35 m/min, 5%, 2-4 h) on a motor-driven treadmill . Control animals were kept in simulated treadmill lanes located directly over the runners . In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05) . Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-alpha, interleukin-1 beta, or reactive oxygen species . Reactive nitrogen species were responsible for enhanced toxicity in EXH only . Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-gamma to a similar maximal level that was the same in all groups . Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro . However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P . acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

J Vet Med Sci, 1994 Apr, 56(2), 293 - 7
Importance of early gamma interferon production in Propionibacterium acnes-induced resistance to Toxoplasma gondii infection in mice; Shirahata T et al.; Treatment of mice with heat-killed Propionibacterium (P.) acnes conferred transient protection against Toxoplasma infection . To investigate the mechanism of this nonspecific resistance, the production of gamma interferon (IFN-gamma) by P . acnes-injected mice was evaluated in comparison with that by noninjected controls upon infection with Toxoplasma . Mice pretreated with this bacterium produced significantly more IFN-gamma than that produced by control mice up to 24 hr of infection . A single injection of anti-IFN-gamma MAb on day 0 but not later than day 3 of infection resulted in a total abrogation of the resistance conferred by P . acnes . Likewise, daily injection of cyclosporin A (Cs-A), a potent inhibitor of T cell function, during the first 3 days of Toxoplasma infection severely exacerbated the infection, in accordance with a marked suppression of the early IFN-gamma production . In contrast, the administration of Cs-A for 3 consecutive days starting at day 4 had no significant consequence on P . acnes-induced anti-toxoplasma resistance, while it reduced greatly the ability of P . acnes-injected mice to produce IFN-gamma in the later phase of infection . Moreover, no significant increase in mortality and suppression of IFN-gamma production was noted in mice receiving anti-asialo GM1 antibody . These results suggest that the early IFN-gamma production by T cells is an essential event for the establishment of P . acnes-induced anti-toxoplasma resistance in mice.

Zhonghua Nei Ke Za Zhi, 1994 Apr, 33(4), 241 - 3
{The protective effect of prostaglandin E1 in experimental model of massive live cell necrosis}; Liu P et al.; The protective effect of PGE1 in mice injected with propionibacterium acnes (P.acnes) and subsequently with a small dose of lipopoly-saccharide-endotoxin (LPS) 7 days later was studied . The results of this study were as follows: (1) When PGE1 was administered one hour before the injection of LPS, the survival rate of mice was significantly higher (90%), than that of a control group (17%) . No necrosis was found in the liver . (2) PGE1 suppressed the release of tumor necrosis factor (TNF) and secreted-interleukin-1 (SIL-1) in culture supernatants of P.acnes-elicited kupffer cells and membrane IL-1 (mIL-1) in kupffer cells in a dose-dependent manner in vitro . These results strongly suggest that PGE1 can prevent liver cell necrosis in the animal model and the mechanism of curative effect of PGE1 in massive liver cell necrosis may result from inhibition of the activity of TNF, sIL-1 and mIL-1 in the kupffer cells.

Infection, 1994 Mar-Apr, 22(2), 99 - 101
Shunt nephritis associated with Propionibacterium acnes; Setz U et al.; Membranoproliferative glomerulonephritis was observed in a 22-year-old male patient in whom a ventriculoatrial shunt and a ventricular catheter were implanted after he was diagnosed in September 1989 with a cerebral cyst . Propionibacterium acnes infection of a central nervous system shunt was diagnosed . The ventriculoatrial shunt was removed (the catheter had become embedded in tissue and was left in place) and the patient was treated with cefotaxime (3 x 2 g) for 14 days . Renal function improved, but recovery was not complete.

Biochemistry, 1994 Feb 22, 33(7), 1663 - 7
Lanthanide pyrophosphates as substrates for the pyrophosphate-dependent phosphofructokinases from Propionibacterium freudenreichii and Phaseolus aureus: evidence for a second metal ion required for reaction; Bertagnolli BL et al.; In the absence of Mg2+, both the dimeric bacterial and tetrameric plant fructose 2,6-bisphosphate-activated pyrophosphate-dependent phosphofructokinases (PPi-PFKs) are inactive at pH 8 and 25 degrees C . In the presence of a low concentration of Mg2+ (5 microM), both enzymes will utilize a variety of metal-pyrophosphate complexes as reactant in the direction of fructose 6-phosphate (F6P) phosphorylation . The Vmax values are about 100-fold lower and the Km values about 10-fold greater than those measured with MgPPi when lanthanide-PPi complexes are used as a substrate . In the presence of added Mg2+, the Km values of the above remain essentially unchanged, while Vmax values increase 10-fold for lanthanide-PPi complexes . These data, along with the 12-16 order of magnitude increased affinity of the lanthanides for PPi compared to Mg2+, indicate that the PPi-PFKs require two metal ions for catalysis, one to form a chelate with PPi and a second as an essential activator . With CePPi, an activation constant of about 25 microM is measured for Mg2+ . In addition, a number of other divalent (but no tripositive) metal ions serve as activators including Mn2+, Co2+, Mo2+, Cr2+, Fe2+, and Ni2+; activation constants are in the range 20-150 microM . The exchange-inert CrIII(PPi)(H2O)4 complex is not a substrate, but is an inhibitor competitive against MgPPi with a Ki of 27 microM . Results are discussed in terms of the possible role of the divalent metal ion activators.

