J Neuropathol Exp Neurol, 1981 Sep, 40(5), 526 - 36 Immunity to transplantable nitrosourea-induced neurogenic tumors . I . Potentiation of tumor immunity with Corynebacterium parvum; Cravioto HM et al.; Various injection schedules of C . parvum and tumor cells of the nitrosourea-induced malignant neurinoma, TR-481, were used to induce tumor immunity in syngeneic CDF rats . Although subcutaneous injection of the poorly immunogenic TR-481 cells alone or with C . parvum caused retardation of growth of 2 x 10(5) TR-481 cells injected 1-3 weeks later, no significant difference in tumor size or incidence was obtained, as judged by tumor growth at 8 weeks . In contrast, injection of TR-481 with C . parvum into C . parvum-presensitized rats caused a more significant degree of tumor immunity with complete inhibition of the challenge tumor growth in 17-33% of the animals . Repeated subcutaneous injection of gamma-irradiated TR-481 tumor cells mixed with C . parvum also proved effective, resulting in absence of tumor growth in 40% of the rats . Tumor immunity was specific, since growth of an unrelated tumor was unaffected . It is suggested that local immunological reactivity to C . parvum in the immunizing tumor promotes development of specific tumor immunity. Yale J Biol Med, 1981 Sep-Oct, 54(5), 367 - 79 Specific and nonspecific immunotherapy as an adjunct to curative surgery for cancer of the lung; Hollinshead AC et al.; Attempts to improve survival following curative surgery for non-small-cell lung cancer are reviewed . Most of these approaches have been designed to stimulate the resistance of lung cancer patients in a non-specific fashion . Living bacteria or products of dead bacteria have been given as adjunctive treatment . Various routes have been used; oral, intradermal, subdermal, or intrapleural, with either BCG or Corynebacterium parvum . No reproducible benefit has been observed . Levamisole has not been proven to be useful . Trials have yet to be completed to confirm the use of thymosin fraction V for small cell carcinoma in improving the effectiveness of chemotherapy . A pilot trial using specific active immunotherapy is described . Prolongation of survival four years after closure of the trial in those patients immunized, compared with non-immunized patients, has prompted two further clinical trials . A small trial has confirmed the effectiveness of specific immunotherapy as adjunctive therapy for squamous cell carcinoma . A large multicenter trial in Canada and the United States should be completed and open to analysis in 1984 and may shed light on the role of tumor-associated antigens in stimulating specific resistance to lung cancer. J Exp Med, 1981 Sep 1, 154(3), 621 - 30 Mechanisms of anti-tumor action of Corynebacterium parvum . II . Potentiated cytolytic T cell response and its tumor-induced suppression; Mills CD et al.; It was shown that subcutaneous implantation of P815 tumor cells admixed with Corynebacterium parvum resulted in the emergence of a tumor that grew for 9-10 d and then regressed . The onset of tumor aggression was preceded by the substantial generation in the draining lymph node and spleen of T cells capable of specifically lysing P815 target cells in vitro . The finding that the magnitude of this cytolytic response was much greater than the cytolytic response to a control tumor that grew progressively is consistent with the hypothesis that the anti-tumor action of C . parvum is based on its capacity to augment the production of T cells sensitized to tumor-specific transplantation antigens . This adjuvant action of C . parvum was revealed by additional experiments in which irradiated, nonreplicating tumor cells were substituted for living tumor cells in the admixture . The results support the conclusion that the potentiated cytolytic response to subcutaneous injection of an admixture of irradiated tumor cells and C . parvum is responsible for the ability of this admixture to cause the regression of a test tumor growing at a distant site . Finally, it was shown that the failure of the therapeutic admixture to cause the regression of distant test tumors above a certain size was associated with a failure of the admixture to cause a potentiated, anti-tumor cytolytic response . We discussed the possibility that this failure was caused by the presence of a tumor-induced state of immunosuppression. J Exp Med, 1981 Sep 1, 154(3), 609 - 20 Mechanisms of anti-tumor action of Corynebacterium parvum . I . Potentiated tumor-specific immunity and its therapeutic limitations; Dye ES et al.; The anti-tumor mechanism in mice induced by a subcutaneous injection of syngeneic tumor cells admixed with Corynebacterium parvum was investigated . When mice were implanted in a hind footpad with x 2 1096) tumor cells admixed with 100 microgram C . parvum, the tumor that emerged grew progressively for about 9 d and then underwent progressive and complete regression . It was found that this C . parvum-induced regression was associated with the acquisition of a systemic, T cell-mediated mechanism of immunity to tumor-specific transplantation antigens, which enabled the host to cause the regression of an untreated test tumor growing simultaneously at a distant site . The generation of a C . parvum-potentiated anti-tumor response was dependent on the presence of tumor cells in close association with C . parvum, tumor immunogenicity, and the quantity of tumor antigen in the admixture . The anti-tumor immunity was specific for the tumor in the therapeutic admixture and could be adoptively transferred to normal recipients with Thy-1.2-positive lymphocytes, but not with serum . Complete regression of a distant test tumor by the C . parvum-tumor admixture was limited to tumors below a certain critical size. J Natl Cancer Inst, 1981 Sep, 67(3), 637 - 43 Naturally arising tumors of the inbred WAB/Not rat strain . II . Immunogenicity of transplanted tumors; Middle JG et al.; The immunogenicity of 28 transplanted naturally arising tumors of the inbred WAB/Not rat was investigated at early passages in strictly syngeneic, contemporary animals . Included were nephroblastomas, histologically benign and malignant mammary tumors, soft tissue and skin tumors, 1 lymphoid tumor, and 2 gastrointestinal lesions . In no case was evidence of immunogenicity observed when animals were treated with multiple grafts of irradiated (15,000 rad) tissue or by excision of a growing tumor . A few of these tumors were further investigated by other methods of immunization, including injection at various sites of irradiated cells followed by challenge at different sites and multiple injections of mitomycin C- or Formalin-treated cells . Again no evidence of immunogenicity was seen . Attempts to immunize with viable cells mixed with BCG or Corynebacterium parvum failed due to lack of tumor suppression by these agents . Limited concomitant immunity experiments yielded similarly negative results, except in one case of a fibrosarcoma for which a slight reduction in second tumor growth was observed when primary implants were very large . Some alterations in biologic properties during transplant passage and the incidence of postexcision recurrence and metastatic spread of some of the tumors are described. Br J Exp Pathol, 1981 Aug, 62(4), 347 - 9 Simple estimation of macrophage activity in tumour-bearing animals treated with Corynebacterium parvum; Wilson RG; The effects of Corynebacterium parvum on the reticuloendothelial system and on tumour growth have been known for many years . The causes of these effects have been the subject of many hypotheses and we here discuss a new method of evaluating macrophage activity and some of its components . These studies show that in macrophage activation the degree of enzymic activity and the cell size are more important than the number of cells present and that by giving silica concurrently it is macrophage enzyme activity and cell size that one affects and not cell number . Consequently, it is of no use simply to count macrophages in a section in studies of this system. Aust J Exp Biol Med Sci, 1981 Aug, 59(4), 455 - 67 Isolation of a group of glycolipid toxins from seedheads of annual ryegrass Lolium rigidum Gaud.) infected by Corynebacterium rathayi; Vogel P et al.; A group of highly toxic compounds was isolated from galled seedheads of annual ryegrass (Lolium rigidum Gaud.) containing Corynebacterium rathayi . Purified extracts were resolved by reverse-phase high-performance liquid chromatography into eight main fractions which have been partially characterised and shown to be toxic to nursling rats . A mixture of the toxins also produced clinical signs and brain lesions in lambs consistent with annual ryegrass toxicity . The name 'corynetoxin' is tentatively proposed for the series, individual members being designated according to their order of elution from the high performance liquid chromatography column as corynetoxins 1 to 8 . The two main fractions are corynetoxins 3 and 4 of which the former has been crystallised . They appear to be of glycolipid character, 3-hydroxyheptadecanoic acid and a C6 amino sugar being identified among the hydrolysis products of corynetoxin 3, and heptadec-2-enoic acid and a C6 amino sugar from corynetoxin 4. Am J Vet Res, 1981 Aug, 42(8), 1433 - 40 Gross and microscopic lesions of middle and inner ear infections in swine; Olson LD; In all infected middle ears from 36 swine, there was purulent material in the tympanic cavity and tympanic bulla . Frequently, there were lysis of the tympanic membrane and ossicles and purulent material in the external ear canal . Sometimes, there were desquamation of the stratified squamous epithelium lining the tympanic cavity, and osteolysis of the underlying osseous wall with subsequent fibrosis . In those swine with inner ear infections, there were infiltration of neutrophils and fibrin in the cochlea and vestibule . The predominant isolation from the infected middle ears was non-groupable beta-hemolytic streptococci, although isolations of streptococcic groups C, E, and G, Pasteurella multocida, and Corynebacterium pyogenes were made. Eur J Biochem, 1981 Aug, 118(1), 183 - 6 Occurrence of phosphatidylcholine in hydrogen-oxidizing bacteria; Thiele OW et al.; 15 strains of hydrogen-oxidizing bacteria were grown heterotrophically, harvested during the stationary phase of growth, and analyzed for their principal phospholipids . All strains - with the exception of Corynebacterium autotrophicum strain SA 32 and Pseudomonas pseudoflava - contained phosphatidylcholine as a major constituent . It is concluded that the presence of phosphatidylcholine is neither characteristic of a peculiar bacterial genus or family, nor is it absolutely correlated to the ability to oxidize hydrogen . The phosphatidylcholines of all strains contain C19 cyclopropane acid which is, in some strains, predominantly located at C-2 position of the glycerol moiety. Br J Vener Dis, 1981 Aug, 57(4), 275 - 8 Comparison of miconazole-coated tampons with clotrimazole vaginal tablets in the treatment of vaginal candidosis; Balsdon MJ; The effectiveness and acceptability of miconazole-coated tampons were compared with those clotrimazole vaginal tablets in the treatment of vaginal candidosis in 100 women . Both treatments were highly effective in reducing the signs and symptoms of infection; 95% of the group treated with miconazole had negative culture results for Candida species immediately after treatment compared with 86% of those treated with clotrimazole . A 17.6% recurrence rate of positive culture results was found four weeks later in the miconazole-treated group compared with that of 30% in the clotrimazole-treated group . The miconazole tampons were highly acceptable to patients . Vaginal pH values did not differ significantly between those patients with candidosis and those treated and cured . Corynebacterium vaginale (Gardnerella vaginalis) vaginitis and nonspecific genital infection were common complicating factors during follow up. J Clin Pathol, 1981 Aug, 34(8), 917 - 20 Rapid identification of Corynebacterium vaginale in non-purulent vaginitis; Wells JI et al.; A simple set of tests is proposed to give excellent probability for the identification of Corynebacterium vaginale from clinical material . Using these tests, 380 C vaginale were isolated from genital tract specimens from 1402 patients . Of these isolates 70 were from symptomatic patients . These 70 isolates were subjected to a further set of tests to confirm their identity . The advantage of these primary tests is that they can be completed on the day of isolation of the organism . Of these 70 isolates 66 were confirmed as C vaginale thus giving the primary set of tests a 94% rate of accurate identification . However this rate may be increased beyond 97% by the promotion of one of