Arch Microbiol, 1983 Jun, 134(3), 243 - 6 Threo-beta-hydroxyornithine: a natural constituent of the peptidoglycan of Corynebacterium species Co 112; Schleifer KH et al.; Peptidoglycan of Corynebacterium species Co 112 (DSM 20606) exhibits an unknown amino acid . The amino acid was isolated from cell wall hydrolysates and identified as threo-beta-hydroxyornithine . This amino acid is found in the interpeptide bridge of the peptidoglycan of Corynebacterium sp . Co 112 . The primary structure of this peptidoglycan is rather similar to that of Microbacterium liquefaciens . The only difference is the replacement of ornithine by threo-beta-hydroxyornithine . The mode of linkage of threo-beta-hydroxyornithine indicates that it is present as D-isomer. Int J Lepr Other Mycobact Dis, 1983 Jun, 51(2), 179 - 84 Immunodiffusion analyses of some diphtheroid organisms isolated from patients with leprosy; Ridell M; Eight strains of diphtheroid bacteria isolated from patients with leprosy were analyzed by immunodiffusion, using precipitation systems representing various species of Corynebacterium, Mycobacterium, Nocardia, Rhodococcus, and related organisms . The analyses showed that six of the eight strains shared several antigens with representatives of these four genera . The largest number of shared precipitinogens was revealed when the corynebacterial precipitation systems were used, thus indicating that these organisms either belong to, or are closely related to the genus Corynebacterium . This assumption was further supported by the fact that the ribosomal precipitinogen beta--earlier demonstrated in mycobacteria but not in corynebacteria--was not found in the diphtheroid strains . Other ribosomal antigens were, however, revealed to be common to the diphtheroid organisms and mycobacteria . Further, the reaction between sera from patients with lepromatous leprosy and the diphtheroid strains was analyzed, very few and faint precipitates being demonstrated . It is concluded that the presence of anti-beta antibodies in leprosy sera is, most likely, not a result of the presence of diphtheroid organisms in the patients. J Hyg (Lond), 1983 Jun, 90(3), 415 - 24 The role of adherence in determining the site of infection by Corynebacterium diphtheriae; Deacock SJ et al.; Twenty-nine strains of Corynebacterium diphtheriae isolated from throats and 29 strains from skin lesions, the latter mainly from communities of low socio-economic status in tropics and cold climates, have been examined for the property of adherence to human buccal epithelial cells . All throat strains showed adherence . In contrast, strains from skin lesions were predominantly poor adherers . These results indicate that strains of C . diptheriae from throats must now be added to the important group of pathogens which possess the property of adherence to surface epithelial cells of mucous membranes, thus providing an essential first step in the process of colonizing their hosts . The possible role of this phenomenon of adherence to bucco-pharyngeal epithelial cells in the evolution of the host-parasite relationship of C . diphtheriae is discussed. Int J Lepr Other Mycobact Dis, 1983 Jun, 51(2), 185 - 90 Crossreactivity between Mycobacterium leprae and various actinomycetes and related organisms; Ridell M; Serological crossreactivity was analyzed between M . leprae and strains of various species of Corynebacterium, Mycobacterium, Nocardia, Rhodococcus, Streptomyces, and related organisms . M . leprae shares antigens with most of these organisms, and sera from patients with lepromatous leprosy contain antibodies against them . The results demonstrate that M . leprae shares more antigens with the mycobacteria than with strains of the other tested genera, thus supporting the view that the leprosy organism belongs to the genus Mycobacterium . One precipitinogen (designated p beta) was found to be common to M . leprae and the streptomycetes, and sera from patients with lepromatous leprosy contain antibodies against this antigen. J Dairy Sci, 1983 Jun, 66(6), 1390 - 5 Germicidal teat dip in a herd with low prevalence of Streptococcus agalactiae and Staphylococcus aureus mastitis; Eberhart RJ et al.; Effectiveness of an iodophor teat dip in reducing new intramammary infection and clinical mastitis was tested in a herd free of Streptococcus agalactiae and with a low prevalence of Staphylococcus aureus infections . In this 6-mo study with an average of 152 lactating cows on trial on sampling dates, right rear and left front teats were dipped after each milking while right front and left rear teats were undipped controls . Teat dipping significantly reduced new infections by Staphylococcus aureus, streptococci (other than Streptococcus agalactiae), coagulase-negative staphylococci, and Corynebacterium bovis and reduced clinical cases caused by infections established during the trial . However, the dip did not reduce new infections or clinical mastitis caused by coliform bacteria . Therefore, use of a germicidal dip is recommended for herds with a low prevalence of Streptococcus agalactiae and Staphylococcus aureus, but the practice should not be expected to control coliform mastitis. Transplantation, 1983 Jun, 35(6), 593 - 600 Further characterization of macrophage adsorption of suppressor cell activity from tumor-allosensitized spleen; Zografos-Miller LE et al.; Suppressor cell activity from P815-allosensitized C57BL/6 spleen can be decreased by incubating the tumor-allosensitized spleen cells on monolayers of thioglycollate-stimulated BDF1 peritoneal macrophages for 2 or 4 hr . The adsorption response appears to be specific for macrophages, because adsorption of suppressor cell activity does not occur following incubation of P815-allosensitized spleen cells on confluent monolayers of mouse spleen cells or mouse embryonic fibroblasts . Pretreatment of macrophage monolayers with X irradiation (2,000 rads) or anti-Thy 1.2 serum (and complement) does not affect their ability to bind suppressor cell activity . Adsorption of suppressor cell activity from P815-allosensitized spleen can also be carried out by proteose peptone-stimulated or Corynebacterium parvum-stimulated macrophages . Blockage of macrophage Fc receptors decreases the ability of thioglycollate-stimulated macrophages to adsorb suppressor cell activity . Monolayers of P815 or P388 cells, two cell types positive for Fc receptors, are unable to adsorb suppressor cell activity from the tumor-allosensitized spleen . The significance of our findings is discussed in terms of the relationship between macrophages and suppressor cells in the immune response to normal or tumor allografts. Clin Immunol Immunopathol, 1983 Jun, 27(3), 387 - 402 Studies of peritoneal macrophage function in mice with systemic lupus erythematosus: depressed phagocytosis of opsonized sheep erythrocytes in vitro; Russell PJ et al.; Resident peritoneal macrophages from systemic lupus erythematosus (SLE)-prone strains, NZB, (NZB X NZW)F1 and MRL/MpJ-lpr/lpr mice, exhibited very low binding and phagocytosis of opsonized 51Cr-labeled sheep erythrocytes (EA) compared with cells from normal mice . Male BXSB mice, which also develop SLE, were not clearly defective in phagocytosis and binding of EA compared with C57B1/6J, the lowest of the "normal" mice tested, but were less effective than their normal female BXSB counterparts . The extent of the defect depended on the age of the animals tested . Young NZB/N mice showed hyperactive binding and phagocytosis and became defective about the time of disease onset . Even young (NZB X NZW)F1 and MRL/MpJ-lpr/lpr mice were defective and worsened with age . Increasing numbers of resident peritoneal macrophages were recovered from the autoimmune mice as they aged . Near normal binding and phagocytosis of EA could be effected by stimulation in vivo by injection of killed Corynebacterium parvum . Resident peritoneal macrophages from congeneic xid (X-linked immune deficiency gene) bearing NZB and (NZB X NZW)F1 mice showed normal reactivity . Binding and phagocytosis of EA was Fc mediated and was inhibited by pretreatment with large doses of heat-aggregated human gamma-globulin . Defective macrophage Fc receptor binding or turnover may play an important role in the observed manifestations of autoimmune disease in murine SLE. Transplantation, 1983 Jun, 35(6), 582 - 8 Regulation of cytotoxic reactivity to minor histocompatibility antigens by administration of Corynebacterium parvum; Lichtenstein A et al.; B10.BR(H-2k) mice were primed with H-2-identical allogeneic CBA/J(H-2k) spleen cells and restimulated in vitro 14 days later to generate specific secondary cytotoxic lymphocytes . A single intravenous injection of primed mice with 700 micrograms of Corynebacterium parvum 7 days after alloimmunization markedly inhibited the subsequent secondary in vitro generation of cytotoxic cells . In addition, regulatory spleen cells were detected in alloimmunized C-parvum-injected mice that prevented the restimulation of primed control spleen cells . Suppressive activity could not be abrogated by treating regulatory cells with anti-theta antibody and complement or by removing phagocytic cells, but it was overcome by treatment with mitomycin C . Unfractionated regulatory cells suppressed responses in an antigen nonspecific fashion . However, cells remaining after carbonyl and iron treatment (nonphagocytic) could no longer suppress responses to third party alloantigens while maintaining significant suppression of anti-CBA responses . These data suggest the generation of two distinct suppressor cell types that can control the cytotoxic response to minor histocompatibility antigens: an antigen-nonspecific phagocytic cell and an antigen specific nonphagocytic, non-theta-bearing cell. Scand J Immunol, 1983 Jun, 17(6), 497 - 506 Comparison of the cytoplasmic antigens of leprosy-derived corynebacteria and some mycobacteria; Gueur MC et al.; The immunological relationship between leprosy-derived corynebacteria (LDC) and reference mycobacteria was analysed by crossed immunoelectrophoresis with intermediate gel . For this purpose, three reference systems (LDC15/anti-LDC15, LDC18/anti-LDC8, and LDC8/anti-LDC8) were developed . They showed 15 to 20 distinct antigenic components in LDC cytoplasm . Extensive cross-reactivity was observed among different LDC isolates, affecting 3 to 17 components . Moreover, several components were shown to cross-react with mycobacteria when anti-bacillus Calmette-Guerin (BCG), anti-Mycobacterium leprae, other antisera and lepromatous leprosy sera were incorporated in the intermediate gel . The major cross-reactive component, antigen M, was present in all LDC isolates and cross-reacted with antigen 7 of M . leprae and antigen 60 of M . bovis BCG . The thermostability of these antigens and the specificity of the cross-reacting antigens were assessed . The data underline the degree of immunochemical homogeneity within the LDC group of micro-organisms and relatedness with M . leprae and other mycobacteria. J Am Vet Med Assoc, 1983 May 1, 182(9), 967 - 72 Cause and pathogenesis of middle ear infection in young feedlot cattle; Jensen R et al.; Two populations of feedlot cattle--weaned calves and yearlings--suffered otitis media . In calves the disease was acute and epizootic and had a prevalence of about 400 cases per 2000 cattle, whereas in yearlings, it was chronic and sporadic and had a prevalence of 1 case per 2000 cattle . Clinical signs were facial paralysis, otorrhea, and head tilt . The middle ears from 64 dead calves and 22 dead yearlings were examined . Calf ears had acute infection, with exudate in air cells and rupture of tympanic membranes . Yearling ears had chronic infection, with exudate in air cells, rupture or destruction of tympanic membranes, and necrosis of air cell partitions . Mixtures of Pasteurella multocida and Corynebacterium pseudotuberculosis were isolated from diseased ears, but Pasteurella multocida predominated in acute infections and Corynebacterium pseudotuberculosis predominated in chronic infections. Immunobiology, 1983 May, 164(5), 349 - 60 Solid tumor-derived target cell susceptibility to macrophages and natural killer/natural cytotoxic cells in the rat; Zoller M et al.; Cytotoxic capacity of rat macrophages (M phi) and natural killer (NK)/natural cytotoxic cells (NC) against adherent growing, solid tumor-derived target cells was evaluated, modulating the activation status of effector cells and growth conditions of target cells . Testing a panel of target cells, cytotoxicity of NK/NC and M phi was strikingly correlated so that besides of target-cell binding structures basic lysability seems to be of influence with respect to cytotoxicity rates . Varying the in vivo growth conditions of target cells altered their lysability by M phi and NK/NC cells in the sense that ascitic versus subcutaneously (sc) grown tumors were more resistant to lysis . On the other hand, in vitro culturing did not influence susceptibility for M phi, but with some tumor lines increased lysis by NK/NC cells was observed . In the rat, the activation status of M phi and NC was not age-dependent, and NK cell activity only declined slowly with age . But cytotoxic potential of M phi obviously presents a strain characteristic, different from NK/NC cell activity, only the latter two correlating in different rat strains . Experiments to augment natural cytotoxic capacity revealed that application of Corynebacterium parvum (CP) activated M phi and NK/NC cells, while sc tumor implantation only resulted in increased NK/NC cell cytotoxicity, leaving M phi unaltered. Mikrobiologiia, 1983 May-Jun, 52(3), 365 - 9 {Characteristics of central metabolism in coryneform bacteria}; Sandanov ChM et al.; The enzyme apparatus of the tricarboxylic acid cycle (TAC), the pathways involving carbohydrate catabolites in the cycle, and the anaplerotic mechanisms were comparatively studied in cultures belonging to two groups of coryneform bacteria, viz . corynebacteria and rhodococci, in order to assess their potential ability for oversynthesis of primary metabolites . It has been shown that corynebacteria and rhodococci (including those producing nucleotides and amino acids) are similar in the TAC structure and the enzyme activity, but differ in the operation of the glyoxylate shunt. