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 m