the key secondary tests to the primary set. Infect Immun, 1981 Aug, 33(2), 380 - 8 Phagocytosis and killing of salmonella typhimurium by peritoneal exudate cells; Briles DE et al.; Normal peritoneal cells from conventional, germfree, or nu/nu mice readily killed opsonized salmonellae, an observation that suggests that this activity in the normal peritoneal cavity may not be dependent on either environmental antigenic stimulation or T-cell mediation . In contrast, peritoneal cells elicited 4 days after injection with thioglycolate medium failed to kill opsonized salmonellae but appeared to be highly phagocytic . Peritoneal cells from thioglycolate-treated mice could be induced to kill opsonized salmonellae by giving the mice a primary footpad injection and a secondary intraperitoneal injection of Corynebacterium parvum . This activation by C . parvum appeared to be thymus dependent, since it did not occur in nu/nu mice. Cancer, 1981 Jul 15, 48(2), 245 - 51 Surgical adjuvant therapy of malignant melanoma with corynebacterium parvum; Hilal EY et al.; The authors' previous surgical adjuvant trial in patients with malignant melanoma at high risk of recurrence has shown no difference in disease-free interval or survival between patients randomized to surgery + BCG or surgery alone . Reported here is a subsequent nonrandomized trial in 30 similar patients who received surgery + Corynebacterium parvum (CP) 4 mg I.V . daily x 5, followed by 4 mg S.C . weekly for up to three years . After I.V . C . parvum, chills, fever, headache, and hypertension were common . After S.C . C . parvum, varying degrees of local induration, erythema, and pain were experienced . Dose reduction was necessary for 14 patients during I.V . treatment and for six patients during S.C . treatment . A marked decrease in absolute lymphocyte count and a decreased proliferative response of lymphocytes to common antigens in vitro was observed after 2-3 days of I.V . C . parvum . Lymphocyte reactivity to mitogens decreased, particularly with Con A . Marked increase in nitroblue tetrazolium reduction by granulocytes was seen in 20 patients . Although changes in delayed cutaneous hypersensitivity reactions to recall antigens followed no consistent pattern, reactivity to DNCB increased in 18 patients . In addition, median time to recurrence was 33 weeks, significantly shorter than in the previous trial, but the survival distribution was no different from before . It can be concluded, therefore, that the administration of C . parvum in this dose and schedule had essentially no effect on the outcome of these patients. Cancer, 1981 Jul 15, 48(2), 238 - 44 Chemoimmunotherapy of small cell bronchogenic carcinoma with VP-16-213, ifosfamide, vincristine, adriamycin, and Corynebacterium parvum; Valdivieso M et al.; Thirty-five consecutive patients with small cell bronchogenic carcinoma (SCBC) received chemoimmunotherapy with VP-16-213, Ifosfamide, vincristine, Adriamycin, and Corynebacterium parvum . Of 33 evaluable patients, 26 (79%) responded with complete (55%) or partial (24%) remissions . Complete remissions were more common among patients with limited disease (11/14 patients, 79%) compared with those with extensive disease (7/19 patients, 37%) and among patients (11/14 patients, 79%) compared with those with extensive disease (7/19 patients, 37%) and among patients who were ambulatory prior to therapy (16/25 patients, 64%) compared with those who were nonambulatory (2/8 patients, 25%) . Myelosuppression consisted primarily of neutropenia . Eight percent of the treatment courses in 29% of the patients were associated with hematuria and/or documented episodes of infection during neutropenia . There were three deaths possibly related to treatment, in two of which there was no evidence of disease at post-mortem examination . Six patients relapsed in the central nervous system (CNS) . In four instances, CNS relapse was the only site of tumor progression . Central nervous system relapse was more common among evaluable patients who did not receive prophylactic brain irradiation (5/17 patients, 29%, vs . 1/15 patients, 7%; P = 0.23) . The median survival duration for all patients was 63 weeks, being slightly longer for patients with limited disease than for those with extensive disease (70.9 weeks vs . 56 weeks; P = 0.18) . This was also true for patients who achieved complete rather than partial remissions (71 weeks vs . 50 weeks; P = 0.09) . Patients receiving prophylactic brain irradiation experienced longer survival (100.8 weeks vs . 48 weeks; P = 0.01). Isr J Med Sci, 1981 Jul, 17(7), 537 - 9 Observations on Mycoplasma mycoides subsp . mycoides infection in Saanen goats; Bar-Moshe B et al.; An epizootic in white Saanen goats, caused by Mycoplasma mycoides subsp . mycoides is described . Twenty-five flocks totalling approximately 4,500 animals were involved . The disease was characterized by a high, transient temperature, general malaise and mastitis in the lactating does, and a keratoconjunctivitis, arthritis, mycoplasmaemia and death among the kids . In one goat flock there was a precipitous change in the character of the disease, from a predominantly mastitis syndrome to a fulminating pleuropneumonia . In another goat flock, twin kids were born with an advanced purulent, proliferative arthritis, suggesting early congenital infection . In yet another infected flock there were cases of subcutaneous abscesses from which both M . mycoides and Corynebacterium pyogenes were cultured . M . mycoides was also isolated from synovial fluid and the parenchymal organs of an Ibex mountain goat that died of a purulent polyarthritis . Experimental infection in kids caused a diffuse cellulitis at the site of inoculation, a high fever, polyarthritis and death. Infect Immun, 1981 Jul, 33(1), 83 - 9 Endotoxin-induced serum factor kills malarial parasites in vitro; Taverne J et al.; We investigated the possibility that malarial parasites may be killed by nonspecific soluble mediators, such as those in tumor necrosis serum, that are obtained from mice given macrophage-activating agents like Corynebacterium parvum or Mycobacterium bovis BCG, followed by endotoxin . Such sera killed parasites in vitro after overnight incubation; killing was measured directly by using an in vivo infectivity assay . Parasite infectivity was not decreased by incubation in sera from mice given C . parvum or BCG alone (no endotoxin) or by incubation in sera from normal mice given endotoxin . Plasmodium yoelii, its lethal variant, and Plasmodium berghei were equally susceptible to inactivation . Sera obtained from mice given endotoxin during the course of infection with these parasites also contained parasite-killing factor . The activity of this factor appeared to be proportional to parasitemia in that it was higher in the sera from mice infected with the lethal parasites than in the sera from mice with infections which resolved either spontaneously or after vaccination. Infect Immun, 1981 Jul, 33(1), 199 - 211 Host defenses in murine malaria: nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation; Murphy JR; Infection with Mycobacterium bovis (BCG) or injection of killed Corynebacterium parvum protected some strain B6D2 F1 (C57BL/6xDBA/2) mice but did not protect strain ICR or A mice from lethal challenge with Plasmodium berghei strain NYU-2 . B6D2 mice were not protected against challenges delivered immediately after intravenous injection of these materials, but rather protection developed by day 7 and persisted through at least day 84 . Infections in protected mice progressed to about 10% parasitemia in parallel with infections initiated with the same inoculum in untreated controls . However, infections in most of the protected mice were cleared subsequently, whereas infections in untreated controls were uniformly fatal . A small number of treated mice developed protracted high-level erythrocytic infections, which led to markedly delayed death . BCG-infected mice which survived P . berghei infections had a factor in their sera which protected passively immunized recipients from P . berghei . BCG-infected mice passively immunized with protective serum controlled P . berghei infections better than normal mice given the same amount of the same serum and challenged with the same P . berghei inoculum . The capacity of BCG-infected B6D2 mice to resist P . berghei infection was not directly related to the pattern of growth of BCG, to the degree of splenomegaly, or to the level of activation of macrophages (measured as microbicidal capacity) caused by BCG infection . Therefore, I concluded that (i) BCG infection or injection of killed C . parvum altered the immunological potential of B6D2 mice in such a way as to allow the production of measurable levels of a protective humoral factor in response to infection with P . berghei; (ii) BCG infection caused the generation of a capacity which, when expressed in the presence of immune serum, provided an anti-P . berghei capacity which was superior to that provided by BCG infection alone or immune serum in the absence of BCG infection; and (iii) not all strains of mice could be protected from P . berghei by BCG or C . parvum injection. Ann Immunol (Paris), 1981 Jul-Aug, 132D(1), 43 - 54 {Passive transfer of "Corynebacterium parvum" anti-tumour protection by stimulated peritoneal cells }; Mazurek C et al.; A partial anti-tumour protection can be induced by transfer of peritoneal cells from mice pretreated with Corynebacterium parvum, in the two experimental tumours studied: a mammary carcinoma syngeneic to C3H mice and a lymphosarcoma syngeneic to XVII mice . This protection is abolished by heating the peritoneal cells at 70 degrees C for 30 min, by a 2,200-rad irradiation or by a non-lethal irradiation of the recipient mice . Transfer of normal peritoneal cells did not produce any anti-tumour protection in C3H mice but induced the same effect as stimulated cells in XVII mice . The difference in these results could be explained by the routes of injection of peritoneal and tumour cells: intraperitoneally in C3H mice and intravenously in XVII mice . It cannot be excluded that the protective effect induced by the injection of the stimulated peritoneal cells could be produced by the anti-tumour activity of the transferred C . parvum phagocytized by these cells. Cancer Res, 1981 Jul, 41(7), 2633 - 9 In vitro cytotoxicity expressed by cells active against established tumors in vivo; Tuttle RL et al.; Although antitumor activity by host cells has been documented in vivo and in vitro, the cellular relationships between these two classes of studies are not clear . Cells capable of causing the regression of solid tumors are generated in lymph nodes draining sites of immunization with Corynebacterium parvum:irradiated P815 mastocytoma admixtures . These cells are active in a 51Cr release assay at a low effector:target ratio producing a characteristic low level of specific 51Cr release which required 24 hr for optimal development . The activity is immunologically specific for the immunizing tumor and is mediated by nonadherent, rapidly dividing (vinblastine-sensitive) cells . They are absent in thymectomized animals and susceptible to alpha-Thy 1.2 antibody and complement . They are present in peritoneal exudates, consistent with the systemic resistance demonstrable in the animal model . The properties and development kinetics of effector cells measured by 51Cr release correlate closely with those of cells showing in vivo activity, supporting the identity of the two populations. Morphol Embryol (Bucur), 1981 Jul-Sep, 27(3), 265 - 9 In vitro cytochemical and cytophysiological study of in vivo activated mouse peritoneal macrophages; Todorutiu C et al.; The morphological, cytochemical (acid phosphatase activity) and cytophysiological (phagocytosis) features of mouse peritoneal macrophages activated in vivo by two bacterial agents . Corynebacterium parvum parvum and Polidin, were investigated in vitro . Both immunostimulants induced an increase in cytochemical and phagocytic activities of the activated peritoneal macrophages but in different degrees, the changes being more extensive in the case of Corynebacterium parvum-activated macrophages. Dtsch Med Wochenschr, 1981 Jun 5, 106(23), 734 - 8 {Varieties of diphtheria: microbiological diagnosis and epidemiological observations (author's transl)}; Degner I et al.; Following several cases of diphtheria an epidemiological investigation was made in and around Aachen . A total of 1458 throat and nose smears were examined for various Corynebacteria species . Other than in two patients who had diphtheria, toxin-producing Corynebacterium diphtheriae was demonstrated in only one person who had been in immediate contact with them . Of a total of 150 Corynebacteria of different species which were isolated, two