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1983 May, 254(3), 326 - 32 Hydrogen peroxide-mediated antagonism against serratia marcescens by Streptococcus mitis; Traub WH et al.; The alpha-hemolytic Streptococcus mitis strain no . 17-1, isolated from the oral cavity of an healthy female adult, antagonized the growth of all 24 test strains of Serratia marcescens examined; furthermore, this strain inhibited the growth of various strains of Staphylococcus aureus, S . epidermidis, Streptococcus pyogenes, S . agalactiae, S . pneumoniae, Haemophilus influenzae, Listeria monocytogenes, and Corynebacterium diphtheriae . However, strans of Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa proved refractory . The mechanism of microbial antagonism was due to production and release of hydrogen peroxide under aerobic atmospheric conditions, which was neutralized through incorporation of bovine liver catalase into the solid assay medium. J Dairy Sci, 1983 May, 66(5), 1180 - 3 Intramammary infections in primigravid heifers near parturition; Oliver SP et al.; Mammary secretion from 32 primigravid heifers was obtained aseptically to determine frequency of bacterial isolation and incidence of intramammary infection near parturition . Quarter samples were collected 14 and 7 days prior to expected parturition, at parturition, and 7 and 14 days postparturition . Analysis of culture data indicated that 77.1% of samples were bacteriologically negative, and 15.7% contained coagulase negative staphylococci, 4.4% streptococci other than Streptococcus agalactiae, 3.8% coliforms, .8% coagulase positive staphylococci, and .1% Corynebacterium bovis . Frequency of bacterial isolation was highest in samples obtained prior to and at parturition . Thirty-five of 128 quarters were infected at parturition . Twenty-six of the 35 infections were caused by coagulase negative staphylococci, 4 by streptococci other than Streptococcus agalactiae, 4 by coliforms, and 1 by coagulase positive staphylococci . Twenty infections were observed during the early postpartum period . Coagulase negative staphylococcal infections decreased markedly . However, the number and type of primary pathogen infections during early lactation were similar to those at parturition. J Dairy Sci, 1983 May, 66(5), 1162 - 6 Susceptibility of bovine mammary gland to infections during the dry period; Oliver SP et al.; Quarter foremilk samples (1,574) were collected for bacteriological analysis from 40 cows during late lactation, early involution, prior to parturition, parturition, and during early lactation . Six of 160 quarters were infected with major pathogens during late lactation . Twelve new infections occurred during early involution . Twenty-two quarters were infected at parturition . Of these infections, 12 occurred after early involution, and 10 infections that originated during early involution persisted throughout the dry period . During early lactation, 21 major pathogen infections were observed . Nine occurred after calving, and 12 persisted from parturition . Most major pathogen infections (93.8%) were caused by coliforms and streptococcal species other than Streptococcus agalactiae . Numbers of streptococcal infections were highest at parturition and early lactation . Numbers of quarters infected with coliforms were similar during early involution, parturition, and early lactation . Coagulase negative staphylococcal infections increased during the dry period, whereas Corynebacterium bovis infected quarters decreased . Udder infections were few in cows completing first or second dry periods . The incidence of udder infection was highest in cows completing third or later dry periods. Cancer Res, 1983 May, 43(5), 1984 - 9 Inhibition of natural killer cell activity by a soluble substance released by rat peritoneal cells; Zighelboim J et al.; We describe here a soluble substance released by nonadherent cells from the peritoneal cavity of W/Fu rats that markedly inhibits the activity of mouse, rat, and human natural killer (NK) cells . The NK-inhibiting substance (NK-IS) has low molecular weight (less than 1000), is heat resistant (100 degrees for 15 min), and is insensitive to nonspecific proteases . NK-IS is produced in the presence of indomethacin (1 to 10 micrograms/ml), suggesting it is not prostaglandin . The inhibitory effect was seen on unstimulated as well as on cells activated in vivo or in vitro by Corynebacterium parvum . The activity of cells mediated antibody-dependent cell cytotoxicity (K-cells) was also inhibited by NK-IS although to a lesser degree . In sharp contrast, the substance had little effect on lysis mediated by murine or human cytotoxic T-lymphocytes . Production of NK-IS from rat peritoneal cells was significantly greater than by spleen cells . since the peritoneal cavity is relatively deficient in base-line NK activity compared to spleen, these data suggest that NK-IS may play an in vivo role in the expression of NK cytotoxicity. Eur J Immunol, 1983 May, 13(5), 364 - 9 Inhibition of lymphocyte proliferation and antibody production in vitro by silica, talc, bentonite or Corynebacterium parvum: involvement of peroxidative processes; Hoffeld JT; This study was undertaken to determine whether and by what means particles which induce granulomata in vivo can affect murine spleen lymphoproliferative and antibody responses in vitro . Particles of silica, talc, Bentonite or C . parvum cells inhibited lipopolysaccharide- or concanavalin A-stimulated proliferation and sheep red blood cell-induced antibody response in vitro . The inhibition required at least 48 hours exposure of the cells to the particles . The late onset of inhibition and its reproducibility at different cell or mitogen concentrations implicated particle-induced injury to both phagocytes and lymphocytes . Either alpha-tocopherol or 2-mercaptoethanol prevented the particle-induced inhibition of spleen cell responses . alpha-Tocopherol and 2-mercaptoethanol have in common the capacity to protect cells against membrane lipid peroxidation . The inhibitory peroxidative process(es) implicated by these studies are most likely attributable to: (a) stimulation of oxidative metabolism of phagocytic cells by particles; and (b) iron-catalyzed peroxidation directly by the particles . These data may be relevant in understanding the pathogenesis of and devising therapeutic approaches toward various granulomatous conditions. Science, 1983 Apr 29, 220(4596), 515 - 7 Cloned fragment A of diphtheria toxin is expressed and secreted into the periplasmic space of Escherichia coli K12; Leong D et al.; An 831-base pair segment of the corynebacteriophage beta tox-45 genome encoding fragment A of diphtheria toxin was cloned into plasmid pUC8 in Escherichia coli K12 . Strains containing recombinant plasmids expressed the adenosine diphosphate ribosyl transferase activity characteristic of fragment A; this activity could be inhibited by polyvalent antiserum to fragment A as well as by the appropriate monoclonal antibodies to diphtheria toxin . The transferase activity was secreted into the periplasmic space of E . coli . These findings have implications for the future construction of genetically engineered chimeric toxins. Cell Immunol, 1983 Apr 15, 77(2), 266 - 78 The suppressive effect of peritoneal exudate macrophages on production of antibody to sheep erythrocytes in vitro; Yoshikai Y et al.; The effects of peritoneal exudate macrophages on antibody response to sheep erythrocytes (SRBC) were investigated in mice . Peritoneal exudate macrophages obtained from mice injected intraperitoneally with proteose peptone or Corynebacterium parvum 4 days earlier had stronger ability to phagocytize and degrade SRBC than normal resident macrophages . These macrophages suppressed antibody formation to SRBC in vitro as well as in vivo . This suppression was overridden by increasing the amount of SRBC and diminished completely by pretreatment of the macrophages with iodoacetate and partly by pretreatment with 2-deoxyglucose, both known to be inhibitors of phagocytosis, but not by addition of indomethacin to the in vitro culture . These results suggest that the suppression of antibody response by peritoneal exudate macrophages was due to the increased activity of these cells as scavenger cells, resulting in a reduced amount of effective antigenic stimulation, and that it was not mediated by a prostaglandin-dependent mechanism . The scavenger function of these macrophages may be due to Ia-negative macrophages. J Am Vet Med Assoc, 1983 Apr 15, 182(8), 806 - 8 Bacterial endocarditis in adult dairy cattle; Power HT et al.; Thirty-one cases of bacterial endocarditis in adult dairy cows were reviewed . Clinical signs were reflective of the stage of the disease . Recurrent or persistent fever, tachycardia and a pounding heartbeat or systolic murmur, polypnea, and lameness were typical . With chronicity, weight loss and poor production developed . The end stage was congestive heart failure . Neutrophilia was typical in early cases . Low-grade anemia and high total serum globulin content developed with chronicity and seemed to be negative prognostic signs . Corynebacterium pyogenes was the organism most frequently identified by blood culture or at necropsy . Twenty cows were necropsied and 2 cows were sent to slaughter . Nine cows in which the diagnosis was made early in the course of the disease responded to long-term penicillin therapy. Vet Rec, 1983 Apr 2, 112(14), 315 - 9 Within herd comparison of teat dipping and dry cow therapy with only selective dry cow therapy in six herds; Robinson TC et al.; A within herd comparison of teat dipping and dry cow therapy (full treatment) with only selective dry cow therapy (partial treatment) was carried out in six commercial dairy herds for a two year period . In four herds, the incidence of clinical mastitis was 2 to 12 per cent higher in the partial treatment group . In another herd, in which the pattern of clinical mastitis isolates was unusual in that minor pathogens were isolated from 30 per cent of mastitis cases, the incidence was 43 per cent higher in the partial treatment group . In the remaining herd the incidence was 10 percent higher in the full treatment group . Streptococcus uberis mastitis was more common in the partial treatment groups of five herds; coliform mastitis was more common in the full treatment groups of two herds and similar in both groups in the other herds . High rates of coliform mastitis were associated with poor herd environmental conditions but this was not true for Strep uberis mastitis . Rates of staphylococcus aureus and Strep dysgalactiae mastitis were low in all herds . The level of major pathogen infection in cows completing the trial in all herds increased in the partial treatment group from 5 per cent of quarters at the start to 12 per cent at the finish of the trial . In the full treatment group, however, there was only a small increase in this level . In contrast, levels of Corynebacterium bovis infection increased by 17 per cent in both treatment groups . Continued use of teat dipping and dry cow therapy was associated with a higher rate of coliform mastitis in two of the three herds where there were poor standards of hygiene and husbandry. Pathology, 1983 Apr, 15(2), 161 - 4 Laboratory diagnosis of bacteremia by headspace gas-liquid chromatography; Hayward NJ et al.; The growth of Staphylococcus aureus, Streptococcus pneumoniae, S . fecalis, S . sanguis, S . bovis, S . mitior, S . agalactiae, Escherichia coli, A-D group, Klebsiella aerogenes, K . oxytoca, Enterobacter cloacae, Proteus mirabilis, Serratia marcescens, Pasteurella multocida or Listeria monocytogenes in 83 blood cultures was detected in a 1.5-min analysis using head-space gas-liquid chromatography . Two hundred and twenty-four blood cultures in which there was no growth of micro-organisms were negative in the analysis . The analysis detected the growth of S . epidermidis in only 6 of 26 blood cultures and failed to detect the growth of Pseudomonas aeruginosa, Candida albicans and species of Micrococcus, Corynebacterium or Bacillus in 18 blood cultures. Biochem Pharmacol, 1983 Apr 1, 32(7), 1275 - 80 Inhibition of hepatic drug metabolism in the rat after Corynebacterium parvum treatment; Farquhar D et al.; Drug-metabolizing enzyme activities, cytochrome concentration, and protein content of hepatic microsomal preparations from adult, female Sprague-Dawley rats were examined at 1-, 3-, 6-, 10-, 14- and 17-day intervals after administration of a single intravenous injection of Corynebacterium parvum (C . parvum) at a dose of 10 mg/m2 . Aniline hydroxylase (AH) activity, aminopyrine demethylase (APD) activity, and cytochrome P-450 concentration were reduced 20-50% on days 3-6 and, thereafter, gradually recovered to control levels by day 17 . Cytochrome c reductase activity and cytochrome b5 concentration were reduced significantly (24%) only on day 10 . Microsomal protein concentration was unchanged . C . parvum added in vitro had no effect on AH or APD activity . Although livers of treated rats were only slightly (less than 20%) enlarged, gross splenomegaly was apparent, reaching a maximum on day 6 . A marked inverse correlation existed between