J Dairy Sci, 1994 Feb, 77(2), 462 - 7
Therapy of experimentally induced coliform mastitis with a Propionibacterium acnes product; Hogan JS et al.; The efficacy of a Propionibacterium acnes product for treatment of coliform mastitis was evaluated following intramammary infusion of Escherichia coli . Ten cows were injected intravenously with a product containing heat-killed P . acnes at 3 h, 3 d, and 7 d after bacterial challenge . Five cows served as untreated negative controls . Bacterial counts in milk, rectal temperatures, and milk SCC did not differ between treated cows and control cows . Intravenous infusion of P . acnes had no effect on milk production or DMI of treated cows compared with untreated controls . Therapy of experimentally induced coliform mastitis with a P . acnes product had no effect on severity or duration of clinical signs.

J Appl Bacteriol, 1994 Feb, 76(2), 124 - 34
Rapid identification using pyrolysis mass spectrometry and artificial neural networks of Propionibacterium acnes isolated from dogs; Goodacre R et al.; Curie-point pyrolysis mass spectra were obtained from reference Propionibacterium strains and canine isolates . Artificial neural networks (ANNs) were trained by supervised learning (with the back-propagation algorithm) to recognize these strains from their pyrolysis mass spectra; all the strains isolated from dogs were identified as human wild type P . acnes . This is an important nosological discovery, and demonstrates that the combination of pyrolysis mass spectrometry and ANNs provides an objective, rapid and accurate identification technique . Bacteria isolated from different biopsy specimens from the same dog were found to be separate strains of P . acnes, demonstrating a within-animal variation in microflora . The classification of the canine isolates by Kohonen artificial neural networks (KANNs) was compared with the classical multivariate techniques of canonical variates analysis and hierarchical cluster analysis, and found to give similar results . This is the first demonstration, within microbiology, of KANNs as an unsupervised clustering technique which has the potential to group pyrolysis mass spectra both automatically and relatively objectively.

Eur J Biochem, 1994 Jan 15, 219(1-2), 463 - 8
In vivo incorporation of copper into the iron-exchangeable and manganese-exchangeable superoxide dismutase from Propionibacterium shermanii . Amino acid sequence and identity of the protein moieties; Meier B et al.; Propionibacterium shermanii, an aerotolerant anaerobe, produces an iron-containing or a manganese-containing superoxide dismutase, depending on the metal supplied in the culture medium {Meier, B., Barra, D., Bossa, F., Calabrese, L . & Rotilio, G . (1982) J . Biol . Chem . 257, 13977-13980} . In this study, we demonstrate in vivo incorporation of copper into an active superoxide-dismutase protein when iron and manganese are absent from the growth medium . Superoxide dismutases containing either iron, manganese or copper were isolated from P . shermanii, their complete amino acid sequences were determined and the identity of their protein moieties was established . The polypeptide chain is made up of 201 amino acid residues, corresponding to a molecular mass of 22.6 kDa . From sedimentation equilibrium experiments, the native protein shows a molecular mass of approximately 86 kDa and therefore consists of four identical subunits . The primary structure was compared with the structure of other Fe-superoxide dismutases and Mn-superoxide dismutases, in particular those possessing a strict metal cofactor specificity.

J Nat Prod, 1994 Jan, 57(1), 9 - 17
Naturally occurring antiacne agents; Kubo I et al.; Antibacterial activity of various secondary metabolites from plants against Propionibacterium acnes was tested . In addition, the study of combinations of compounds to enhance the total activity against this follicular bacterium was investigated . A series of long-chain alcohols was studied in great detail to gain new insights into the role of the hydrophobic alkyl groups in the activity.