further isolates proved to be non-toxin-producing diphtheria bacteria . All five strains were found in foreigners, who represented 46.8% of all tested subjects . The number of isolated Corynebacteria of different species was, at 13.62%, almost double that in a group of non-foreigners (7.35%). Gann, 1981 Jun, 72(3), 446 - 50 Effect of intracerebral administration of Corynebacterium parvum on the growth of brain tumors in mice; Kiya K et al.; The effect of intracerebral administration of Corynebacterium parvum (C . parvum) on the growth of syngeneic brain tumors in C57BL/6 mice and the mechanism of its action were investigated . Mice were inoculated with 10(4) malignant glioma cells intracerebrally, and treated with various doses of C parvum on day 6 after tumor inoculation . The growth of tumors was significantly inhibited in proportion ot the dose of C . parvum . The cytotoxic activity of effector cells was enhanced when C . parvum was administered at the site of tumor inoculation . Significant cytotoxic activity was observed in the adherent cell fraction of brain mononuclear cells, while less cytotoxic activity was observed in the nonadherent cell fraction . These results indicate that activated intracranial macrophages may participate in the tumoricidal effect of intracerebral C . parvum administration. Inflammation, 1981 Jun, 5(2), 165 - 76 Activation of the alternative pathway of complement in human serum by Propionibacterium acnes (Corynebacterium parvum) cell fractions; Webster GF et al.; Activation of the alternative pathway of complement is known to be initiated by bacterial structures . We have fractionated Propionibacterium acnes cells, purified various cell fractions, and tested their complement-activating ability in human serum chelated with ethyleneglycol bis-(beta-aminoethylether)-N,N1-tetraacetic acid . The majority of complement-activating activity was localized in the wall fraction . This activity was resistant to lipid extraction, protease, RNAse, DNAse and lysozyme treatment . NaIO4, formamide, and hot (but not cold) trichloroacetic acid (TCA) extraction ablated the complement-activating capacity of cell walls . Compounds removed by extraction failed to consume significant hemolytic activity against antibody-coated sheep erythrocytes (EA) . Addition of TCA-extracted soluble material to cell wall suspensions resulted in an inhibition of hemolytic consumption by the cell wall . These results indicate that, in P . acnes, complement-activating molecules are located in the cell wall and are carbohydrate in nature . Peptidoglycan, lipid, protein, and nucleic acid do not appear to contribute to the cell wall's ability to activate complement. Anasth Intensivther Notfallmed, 1981 Jun, 16(3), 150 - 3 {Nosocomial infections--a consequence of modern therapeutic and diagnostic methods (author's transl)}; Krasemann C; Nosocomial infections are an increasingly observed complication of modern therapeutic and diagnostic procedures . They may arise exogenously, i.e . during nursing or medical care (contaminated instruments, catheters, inhalers, infusions) or endogenously by the patient's own bacterial flora . Characteristic of exogenous nosocomial infections are enterobacteriaceae and Pseudomonas strains; they are of low virulence, are generally highly resistant to antibiotics and able to survive for long periods even in an unfavourable environment . Endogenous infections are most easily induced during operations on parts of the body that normally show a dense bacterial population such as the intestine; but they are also a dreaded complication of foreign body implants . Endogenous infections after non-sterile operations are most frequently due to enterobacteriaceae and bacteroides, especially Bacteroides fragilis . Endoprostheses are mainly infected by micro-organisms present on the skin, such as staphylococci, streptococci and corynebacterium . An important cause of nosocomial infections is a disturbance of the balance of the normal bacterial flora by uncritical and haphazard use of antibiotics. Immunopharmacology, 1981 Jun, 3(2), 101 - 6 Depression of hepatic mixed-function oxidase activity by B . pertussis in splenectomized and athymic nude mice; Williams JF et al.; Administration of Bordetella pertussis (B . pertussis), Corynebacterium parvum (C . parvum), and several other immunoactive substances is known to cause a marked decrease in the activity of the hepatic microsomal mixed-function oxidase system . The effect of C parvum has been reported to involve the reticuloendothelial system . In the present study, the effect of B . pertussis administration to decrease hepatic microsomal drug metabolism was studied in unoperated, sham-operated, and splenectomized mice as well as in athymic nude (nu/nu) mice and their phenotypically heterozygous (+/nu) littermates . Administration of B . pertussis to the splenectomized, sham-operated, and unoperated mice resulted in a decrease in the activity of the microsomal enzyme system that was approximately the same for each of the three groups of animals . Administration of B . pertussis to nu/nu mice and the +/nu mice also decreased the microsomal enzyme activity measured 24 hr after injection . However, at 7 days after B . pertussis administration, the hepatic drug-metabolizing activity of the nu/nu mice was not significantly different from control values, whereas the activity of the +/nu mice was still significantly depressed . The failure of splenectomy to prevent the decrease in microsomal mixed-function oxidase activity caused by B . pertussis indicated that the effect of this agent differs from that of C . parvum, whose effect was prevented by splenectomy . Indeed, the results obtained with the athymic nude mouse suggests that the depression of hepatic mixed-function oxidase activity by B . pertussis may involve T-cell dependent responses. Cancer Res, 1981 Jun, 41(6), 2394 - 400 Systemic adoptive transfer of immunity to 13762A rat mammary adenocarcinoma; Boyer CM et al.; Rats cured of metastatic 13762A rat mammary adenocarcinoma by Corynebacterium parvum immunotherapy possess strong tumor-specific rejection immunity . Systemic adoptive transfer of lymphoreticular cells from cured rat donors conferred protective immunity on naive recipients . Fewer oil-induced peritoneal exudate cells than lymph node cells were required to transfer tumor rejection immunity . The adoptive immunity was specific since it strongly inhibited 13762A tumor growth but did not inhibit the growth of the antigenically unrelated R3230AC rat mammary tumor . Rats sensitized to the bacterial immune stimulant used to effect cure were unsuitable donors of PEC capable of transferring tumor rejection immunity . Macrophages or bone marrow-derived lymphocytes from immune donors did not transfer immunity . Treatment of peritoneal exudate with a xenogeneic antiserum specific for rat thymus-derived lymphocytes significantly reduced the efficiency of transfer . We conclude that thymus-derived lymphocytes from rats cured of 13762A tumor were required for the adoptive transfer of tumor-specific rejection immunity. J Natl Cancer Inst, 1981 Jun, 66(6), 993 - 1002 Effect of immunotherapy with Corynebacterium parvum and methanol extraction residue of BCG administered intravenously on host defense function in cancer patients; Hersh EM et al.; The effects of active nonspecific immunotherapy were studied in 42 patients receiving daily iv Corynebacterium parvum at 2 mg/m2 in 14-day courses and in 14 patients receiving iv methanol extraction residue of BCG (MER) at 0.5 mg/m2 weekly . The host defense evaluations included measurement of the number of adherent macrophage precursors per milliliter of blood (monocyte adherence), serum lysozyme, and antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells to chicken red blood cells (CRBC) or human red blood cells (HRBC) . During a single course of C . parvum, monocyte adherence did not rise significantly, whereas ADCC of peripheral blood mononuclear cells to CRBC and HRBC rose significantly (15.7-49.9% and 34.8-53.5% lysis of target cells, respectively) . However, after a mean of 4.5 months on therapy, monocyte adherence increased an average of 7.5-fold . During weekly MER therapy, monocyte adherence, serum lysozyme, and ADCC of peripheral blood mononuclear cells to CRBC rose significantly within 4-7 days after the first dose (3.8-8.7 adherent cells/ml blood x 10(4), 7.6-10.8 microgram, and 34.4-41.4% target cell lysis, respectively) . The host defense parameter, which was subnormal in the cancer patients (monocyte adherence), was boosted into the normal range in all the deficient patients by iv MER . The host defense parameters, which were normal or slightly elevated in the patients before therapy (serum lysozyme and ADCC of peripheral blood mononuclear cells to CRBC and HRBC), were hyperactivated above the upper limit of the normal range in 71.4, 71.4, and 50% of the patients, respectively, by iv MER . These methods can quantitatively reflect activation of monocytes and killer cells by C . parvum and MER and may be useful for evaluation and quantitation of both active nonspecific and immunorestorative immunotherapy in general. Ann Trop Paediatr, 1981 Jun, 1(2), 97 - 101 Complications of diphtheria seen during the 1978 outbreak in Khartoum; Salih MA et al.; PIP: The clinical presentation and outcome in 29 children admitted to 2 Khartoum, Sudan, hospitals with complications of diphtheria are described . The patients ranged from 10 months to 11 years, and 66% were in the 2-5-year age group . The organism implicated was Corynebacterium diphtheriae subspecies gravis with an unusual property of fermenting sucrose . Only 2 of the 29 children had received immunizations against diphtheria . The most common complications were neurological . Palatal palsy was present in 21 children (72%) and 8 patients (28%) developed weakness of neck extensors . Bronchopneumonia was seen in 13 children (45%), while cardiovascular complications occurred in 6 children (21%) . There were 6 deaths in this group, for a case fatality rate of 21% . 5 of these deaths were attributable to cardiovascular complications and the other followed tracheostomy . Analysis of the number of days from the onset of pharyngeal symptoms to the appearance of complications followed a set pattern . Cardiovascular symptoms were the 1st to appear, followed by palatal palsy, peripheral weakness or paralysis, pharyngeal paralysis, weakness of neck flexors, and 6th and 7th nerve palsies . Although 4 doses of DPT vaccine are not an absolute guarantee diphtheria will not occur, there are significant differences between vaccinated and unvaccinated children in the relative incidence, morbidity, and mortality from the disease . This suggests a justification for mass immunization programs in regions such as the Sudan where diphtheria is common . Infect Immun, 1981 Jun, 32(3), 1128 - 31 Protection of mice against mouse hepatitis virus by Corynebacterium parvum; Schindler L et al.; C57BL/6 mice that are highly susceptible to infection with mouse hepatitis virus type 3 were protected against intraperitoneal viral infection by simultaneous intraperitoneal injection of Corynebacterium parvum . No protection was observed when C . parvum was given intravenously or when it was injected intraperitoneally 3 days before viral infection . Protective effects were, however, consistently found when C . parvum was given 2 h before or 2 h after viral infection . Activity was seen only against 10 50% lethal doses and not against 100 50% lethal doses . C . parvum also caused a significant decrease of virus type 3 . These data suggest a direct effect of C . parvum on virus-susceptible cells . Injection of C . parvum in mice caused activation of natural killer (NK) cells and of interferon production . However, these two effects were equally demonstrable at high and low doses of C . parvum, whereas protection against mouse hepatitis virus type 3 was not demonstrable at low doses of C . parvum . Thus, antiviral protection may be dissociated from activation of NK cells and induction of interferon. Infect Immun, 1981 Jun, 32(3), 1058 - 66 Possible importance of macrophage-derived mediators in acute malaria; Clark IA et al.; Tumor necrosis factor, lymphocyte-activating factor, and enhanced levels of type I interferon were found in serum samples taken 2 h after mice infected with Plasmodium vinckei subsp . petteri received a small intravenous injection of endotoxin . These three mediators are among those released when mice receive an endotoxin injection 2 weeks after Mycobacterium bovis BCG or Corynebacterium parvum have been administered . There is indirect evidence that this wider range of mediators is also released in P . vinckei subsp . petteri-infected mice given parenteral endotoxin . A recent report that endotoxin