the temporal variation in the size of the spleen and APD activity . In rats killed 6 days after administration of C . parvum at 0.67 to 10.00 mg/m2, a direct relationship was apparent between the adjuvant dose and the magnitude of reduction of APD activity . A similar relationship was apparent between splenomegaly and APD activity . Histopathologic examination of liver sections from treated rats revealed numerous granulomas throughout the parenchyma . The magnitude of enzyme inhibition generally paralleled the severity of the hepatic lesions. Jpn J Exp Med, 1983 Apr, 53(2), 95 - 102 Peritoneal exudation of macrophages by irritants and its effect on immune responses against sheep erythrocytes and Listeria monocytogenes; Miake S et al.; Relation between the degradation of antigenic substances by peritoneal exudate macrophages induced by different irritants and subsequent induction of immune responses against SRBC or Listeria monocytogenes were studied . Delayed footpad reaction and antibody production to SRBC were both suppressed by pretreatment with thioglycollate or with killed Corynebacterium parvum . In contrast, delayed footpad reaction and acquired cellular resistance to Listeria were augmented by pretreatment with thioglycollate . When pretreated with C . parvum, however, such augmentations in immune responses to Listeria were not observed but these responses were suppressed . It was suggested that the amount of antigenic stimuli was determined by the mutual relationship between the level of macrophage activity as scavenger cells and the susceptibilities of the antigenic substances to degradation by macrophages, and that induction of immune responses were affected by this mutual relationship. J Bacteriol, 1983 Apr, 154(1), 245 - 52 Regulation of toxinogenesis in Corynebacterium diphtheriae: mutations in the bacterial genome that alter the effects of iron on toxin production; Cryz SJ Jr et al.; Mutants of Corynebacterium diphtheriae C7(beta) that are resistant to the inhibitory effects of iron on toxinogenesis were identified by their ability to form colonies surrounded by toxin-antitoxin halos on agar medium containing both antitoxin and a high concentration of iron . Chromosomal mutations were essential for the altered phenotypes of four independently isolated mutant strains . During growth in deferrated liquid medium containing various amounts of added iron, these mutants differed from wild-type C . diphtheriae C7(beta) in several ways . Their growth rates were slower under low-iron conditions and were stimulated to various degrees under high-iron conditions . The concentrations of iron at which optimal toxin production occurred were higher for the mutants than for wild-type C . diphtheriae C7(beta) . Toxin production by the mutants during growth in low-iron medium occurred throughout the period of exponential growth at nearly constant rates that were proportional to the bacterial growth rates . In contrast, toxin production by wild-type C . diphtheriae C7(beta) in similar low-iron cultures occurred predominantly during the late exponential phase, when iron was a growth-limiting nutrient . Additional studies demonstrated that these mutants had severe defects in their transport systems for ferric iron . We propose that the altered regulation of toxinogenesis by iron in our mutants was caused by the severe defects in their iron transport systems . As a consequence, the mutants exhibited a low-iron phenotype during growth under conditions that permitted wild-type C . diphtheriae C7(beta) to exhibit a high-iron phenotype. J Vet Pharmacol Ther, 1983 Mar, 6(1), 67 - 73 Pharmacokinetics of erythromycin in foals and in adult horses; Prescott JF et al.; The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks . The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based . Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10-12-week-old foals given 20.0 mg/kg intravenously . The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10-12 weeks) was 1.0-1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h . No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally . Peak levels in foals given the drug orally were 0.42 micrograms/ml at 120 min after administration . Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later; the peak level achieved was 1.44 micrograms/ml serum 90 min after administration and concentrations exceeded 0.25 micrograms/ml for 6 h . In the mares the milk concentrations were approximately twice those in serum . Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals. J Clin Microbiol, 1983 Mar, 17(3), 500 - 6 Cross-reactivity of Haemophilus somnus antibody in agglutination and complement fixation tests and in the enzyme-linked immunosorbent assay; Canto J et al.; The specificity and sensitivity of agglutination, complement fixation, and enzyme-linked immunosorbent assay (ELISA) procedures in the detection of antibodies to Haemophilus somnus was investigated . H . somnus rabbit immune sera were found to agglutinate Pasteurella multocida, Staphylococcus aureus, and Haemophilus agni and, in some instances, also Pasteurella haemolytica, Salmonella dublin, Streptococcus agalactiae, and Corynebacterium pyogenes . In complement fixation tests with saline extracts as antigens, only H . agni reacted with H . somnus antisera to any significant degree . In ELISA tests with sonicated or heat-extracted antigens, cross-reactions were seen with the two Pasteurella spp . and with H . agni . When whole cells and saline extracts were used as antigens in ELISAs, only H . agni showed any cross-reactivity . The greatest specificity in distinguishing homologous from heterologous reactions was achieved by ELISA with saline extracts as antigens . Escherichia coli and Brucella abortus antigens failed to react with H . somnus antibody in any of the tests . A rabbit serum containing antibody to bovine type isolates of P . multocida, P . haemolytica, S . aureus, S . agalactiae, S . dublin, C . pyogenes, and E . coli gave no positive reaction in ELISA tests with saline extract of H . somnus as antigen . It is concluded that such saline extract, which appears to consist largely of H . somnus common antigen, has the potential of being a useful diagnostic reagent in the study by ELISA of antibody response to H . somnus. Cancer Lett, 1983 Mar, 18(2), 229 - 34 Mutagenicity of pyrolysates of salt-tolerant bacteria from food and cigarettes; Morishita Y; Smoke condensates obtained by pyrolysis of the cells of microorganisms isolated from food and cigarettes and of laboratory cultures were shown to be mutagenic to Salmonella typhimurium TA98 and TA100 in incorporation with liver microsomal fraction S-9 mix . The smoke condensates from salt-tolerant bacteria, which belonged to Micrococcus, Bacillus and Corynebacterium spp., showed higher mutagenic activity than those from other less salt-tolerant organisms, fish flesh or pork . Smoke deriving from microorganisms, especially salt-tolerant ones, in food or cigarettes as well as from food components might take part in human carcinogenesis because of the correlation between mutagenicity and carcinogenicity. Cancer Res, 1983 Mar, 43(3), 1395 - 401 Intraperitoneal immunotherapy of human ovarian carcinoma with Corynebacterium parvum; Bast RC Jr et al.; Corynebacterium parvum has been administered i.p . to 14 patients with advanced ovarian cancer . Two patients had responded completely to cytoreductive surgery and combination chemotherapy prior to immunotherapy, and one patient with residual disease had received only a single course of C . parvum due to i.p . catheter malfunction . Among the 11 patients with residual disease evaluable for response, from three to eight i.p . treatments with C . parvum produced surgically confirmed tumor regression in five patients (45%) with three partial responses and two complete responses of 5 and 12 months duration . All responders had (a) multiple tumor nodules less than 0.5 cm at the initiation of immunotherapy, and (b) severe abdominal pain and fever after C . parvum injection . Overall, 58 courses of immunotherapy were associated with abdominal pain (91%), fever (67%), nausea (52%), vomiting (31%), and hypotension that responded promptly to i.v . infusion of fluids (10%) . Use of i.p . cathethers was associated with two episodes each of infection and intraabdominal bleeding . Administration of C . parvum i.p . has augmented the ability of human peritoneal cells to lyse human ovarian carcinoma cell lines in the presence of specific rabbit heteroantiserum . C . parvum administered i.p . has inhibited the growth of human ovarian carcinoma and may prove useful for modulating the activity of human effectors for antibody-dependent cell-mediated cytotoxicity. Arch Surg, 1983 Mar, 118(3), 328 - 32 Improved survival after pneumococcus in splenectomized and nonsplenectomized mice with Corynebacterium parvum; Hebert JC et al.; Splenectomy increases the susceptibility to infections with certain bacteria, particularly Streptococcus pneumoniae . Because the immunomodulator Corynebacterium parvum expands the phagocytic cell compartment and enhances reticuloendothelial function, we tested the effect of C parvum in mice challenged with aerosolized pneumococci . Mice splenectomized seven days before pneumococcal challenge and treated intraperitoneally with 700 micrograms of C parvum immediately after exposure were protected when compared with splenectomized or sham-operated saline-injected controls . Analysis of proportional hazards showed the risk of dying in order of greatest to least as follows: splenectomy/saline, sham/saline, splenectomy/C parvum and sham/C parvum . The benefits of an intact spleen and C parvum seemed to be additive in their protective effects after aerosol pneumococcal challenge . After intravenous challenge, bloodstream clearance was improved in sham-operated mice at three days after C parvum injection compared with saline-injected sham-operated controls and C parvum-injected splenectomized mice . A significant improvement in bacterial clearance did not occur until seven days after C parvum treatment in splenectomized mice . The results demonstrate the value of a nonspecific immunomodulator for enhancing the defense mechanisms of both normal and splenectomized animals. Indian J Pediatr, 1983 Mar-Apr, 50(403), 145 - 8 Prevalence of diphtheria carriers among pre-school children; Leelamoni K et al.; PIP: The carrier rate of Corynebacterium diphtheriae in 453 pre-school children in Ulloor Panchayat, Trivandrum, Kerala State, India was assessed from November 1976-July 1977 . Throat and nasal swabs were cultured by standard techniques, and suspect colonies tested for virulence in rabbits . 16 or 3.5% of the children harbored diphtheria; 7 of these were 4-5 years old . Only 1 of the C . diphtheriae strains was found to be virulent . Several of the isolates were nonvirulent mitis strains, while no intermedius strains were found . 9 of the children were partially immunized, 4 were completely immunized and 3 were not immunized . Proportionally more carriers lived in thatched huts with mud floors or less ventilation than did children from wood or plaster houses . J Bacteriol, 1983 Mar, 153(3), 1202 - 10 Integration of corynebacteriophages beta tox+, omega tox+, and gamma tox- into two attachment sites on the Corynebacterium diphtheriae chromosome; Rappuoli R et al.; The bacterial attachment sites of independently isolated Corynebacterium diphtheriae strains C7s and (belfanti)1030 lysogenic for corynebacteriophages beta tox+, omega tox+, and gamma tox- were determined by Southern blot analysis . Both corynebacterial strains contained two distinct bacterial attachment sites (attB1 and attB2) . We found that infection by any of the three closely related corynebacteriophages may give rise to single, double, and triple lysogens . In the case of toxigenic C . diphtheriae strains C7s(beta tox+) and C7s(omega tox+), the final yields of diphtheria toxin produced under optimal conditions were equivalent and varied by one-, two-, or threefold depending upon the number of integrated prophage. J S Afr Vet Assoc, 1983 Mar, 54(1), 25 - 8 The frequency and some characteristics of anaerobic bacteria isolated from various forms of bovine mastitis; Greeff AS et al.; The prevalence of strictly anaerobic bacteria in the secretions from untreated cases of mastitis in lactating dairy cows was investigated . The study involved 147 Friesland cows in 12 highveld herds . All herds yielded cows with anaerobic udder infections . No anaerobic bacteria were recovered from cows with normal quarters or those with latent aerobic infections . Only anaerobes were present in 10% of so-called 'aseptic' mastitis cases . A variety of anaerobic organisms was isolated concurrently with facultative bacteria from 5,3% and 58,8% of cases classified as subclinical and clinical respectively . Peptococcus spp . was associated with Corynebacterium pyogenes and Bacteroides spp . with Staphylococcus aureus and/or Streptococcus agalactiae in 80% anaerobic udder infections . Gram positive anaerobic species were mostly sensitive to penicillin-G but all the Gram negative rods were resistant . In addition, all B . fragilis strains produced beta-lactamase . The ability to produce heparinase was demonstrated in one strain of Peptococcus indolicus and a Peptostreptococcus sp. Am J Trop Med Hyg, 1983 Mar, 32(2), 286 - 95 Efficacy of combined immunostimulation and chemotherapy in experimental visceral Leishmaniasis; Haidaris CG et al.; A regimen of combined immunostimulation and chemotherapy for the elimination of Leishmania donovani amastigotes was evaluated . An in vitro experimental model utilized cultured peritoneal macrophages from C57B1/6 mice infected with L . donovani tissue forms . Partial or complete