Dermatology, 1994, 189(2), 117 - 9
Itching in acne--an unusual complication of therapy; Yee KC et al.; Pruritus at the site of active acne has not been described before as a complication of acne therapy . We report 8 cases seen over a 3-year period at our department with localized itching mainly at the active acne sites, within 2-6 weeks of starting effective acne therapy . Seven had oral tetracyclines (oxytetracycline, Vibramycin or Minocin) with or without topical antibiotics or benzoyl peroxide . Only 1 patient received oral isotretinoin . The severity of itch was mild to moderate in most cases with the severest reaction in the isotretinoin-treated patient . All cases resolved within 4 weeks, 7 with non-sedative antihistamine therapy (terfenadine), and 1 resolved spontaneously upon cessation of antibiotic therapy . The pathogenesis of this localized itch is presumed to be related to the change in pH of the micro-environment of the acne follicle providing an optimal environment for the production of histamine or histamine-like products by Propionibacterium acnes . This report highlights the self-limiting nature of pruritus during effective anti-acne therapy . Increased awareness of this uncommon complication helps prevent the unnecessary discontinuation of effective acne therapy.

Med Dosw Mikrobiol, 1994, 46(1-2 Suppl), 35 - 42
{Clinical evaluation of serious forms of acne treated with autovaccine}; Rubisz-Brzezinska J et al.; In this paper a clinical assessment of the treatment of serious forms of acne vulgaris with the use of autovaccines containing Propionibacterium strains was presented . It was shown that the associative therapy including parallel administration of both autovaccine and the antibiotic is remarkably efficacious.

Med Dosw Mikrobiol, 1994, 46(1-2 Suppl), 27 - 34
{Bacteriology of acne changes}; Kasprowicz A; In this work it was demonstrated that the main microorganisms which cause, together with other, the generation of inflammatory changes are anaerobic bacteria from the genus Propionibacterium . P . acnes type I causes mild course acne changes while serious changes are generated by P . granulosum type II . It was observed that a high percentage of all tested Propionibacterium strains showed susceptibility to antibiotics but it did not reach 100% . In the treatment of acne changes all agents which could be conducive to generating them should be taken into consideration . The therapy should be complex and applied with regard to the course of disease of each individual patient.

Dermatology, 1994, 189(4), 344 - 9
Delayed hypersensitivity to Propionibacterium acnes in patients with severe nodular acne and acne fulminans; Karvonen SL et al.; BACKGROUND: Increased hypersensitivity reactions to Propionibacterium acnes may be involved in the pathogenesis of severe acne . OBJECTIVE: To study delayed and immediate hypersensitivity reactions to P . acnes in patients with severe nodular acne (SNA) and acne fulminans (AF) . METHODS: We performed lymphocyte stimulation and skin tests for P . acnes antigens on 11 patients with SNA and 7 patients with AF . RESULTS: The patients with SNA had similar mean lymphocyte stimulation indices (mean 13.96, SD 8.6) to P . acnes during active disease as had healthy controls (12.63, SD 6.46) . After the treatment the mean stimulation index was significantly elevated (23.47, SD 13.84, p = 0.006) . A similar increase occurred in the patients with AF (mean 17.04, SD 5.74, and 33.42, SD 27.17, respectively) . Two of 7 patients with SNA and 3 of the 7 patients with AF but none of the 10 control subjects showed positive 48-hour intradermal tests to P . acnes . CONCLUSION: Specific cell-mediated immunity to P . acnes increases during the course of severe inflammatory acne.

Acta Univ Palacki Olomuc Fac Med, 1994, 137, 39 - 43
Some biochemical characteristics of the early phase of immunomodulation; Hajduch M et al.; The study estimates some biochemical changes of chosen immunological and biochemical parameters after intraperitoneal application of a) immunomodulators of microbial origin--Propionibacterium acnes and Geotrichum candidum, b) chemical substances--indomethacin and phenobarbital . The estimation was concentrated above all to the changes of chemiluminiscence, phagocytic activities, the amount of cAMP in peritoneal macrophages, the amount of liver cytochrome P-450 and cAMP in the liver, spleen and thymus . The experiments also included histological examination of the spleen, thymus, lungs and diaphragm . The effect of Propionibacterium acnes was evident as soon as 24 hrs after application . In the frame of studied parameters, there was manifested the nonspecific activation of the immune system by the mechanisms independent to oxygen . The early changes were accompanied by the increase of cAMP in macrophages . In contrary, the intraperitoneal application of Geotrichum candidum activated the release of oxygen radicals from peritoneal macrophages . The amount of the cytochrome P-450 correlated to the intensity of immunomodulation . On the other hand, the induction of cytochrome P-450 by phenobarbital decreased the value of several immunity indices.