is detectable in the plasma of malaria-infected mice and children implies that these mediators may also be released in the acute phase of the natural infection . We propose that these macrophage-derived mediators may be important in the glucocorticoid antagonism, bone marrow depression, fever, hypergammaglobulinemia, splenomegaly, elevation of serum amyloid A, consumptive coagulopathy, and shock syndrome with associated organ damage which can accompany malaria . The intraerythrocytic parasite death seen at crisis in some malarias, as well as the subsequent development of specific protective immunity, may also depend on these mediators. J Am Vet Med Assoc, 1981 May 15, 178(10), 1061 - 4 Mannitol agar for microbiologic diagnosis of bovine mastitis; Ward GE et al.; A medium containing mannitol (mannitol agar) was developed and evaluated as a tool for the microbiologic diagnosis of bovine mastitis . Mannitol agar supported growth of all important bacterial mastitis pathogens (staphylococci, streptococci, coliforms, and pseudomonads) except Corynebacterium pyogenes . Color change around colonies in the agar permitted the differentiation of pathogenic from nonpathogenic staphylococci . Most Staphylococcus aureus strains and some Staphylococcus epidermidis strains produced yellow zones . These yellow zone-producing strains (mannitol fermenters) of staphylococci were obtained from quarters with significantly elevated (P less than 0.05) somatic cell counts (SCC) in the milk, as compared with uninfected quarters and, therefore, would be considered pathogens . Mannitol-negative strains of S epidermidis (those with red zones) were obtained from quarters with SCC similar to those of uninfected quarters . The streptococci could be divided into 2 groups on the basis of color change around the colonies: Streptococcus agalactiae, Str dysgalactiae, and group G streptococci produced red zones; Str uberis, Str bovis, and enterococci produced yellow zones . Pathogenic streptococci (Str agalactiae, Str dysgalactiae, Str uberis, and group G streptococci) were obtained from quarters with SCC significantly higher (P less than 0.01) than those of uninfected quarters . Streptococcus bovis and enterococci were obtained from quarters with SCC similar to those of uninfected quarters and were considered nonpathogenic . Pathogenic streptococci were found in much higher concentration than nonpathogenic streptococci and could be differentiated on that basis. Med J Aust, 1981 May 2, 1(9), 470 - 2 Corynebacterium vaginale in non-purulent vaginitis; Goei SH et al.; The diagnostic importance of a cytological evaluation of a Gram-stained smear of the discharge from a case of non-purulent vaginitis (NVP) due to corynebacterium vaginale is emphasized . A battery of rapid laboratory tests designed to identify the organism on the second day of incubation with an accuracy of at least 97% is proposed . In a prospective study of 1402 patients, 310 (22%) were found to be asymptomatic carriers of C . vaginale and 42 (3%) had vaginal discharge attributable only to C . vaginale . The clinical features of NVP and results of several treatment regimens in a controlled trial of treatment are compared . Metronidazole given by mouth (1200 mg/day in divided doses) produced the best remission rate, although complicating candidiasis developed in 25% of cases. Br J Cancer, 1981 May, 43(5), 684 - 8 Increased tissue histamine in tumour-bearing mice and rats; Burtin C et al.; Tissue histamine levels were studied in C3H and C57BL/6 mice bearing a methylcholanthrene-induced fibrosarcoma, in Wag rats bearing an aflatoxin B1-induced hepatoma, and in Commentry rats bearing a grafted hepatoma . Histamine levels were significantly higher (1.5 to 3 fold) in the tumour-bearing animals for ventral and dorsal skin, skeletal muscle and stomach fundus . Total histamine content was increased in the spleen . In C3H mice with McC3-1 fibrosarcoma, the excision of the tumour or its partial regression by intratumoral injections of corynebacterium parvum induced a reversion to normal values . The tumour thus appears responsible for the increased histamine levels in tissues distant from the tumour. Blut, 1981 May, 42(5), 283 - 95 {Macrophage precursors as cytotoxic effector cells (author's transl)}; Lohmann-Matthes ML et al.; We have shown previously that in liquid cultures of mouse bone marrow cultured in the presence of fibroblast-conditioned medium macrophage precursor cells are generated which show K- and NK-activity . We have now presented evidence that macrophage precursor cells are released from the bone marrow into the periphery under in vivo conditions . Both in the corynebacterium parvum-induced mouse peritoneal exsudate and in the spleen of nu/nu mice the existence of macrophages precursor cells can be demonstrated . If these cells are eliminated by the use of the alloantimacrophage serum Mph 1.2 + C' the NK-activity of both populations is greatly reduced . Also human peripheral blood leucocytes contain macrophage precursor cells in varying amounts . After complete depletion of mature macrophages from peripheral blood macrophage precursor cells mature to typical adherent macrophages within a culture period of 5 days . These macrophage precursor cells resemble morphologically medium-sized lymphocytes . They are nonadherent and nonphagocytic and stain negative for nonspecific esterase. Br J Dermatol, 1981 May, 104(5), 567 - 73 Idiopathic pyoderma gangrenosum and impaired lymphocyte function: failure of azathioprine and corticosteroid therapy; Breathnach SM et al.; A 58-year-old man with chronic "idiopathic' pyoderma gangrenosum, recurrent secondary staphylococcal infection, nail candidiasis, markedly impaired lymphocyte function and a serum blocking factor is described . Despite an initially favourable response to immunosuppressive therapy, the patient later relapsed whilst on high dose systemic corticosteroids and azathioprine . Immune function remains abnormal 3 years cessation of azathioprine . Attempted immunostimulation with Corynebacterium parvum proved unsuccessful . A striking but transient increase in lymphocyte function followed parenteral iron therapy for an unexplained iron-deficiency anaemia . Gradual reduction in prednisone dosage to 5 mg daily has coincided with a period of clinical resolution and modest improvement in lymphocyte reactivity . Prolonged immunosuppressive therapy may be inadvisable in chronic idiopathic pyoderma gangrenosum associated with defective cellular immunity. Fertil Steril, 1981 May, 35(5), 549 - 51 Survival of bacteria after freezing of human semen in liquid nitrogen; Garcia A et al.; Thirty-four semen samples from fertile men were subjected to bacteriologic evaluation before and after freezing to -196 degrees C using 10% glycerol as the protective medium . Cultures of the fresh portions from all ejaculates examined showed the presence of aerobic bacteria . Staphylococcus epidermidis, Corynebacterium sp., alpha-streptococci, and nonhemolytic streptococci were found so commonly that they were considered commensals . Enterococci, Escherichia coli, S . aureus, and beta-hemolytic streptococci group B, as well as Pseudomonas aeruginosa, P . maltophilia, and P . fluorescens, were also recovered from a few semen samples of these fertile men . Practically all bacteria isolated from the fresh ejaculate were also recovered from the portions frozen in liquid nitrogen. J Invest Dermatol, 1981 May, 76(5), 396 - 9 Modulation of suppressor mechanisms in allergic contact dermatitis: 2 . Inhibition of suppressor T-lymphocytes by Corynebacterium parvum; Knop J et al.; Pretreatment of BALB/c mice with Corynebacterium parvum inhibited the induction of tolerance to the contact sensitizing agent 2,4-dinitrofluorobenzene induced by intravenous injection of DNBSO3 . The suppressive effect on tolerance induction has further been analyzed by adoptive transfer experiments . Injection of C . parvum intraperitoneally (0.7-2.8 mg/mouse) before injection of the tolergen inhibited the generation of T-suppressor cells as shown by transfer of spleen cells from the tolerized donor to naive recipients . Pretreatment of the recipients of the suppressor T-cells from tolerized animals with C . parvum also inhibited the function of these cells in the recipient animals . Time-kinetic experiments suggested that more than one mechanism appeared to be responsible for the tolerance induced by DNBSO3; C . parvum (probably via activated macrophages) suppressed tolerance which is mediated by T-suppressor lymphocytes . These results suggest that T-suppressor lymphocytes may--similarly as T-helper cells--be modulated by an activated monocytic-phagocytic system. Transplantation, 1981 May, 31(5), 347 - 52 Lasting engraftment of histoincompatible bone marrow cells in dogs; Vriesendorp HM et al.; Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells . Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective . These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays . The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection . Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI . Low efficiency and significant extra toxicity restrict the applicability of these procedures . The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval . Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor . Possibilities for further improvement of this protocol are discussed. J Natl Cancer Inst, 1981 May, 66(5), 837 - 42 Role of macrophage in in vitro augmentation of rat, mouse, and human natural killer activities; Reynolds CW et al.; Requirement for macrophages in in vitro augmentation, by interferon (IFN), polyinosinic-polycytidylic acid (poly I:C), or Corynebacterium parvum, of rat, mouse, and human natural killer (NK) activities was examined . Several differences were seen among the species . Mouse NK activity demonstrated some lability at 37 degrees C and a strict macrophage requirement for in vitro production of IFN, and augmentation of NK activity was demonstrated by either poly I:C or C . parvum . In contrast, human peripheral blood leukocytes (PBL) depleted of monocytes by adherence on nylon wool demonstrated NK activity, which was not labile but rather increased substantially upon overnight culture at 37 degrees C alone or with poly I:C or C . parvum . Monocyte-depleted human PBL also produced IFN in these cultures . The pattern of reactivity seen with rat spleen cell cultures was different from either that of mouse and human cells . This pattern of reactivity had no lability at 37 degrees C and had a macrophage requirement for IFN production and NK cell augmentation upon culture alone or with poly I:C but not with C . parvum . These results indicated some major differences among species in the regulation of NK activity in vitro and the requirement for macrophages for the in vitro production of IFN . A better understanding of these differences will be helpful in choosing appropriate models for in vitro and in vivo studies of NK cell activity. Med J Aust . 