activation of macrophages as judged by killing of tumor cells significantly enhanced the efficacy of sodium antimony gluconate (Pentostam) . The quantity of drug required for elimination of parasites from immunostimulated cells was considerably lower than that required to achieve comparable amastigote killing in thioglycolate-elicited macrophages . In contrast, amphotericin B cleared infected cells of amastigotes at comparable drug levels when tested with immunostimulated and unstimulated macrophages . Several drugs tested inhibited the conversion of amastigotes to promastigotes in vitro but were ineffective in killing of intracellular tissue forms . Allopurinol and difluoromethylornithine (DMFO) blocked amastigote conversion significantly . These drugs at high concentrations, however, exerted only minimal toxicity for amastigotes residing within macrophages . Efficacy of combined therapy was also demonstrated in vivo . Immunoenhancement of L . donovani-infected mice with Corynebacterium parvum vaccine combined with a regimen of sodium antimony gluconate was significantly more effective than was immunotherapy or drug therapy alone. Br Med J (Clin Res Ed), 1983 Feb 19, 286(6365), 624 - 6 Immunisation of adults during an outbreak of diphtheria; Palmer SR et al.; In an outbreak of infection due to Corynebacterium diphtheriae in a hospital for mentally subnormal adults sera from 211 members of staff were screened for diphtheria antitoxin titres . Of these, 79 (37%) required immunisation, and a low dose preparation (1 LfU of diphtheria and 10 LfU tetanus toxoids) was offered . Of the 64 subjects who accepted a single immunisation and were subsequently retested, seroconversion to diphtheria toxoid occurred in 45 (70%), the rate being highest in younger adults . Seroconversion to tetanus toxoid occurred in 59% of subjects . Local reactions to the single dose were reported by 29 (43%) subjects, and nine (13%) experienced moderately severe local reactions and systemic symptoms . We conclude that adults should not be vaccinated without previous screening for susceptibility to diphtheria; that neither previous immunisation nor age is reliable in predicting the need for vaccination; and that though a single booster dose of diphtheria toxoid is probably effective in adults under 45, two doses should be given to those in the older age group. S Afr Med J, 1983 Feb 19, 63(8), 285 - 7 Infective endocarditis due to non-toxigenic Corynebacterium diphtheriae in a child . A case report; Marcus JC et al.; A case of infective endocarditis (IE) in a 5 1/2-year-old boy in whom blood and bone marrow cultures yielded an unusual organism, a non-toxigenic strain of Corynebacterium diphtheriae, is reported . This proved fatal, and at autopsy congenital valvar aortic stenosis was found, but the vegetations occurred on an anatomically normal mitral valve . Organisms such as C . diphtheriae should not be ignored when isolated from blood cultures in suspected cases of IE. Cell Immunol, 1983 Feb 15, 76(1), 49 - 57 Role of Corynebacterium parvum in the activation of peritoneal macrophages . II . Identification of distinguishable anti-tumor activities by macrophage subpopulations; Chapes SK et al.; Two different mechanisms of murine macrophage (MP) antitumor activity are described in this report . C . parvum-activated peritoneal MPs were tested for cytotoxic and cytostatic activity 4 days after ip immunization . Cytotoxic activity could be distinguished from cytostatic activity using two different assay protocols . When MPs were separated by 1g velocity sedimentation, cytotoxic MPs were confined to high velocity fractions . In contrast, cytostatic MPs were found in cell fractions with velocities as low as 5.2 mm/hr . These two MP activities were also distinguishable by culturing at 37 degrees C for 24 hr . Cytotoxicity was abrogated when MPs were incubated in MEM, or MEM supplemented with lymphokine (LK) or indomethacin . In contrast, cytostasis remained at high levels when the cells were incubated with LK or indomethacin . Cytotoxicity was not retained after overnight culture even if LPS was present, or if various spleen or non-adherent peritoneal exudate cells were cocultured with the cytotoxic effector cells . Assays done to determine the presence of suppressor cells failed to find any inhibitory cell type . The phagocytic index, acid phosphatase activity, and H2O2 secretion were also measured before and after overnight culture . Acid phosphatase and phagocytic activities did not decline whereas H2O2 secretion declined significantly . These data indicate that in response to C . parvum, at least two different effector cell types with distinct antitumor activities are generated . Cytotoxicity, like the ability of cells to secrete H2O2, is found to be a short-lived function of CP stimulated MPs . In contrast, cytostasis is a function retained longer by MPs in culture. Biochim Biophys Acta, 1983 Feb 15, 742(3), 630 - 46 Steady-state kinetics and spectral properties of Corynebacterium sarcosine oxidase; Hayashi S et al.; The overall reaction kinetics of Corynebacterium sarcosine oxidase were investigated and the reaction was shown to follow a ping-pong, bi-bi mechanism with two substrates, sarcosine and molecular oxygen . Sarcosine analogs, such as acetate, propionate and methoxyacetate, were competitive inhibitors of the reaction . Acetate caused characteristic alterations in optical and circular dichroic spectra, indicating that the microenvironment of the substrate-binding region of the enzyme increased in hydrophobicity on binding with the substrate analog . The dissociation constants of the analogs calculated from the spectral changes were in agreement with the kinetic inhibition constants . Inorganic metallic ions were also inhibitory . Of interest was the finding that the inhibition by Hg2+ was proportional to the square of its concentration, which suggests that at least two sulfhydryl groups are related to the catalytic activity of the enzyme. Aust J Exp Biol Med Sci, 1983 Feb, 61(Pt 1), 11 - 25 Leishmania tropica major in mice: vaccination against cutaneous leishmaniasis in mice of high genetic susceptibility; Mitchell GF et al.; BALB/c and BALB/c.H-2b mice are genetically susceptible to development of persistent and severe disease following cutaneous injection of promastigotes of the protozoan parasite, Leishmania tropica major, whereas C57BL/6 are relatively resistant . Resistance in C57BL/6 can be further increased by intraperitoneal injection of living, but not killed, promastigotes prior to cutaneous challenge . Severely diseased BALB/c mice can show resistance to development of a second cutaneous lesion but apparently only in the advanced stages of systemic life-threatening disease . A striking level of resistance to persistent disease has been demonstrated in BALB/c.H-2b mice pre-injected with frozen and thawed L . t . major-infected macrophages of the continuous macrophage cell line IC-21 (H-2b) together with Corynebacterium parvum . No resistance is seen in recipients of either C . parvum or the crude antigen mixture alone . Protection is afforded by intraperitoneal and not subcutaneous injection of crude antigen plus adjuvant . In these vaccination studies all evidence points to the infected macrophage as most appropriate source of 'host-protective' antigens as well as being the most likely target of host-protective immunity . Resistance is expressed in vaccinated mice as minimal signs of cutaneous disease and rapid resolution of any small lesions which do develop . Frozen and thawed promastigotes plus C . parvum will not induce resistance to persistent disease in BALB/c.H-2b mice and preincubation of promastigotes with sera from resistant vaccinated mice does not influence their capacity to cause cutaneous disease . The results provide baseline data for vaccination attempts in genetically susceptible hosts using isolated L . t . major antigens (and, in particular, infected macrophage antigens) and highlight the utility of the intraperitoneal route of injection and the use of the therapeutic biological, C . parvum, as an adjuvant in such studies. J Immunol, 1983 Feb, 130(2), 974 - 80 Enhancement of tumor metastasis and suppression of natural killer cell activity by beta-estradiol treatment; Hanna N et al.; Treatment of mice with 17 beta-estradiol leads to a selective inhibition of natural killer (NK) cell activity as measured by in vitro cytotoxicity against YAC-1 lymphoma and UV-2237 fibrosarcoma target cells . Activation of NK cells by polyinosinic-polycytidylic acid (poly I.C) and Corynebacterium parvum also was impaired in beta-estradiol-treated mice, whereas activation of tumoricidal macrophages was uncompromised . The beta-estradiol-induced suppression of NK cell activity was associated with a higher incidence of experimental and spontaneous pulmonary metastasis of the syngeneic UV-2237 fibrosarcoma and K-1735 and B16 melanoma tumors . Injection of poly I.C or C . parvum before i.v . tumor challenge markedly inhibited the development of lung tumor colonies in normal recipients, but it was less effective in beta-estradiol-treated mice . Adoptive transfer of normal spleen cells enhanced the NK cell activity and increased the resistance of beta-estradiol-treated mice against hematogenous tumor metastasis . Nude mice treated with beta-estradiol also exhibited a low level of NK cell activity and an enhanced susceptibility to metastasis of allogeneic tumor cells . The potential use of this in vivo model for studies of metastasis of human malignant neoplasms is discussed. Infect Immun, 1983 Feb, 39(2), 609 - 14 Production, purification, and properties of a bacteriocin from Staphylococcus aureus isolated from saliva; Nakamura T et al.; Staphylococci from samples of human saliva were isolated on staphylococcal-selective agar plates . These strains were tested for the inhibition of the growth of Staphylococcus aureus FDA209P . The frequency of inhibitory strains among all of the staphylococcal isolates was 5.2% . Strain IYS2, which formed the biggest inhibitory zone against the growth of the indicator strain, was used as the producer of bacteriocin . IYS2 was identified to be S . aureus, based on its biological properties . The bacteriocin was purified by sequential procedures, including ammonium sulfate precipitation, fractionation with ethanol, ion-exchange chromatography, and gel filtration . Its molecular weight was determined to be 5,000 . The isoelectric point was 10.0 . In amino acid composition, lysine, histidine, aspartic acid, valine, and phenylalanine were predominant . The bacteriocin was heat stable but inactivated by proteases or peptidase . The bacteriocin had a bactericidal effect on susceptible cells . An analysis of the inhibitory spectrum among typical oral indigenous bacteria showed that Streptococcus salivarius, Propionibacterium acnes, Corynebacterium parvulum, and Actinomyces israelii were susceptible to the bacteriocin . Streptococcus mutans, Streptococcus sanguis, Streptococcus mitis, Actinomyces viscosus, Actinomyces naeslundii, Fusobacterium nucleatum, Bacterionema matruchotii, and Bacteroides melaninogenicus were resistant . The majority of S . aureus tested were susceptible, and all Staphylococcus epidermidis strains tested were resistant. Cell Immunol, 1983 Feb 1, 75(2), 367 - 77 Evidence for granulocyte-mediated macrophage activation after C . parvum immunization; Chapes SK et al.; It has been previously demonstrated that at the peak of the peritoneal response to Corynebacterium parvum (Day 4), cytolytic macrophages can be characterized by the presence of intracellular bacteria . In the present study, the role of neutrophils in the activation of peritoneal macrophages by C . parvum was investigated . Inflammatory neutrophils isolated 5 hr after ip administration of C . parvum were transferred to normal, syngeneic mice and the peritoneal macrophages of recipients harvested 4 days later were tested for cytoxicity against HeLa cells . Neutrophils isolated from mice 5 hr after C . parvum immunization were effective in inducing cytolytic macrophages . Less than 100-fold as much bacteria was needed to induce comparable levels of cytotoxic activity when introduced inside granulocytes . Neutrophils obtained from mice 48 hr after C . parvum injection or mononuclear cells were not good macrophage activators . Viable neutrophils were not required as freeze-thawed cells were able to activate macrophages in recipient mice . The intracellular distribution of C . parvum changed dramatically with time . Initially almost all bacteria were found within neutrophils . By 24 hr, many macrophages contained either bacteria or granulocytes which had ingested C . parvum . Pyridine extracts of C . parvum, which do not activate peritoneal macrophages when injected directly into mice, did not induce neutrophils capable of activating macrophages . The residue of pyridine-extracted C . parvum did induce neutrophils that could activate macrophages when transferred . The results suggest that processing of the bacteria by inflammatory granulocytes may be an obligatory step in macrophage activation by this agent . The peak response occurred earlier than T-cell immunity is usually observed and it is suggested that direct activation of macrophages via ingestion of neutrophils may represent the earliest stage of macrophage activation by C . parvum. Zh Mikrobiol Epidemiol Immunobiol, 1983 Feb, (2), 44 - 8 {Improvement of the preliminary classification of Corynebacterium diphtheriae v . gravis}; Krylova MD et al.; In this study the previously published preliminary scheme for the subdivision of toxigenic and nontoxigenic Corynebacterium diphtheriae, classified with cultivar gravis, is made more precise . 