Neurol Neurochir Pol, 1994, 28(1 Suppl 1), 67 - 78
{Selective problems from catamnestic studies of SSPE patients (1980-1989)}; Sobczyk W et al.; The analysis of disease courses and survival times of 132 cases of SSPE treated by various methods in the I Department of Neurology, Institute of Psychiatry and Neurology, in years 1980-1989 is reported . Follow-up data were obtained during control examinations of patients or from an inquiry answered by parents or doctors at the place of residence of the patients . In the treatment all patients were given immunomodulating drugs . About 25% of the patients were treated with isoprinosine, in the remaining groups other drugs active on the immune system were added: TFX, alpha interferon (intraventricularly through a Rickham chamber), beta interferon (through lumbar tap) or Propionibacterium granulosum strain K 14 vaccine as an inductor of endogenous interferon . The reference group comprised 22 patients who had not been systematically treated for various reasons . The statistical analysis of the clinical courses showed that early begun immunomodulatory treatment increases the number of cases with remissions in the group of patients with the subacute form of the disease . In primarily acute cases no effect of the treatment was noted . The best results were obtained using Propionibacterium granulosum vaccine and treating with interferons . The survival times were shortest in the group not treated systematically.

J Immunol, 1993 Nov 1, 151(9), 5088 - 95
Inhibition of inflammatory liver injury by a monoclonal antibody against lymphocyte function-associated antigen-1; Tanaka Y et al.; When mice were given an i.v . injection of LPS 7 days after an i.v . injection of Propionibacterium acnes, liver injury and a rapid increase of serum alanine aminotransferase and asparagine acid aminotransferase occurred . The in vivo administration of mAb against LFA-1 on days 1, 2, and 3 after the i.v . injection of P . acnes resulted in a potent inhibition of all these dysfunctions . Using P . acnes and the LPS model, we found that anti-LFA-1 mAb protected the mice from P . acnes and LPS-induced lethal shock . During the course of P . acnes and LPS-induced liver injury, inflammatory cells infiltrated the liver and caused a massive hepatic cell necrosis . Flow cytometry revealed that the liver-infiltrating cells were mainly leukocytes expressing a higher level of LFA-1 antigen than that seen in the normal liver . These results suggested that the LFA-1 molecule on liver-infiltrating leukocytes may play an important role in the induction of inflammatory liver injury.

Clin Infect Dis, 1993 Nov, 17(5), 892 - 3
Propionibacterium propionicum and infections of the lacrimal apparatus; Brazier JS et al.; Analysis of the clinical details associated with 26 referred isolates of Propionibacterium propionicum revealed the marked propensity of this anaerobe to be involved with infections of the lacrimal apparatus; 18 (69%) of the 26 referred isolates were from cases of canaliculitis in which this organism was regarded as the significant pathogen . Further analysis of data showed a significant correlation with the sex of the patient . Of the 18 cases of canaliculitis, the sex of the patient was reported in 16; 14 (88%) of these 16 patients were females (P < .005) . The age of 13 of the 18 patients with canaliculitis was known (mean, 61.6 years; range, < 1-80 years); it appears from these cases that P . propionicum lacrimal infections are more common in later life . None of the referred isolates were identified as Actinomyces species . Despite the fact that infection of the lacrimal apparatus is known as ocular actinomycosis, it appears that P . propionicum is more frequently associated with the condition than are true Actinomyces species.

Br J Dermatol, 1993 Nov, 129(5), 533 - 40
The carriage of Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrhoeic dermatitis and controls; Ashbee HR et al.; The aetiological role of Malassezia furfur in various dermatoses is controversial . The role of the three serovars of M . furfur in Malassezia-associated diseases has not been investigated . This study measured population densities of M . furfur serovars A, B and C, propionibacteria and Micrococcaceae on the chest, back, forehead, left and right cheeks of 10 patients with pityriasis versicolor, and 10 age- and sex-matched controls; and 10 patients with seborrhoeic dermatitis, and 10 age- and sex-matched controls . The population densities of M . furfur, propionibacteria and Micrococcaceae did not vary at a given site between patients and the corresponding control subjects . Malassezia furfur serovar A was found to be the predominant isolate on the chest and back of all four groups, but there was no difference in the distribution of serovars on the forehead and cheeks . No serovar was specifically associated with lesional skin in either disease . Thus, this data indicated that there was no difference in either the total population density of M . furfur or the distribution of serovars on lesional skin compared with control skin in either pityriasis versicolor or seborrhoeic dermatitis.

Mikrobiologiia, 1993 Nov-Dec, 62(6), 1135 - 43
{Reactivation of Escherichia coli inactivated by ultraviolet light by cell extracts of propionic acid bacteria}; Vorob'eva LI et al.; For the first time reactivation of cell extract of three strains of Propionibacterium shermanii in UV inactivated not filament-forming strain Escherichia colli AB 1157 is shown . Reactivation was demonstrated in preincubated and postincubated test-culture and increased as survival of E . coli decreased in a range 1.8-0.006% . The factor (factors) of defense is dialysable, thermolabile and is present as in a fraction of nucleoproteins and nucleic acids so in a fraction of soluble proteins . The extracts were inactivated by incubation with proteinase K and trypsin, partly decreased activity by incubation with alpha-amylase and selected nuclease but not with lipase . Polypeptide nature of reactivating factor is supposed.

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