1981 Apr 4;1(7):366. Intracranial complications of sphenoidal sinus inflammation; Cook IF et al.; A young man who presented with bacterial meningitis and visual disturbance developed a left sixth nerve palsy due to an isolated sphenoidal sinus inflammation caused by Corynebacterium haemolyticum . Sphenoidal sinusitis and intracranial infection by C . haemolyticum are uncommon complications. Vet Res Commun, 1981 Apr, 4(4), 291 - 4 Corynebacterium equi in the gastrointestinal tract of ruminants; Woolcock JB et al.; Corynebacterium equi has been recovered from the gastrointestinal tract of sheep and cattle . It can be found in all parts of the gut, and around 80% of animals have the organism in one or more intestinal sites . C . equi could be detected in the faeces of sheep which were kept caged and free from recontamination by the organism. Gann, 1981 Apr, 72(2), 305 - 9 Scanning electron microscopic studies on the surface structure of activated macrophages and on their interaction with tumor cells; Toge T et al.; Experiments on peritoneal macrophages obtained from Corynebacterium parvum (C . parvum)-treated or untreated normal mice were performed in order to quantitate the cytotoxic activities and surface morphological modifications . The cytotoxic activities of activated macrophages were significantly higher than those or normal macrophages . There were prominent differences in surface morphology between C . parvum-activated and normal macrophages as seen by scanning electron microscopy . The activated macrophages were larger and exhibited higher surface membrane activities than normal macrophages . In interaction between macrophages and tumor cells, both activated and normal macrophages were observed to come into contact with target tumor cells during the first 24 hr . The surfaces of tumor cells entirely lost their microvilli and showed pores . Tumor cells finally died after interaction with activated macrophages for 48 hr . In contrast, no significant alterations were observed on the surfaces of tumor cells incubated with normal macrophages . In conclusion, it seems that the cytotoxic activities of macrophages correlate with the extent of macrophage activation, and the activation correlates with the surface membrane alterations. Endocrinologie, 1981 Apr-Jun, 19(2), 105 - 10 Influence of the "Corynebacterium parvum" vaccine and stilbostat on intratesticular development of Walker 256 carcinosarcoma in hyper- or hypothyroidized Wistar rats; Zimel A et al.; This work studies the effect of nonspecific antitumoral immunity produced by the "Corynebacterium Parvum" vaccine (C.P.) and Stilbostal on the development of Walker 256 carcinosarcoma intratesticularly grafted to hyper- or hypothyroidized Wistar rats . The thyroid hormone level was altered by administration of thyroxin, Alkiron or surgical thyroidectomy . The C.P . vaccine was given in a mixture with tumoral cells suspension and the treatment with the Stilbostat drug was started 5 days from grafting . The results show that C.P . administered in a mixture with tumoral cells suspension causes marked inhibition of the development of the primary tumor and metastasis, an effect which is not significantly influenced by the thyroid hormone level . The antitumoral effect of the Stilbostat drug is enhanced by administration of C.P . in tumoral cells suspension . The greatest effect produced by Stilbostal was noted in the hyperthyroidized lots in which the tumor was administered in a mixture with C.P. Immunology, 1981 Apr, 42(4), 513 - 9 Comparison of cytotoxic and microbicidal function of bronchoalveolar and peritoneal macrophages; Ryning FW et al.; Studies were carried out with mice to explore in vitro the effector function(s) of macrophages from two different anatomical compartments (peritoneal cavity and lungs) . The cytotoxic capacity of macrophages was measured by determining their cytostatic and cytocidal effects on EL-4 tumour target cells, and the microbicidal capacity of macrophages was measured by determining their ability to kill or inhibit the intracellular protozoan, Toxoplasma gondii . Neither peritoneal macrophages (PM) nor bronchoalveolar macrophages (BAM) from normal mice were ever microbicidal or cytotoxic . Intravenous treatment with Corynebacterium parvum greatly enhanced (activated) both effector functions of PM but did not activate BAM . Chronic infection with Toxoplasma activated PM throughout the period of observation (greater than 140 days), but the presence of activated BAM was transient and appeared to coincide with the occurrence of an inflammatory response in the lungs. Br J Exp Pathol, 1981 Apr, 62(2), 131 - 5 Coumarin or warfarin treatment of mice does not increase the microbicidal or tumoricidal capacities of macrophages; Filice GA et al.; Benzopyrones have been shown to affect several functions of macrophages . We examined the effects of two benzopyrones, coumarin and warfarin, on the capacity of mouse macrophages to inhibit microorganisms and tumour target cells . Mice were treated with daily i.v . doses of either drug . Then the mice were challenged with lethal doses of Toxoplasma gondii or peritoneal macrophages from these mice were challenged in vitro with T . gondii or tumour target cells Survival of coumarin or warfarin-treated mice challenged with T . gondii was similar to that of control mice . Multiplication of T gondii and growth of tumour target cells were similar in preparations of macrophages from coumarin-treated, warfarin-treated, or control mice and were inhibited in preparations of activated macrophages from Corynebacterium parvum-treated mice that served as positive controls . Under our experimental conditions, benzopyrones did not activate mouse macrophages. Br J Cancer, 1981 Apr, 43(4), 496 - 504 Effects of the Landschütz ascites carcinoma and ascitic fluid on macrophage activity in C . parvum-injected mice; McIntosh LC et al.; I.p . administration of 1.4 mg Corynebacterium parvum (C . parvum) 24 h before inoculation of Landschutz ascites carcinoma (LAC) cells significantly impaired growth of the tumour in MF1 mice . The injection of tumour cells caused a transient inhibition of the activity of the mononuclear phagocyte system (MPS) in both normal and C . parvum-treated hosts, as evidenced by impaired clearance of colloidal carbon from the bloodstream and reduction in hepatic phagocytosis of 51Cr-labelled sheep erythrocytes . Depression in Kupffer-cell activity was associated with a shift in particle distribution towards the spleen . The pronounced hepatosplenomegaly in response to C . parvum was significantly less in animals which also received tumour cells . Histological examination of liver and spleen revealed evidence of depressed MPS activity . Granuloma production in the liver in response to C . parvum was inhibited in tumour-bearing mice, and macrophage proliferation within the spleen was also reduced . Ascitic fluid showed similar inhibitory effects to those of tumour-cell suspensions, suggesting production by LAC of a heat-stable macrophage-inhibitory factor. Cancer, 1981 Apr 1, 47(7), 1752 - 61 Treatment of invasive or metastatic thymoma: report of eleven cases; Chahinian AP et al.; The clinical presentation and therapeutic modalities of 11 patients with invasive or metastatic thymoma are presented . Two patients had myasthenia gravis, and five had extrathoracic metastases . Survival exceeded five years in five patients, and four patients remain free of recurrence between 2.1 and 9.0 years after diagnosis . Surgery, with an attempt at complete resection, is the first step of therapy . A second thoracotomy for local relapse or attempt at curative resection was carried out in four patients . Radiotherapy to the mediastinum and/or metastatic sites was given to ten patients with doses ranging from 3600-6000 rads (median = 4500 rads) in the nine nonmyasthenic patients . Inclusion of supraclavicular fossae in the radiotherapy field is recommended because it was a site of relapse in two patients . Systemic therapies were given to eight patients . Objective responses were seen with two of various chemotherapeutic regimens . A combination of bleomycin, Adriamycin, cisplatin, and prednisone ("BAPP") produced a partial remission in two of five patients, during 12 and 4 months, respectively . Two of three patients responded to maytansine as a single agent after failure of other agents . Immunotherapy with intravenous Corynebacterium parvum or intradermal Methanol-Extraction Residue of bacillus Calmette-Guerin (MER-BCG) was ineffective in one patient each . The importance of combined modalities in the management of the disease is emphasized. Am J Clin Pathol, 1981 Apr, 75(4), 631 - 4 Corynebacterium diphtheriae septicemia; Isaac-Renton JL et al.; This report describes the case of a patient with chronic lymphocytic leukemia in whom septicemia caused by a nontoxigenic strain of Corynebacterium diphtheriae developed . Numerous abscesses were present in sections of liver and spleen taken at autopsy . The case is discussed, and the literature on infections caused by organisms of the genus Corynebacterium is briefly reviewed. Gastroenterology, 1981 Apr, 80(4), 647 - 54 Proteolytic enzymes released by liver macrophages may promote hepatic injury in a rat model of hepatic damage; Tanner A et al.; Using macrophages isolated from the livers of normal rats and from rats injected intravenously with Corynebacterium parvum 6 days previously, N-acetyl-glucosaminidase (NAG) and plasminogen activator (PA) production have been measured during in vitro culture . There was a significant increase (p less than 0.02) in the supernatant activity of NAG by the C . parvum recruited macrophages 8.05 +/- 1.17 nmol product/mg protein/h as compared with normal, 3.86 +/- 0.77 nmol product/mg protein/h . There was a similar increase in cellular NAG content by recruited macrophages 412 +/- 66 nmol product/mg protein compared with 153 +/- 35 nmol product/mg protein (p less than 0.01) in normals . When macrophages of either group were exposed in vitro to endotoxin alone or a combination of endotoxin followed by latex particles, NAG values were similar to those obtained from nonexposed cells . In contrast, PA supernatant production increased significantly (p less than 0.02) on exposure to endotoxin with a corresponding reduction in cellular PA content, but the cellular PA content and supernatant release were similar for each group of cells . There was a fourfold increase in the number of macrophages isolated from the C . parvum-treated livers/g liver weight . Thus, the hepatocytes in this model of liver injury are potentially exposed to a 10-fold increase in the concentration of the acid hydrolase NAG; potentiation of cell damage by the administration of endotoxin may be mediated through the observed increase in production of secretory enzymes such as plasminogen activator . In conclusion, this study supports the hypothesis that proteolytic products released by recruited and activated macrophages may result in hepatocyte damage. Gene, 1981 Apr, 13(3), 211 - 20 Chromogenic detection of antigen in bacteriophage plaques: a microplaque method applicable to large-scale screening; Kaplan DA et al.; We have developed a simple and rapid (24 h) enzyme-linked immuno-detection method to screen for rare antigen-positive phage among large numbers of antigen-negative ones . Horse-radish peroxidase-antibody conjugate, incorporated into the soft agar layer of a plaque assay system, is precipitated locally by antigen produced during plaque formation, and is detected by standard chromogenic methods . The method has been used to screen plaques of bacteriophage beta tox+ for the presence of diphtheria toxin and related cross-reacting material . When phage were plated on very dense bacterial lawns, they formed minute plaques (microplaques) . Because of the high local concentration of antigen generated by lysis of the dense lawn, the microplaques gave more intense chromogenic signals than larger plaques formed on less dense Corynebacterium diphtheriae lawns . Thus, antigen-positive microplaques could be easily recognized even in the presence of very large numbers of antigen-negatives . In a reconstruction experiment, small numbers of antigen-positive phage were detected with high efficiency (greater than 75%) against a background of 3.8 X 10(4) antigen-negatives/cm2 of agar surface (equivalent to 2.4 X 10(6) plaques/9 cm petri plate) . This screening method should facilitate isolation of phage mutants affecting production of given antigens and may be of particular value in detecting specific genes cloned into phage vectors. Can J Comp Med, 1981 Apr, 45(2), 130 - 4 Capsular serotypes of Corynebacterium equi; Prescott JF; Antisera were prepared against 26 isolates of Corynebacterium equi . A capsular antigen preparation was made by washing a heavy suspension of individual C . equi isolates in saline overnight . Ninety-seven isolates from a variety of sources were tested by a double diffusion immunoprecipitin test and seven capsular serotypes identified . The majority of isolates belonged to capsular serotype 1 (59.8%) and 2 (25.8%) . No clear relationship was established between capsular serotype and the source of origin of the isolates (disease processes in horses, pigs, man, cattle, dogs or cats). J Immunol, 1981 Apr, 126(4), 1581 - 5 In vitro augmentation of rat natural killer (NK) cell activity; Reynolds CW et al.; In vitro augmentation of rat natural killer (NK) cell activity was produced by 2 types of treatment . Increased activity occurred "spontaneously" when spleen cells were cultured alone at 37 degrees C . This augmentation was dependent on the presence of adherent, phagocytic cells, presumably macrophages, and was independent of LPS of FCS . Normally low levels of NK activity, present in macrophage-depleted cultured cells, could also be boosted in vitro by incubation with Corynebacterium parvum . This augmentation appeared to be independent of both B cells and macrophages and may be due to stimulation of rat NK cells themselves . Both forms of augmentation were associated with the production of interferon, were found in rats of all ages and strains tested, and should provide an excellent in vitro system for detailed studies of activation of rat NK cells. Immunology, 1981 Apr, 42(4), 561 - 8 Detection of either rapidly cytolytic macrophages or NK cells in "activated" peritoneal exudates depends on the method of analysis and the target cell type; Gray JD et al.; The nature of the cytotoxic cells present in the peritoneal cavity of rats treated with Bacille Calmette-Guerin (BCG) or Corynebacterium parvum was investigated using a 6 hr