3 groups remain in this scheme: I, II and III; each of them contains toxigenic C . diphtheriae (subgroup a) and nontoxigenic precursors of C . diphtheriae (subgroup b) . For the first time nontoxigenic analogs of C . diphtheriae, phagovar OPQSTg, have been introduced into group I and newly discovered toxigenic C . diphtheriae, phagovar K, with their nontoxigenic precursors converted by phages 5 tox+, 6 tox+ and W tox+ have been introduced into group III . Group IV has been provisionally excluded from the scheme because this group comprises a small number of strains (3 strains) . This classification can already be used in research practice for a finer differentiation of strains classified with cultivar gravis and for correct epidemic orientation. J Dairy Sci, 1983 Feb, 66(2), 253 - 8 Milking frequency as related to udder health and milk production; Waterman DF et al.; Twenty-four cows each in two trials were paired on age, stage of lactation, and projected milk production to compare the incidence of mastitis with milking two or three times per day over 12 wk . Teats of all cows were dipped daily in a suspension of Streptococcus agalactiae (one of two strains) . Average daily milk production for the combined trials was 24.0 kg for the thrice daily group and 22.0 kg for the twice daily group . Quarter foremilk samples were taken every 2 wk for somatic cell counts and bacterial isolations . Somatic cell counts of cows milked twice per day averaged 31 x 10(3) per milliliter compared to 26 x 10(3) for three milkings . There were no significant differences in numbers of new bacterial infections between groups . Cows milked twice per day had 41 new infections and 7 clinical infections and the three-time group had 39 new infections and 2 clinical infections . The many corynebacteria infections were related to the experimental design in which no disinfectant teat dip was used . Three milkings per day did not affect udder health. Immunology, 1983 Feb, 48(2), 321 - 7 Effect of human monocyte killing of tumour cells of antibody raised against an extracellular monocyte cytotoxin; Matthews N; Human monocytes can kill or inhibit the growth of certain tumour cell lines . Amongst the possible mediators is a cytotoxin synthesized in readily detectable amounts by endotoxin-stimulated monocytes . A neutralizing antiserum to the cytotoxin has been used to assess the cytotoxin's contribution to monocyte killing of tumour cells . The antiserum was tested for possible inhibition of monocyte killing of three tumour cell lines--L929, K562 and A549 . Inhibition was complete with L929, partial with K562 and insignificant with A549 . Thus the contribution of the cytotoxin to monocyte killing of tumour cells depends upon the tumour line under test . Antibody against endotoxin-induced cytotoxin also neutralized cytotoxin induced in monocytes by other agents including BCG, Corynebacterium parvum, pokeweed mitogen and zymosan . Cytotoxin could be quantitatively removed from monocyte supernatants by Sepharose-bound, anticytotoxin antibody . Recovery of the cytotoxin from the immunoadsorbent was difficult because of its lability in the solutions commonly used for desorption . The best recovery has been achieved with 2 M urea, 2 M MgCl2 giving a 25% yield and a forty-fold increase in purity in a single step. J Virol, 1983 Feb, 45(2), 524 - 30 Restriction endonuclease map of corynebacteriophage omega ctox+ isolated from the Park-Williams no . 8 strain of Corynebacterium diphtheriae; Rappuoli R et al.; The toxigenic corynebacteriophage omega tox+ was isolated from the hypertoxigenic Park-Williams no . 8 (PW8) strain of Corynebacterium diphtheriae and compared with the toxigenic corynebacteriophage beta tox+ . The physical size and host range of both phages were found to be identical . An endonuclease restriction map of omega tox+ was constructed, and the locations of the cohesive ends (cos), phage attachment site (attP), and the diphtheria tox operon were identified . The genome of omega tox+ was found to differ from that of beta tox+ in three regions . In addition, omega tox+ was shown to be integrated into two nontandem corynebacterial phage attachment sites (attB1, attB2) in the PW8 chromosome . The differences in the restriction endonuclease digestion maps of omega tox+ and beta tox+ and the contribution of double lysogeny are discussed in relation to the hypertoxigenicity of the PW8 strain. Scand J Infect Dis, 1983, 15(2), 179 - 83 Infective endocarditis caused by uncommon bacteria; Ben-Chetrit E et al.; The present study is an attempt to define the uncommon bacteria (UB) causing endocarditis and to evaluate their prevalence and clinical significance . Review of 13 series (including ours) revealed that UB were the infecting organisms in 105/1989 patients (5.3%) . The leading bacteria were: Pneumococcus, Haemophilus sp., Corynebacterium sp., Neisseria sp., Streptobacillus moniliformis, Cardiobacterium hominis and Erysipelothrix sp . These data are similar to those obtained from 111 sporadic case reports published in English during the last 6 yr and cited in the Index Medicus . Infection by UB usually resembles that by the common bacteria . However, Haemophilus sp . seems to affect mainly the young and is associated with major arterial occlusions, and Brucella is claimed to have a greater affinity to the aortic valve . UB are more frequent in patients with polymicrobial infections and their diagnosis is often delayed . Greater awareness to the possibility of infections with UB is needed for early diagnosis and improved prognosis. Int J Immunopharmacol, 1983, 5(2), 137 - 44 Augmentation of NK activity by Corynebacterium parvum fractions in vivo and in vitro; Lichtenstein A et al.; Biochemically modified whole cell preparations and derived fractions of Corynebacterium parvum (C . parvum) were evaluated for the ability to augment natural killer cell cytoxicity in vivo and in vitro in rats . Unfractionated C . parvum enhanced peritoneal cell (Pc) NK activity in a dose dependent fashion . This activity appeared to be enriched in insoluble light residue material obtained from hot phenol water extraction . Enhancement of Pc cytotoxicity was significantly greater at all time points tested in rats injected with light residue when compared to rats injected with comparable amounts (by dry weight) of unfractionated organisms . In addition, pyridine extractable material and HCl modified preparations were capable of boosting Pc NK activity following intraperitoneal (I.P.) injection . Periodate treatment abrogated C . parvum's ability to boost Pc cytotoxicity and insoluble residue material obtained from pyridine extraction was likewise devoid of NK-enhancing properties . Culture of rat spleen cells overnight with unfractionated C . parvum, light residue and pyridine residue materials enhanced NK cytotoxicity whereas HCl and periodate modified whole cell preparations as well as phenol and pyridine extractable material were incapable of boosting cytotoxicity in vitro . In vitro augmentation by culturing with light residue was dependent on the presence of adherent cells in rat spleen cell populations . Pyridine extracts boost cytotoxicity in vivo and have no effect in vitro while the opposite is true of pyridine residue material suggesting different mechanisms of NK augmentation by C . parvum between in vitro and in vivo systems. Int J Immunopharmacol, 1983, 5(2), 115 - 21 Platelet activating factor (PAF) induces the oxidative burst in macrophages; Hartung HP et al.; The response of guinea pig peritoneal macrophages to platelet activating factor (1-O-octadecyl-2-acetyl-sn-glycero-3-phosphoryl-choline) was examined . In Corynebacterium parvum induced macrophages, platelet activating factor, over a wide dose range (3.8 X 10(-5) to 3.8 X 10(-9)M) triggered the oxidative burst as indicated by increased luminol-dependent chemiluminescence and hydrogen peroxide release into culture supernatants . This effect of PAF was inhibited by superoxide dismutase and catalase . Resident macrophages exhibited only slight respiratory activity in response to platelet activating factor which could be increased by adding 1% gelatine to the medium . Activation of macrophages is a new biological effect exerted by platelet activating factor . In immuno-inflammatory reactions, cells capable of generating platelet activating factor may come into close contact with macrophages and by liberating this mediator cause them to release highly toxic oxygen species known to be microbicidal and cytocidal and able to produce vascular endothelial injury . Our findings lend further support to the view that platelet activating factor is a potent and rapid activator of physiological defence mechanisms. Ann Acad Med Singapore, 1983 Jan, 12(1), 92 - 7 Bacterial infections of the skin . I: primary and secondary infections; Chan HL; Bacterial skin infections are important to recognize because we have the means to eradicate almost all of them . Primary skin infections are mainly caused by staphylococci or streptococci . Staphylococci infections present as furuncles and carbuncles, superficial folliculitis, impetigo or rarely the Scalded Skin Syndrome . Streptococcal infections present as impetigo, ecthyma, erysipelas or cellulitis . Corynebacteria causes erythrasma, trichomycosis or pitted keratolysis . Gram-negative primary skin infections, although uncommon, may occur; bacterial cultures are generally necessary for diagnosis . Secondary bacterial infections of pre-existing wounds, burns, dermatitic skin, or retention cysts are common events. Int Arch Allergy Appl Immunol, 1983, 70(1), 34 - 9 Immunopotentiation of cell-mediated hypersensitivity by Corynebacterium parvum (Propionibacterium acnes); Maguire HC Jr et al.; We have investigated the activity of local Corynebacterium parvum (Propionibacterium acnes) as an immunopotentiator of allergic contact dermatitis (ACD) and photo-ACD in rodents . C . parvum given into the sensitization site, but not at a distance, increased the delayed-type hypersensitivity to the chemical allergen . An immunoadjuvant effect could be realized even when C . parvum was given several days after allergen; it was readily obtained in B cell-deficient mice . Cyclophosphamide pretreatment heightened the immunopotentiation seen with local C . parvum . It is unlikely that the specific immunopotentiation by C . parvum is mediated by enhanced macrophage processing of antigen, as proposed by others, since C . parvum immunostimulation occurs just as well 2 days after allergen as on the same day as allergen . We hypothesize that a major mechanism of C . parvum immunopotentiation is the inhibition by stimulated macrophages of the generation of specific T suppressor cells. Thorax, 1983 Jan, 38(1), 22 - 4 Intrapleural Corynebacterium parvum for malignant pleural effusions; Felletti R et al.; A pilot study of topical (intrapleural) treatment with Corynebacterium parvum was carried out in 10 patients with malignant pleural effusions complicating primary or secondary neoplasms and necessitating frequent thoracocentesis for symptomatic relief . The method was aspiration of all intrapleural fluid except a small portion left for dilution, and then injection of 7 mg of a preparation of Corynebacterium parvum suspended in 20 ml of normal saline solution . The treatment was repeated in each case as clinical conditions called for further thoracocentesis . In eight of these 10 patients the treatment resulted in prompt reduction of the rate of accumulation of pleural fluid and a striking change of cell sediment composition, with appreciable reduction in or complete disappearance of malignant cells and a rise in lymphocyte and neutrophil polymorph counts . The best responders were patients with primary pleural mesothelioma . Clinical improvement was evident in all responders. Histochem J, 1983 Jan, 15(1), 59 - 69 Concanavalin A receptors and capping in control and activated macrophages; Donaldson K et al.; Macrophages activated in vivo with Corynebacterium parvum and asbestos showed an increased sub-population of cells which capped spontaneously on incubation with fluoresceinated Concanavalin A compared to saline-induced control macrophages . This capping was unaffected by colchicine but was inhibited by cytochalasin B . The spontaneous capping of activated macrophages did not appear to be directly related to the total number of Concanavalin A receptors as measured by specific 125I-labelled Concanavalin A binding to activated and control macrophages . Capping also did not appear to be related to the position of Concanavalin A receptors as judged by trypsin accessibility of bound 125I-labelled Concanavalin A. Folia Microbiol (Praha), 1983, 28(1), 17 - 21 The mutagenic activity of nickel in Corynebacterium sp; Pikalek P et al.; Ni2+ ions exhibit a mutagenic effect on the bacterial strain Corynebacterium sp . 