chromium release assay and a quantitative method of analysis based on consideration of target-cell killing as an enzyme-substrate reaction . When the results of cell-fractionation experiments were evaluated in terms of recovery of total lytic units and when appropriate target cells (such as sarcoma Mc7) were used, the simultaneous presence of both cytotoxic macrophages and NK cells in peritoneal exudates could be readily demonstrated . With certain other target cells different results were obtained . Thus, with normal thymocytes, normal hepatocytes, or myeloma P3NSI as targets, NK cells were preferentially detected, whereas with leukaemias L5178Y, P815, and EL4 as targets, cytotoxic macrophages were preferentially detected . These findings resolve the previously conflicting reports concerning the nature of cytotoxic cells in activated peritoneal exudates. Proc R Soc Lond B Biol Sci, 1981 Mar 11, 211(1184), 269 - 86 Cellular basis for the loss of carcinogen from methylcholanthrene-impregnated Millipore membrane; Woodruff M et al.; Millipore 'discs' impregnated with methylcholanthrene dissolved in wax or in crystalline form implanted subcutaneously in mice evoke an early intense macrophage and giant cell reaction; later the discs become covered with connective tissue, and eventually fibrosarcomas develop in their vicinity . Studies with tritium-labelled material show that under these conditions methylcholanthrene (MC) is removed from the discs and broken down rapidly (half life about 7 days) to a water-soluble product, which diffuses locally, is distributed widely via the blood stream, and is excreted in faeces and urine . Removal of label is halted by whole-body irradiation (550 R) with the disc area shielded; this observation, in conjunction with the histological and autoradiographic findings and the paucity of label in cells stripped from excised discs, points to the conclusion that the removal of MC from impregnated discs, and its subsequent degradation, depend on the presence of macrophages and the continual replacement of spent macrophages by new cells generated centrally . The rate of disappearance of label from implanted {3H}MC discs was not altered by administration of Corynebacterium parvum; this, however, does not exclude the possibility that the metabolic pathways involved in the removal of MC are altered . To investigate this it is proposed to study, in both normal mice and mice treated with C . parvum, the extent to which cytochrome P450 and other enzymes concerned in the activation and detoxification of polycyclic hydrocarbons by liver microsomal fractions are inducible in the macrophages that accumulate in inflammatory exudates . This histological techniques used should be readily applicable to the study of the early stages of chemical carcinogenesis and the host reaction to transformed cells. J Vet Pharmacol Ther, 1981 Mar, 4(1), 27 - 31 The susceptibility of isolates of Corynebacterium equi to antimicrobial drugs; Prescott JF; Fifty-one isolates of Corynebacterium equi recovered from pigs and horses belonging to two capsular serotypes were tested for susceptibility to antimicrobial agents . No clear differences were detected in sensitivity between isolates of different sources or serotypes . All isolates were sensitive to less than 0.25 micrograms/ml of erythromycin and gentamicin . The following minimum inhibitory concentrations (MICs) of antimicrobial agents were determined for greater than or equal to 90% of isolates: methicillin greater than 16 micrograms/ml, clindamycin 1-2 micrograms/ml, tobramycin less than or equal to 1 microgram/ml, cephalothin 8-64 micrograms/ml, kanamycin 2-8 micrograms/ml, amikacin less than or equal to 1-2 micrograms/ml, penicillin 2-greater than or equal to 4 micrograms/ml, ampicillin 2-8 micrograms/ml, trimethoprim-sulfa 4/76-32/608 micrograms/ml tetracycline 1-4 micrograms/ml and chloramphenicol 8-16 micrograms/ml. J Adolesc Health Care, 1981 Mar, 1(3), 217 - 20 Preliminary study of the flora in the lower genital tracts of sexually active adolescent females in relation to symptoms and inflammatory response; Russo JF et al.; The lower genital tracts of 20 sexually active adolescent females were examined for the presence of Mycoplasma hominis, Ureaplasma urealyticum, Corynebacterium genitalium, and Corynebacterium pseudogenitalium . Fifty percent of the asymptomatic adolescent females and 50% of the symptomatic adolescent females were colonized with M . hominis, which is higher than the percentage reported in adult females . None of the asymptomatic adolescent females and only 10% of the symptomatic adolescent females were colonized with U . urealyticum, which is much lower than the percentage reported in adults . None of the study patients was colonized with C . genitalium, but 25% were colonized with C . pseudogenitalium . No relationship was found between the presence of M . hominis in the lower genital tract and a clinically identifiable vaginal discharge or inflammatory changes in exfoliated cervical and vaginal epithelial cells . The presence of M.hominis in the lower genital tract does not appear to be influenced by use of oral contraceptives or antecedent pregnancy. Am J Med, 1981 Mar, 70(3), 646 - 50 The emergence of coryneform bacteria as a cause of nosocomial infections in compromised hosts; Young VM et al.; Corynebacterium species that are normally abundant on the skin and mucous membranes rarely cause infections and are susceptible to most antibiotics . The report in 1976 of four cases of sepsis at the National Institutes of Health caused by a hitherto undescribed corynebacterium that is highly antibiotic resistant, but uniformly susceptible to vancomycin, alerted the medically oriented scientific community to the emergence of these organisms as a possible new cause of nosocomial infections . Although we have always performed antibiotic susceptibility tests on all microorganisms recovered from normally sterile body fluids, our first recovery of these organisms was in August 1977 . Since then we have recovered 52 such strains from 39 patients, most frequently from the rectum, followed by the groin, blood, lesions and urine in order of predominance . Characterization by API 50 L strips revealed that most, but not all strains resemble the JK group of Riley et al . {1} . Cell wall studies and DNA base ratios further confirmed their status as corynebacteria . Hospital acquisition has been proved; cross infection between patients is the most likely mode of spread . Their recognition is necessary for optimal preventive and therapeutic care of patients with compromised host defenses. Cancer Res, 1981 Mar, 41(3), 980 - 3 Requirements for successful immunotherapy and chemoimmunotherapy of a murine model of ovarian cancer; Vanhaelen CP et al.; A comprehensive study of nonspecific immunotherapy has been conducted in an established murine model of ovarian cancer in order to determine the relative effectiveness of commonly used bacterial immunostimulants, the importance of the route and schedule of administration of these agents, and their effects in combination with chemotherapy . Implants of 10(5) or 10(6) ovarian tumor cells i.p . kill all syngeneic C3HeB/FeJ mice within 25 days . Corynebacterium parvum (700 microgram/mouse i.p . 24 hr after a 10(5) tumor cell inoculum) cures 75% of the mice; in contrast, neither i.v . nor s.c . administration improves survival rates . After the same tumor challenge, Bacillus Calmette-Guerin was minimally effective at extremely high doses only, while the methanol extraction residue of B . Calmette-Guerin was ineffective . Two days after an implant of 10(6) tumor cells, neither cyclophosphamide, nor cis-diamminedichloroplastinum(II) (cisplatin), nor C . parvum increased survival . Combination of C . parvum with cyclophosphamide or cisplatin resulted in a synergism shown by the 40 and 60% cure rates, respectively . However, combination of C . parvum with an active agent, doxorubicin, resulted in toxicity even in untumored animals . This study demonstrates that therapeutic efficacy of immunotherapy depends critically on the choice of an appropriate agent and route of administration and, to a lesser extent, on the dose and schedule used . The observation provides a rationale for carefully conducted Phase I and Phase II studies of treatment with bacterial immunostimulants, alone or in combination with chemotherapy, in human ovarian cancer. Aust Vet J, 1981 Mar, 57(3), 105 - 10 Caseous lymphadenitis in goats; Burrell DH; Two dairy goat stud herds were surveyed for Corynebacterium ovis infection by clinical examination and serum tests using both the haemolysis inhibition and double immunodiffusion techniques for detection of C . ovis antitoxin . In one herd, of 53 goats 11 had abscesses from which C . ovis was recorded; 33 and 29 goats were positive to the haemolysis inhibition and double immunodiffusion tests respectively . Serums from 10 and 9 of 23 kids gave reactions positive to the respective tests with 19 of 23 kids having been born to does with demonstrable antibody . In a second herd of 57 goats 16 had superficial abscesses containing C . ovis; serums from 34 and 45 goats gave positive reactions to the haemolysis inhibition and double immunodiffusion tests respectively . The prevalence of caseous lymphadenitis in these stud herds was a cause of economic loss to the owners through euthanasia of severely affected goats, reduced milk production and emaciation, the cost of labour and drugs for treatment, jeopardisation of income from boarding or mating with outside stock and the appearance of goats at stud shows, and sale of valuable breeding stock to local and export markets. J Virol, 1981 Mar, 37(3), 946 - 54 Regulation of toxinogenesis in Corynebacterium diphtheriae . II . Genetic mapping of a tox regulatory mutation in bacteriophage beta; Welkos SL et al.; The structural gene for diphtherial toxin is present in corynebacteriophage beta . Previous studies located several point mutations within the tox locus and determined the orientation of transcription of the toxin structural gene . The production of maximal quantities of toxin by Corynebacterium diphtheriae C7(beta) occurs only when the bacteria are iron deficient . Mutations in phage beta can affect this control of toxin production by iron . The tox-201 mutation regulates expression of the toxin structural gene in a cis-dominant manner and permits large amounts of toxin to be made under high-iron conditions when phage beta tox-201 infects C . diphtheriae C7 . In this study tox-201 was found to be closely linked to the structural gene for toxin . We performed a series of multifactor matings to determine the relative positions of tox-201 and several point mutations within the toxin structural gene . The order of these markers on the vegetative genetic map of phage beta was tox-201-tox-4-tox-2-tox-30 . These findings establish that the tox-201 regulatory site is closely linked to the end of the toxin structural gene corresponding to the origin of transcription . This location is consistent with our hypothesis that tox-201 defines a cis-dominant regulatory element, such as an operator, promoter, or attenuator, involved in control of toxinogenesis in C . diphtheriae C7(beta). J Virol, 1981 Mar, 37(3), 936 - 45 Regulation of toxinogenesis in Corynebacterium diphtheriae . I . Mutations in bacteriophage beta that alter the effects of iron on toxin production; Welkos SL et al.; Diphtherial toxin is produced in maximal yields by Corynebacterium diphtheriae (C7(beta tox+) only when iron is present in growth-limiting amounts . Toxin production is markedly decreased under high-iron conditions . We studied the role of the bacteriophage beta genome in this apparent regulation of toxin production by iron . Using a passive immune hemolysis assay to detect toxin antigen production in individual plaques, we identified rare phage mutants that were toxinogenic in high-iron medium . Lysogenic derivatives of C . diphtheriae C7 harboring such phage mutants were constructed . The lysogens were compared with wild-type strain C7(beta) for their ability to produce toxin in deferrated liquid medium containing varying amounts of added iron . Quantitative tests for extracellular toxin were performed by competitive-binding radioimmunoassays . We identified phenotypically distinct mutant strains that produced slightly, moderately, or greatly increased yields of toxin antigen under high-iron conditions . The toxin produced by the mutant lysogens was biologically active and immunochemically indistinguishable from wild-type toxin . Complementation experiments demonstrated that the phage mutation designated tox-201 had a cis-dominant effect on the expression of the toxin structural gene of phage beta . The characteristics of the tox-201 mutation suggest that it defines a regulatory