887 (hom) . The mutagenic activity of the divalent nickel was demonstrated by both the simplified fluctuation test and the so-called clone method . However, when using the clone method and low nickel concentrations the frequency of induced mutants decreases considerably as compared with the control and Ni2+ ions have an antimutagenic effect under these conditions. Can J Comp Med, 1983 Jan, 47(1), 73 - 8 An observational study of Corynebacterium bovis in selected Ontario dairy herds; Brooks BW et al.; An observational study of Corynebacterium bovis was conducted in 74 Ontario dairy herds . The levels of infection with C . bovis were 19.9, 36.2 and 85.6% at the quarter, cow and herd level, respectively . Teat disinfection was found to be the variable best able to distinguish between herds with a high or low C . bovis quarter infection rate . Mean total milk somatic cell counts for 1103 quarters and 107 cows infected with only C . bovis ranged between 150,000 and 200,000/mL and were significantly higher than for uninfected quarters or cows . The rate of infection with mastitis pathogens was not significantly different in quarters previously colonized with only C . bovis compared to previously uninfected quarters. Cancer, 1983 Jan 1, 51(1), 57 - 60 Corynebacterium parvum versus BCG adjuvant immunotherapy in human malignant melanoma; Lipton A et al.; One-hundred and sixteen patients with Stage I and Stage II malignant melanoma were randomized to treatment with either Bacillus Calmette-Guerin (BCG) (Tice) or subcutaneous Corynebacterium parvum (Burroughs-Wellcome) . Life table analysis failed to reveal a difference between these two forms of treatment in 68 Stage I patients . The relapse rate was significantly reduced in Stage II patients treated with C . parvum. Natl Inst Anim Health Q (Tokyo), 1983 Fall, 23(3), 82 - 91 A study on heifer mastitis in Japan and its causative microorganisms; Seno N et al.; Survey and bacteriological examination were conducted on heifer mastitis in Hokkaido, the northern island of Japan over a period from 1976 to 1981 . The disease occurred in heifers, mostly 13 to 18 months old, less than a half of which was pregnant in late summer or in August and September . Infection occurred predominantly in a front quarter than a rear one . Some microorganisms were isolated by the CO2 gas jet method from all the 74 secretions from the affected quarters of 67 heifers . Actinomyces pyogenes ( Corynebacterium pyogenes) was isolated from 49 secretions (66.2%), forty-six of which were involved in mixed infection with other microorganisms, including Peptococcus indolicus that was found in 41 secretions . Streptococcus dysgalactiae was isolated from 13 secretions, from nine of which were obtained pure cultures . The microorganisms harbored in secretion were much more closely associated simultaneously with A . pyogenes and P . indolicus than with A . pyogenes alone or a combination of A . pyogenes and any other microorganism than P . indolicus . This is the first report that P . indolicus was isolated from heifer mastitis in Japan . The "score" used for the expression of quality of milk secretion seemed to be useful for the clinical diagnosis of heifer mastitis . The disease in Hokkaido may be etiologically identical with summer mastitis found in the northern European countries. Invasion Metastasis, 1983, 3(1), 32 - 51 Changes in anatomical distribution of tumour lesions induced by platelet-active drugs; Willmott N et al.; To examine the effect of platelet-active drugs on the spread of blood-borne tumour cells, two murine tumours, sarcoma 180 (S-180) and TLX-5 lymphoma, were selected . Following intravenous (IV) injection into CBA mice the former elicited thrombocytopenia and formed discrete pulmonary tumours, whereas the latter failed to elicit thrombocytopenia and formed discrete tumours in all visceral organs examined except the lungs . S-180 cells were injected IV into mice pre-treated with RA233 (known to prevent thrombocytopenia and thrombus formation) and TLX-5 cells were injected IV into mice pre-treated with Corynebacterium parvum (known to induce thrombocytopenia and thrombus formation) . RA233 pre-treatment did not change survival time or incidence of S-180 pulmonary tumours but did result in a higher incidence of extrapulmonary tumours and a lower tumour cell burden immediately after injection . Pre-treatment with C . parvum resulted in a higher TLX-5 tumour cell burden but not discrete tumours in the lungs . On the basis of known drug activities it is proposed that thrombocytopenia induced in these experiments is in part a reflection of thrombus formation in the lungs which influences the speed of passage of tumour cells through capillaries . In some cases this may lead to a changed anatomical distribution of tumour lesions. Arch Immunol Ther Exp (Warsz), 1983, 31(5), 611 - 3 Antibacterial activity of Wratizolin; Mulczyk M; Wratizolin in the concentration of 1-10 micrograms/ml was found to inhibit the growth of Gram-positive bacteria such as: Staphylococcus, Streptococcus, Sarcina, Corynebacterium, and some representatives of aerobic bacilli . Gram-negative bacteria of Enterobacteriaceae and Pseudomonas were not sensitive to Wratizolin even in the concentration of 100 micrograms/ml. Arch Dermatol Res, 1983, 275(4), 251 - 4 Effect of occlusion on resident flora, skin-moisture and skin-pH; Hartmann AA; The effects of a 3-day test of an occlusion dressing of the forearm on the resident flora of the skin, relative skin-moisture and skin-pH were studied in 26 male and female volunteers . The geometrical mean values of coagulase-negative Staphylococci and Corynebacterium species increased five and four logs and decreased 1 day post occlusion only two logs . Relative skin-moisture increased from 20% to 75% under occlusion and decreased to 5% 24h after removal . Skin-pH increased from 4.9 to 7.1 and decreased to pH 5.2 . Investigations of the resident flora should be made, if the influence of external, not antimicrobial active agents, is to be examined, because changes in the substrate can cause secondary changes in the resident flora. Scand J Infect Dis Suppl, 1983, 40, 7 - 10 "Non-specific" vaginitis: a non-entity; Gardner HL; The author alleges that any knowledgeable physician owning a vaginal speculum and a microscope should rarely find the need for using the diagnosis, "non-specific" vaginitis, and that its too frequent use might well imply carelessness, indifference or a failure to employ available diagnostic methods . The suggestion is made that if the term "non-specific" vaginitis is to be retained in gynecologic nomenclature it should be assigned its rightful position and should include only those conditions without assignable etiology . The evidence shows that Gardnerella vaginalis (Haemophilus vaginalis, Corynebacterium vaginale) vaginitis is a precisely defined, specific vaginal infection, that the disease is sexually transmitted and that it accounts for most vaginitides previously classified as "nonspecific". Cancer Immunol Immunother, 1983, 15(3), 172 - 7 Intratumoral BCG and Corynebacterium parvum therapy of canine mammary tumours before radical mastectomy; Parodi AL et al.; In two parallel studies, bitches with mammary tumour received single intralesional injections of BCG (1 mg: 10(7) living bacteria) and Corybacterium parvum (10(9) killed bacteria) (53 bitches) or C . parvum alone (129 bitches) at the same dosage . Control groups received injections, following the same protocol, of 1 ml BCG suspension medium diluted in saline in the first study (51 bitches) or no injections at all (120 bitches in the second study) . A block dissection, including mammary tumours, adjacent mammary glands, and regional lymph nodes, was performed 2 weeks later in all animals . On the basis of histologically confirmed malignant tumours, 48 bitches (25 treated by-immunotherapy and 23 controls) in the first study and 67 bitches (30 treated by immunotherapy and 37 controls) in the second study remained for postsurgical follow-up . The clinical tolerance of the treatment was generally good . No significant differences were found in cumulative survival rates between treated and control group in either studies. Cancer Immunol Immunother, 1983, 16(2), 88 - 92 Adjuvant immune stimulation with Corynebacterium parvum during maintenance chemotherapy of acute myeloid leukemia . A prospective randomized study; la Cour Petersen E et al.; Of 93 consecutively treated patients with acute myeloid leukemia 36 (39%) achieved complete remission (CR) . Thirty-five patients were randomized to receive either maintenance chemotherapy alone (C) or a combination of active nonspecific immunotherapy with Corynebacterium parvum and chemotherapy (C + I) . Maintenance therapy was given monthly for 1 year or until relapse . The median survival time was 21 months for patients treated with chemotherapy alone, compared with 30 months for patients treated with chemotherapy and immunotherapy . The median remission duration was 15 months for patients treated with chemotherapy, compared with 18 months for chemotherapy and immunotherapy group . While no statistically significant difference in remission duration or survival time could be attributed to the use of immune stimulation, a plateau of 40% long-term time survivors was defined in the chemotherapy and immunotherapy group . Age and sex were found to be the major prognostic factors for achievement of CR . No difference was found in remission duration or survival between the two different induction schedules . Neither did the morphological subtype of AML (FAB classification) or the leukocyte count at diagnosis correlate with remission rate or survival. Microbiol Immunol, 1983, 27(8), 663 - 71 Growth of the surface of Corynebacterium diphtheriae; Umeda A et al.; Surface structure and growth of the surface of Corynebacterium diphtheriae mitis strain were investigated by scanning electron microscopy and the immunofluorescence technique . The surface of the cell revealed by the scanning electron microscope showed a few elevated circular zones which encompassed the cell . The cell diameter increased at this zone and this gave the club-shaped appearance to this species . The cell surface labeled with specific antibodies against the whole bacterial cell and tagged with ferritin remained at a constant length during cell division cycles and the new cell surface emerged from the polar ends of the cell . This new wall surface was completely devoid of the ferritin particles indicating that the cell wall component on the old preexistent wall was completely conserved . A similar finding was obtained by immunofluorescence microscopy . C . diphtheriae, unlike Bacillus spp., showed apical growth as has been observed in fungal cells. Arzneimittelforschung, 1983, 33(4), 524 - 8 An evaluation of the antifungal effect of bifonazole on Torulopsis glabrata and Candida albicans under various in vitro test conditions; Barug D et al.; 1-{(4-Biphenylyl)-phenylmethyl}-1H-imidazole (bifonazole, Bay h 4502, Mycospor) showed in vitro significant inhibitory activity against Torulopsis glabrata, Candida albicans, Pityrosporum ovale, Corynebacterium acnes and Staphylococcus epidermidis . The antifungal activity of bifonazole against T . glabrata and C . albicans varied with the in vitro test conditions . There was a tendency for minimal inhibitory concentrations to increase as fungal inoculum size was increased and as incubation time was prolonged . For T . glabrata, but not for C . albicans, minimal inhibitory concentrations were lower in liquid than on solid culture media . The antifungal activity was less pronounced at low pH values . Because of these variations laboratory tests for the in vitro determination of antifungal sensitivities should be carried out under standardized test conditions such as small inocula, a limited incubation period and appropriate culture media . The solubility of bifonazole in aqueous solution is very low . In addition, more bifonazole dissolves at low than at high pH values. Cancer Immunol Immunother, 1983, 16(2), 114 - 6 A phase-II trial of Corynebacterium parvum as adjuvant to surgery in the treatment of operable lung cancer; Woodruff M et al.; A phase-II randomized trial has been undertaken in 49 patients with operable lung cancer, to determine the effect of a single IV infusion of killed C . parvum vaccine as an adjuvant to surgery . The number of patients was insufficient to provide a decisive result, but analysis 6 years after the last patient was admitted shows that the adjuvant therapy certainly did not shorten, and may well have prolonged, survival . Of the patients with squamous cell carcinoma who were alive 1 year after operation all except one in the C . parvum-treated group were alive 4 years later, whereas five in the control group died during this interval . Judgement concerning the value of IV administration of CP as adjuvant therapy in patients with operable lung cancer should be deferred until further evidence is available. J Cancer Res Clin Oncol, 1983, 106(1), 36 - 43 The seeding of a transplanted murine leukemia and its influence on hemopoietic stem cells and immune function of the host; Seidel HJ et al.; A butylnitrosourea-induced murine T-cell leukemia, L40, was transplanted in BDF1 mice; 1 X 10(3) cells killed all recipients after conditioning with 400 rad, whereas 1 X 10(5) were needed with normal recipients . No leukemic cells could be detected by transplantation or cytogenetic analysis in the femur or the spleen at day 6 after L40 inoculation and, at day 11, leukemic cells were found in one out of two experiments, more if the host had been irradiated . Up to day 17, when leukemic cells were present, the CFU-S and CFU-C content of the femur was normal, but later a loss was observed with an increase in the enlarging spleen . Lymphocyte-stimulation assays with spleen cells gave normal results up to day 17, but later the 3H-thymidine uptake of stimulated T and B cells was reduced . The NK-cell activity with and without stimulation by Corynebacterium parvum in the spleen began to fall at day 17 and was absent later; this loss was also observed with peritoneal exudate cells . In vitro mixing experiments of L40 cells with normal spleen cells showed "cold target inhibition" by L40 cells in the NK-cell assay as well as interference with the lymphocyte stimulation. Microbiol Immunol, 1983, 27(3), 273 - 82 Increased susceptibility to Escherichia coli infection in mice pretreated with Corynebacterium parvum; Yoshikai Y et al.; The contribution of activated macrophages to protection against Escherichia coli was studied in mice treated intravenously with Corynebacterium parvum 7 days before infection . C . parvum-treated