locus of phage beta that is involved in control of toxinogenesis by iron in C . diphtheriae. J Invest Dermatol, 1981 Mar, 76(3), 193 - 6 Modulation of suppressor mechanisms in allergic contact dermatitis: 1 . Effect of C . parvum on the induction phase of contact allergy; Knop J et al.; The effect of a pretreatment with corynebacterium parvum (C . parvum) on contact allergy in BALB/c mice was studied . Mice sensitized with 50 microliter (supraoptimal dose) 2.4-dinitrofluorobenzene (DNFB, 0.5%) showed a suppressed response as measured by ear swelling after painting the right ear with 0.3% DNFB in comparison to an allergic response obtained with an optimal sensitization dose (15 microliter DNFB 0.5%) . By transfer of spleen cells from donors sensitized with a supraoptimal or an optimal dose to recipients either challenged ro sensitized shortly afterwards with DNFB it could be shown that less functionally active immune T-lymphocytes of the delayed hypersensitivity type and significantly more suppressor T-cells were induced in supraoptimally sensitized mice in comparison to the optimally sensitized animals . Intraperitoneal injection of C . parvum (2.8 mg/mouse) one week before sensitization enhanced the contact allergic response in mice sensitized with a supraoptimal dose of DNFB, with little effect on the response in optimally sensitized animals . Further analysis of this enhancement in transfer experiments showed that C, parvum selectively suppressed the generation and/or functional expression of T-suppressor cells and, probably by this mechanism, increased the number of functionally active T-immune lymphocytes . It is proposed that possibly by activation of the immune system C . parvum will suppress suppressor cells in contact allergy and by this mechanism might facilitate sensitization to the contact allergen. J Bacteriol, 1981 Feb, 145(2), 775 - 9 Primary structure of the wall peptidoglycan of leprosy-derived corynebacteria; Janczura E et al.; The cell walls isolated from axenically grown leprosy-derived corynebacteria were submitted to various chemical and enzymatic degradations . The glycan strands of the wall peptidoglycan are essentially composed of N-acetylglycosaminyl-N-acetylmuramic acid disaccharide units . Small amounts of N-acetylglycosaminyl-N-glycolylmuramic acid (less than 10%) were also detected . The muramic acid residues of adjacent glycan strands are substituted by amidated tetrapeptide units which, in turn, are cross-linked through direct linkages extending between the C-terminal D-alanine residue of one tetrapeptide and the mesodiaminopimelic acid residue of another tetrapeptide . Such a structure is very similar to that of the wall peptidoglycan found in the taxonomically related microorganisms of the Corynebacterium, Mycobacterium, and Nocardia groups. Surgery, 1981 Feb, 89(2), 237 - 42 Improved survival in severely burned animals using intravenous Corynebacterium parvum vaccine post injury; Stinnett JD et al.; This study was designed to determine the potential benefit or toxicity of an immunomodulator, Corynebacterium parvum vaccine, when it is given after severe burn injury . Forty conditioned beagles received a 33% total body surface 3-degree flame burn and were resuscitated with Ringer's lactate solution (3 ml/kg/% burn) . Wounds were treated daily for 10 days with silver sulfadiazine cream . Two days and nine days after burn, 21 of the animals received C . parvum vaccine (10 mg/kg IV) in a saline infusion, while 19 control animals were given only saline infusion according to a double-blind protocol . Serial measurements were made of temperature, weight, food intake, hematocrit, hemoglobin, red blood count, white blood count, differential, platelet count, fibrin degradation products, activated partial thromboplastin time, clot retraction, C3, blood cultures, neutrophil function, monocyte function, opsonic index, Na, K, Cl, BUN, glucose creatinine, total protein albumin, albumin/globulin ratio, alkaline phosphatase, SGPT, and SGOT . During 45 days of observation, only 16% of the saline control dogs survived compared to 47% of the treated animals . Total white counts and neutrophil function were the only values which were significantly better in animals receiving C . parvum . However, their correlation with increased survival was marginal This preclinical trial suggests that C . parvum is an effective immunodulator for prevention of fatal infection following burn injury . There were no demonstrable toxic effects of the material in this study. Cancer Res, 1981 Feb, 41(2), 573 - 80 Growth-regulatory control of human cell hybrids in nude mice; Stanbridge EJ et al.; The role of natural killer (NK) cells in the control of growth of human cell hybrids in nude mice was evaluated . Both nontumorigenic and tumorigenic HeLa-fibroblast hybrids were highly sensitive to NK-mediated cytotoxicity, but neither hybrid induced such activity when injected into nude mice . Furthermore, tumorigenic hybrids grew in mice which had high levels of NK activity induced by i.p . inoculation of Corynebacterium parvum vaccine . Histological examination of the nontumorigenic and tumorigenic populations inoculated s.c . into nude mice indicated that both populations initially divide actively for the first 3 to 4 days . After this time, the nontumorigenic cells showed a dramatic decline in mitotic activity accompanied by a morphological shift to a more fibroblastoid appearance . The cells remained in the animal as a viable nondividing tissue . The tumorigenic population continued to actively divided and produced a large progressively growing tumor . This series of events determined from histological examination was supported by kinetic studies . These results suggest that NK cells play no role in the suppression of growth of the nontumorigenic hybrid cells and that host-mediated growth-regulatory control is responsible for the shutdown of mitotic activity of these cells without causing their death. Cancer Res, 1981 Feb, 41(2), 438 - 44 Expression of metastatic potential of allogenic and xenogeneic neoplasms in young nude mice; Hanna N et al.; Several different mouse and rat tumors were injected s.c . or i.v . into specific-pathogen-free young (3-week-old) and adult (6-week-old) nude mice . All tumors grew s.c.; however, following i.v . injections, only metastatic neoplasms produced visible pulmonary tumor foci in the 3-week-old (but not in the 6-week-old) nude mice . The quantitative differences in metastatic potential among tumor lines and clones observed in syngeneic hosts were maintained also when 3-week-old nude mice were used . The enhanced survival of tumor cells in the lungs and the large numbers of visible pulmonary metastases observed in the young nude recipients correlated closely with the low levels of natural killer cell activity detected in 3-week-old (but not in 6-week-old) nude mice . In vivo activation of natural killer cells by treatment of mice with polyinosinic-polycytidylic acid or Corynebacterium parvum, 24 hr prior to tumor challenge rendered th 3-week-old nude mice resistant to development of metastases . We conclude that specific-pathogen-free 3-week-old nude mice, which lack functional T-lymphocytes and demonstrate low natural killer cell activity, could serve as an in vivo model to ascertain the metastatic potential of allogeneic and xenogeneic tumors. Clin Exp Immunol, 1981 Feb, 43(2), 376 - 80 A comparative study of lysosomal enzyme activity in monocytes and Kupffer cells isolated simultaneously in a rat model of liver injury; Reiner RG et al.; Macrophages have been isolated and cultured in vitro from normal rat livers and from livers into which macrophages have been recruited in vivo, following an intravenous injection of killed Corynebacterium parvum . Simultaneously, peripheral blood monocytes have been isolated and cultured in vitro . After 24 hr in culture, supernatants and cell lysates were harvested and the activity of a lysosomal enzyme, N-acetyl-glucosaminidase (NAG), measured . NAG activity in the cell lysates of the recruited tissue macrophages was significantly higher than that measured in control tissue macrophages . Increased NAG activity was also observed in the supernatants from the recruited macrophages . In contrast, the NAG activity in cell lysates and supernatants of peripheral monocytes was not significantly changed after C . parvum injection . In this animal model, measurement of a lysosomal enzyme produced by peripheral monocytes did not reflect the magnitude of the changes observed for the tissue macrophages. Am J Vet Res, 1981 Feb, 42(2), 351 - 5 Scanning electron microscopy of experimentally induced pyelonephritis in the rat; Appleton JA et al.; Scanning electron microscopy was used to observe epithelial and inflammatory changes in kidneys of rats during Corynebacterium renale-induced experimental ascending pyelonephritis . Bacteria were not observed adhering to pelvic epithelium, although there was evidence of cell sloughing . Bacteria was observed in the interstitium of the renal medulla . Bacteria, when present in the tubular lumen, were associated with discontinuities in cell membranes . Phagocytic cells appeared in the interstitium and phagocytosis was evident in the renal medulla. Exp Hematol, 1981 Feb, 9(2), 149 - 55 Augmentation of natural killer cell activity in spleens of infant, aged, and low responder strain mice by Corynebacterium parvum; Gallagher MT et al.; Murine natural killer (NK) cell activity is both age- and strain-dependent . NK activity does not appear in murine spleen cells until three weeks after birth . Activity peaks at approximately 10 weeks, decreasing thereafter with mice over one year old showing significantly reduced levels . Mice showing low or no NK activity because of age (aged and infant mice, respectively) can be stimulated to show significant levels of NK lysis by i.p . injection of formalin killed Corynebacterium parvum (CP) . In addition, CP treatment is also capable of increasing NK activity in mice from the normally low responding AKR strain . The NK activity induced or stimulated by CP appears to be like normal NK reactivity in that it is not decreased by removal of T-cells or adherent cells . Thus, in addition to increasing NK activity in normally responsive mice, CP is capable of augmenting NK activity in mice which normally show low or no levels of NK lysis. J Clin Microbiol, 1981 Feb, 13(2), 335 - 43 Phospholipase D activity of Corynebacterium pseudotuberculosis (Corynebacterium ovis) and Corynebacterium ulcerans, a distinctive marker within the genus Corynebacterium; Barksdale L et al.; A search has been made for corynebacterial phospholipase D, "ovis toxin," a sphingomyelinase (phosphatidylcholine phosphohydrolase, EC 3.1.4.4), among a wide variety of corynebacteria . Phospholipase D activity has been found in strains exhibiting the biochemical properties characteristic of Corynebacterium pseudotuberculosis or of Corynebacterium ulcerans and in no other species of Corynebacterium . Methods for the assay of phospholipase D as a sphingomyelinase and methods for screening for phospholipase D in the presence of Corynebacterium equi on washed sheep blood agar are discussed. Br J Vener Dis, 1981 Feb, 57(1), 62 - 6 Haemophilus vaginalis (Corynebacterium vaginale, Gardnerella vaginalis) in a family planning clinic population; Bramley HM et al.; PIP: This study examines the prevalence of H vaginalis, with and without other infections, in healthy women attending a family planning clinic . Vaginal specimens were obtained at 902 attendances from 522 women requiring vaginal examination at a family planning clinic . Culture methods used were similar to those devised by Dunkelberg with some modification . Patients were followed up after a year, and clinical examination was repeated in 380 women . Haemophilus vaginalis was found in 8% of specimens either by culture or by at least two out of three microscopic tests; lactobacilli were seldom found in the presence of the organism . Increased signs and symptoms, especially an offensive odor, were found only when H vaginalis and staphylococci were isolated together . The organism was found less often in patients using contraceptive methods which protected the vagina, thus suggesting sexual transmission . Treatment is advisable when H vaginalis is in contact with a vascular bed . J Pathol, 1981 Feb, 133(2), 89 - 105 Proliferative glomerulonephritis in mice given intravenous Corynebacterium parvum; Uff JS et al.; Mice given a killed suspension of Corynebacterium parvum (C.p.) developed nephritis as part of an immune complex disease . The nephritis was dose-related . After a single dose of 70 microgram (a human-equivalent dose) or of 466 microgram there was a mesangiopathic glomerulonephritis and after repeated human-equivalent doses there was a