mice showed increased phagocytic activity and enhanced resistance to Listeria infection . In contrast, these mice showed increased susceptibility to a subsequent challenge with E . coli that correlated closely with a reduction in the LD50 of lipopolysaccharide (LPS) in these mice . The peritoneal macrophages obtained from C . parvum-treated mice had a strong ability to phagocytize and kill E . coli in in vitro experiments . A rapid decline in the number of bacteria in the liver of C . parvum-treated mice was observed in the early period of infection . However, the number of bacteria in liver and spleen increased progressively to a lethal dose from 6 hr after infection . At this time, a significant increase in beta-glucuronidase, a lysosomal acid hydrolase, was found in the serum of these mice . In vitro experiments revealed that the peritoneal macrophages from C . parvum-treated mice were highly susceptible to the cytotoxic effect of LPS after 6 hr of incubation with LPS . It is suggested that the hypersensitivity of activated macrophages to the cytotoxic effect of endotoxin derived from E . coli may be partly responsible for the increased susceptibility of C . parvum-treated mice to E . coli infection. Med Cutan Ibero Lat Am, 1983, 11(1), 61 - 4 {Pitted keratolysis . Presentation of 2 cases with culture of lesions positive for bacteria of the genus Corynebacterium}; Valente NY et al.; The authors briefly review the literature about Pitted keratolysis emphasizing the etiopathogenesis . They report two cases of the disease in which the lesions were investigated for the etiologic agent . The search for Fungi using direct exam and culture in Sabouraud's medium was negative . Gram, Neisser and Neisser-Gins' stains, culture in BHI medium and the biopsy were positive for bacteria of the Corynebacterium genus . These results are discussed. Cancer Immunol Immunother, 1983, 15(2), 149 - 54 Cellular suppression of murine ADCC and NK activities induced by Corynebacterium parvum; Milisauskas VK et al.; Administration of a single dose of C . parvum (CP) induces depression of splenic NK activity in mice after a lag period of 3-5 days and this depression lasts about 2 weeks . The depressed levels of NK activity noted in this study depended on time of CP administration and were associated with the induction of suppressor cell activity . Neonatally thymectomized or sublethally irradiated mice had unimpaired ability to generate suppressor cells following CP treatment . Depletion of adherent/phagocytic cells by carbonyl iron plus magnetism, Sephadex G-10 filtration, or both neither enriched NK activity nor removed suppressor activity from the spleens of CP-treated mice . Antibody-dependent cellular cytotoxicity (ADCC) against lymphoma targets was also depressed in CP-treated mice, accompanied by a concomitant appearance of suppressor cells that interfere with ADCC at the effector level. Vet Med Nauki, 1983, 20(1), 24 - 9 {Experimental mastitis in cows caused by Staphylococci, Streptococci and Corynebacteria}; Orosko E et al.; Mastitis was experimentally induced in seven cows of the Black-and-white breed through the intramammary or i/v application of bacterial cultures of the encapsulated variant of Staph . epidermidis as well as of Str . agalactiae and Cor . pyogenes . The disease ran a course with high body temperature, strongly manifested inflammatory changes in the mammary gland, and altered phagocytic activity . It was found that the introduction into the mammary gland of a 'stable-specific' bovine blood serum in combination with the preparation nitrofuridine (a Shiff base of the 5-nitrofurfurol with sulfaguanidine) which boosts the phagocytic activity, had produced a therapeutic effect. J Reticuloendothel Soc, 1983 Jan, 33(1), 35 - 46 Induction of resistance to ectromelia virus infection by corynebacterium parvum in murine peritoneal macrophages; Cohen DA et al.; An in vitro model has been developed to study the replication of ectromelia virus in murine macrophages (M phi) . Infection of mineral oil-elicited peritoneal M phi cultures with either the virulent (Moscow) or attenuated (Hampstead) strain of ectromelia virus led to productive infections . The kinetics of virus synthesis was similar to those seen following infection of murine fibroblasts . In contrast, peritoneal M phi s activated by intraperitoneal injection of Corynebacterium parvum vaccine were found to be totally refractory to infection by the attenuated strain and significantly more resistant to the virulent strain of ectromelia virus . Administration of C . parvum doses as small as 7 micrograms were sufficient to induce antiviral activity . M phi resistance became maximal at 5-9 days after C . parvum administration; however, M phi resistance was unstable during in vitro culture . Decay of antiviral activity was detected within the first 24 hr of culture and complete virus susceptibility returned after 5 days in culture . Peritoneal exudate cells (PEC) from C . parvum-immunized mice could induce resistance in susceptible M phi cultures during overnight cocultivation . In addition, cell-free culture supernatants from C . parvum-immune PEC could also induce resistance in susceptible M phi cultures, suggesting that a soluble factor, induced by C . parvum immunization and possessing interferon activity, may account for the intrinsic resistance to ectromelia virus by activated M phi s. Nat Immun Cell Growth Regul, 1983-84, 3(1), 22 - 33 Regulation of natural killer cell activation: implementation for the control of tumor metastasis; Hanna N; The cellular interactions that regulate natural killer (NK) cell-mediated cytotoxicity and antimetastatic activity following treatment with biological response modifiers (BRM) were studied . The transient activation of NK cells by a single injection of Corynebacterium parvum is followed by a refractory period during which a second injection of BRM fails to stimulate the already depressed NK cell activity . During this hyporesponsive period, the in vivo NK cell-dependent BRM-induced antimetastatic activity is markedly reduced and cannot be enhanced by multiple injections of BRM . A correlation exists between the generation of hyporesponsiveness to NK cell activation and the activation of suppressor macrophages by C . parvum . BRM that selectively activate NK cells without subsequently activating suppressor macrophages do not induce hyporesponsiveness to further activation of NK cells in vivo and, when given in multiple injections, retain the ability to inhibit hematogenous tumor metastasis. Nat Immun Cell Growth Regul, 1983-84, 3(3), 134 - 42 Protection by polyI:polyC against infection with herpes simplex virus in mice pretreated with Corynebacterium parvum; Storch E et al.; The effect of Corynebacterium parvum on the protection by polyinosinic-polycytidylic acid (polyI:polyC) against lethal infection with Herpes simplex virus type 1 (HSV) was studied in mice . Pretreatment with C . parvum resulted in prolonged survival times in all experiments . One third of the mice survived an infection with 100 LD50, whereas all mice died when treated with polyI:polyC alone . Increased protection was observed up to 6 weeks after pretreatment and only seen when both C . parvum and polyI:polyC were given at the same site of injection (intraperitoneally) . Protection against HSV correlated with increased interferon (IFN) activities induced by polyI:polyC in the peritoneal cavity of C . parvum-pretreated mice . In these mice, natural killer cell activity of peritoneal exudate cells (PEC) was also augmented in response to polyI:polyC . Protection was markedly decreased by intraperitoneal injection of silica or of an antiserum against murine IFN . It appears that increased local levels of IFN presumably produced by macrophages in response to polyI:polyC in C . parvum-pretreated mice play the major role in the antiviral defence in our model and that activation of NK cells may be a secondary effect of IFN. Cancer Immunol Immunother, 1983, 16(1), 35 - 9 Antitumour activity of endotoxin, concanavalin A and poly I: C and their ability to elicit tumour necrosis factor, cytostatic factors, and interferon in vivo; Bloksma N et al.; Concanavalin A, endotoxin, poly I: C, and tumour necrosis serum (TNS) were compared for antitumour activity against Meth A sarcoma transplanted in syngeneic BALB/c mice and their capacity to induce tumour necrosis factor (TNF), heat-stable cytostatic factors, and heat-labile interferon in the blood of normal and Corynebacterium parvum-pretreated mice . All the agents induced hyperemia and inhibition of mitosis at 4 h, and by 24 h many tumours had a dark necrotic centre . Subsequent tumour growth was inhibited and in some of the treated mice tumours regressed completely . Poly A: U and normal mouse serum did not induce regression and their effects were less marked in all other respects, suggesting that these events may be linked . The necrotizing effects of concanavalin A and poly I: C are unlikely to be mediated by TNF, because neither agent could mimic endotoxin in eliciting RNase-resistant necrotizing and regressing activity in the serum of mice pretreated with C . parvum . Poly I: C did not induce strong cytostatic activity in the sera of C . parvum-treated mice, and for this and other reasons these factors are unlikely to be responsible for the observed effects . Concanavalin A, endotoxin, and poly I: C induced high levels of serum interferon but purified interferon had only weak antitumour activity in the Meth A system, suggesting that interferon may not be the mediator . From these and other data it is concluded that there is no clear relationship between the capacity of the agents to induce tumour necrosis and their capacity to elicit TNF, cytostatic factors, and interferon. Ann Immunol (Paris), 1983 Jan-Feb, 134C(1), 159 - 64 Effects of various coryneforms on mononuclear phagocyte system function and on production of tumour necrosis factor in mice; Bloksma N et al.; Vaccines of 6 strains of the genera Corynebacterium and Propionibacterium were tested for induction of hepatosplenomegaly and stimulation of clearance of injected colloidal carbon and viable Listeria monocytogenes . These effects were compared with the ability of these strains to support the endotoxin-induced liberation of tumour necrosis factor, interferon and heat-stable cytostatic factors in mouse circulation . Five strains caused good stimulation of macrophage functions and induced high levels of all factors . One strain was nearly lacking in macrophage stimulatory capacity and also failed to support factor production . These data are discussed in relation to the production mechanisms of the factors. Southeast Asian J Trop Med Public Health, 1982 Dec, 13(4), 568 - 74 Epidemic leg ulcers in Thailand; Kotrajaras R et al.; In 1981, two outbreaks of chronic leg ulcers occurred in central Thailand and affected thousands of persons . The lesions were characterized by granulomatous bases with erythematous edges and purulent slough . They were about 1 cm in diameter with irregular shapes . The ulcers lasted two weeks to one month . Ninety percent of the lesions were found on the lower extremities . The outbreak in Nakorn Pathom province occurred in fruit yards . Most of patients were gardeners and students . The outbreak in Ratchaburi province occurred on a sugar cane plantation . The age group of 5-19 years had the highest attack rate in all areas, and there was no significant difference between the attack rates in males and females . The peak incidence occurred in the rainy season with an abrupt decrease at the onset of the dry season . It is hypothesized that trauma precedes the occurrence of the leg ulcer and that a small fly may be a mechanical vector of the causative organism . The organism may be corynebacterium pyogenes, which is a pathogen of certain livestocks and is found in soil . Further studies are planned. Clin Exp Immunol, 1982 Dec, 50(3), 487 - 94 The effect of intravenous Corynebacterium parvum on gut associated mononuclear phagocytes in normal and tumour bearing rats; Souter RG et al.; Corynebacterium Parvum, which has been used in the treatment of human colorectal cancer, probably exerts its action through cells of the mononuclear phagocyte system (MPS) . In this study the effect of systemically administered C . parvum has been measured on gut associated MPS cells in normal and colorectal cancer bearing rats . MPS cells are not normally found in samples of lymph obtained after cannulation of the thoracic duct (TDC) . However, after total extirpation of the mesenteric lymph nodes, TDC yields samples in which up to 5% of the total cell population appear to be MPS cells . This procedure has been carried out in adult Wistar rats enabling an in vivo study to be made on the effect of C . parvum treatment on the effluent gut cells . Measurements have been made both of the number of cells found in thoracic duct lymph and of their capacity to phagocytose sensitized sheep red blood cells . These measurements were repeated in a mesenteric lymphadenectomized group of rats which had also undergone induction of colonic cancer using dimethylhydrazine . C . parvum treatment did not effect total cell, or phagocyte numbers in thoracic duct lymph (TDL) . However rats with colonic cancers showed a marked reduction in the numbers of phagocytic cells in TDL irrespective of C . parvum treatment. Am J Vet Res, 1982 Dec, 43(12), 2244 - 7 Effect of Corynebacterium parvum on bone marrow macrophage colony production, peripheral blood leukocytes, and histologic changes of tissues in calves; Al-Izzi SA et al.; An IV injection of formalin-killed Corynebacterium parvum in calves did not cause a marked increase in the number of bone marrow macrophage colonies or peripheral blood monocytes, granulocytes, or lymphocytes . In treated calves, the spleen increased in weight and there were macrophage infiltrations in liver, lungs, spleen, and lymph nodes . Lymphoid hyperplasia was observed in bronchial-associated lymphoid tissue, cortical areas of the thymus, and in primary and secondary follicles and the paracortical area of lymph nodes. Am J Vet Res, 1982 Dec, 43(12), 2143 - 6 Dynamics of nonclinical bovine intramammary infections with major and minor pathogens; Rainard P et al.; Udder infections were recorded in 3 herds throughout a lactation period with bacteriologic examination being done at 3-week intervals . New infection rates and levels of infection at calving differed significantly (P less than 0.001) between herds, but persistence of infection did not . Of the 324 infections, 80.5% lasted up to drying off . Of quarters infected with major pathogens, 16.8% eliminated their infection (63% became reinfected); 20.8% of quarters infected with minor pathogens eliminated their infection (43% became reinfected) . Significant differences in persistence of infections, quarter clearing rate (defined as the rate at which infected quarters become and remain noninfected) and ability to give way to and to take place of a preexistent infection, did not occur between Corynebacterium bovis and major pathogens . Though 66% of coagulase-negative staphylococci infections persisted up to drying off, they disappeared more frequently (P less than 0.01). Br J Exp Pathol, 1982 Dec, 63(6), 639 - 43 Serum biochemical changes in c . parvum-injected mice bearing the Landschütz ascites carcinoma; McIntosh LC et al.; Mice injected i.p . with 1.4 mg Corynebacterium parvum (C . parvum) displayed minor transient impairment of hepatic function, as evidenced within 5-8 days by significant elevations in serum aspartate aminotransferase and reductions in total protein, albumin and alkaline phosphatase . Inoculation of animals with the Landschutz ascites carcinoma (LAC) caused similar but more marked and prolonged liver injury with serological evidence of nephrotoxicity at advanced stages of tumour growth . Injection of C . parvum 24 h before tumour had no further influence on these serological changes observed in animals given tumour alone . No evidence was obtained to support histological findings that the LAC inhibits the granulomatous inflammatory response to C . parvum in mouse liver. J Natl Cancer Inst, 1982 Dec, 69(6), 1337 - 42 Immunoadjuvant effects of Blastomyces dermatitidis against EL 4 lymphoma in C57BL/6J mice; McDaniel LS et al.; The ability of thimerosal-killed Blastomyces dermatitidis yeast cells, which greatly enhance the cell-mediated immune response in C57BL/6J mice, to act as an immunopotentiator against EL 4 lymphoma was investigated . Mice treated with yeast cells were protected from as many as 10(4) tumor cells . Complete suppression of tumor growth was observed in treated animals that received ip injections of 10(2) or 10(3) tumor cells . The mice, however, were not immune to further EL 4 lymphoma cell challenge . The lack of tumor-specific immunity indicated nonspecific suppression of tumor growth probably by macrophages . Ten days after treatment, the peritoneal macrophages from mice that showed complete tumor suppression were tested for their ability to prevent in vitro tumor cell proliferation . These macrophages demonstrated 90% inhibition of {3H}thymidine incorporation by EL 4 tumor cells at a 100:1 effector-to-target cell ratio . Macrophages from B . dermatitidis-treated animals exhibited a twofold increase in specific lysis of EL 4 at 10 and 15 days compared to resident macrophages . Spleen and lymph node cells from protected animals showed no cytotoxic activity against EL 4 in a 51Cr release assay . Treatment of tumor-bearing mice with a single dose of B . dermatitidis was effective only if administered within 24 hours of tumor establishment . These results demonstrated that nonviable B . dermatitidis prohibits the growth of EL 4 under conditions where Corynebacterium parvum fails to do so. J Gen Microbiol, 1982 Dec, 128 (pt 12), 2851 - 5 Physiological and nutritional features of Corynebacterium pyogenes; Reddy CA et al.; Growth and acid metabolic products were similar when Corynebacterium pyogenes was grown aerobically or anaerobically in a serum-free medium (SFM) . This indicated that C . pyogenes obtains energy for growth primarily by fermentative metabolism even under aerobic growth conditions . Growth yield was reduced by 90% in SFM minus glucose, 50% in SFM minus NaHCO3, 90% in SFM minus yeast extract, 100% in SFM minus Trypticase and yeast extract, and 30% in SFM minus haemin or Trypticase . Growth was not detectable when a known mixture of amino acids, vitamins, and nucleic acid bases were substituted for Trypticase and yeast extract in SFM; addition to the latter medium of a peptide source such as Trypticase or casitone supported good growth of the organism . When NaHCO3 was omitted from SFM and dissolved CO2 in the medium was rigorously excluded, growth was undetectable indicating that C . pyogenes has an obligate requirement for CO2 for growth . Succinate, formate and acetate were the major fermentation products in SFM, whereas in SFM minus HCO-3 or haemin, lactate was the major product and only small quantities of other acids accumulated. J Gen Microbiol, 1982 Dec, 128 (pt 12), 2857 - 63 Effects of Corynebacterium parvum on Escherichia coli infection in mice; Yoshikai Y et al.; The contribution of activated macrophages to protection against Escherichia coli was studied in mice . Mice treated intraperitoneally with killed Corynebacterium parvum organisms 1 d prior to challenge showed an increased resistance to intraperitoneal infection with E . coli; the predominant leucocytes in the peritoneal cavity of these animals were polymorphonuclear cells . However, treatment with C . parvum 4 d prior to challenge induced mainly activated macrophages in the peritoneal cavity and host resistance to the infection was not increased . Activated macrophages from such mice showed both enhanced phagocytic activity in vivo and a high degree of intracellular killing of E . coli in vitro . At the same time these cells became more susceptible to the cytotoxic effect of endotoxin . After challenge with E . coli there was a marked decrease in the number of peritoneal macrophages in mice that were treated with C . parvum 4 d prior to challenge . Increased susceptibility of activated macrophages to the cytotoxic effect of endotoxin could explain the absence of enhanced resistance to E . coli infection in such animals. J Am Acad Dermatol, 1982 Dec, 7(6), 787 - 91 Pitted and ringed keratolysis . A review and update; Zaias N; The varied clinical manifestations of pitted keratolysis in the soles and of ringed keratolysis in the palms are presented . The etiologic agent, a species of Corynebacterium, has been proved to produce similar lesions in experimental patients . The histopathology in the stratum corneum and its treatment are also summarized. Cancer, 1982 Dec 1, 50(11), 2295 - 300 Methotrexate alone or with regional subcutaneous Corynebacterium parvum in the treatment of recurrent and metastatic squamous cancer of the head and neck; Vogl SE et al.; Patients with advanced, incurable squamous cancer of the head and neck were randomly assigned to treatment with weekly methotrexate alone or methotrexate with Corynebacterium parvum given subcutaneously in weekly bilateral doses in sites around the neck . The addition of C . parvum did not alter the response rate, response duration, survival (either median or long-term) or severity of toxic effects compared to treatment with methotrexate alone . Response rates were higher for patients without distant metastases, ambulatory patients, and those younger than age 65 years . Median survival was improved for responders to chemotherapy and for those initially ambulatory . C . parvum given subcutaneously has no place in the treatment of far advanced cancer of the head and neck. Antiviral Res, 1982 Dec, 2(6), 361 - 7 Effect of cyclosporin A on the production of interferon by human peripheral blood leukocytes in vitro; Abb J et al.; Cyclosporin A (CsA) was assessed for its effect on the production of antiviral activity by human peripheral blood leukocytes (PBL) . CsA markedly reduced the production of interferon-gamma (IFN-gamma) in response to stimulation with lectin mitogens, bacterial products, alloantigens, or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) . CsA-mediated suppression of IFN-gamma secretion was dose-dependent and did not result from a shift of kinetics of the production of antiviral activity . The production of IFN-alpha in response to stimulation with Corynebacterium parvum (CP), viruses, and synthetic polynucleotides was not affected by the addition of CsA . These findings confirm earlier observations that CsA predominantly acts on T lymphocyte function . CsA may prove a valuable agent to study the role of IFN-gamma in the pathogenesis of virus-associated malignant lymphoproliferative disease. J Natl Cancer Inst, 1982 Dec, 69(6), 1293 - 7 Accessory cell function in tumor-bearing mice and effects of Corynebacterium parvum; Okuda S et al.; Primary in vivo production of antibody to sheep red blood cells (SRBC) was consistently suppressed in EL 4 tumor-bearing C57BL/6 mice, but the secondary response was not suppressed . This suppressed primary in vivo production of antibody was partially restored by systemic administration of Corynebacterium parvum . For investigation of the mechanism of the immunosuppression in tumor-bearing mice and the effects of C . parvum, the accessory cell function of adherent cells from tumor-bearing mice and C . parvum-treated tumor-bearing mice in in vitro cultures was studied . Peritoneal and splenic cells from tumor-bearing mice were less efficient in promoting in vitro production of antibody to SRBC by macrophage-depleted normal nonadherent cells than the adherent cells from normal mice . C . parvum treatment restored the accessory cell function of splenic adherent cells from tumor-bearing mice but not that of peritoneal cells . Furthermore, adherent cells from tumor-bearing mice did not show suppressive activity against the in vitro plaque-forming cell response. J Invest Dermatol, 1982 Dec, 79(6), 385 - 8 Modulation of suppressor mechanisms in allergic contact dermatitis: 5 . Evidence that inhibition of suppressor T lymphocytes by Corynebacterium parvum is mediated by interferon; Knop J et al.; Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynebacterium parvum or C . parvum serum (C.p.s.) of mice treated 24 hr before with C . parvum inhibited the suppressor T-lymphocyte (Ts-cell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v . injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell) . In the present investigation we further analyzed the factor responsible for Ts-cell inhibition . Treatment of the C.p.s . with sheep-antimouse interferon (IFN) globulin neutralized its Ts-cell inhibitory effect . Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2 hr after i.v . application of a dose of DNBSO3 inducing tolerance had a similar Ts-cell inhibitory effect as observed with C.p.s . Injection of an electrophoretically pure alpha- and beta-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of Ts-cells by DNBSO3 i.v . This result is highly suggestive that the Ts-cell inhibitory factor in serum of C . parvum-treated mice is IFN and it shows that Ts-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN . This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense. J Med Microbiol, 1982 Nov, 15(4), 485 - 92 Classification of Corynebacterium species from axillary skin by numerical analysis of electrophoretic protein patterns; Jackman PJ; The genus Corynebacterium, defined by the presence of mesodiaminopimelic acid, arabinose and corynomycolic acids in the cell wall, contains a very diverse group of organisms according to the results of numerical analysis of protein patterns; 13 groups were distinguished in this study . Strains isolated from axillary skin and hair included representatives of several groups but many strains were placed in groups 1 and 6A . Neither of these groups contained any reference strains and may constitute hitherto undescribed species . The reference strains of C . diphtheriae formed a coherent group not closely related to any non-pathogenic Corynebacterium species. Ann Immunol (Paris), 1982 Nov-Dec, 133D(3), 305 - 11 Corynebacterium parvum: antibodies measured with the enzyme-linked immunosorbent assay (ELISA) in normal human sera and sera from cancer patients undergoing treatment; Ruitenberg EJ et al.; An enzyme-linked immunosorbent assay (ELISA) was developed to monitor the antibody response to Corynebacterium parvum during cancer immunotherapy . Firstly, in sera from 176 clinically healthy individuals not treated with C . parvum, elevated ELISA extinction values were observed from the age of 11 years onwards for both sexes; these high values were probably due to preexisting antibodies to C . parvum or related organisms . Consequently, in order to evaluate C . parvum antibody levels after treatment it was essential to compare post- with pre-treatment sera . Next, a series of sera from 20 male patients with inoperable squamous cell carcinoma of the bronchus were tested . They originated from three different groups . The first group received both chemotherapy (cyclophosphamide) and immunotherapy (C . parvum), the second group cyclophosphamide alone and the third group neither of these agents . Compared to pre-treatment values, an increase in extinction values was already observed as from day 12 of C . parvum treatment; cyclophosphamide did not influence the extinction values . Anti