mesangiocapillary glomerulonephritis . Antibodies to C.p . increased and circulating immune complexes were detected . Mice receiving repeated doses also developed an arteritis . Study of this model may help in the understanding of human immune complex disease and the pathogenesis of glomerulonephritis. Immunopharmacology, 1981 Feb, 3(1), 19 - 29 Enhanced chemiluminescence production by purified macrophage monolayers from C . parvum-treated mice; Bryant SM et al.; Chemiluminescence (CL) of both Corynebacterium parvum (C . parvum) and saline elicited murine peritoneal macrophage monolayers was studied employing a luminol-dependent assay . Glycogen-induced macrophages were obtained from animals that had been injected 7-10 days previously with either C . parvum or phosphate buffered saline (PBS) . Peritoneal exudate cells (3 x 10(6)) were allowed to attach to an 18 mm diameter glass cover slip, and then were cultured an additional 20-24 hr . The cover slips were removed from the culture medium, and were washed thoroughly with PBS to remove contaminating nonadherent lymphocytes and nonviable neutrophils . The macrophage monolayers were then placed in plastic scintillation vials with a suspension of luminol (5 x 10(-6 M in PBS) and opsonized zymosan particles . CL was measured at intervals over a 1-2 hr period with a scintillation counter in an out-of-coincidence mode . C . parvum-elicited macrophages demonstrated a 3- to 4-fold increase in CL when compared to control macrophages . Attachment of cells to cover slips did not in itself significantly elevate macrophage CL . Chemiluminescence production by purified macrophage monolayers correlated directly with glucosamine incorporation and inversely with phagocytic uptake . This sensitive, quantitative assay appears to be an excellent indicator of macrophage-specific metabolic activation. Cancer, 1981 Jan 15, 47(2), 285 - 90 Effects of Corynebacterium parvum on cellular immunity of cancer patients, assayed sequentially over 63 days; Thatcher N et al.; The immunologic effects of Corynebacterium parvum (2 mg/M2) infused at three-week intervals were determined by 19 sequential assays in each of nine patients with metastatic malignancy . Peripheral blood immunologic profiles were followed for 63 days . No statistical significant changes (P greater than 0.05) occurred in total white cell, lymphocyte, or monocyte counts . Subpopulation assays demonstrated significant increases in E rosetting cells but not in sIg-bearing cells; there was a corresponding significant decrease in null-cell proportions . Killer cell lymphocytotoxicity was measured by 51Cr release from Chang target cells . Significant increases were observed one week after immunization and were maintained on subsequent immunizations . NK- and K-cell cytotoxicity were particularly augmented; T-cell cytotoxicity expressed as lytic units/ml was significantly increased on fewer assay occasions . Killer cell function has a possible in vivo antitumor role and methods of boosting and maintaining the activity deserve consideration . A three-week immunization schedule with C . parvum is supported by the current work and is the basis of a randomized adjuvant immunotherapy study of patients with malignant melanoma. Immunology, 1981 Jan, 42(1), 99 - 109 Immunomodulation by corynebacterium parvum in two strains of guinea-pigs and the effect of cyclophosphamide; Gauthier-Rahman S; An early immunosuppressive phase in the overall stimulatory effect of Corynebacterium parvum on the immune response of two strains of guinea-pigs to ovalbumin (Oa) is described . Boosters given soon after treatment with C . parvum elicited lower secondary responses than those given later on, the peak secondary antibody titre increasing with the interval between primary immunization and the booster injection . Transfer of blood leukocytes (lymphocytes) of immunized donors to virgin syngeneic recipients showed the cellular nature of this effect . Cells transferred from donors boosted on day 40 after primary immunization showed a mean adoptive response that was 3.5 times less than that of a similar number of cells from donors boosted on day 90 . The increase in the immunocompetence and/or memory of the transferred cells was related to the moment of injection of the booster antigen (Ag) and not to the interval between priming and transfer, since cells transferred during the primary response failed to show a parallel increase . The early, lesser enhancement of the secondary response by C . parvum would thus appear to be due to a limitation of the number and/or immunocompetence of memory cells developing after the injection of Ag . A marked strain difference was observed in the response of strain 2 and Hartley guinea-pigs to immunization with C . parvum and Oa, delayed-type hypersensitivity (DTH) being relatively inhibited, and antibody (Ab) production relatively increased in the latter, the reverse being true of strain 2 guinea-pigs . The existence of a suppressor or regulatory mechanism sensitive to cyclophosphamide (Cy) during the development of DTH after C . parvum treatment was established . Cy pretreatment, 250-300 mg/kg i.p., of both strains led to the development of a larger number of positive skin tests in animals given C . parvum i.v . and Oa i.d . but not when C . parvum was injected i.d . mixed with Oa . The inhibition of the migration, in the presence of Ag, of peritoneal exudate cells of Cy-pretreated guinea-pigs was also accelerated and enhanced during the first week of the primary response after i.v . C . parvum. Stem Cells, 1981, 1(2), 81 - 96 Early changes in the radiosensitivity of Corynebacterium parvum-stimulated CFU-S; Maruyama Y et al.; Corynebacterium parvum injected intraperitoneally into C57BL mice induced a progression of hemopoietic CFU-S of C57BL mice from the resting state immediately after, and in the early period (approximately 8 h) after stimulation . Dose-response survival curves of the stimulated endogenous spleen CFU-S after the C . parvum injection revealed changing slopes or D0 of dose-response survival curves indicative of changing sensitivity states . Shortly after stimulation, the cells were sensitive to high specific-activity tritiated thymidine (HSATT) or hydroxyurea (HU), indicating they were in the DNA-S phase . This commenced shortly after the C . parvum injection . Beginning at about 6 h, sensitivity to HSATT disappeared and there was an increase in radiosensitivity . Sensitivity to vinblastine (VLB) also became evident at 7 h . This was consistent with beginning mitosis and mitotic cell sensitivity to VLB . A dose-response survival curve for the G2 phase CFU-S was determined using both HSATT and VLB to eliminate the DNA-S phase and mitotic cells . The radiosensitivities of the resting G1, S, and G1-S phase cells were determined by D0 to be 80, 105 and 85 rad, respectively, measured in vivo . G2 sensitivity using a combined HSATT and VLB method showed a complex, bending dose-response curve with a terminal D0 of 58 rad . CFU-S progression was blocked by the anti-histamine H2 receptor agent, metiamide. J Immunopharmacol, 1981, 3(2), 251 - 64 Depression of hepatic biotransformations by chemical immunoadjuvants; Giampietri A et al.; Administration of BCG and Corynebacterium parvum is known to cause depression of the hepatic microsomal enzyme system (HMES) in mice . In the present study we explored the effects on HMES of two chemical immunoadjuvants, one of which (pyran copolymer) with peculiarly long-lasting biological activities . The two synthetic immunoadjuvants proved to be potent HMES inhibitors and, for pyran copolymer, peak levels of inhibition concurred with maximal macrophage activation . The inhibition was largely dose-dependent and could not be prevented by immunopharmacologic maneuvers that are known to block the C . parvum effect on HMES . The possibility is discussed that common mechanism(s) underlie the depression of HMES by immunoactive substances of both bacterial and chemical origin. Vet Med Nauki, 1981, 18(1), 49 - 54 {Etiological study of mastitis in cows}; Todorov D et al.; The rapid mastitis test was employed to study a total of 13 880 cows on 40 farms . Positive for mastitis proved 2384 udder quarters . Clinically manifested mastitis was established in 3.23 per cent of the cases, subclinical mastitis - in 58.14 per cent, carrier status - in 12.55 per cent, secretion disturbances - in 22.58 per cent, and normal proved 3.84 per cent . In the mastitis-positive cases pathogenic streptococci were isolated in 57.14 per cent of the quarters, staphylococci - in 20.77 per cent, Corynebacteria - in 9.09 per cent, and other bacteria - in 5.19 per cent . In the cases with subclinical mastitis staphylococci accounted for 40.93 per cent, streptococci - for 38.7 per cent, Corynebacteria - for 14.22 per cent, and other organisms - for 6.0 per cent . Most frequently encountered were the carriers of staphylococci - 46.8 per cent, followed by those of Corynebacteria - 26.4 per cent, and of streptococci - 20.73 per cent. Int J Immunopharmacol, 1981, 3(2), 141 - 5 Organ distributions and clearance studies of 99mtechnetium-labeled Corynebacterium parvum in patients with leukemia; Toki H et al.; The clearance, metabolism and localization of Corynebacterium parvum (C . parvum) labeled with 99mtechnetium (99mTc) given intravenously was studied in various leukemia patients to develop the method and to evaluate reticuloendothelial systems (RES) function . A computer program was utilized to characterize the clearance . C . parvum 0.05 mg was labeled aseptically with 10 mCi of 99mTc with a reducing agent . It was injected intravenously over 5 s and clearance was characterized over the next 60 min . The low dose of C . parvum did not cause any symptoms . The blood or plasma clearance time (t 1/2) was in the range of 0.65 to 1.96 min, in eight patients . By whole body imaging, the distribution of C . parvum was found mainly in the liver, and to a much lesser extent in the spleen, lungs, and bone marrow . Nonparticulate 99mTc (which was not sedimented by centrifugation of blood samples at 3000 rpm for 30 min) appeared rapidly in the blood after i.v . injection accounting for more than half of the radioactivity in a few minutes . In vitro incubation of 99mTc labeled C . parvum with saline, whole blood, serum or leukocytes revealed that the release of free 99mTc resulted from the combined action of serum and leukocytes . The rapid clearance will limit the utility of this preparation in characterizing RES function in man and its modification by disease or therapy. J Surg Oncol, 1981, 17(3), 235 - 40 Delayed hypersensitivity reactions vs chemotherapy and immunotherapy responses in women with ovarian adenocarcinoma; Piver MS et al.; Fifty-one previously untreated women with FIGO Stages III and IV ovarian adenocarcinoma underwent sequential monthly skin testing utilizing Keyhole Limpet Hemocyanian, Varidase, mumps, monilia, and a purified protein derivative Tuberculin (PPD) prior to each course of systemic chemotherapy (with or without Corynebacterium parvum) . The purpose of the study was to evaluate the patients' ability to demonstrate a delayed cutaneous hypersensitivity reaction to these sensitizing antigens and response to therapy . There was no statistically significant correlation with response to therapy and: 1) Positive pretherapy skin test reactions vs anergy to pretherapy skin tests . 2) Negative pretherapy and positive post-therapy skin tests . 3) Anergy pre- and post-therapy vs positive skin test pre- or post-therapy . 4) Age of the patient vs skin test reactivity . 5) Skin test reactivity to any one of the five antigens tested . 6) Skin test reactivity in response to therapy in those women also receiving Corynebacterium parvum . It is concluded that the battery of skin tests utilized do not predict the patient's response to systemic chemotherapy in advanced ovarian adenocarcinoma. J Immunopharmacol, 1981, 3(1), 49 - 66 Corynebacterium parvum treatment of P388 tumor-bearing mice . II . Lysosomal enzyme levels associated with P388 tumor cells; Astry CL et al.; The number of tumor cells recovered form the peritoneal cavity of mice administered Corynebacterium parvum (C . parvum), Bacillus Calmette-Guerin (BCG) or saline 2 days before tumor implant was assessed on days 1, 2, 3, 5 and 7 following the intraperitoneal (ip) administration of 10(6) P388 leukemic cells . C . parvum-treated mice manifested a significant decrease in the number of tumor cells recovered from the peritoneal cavity on days 3-7, while BCG-treated mice had tumor cell yields comparable to saline control values . Lysosomal enzyme activity (acid phosphatase and beta-glucuronidase) in the nonadherent lavage cell population, which comprised tumor cells and host cells obtained form tumor-bearing animals, closely reflected the changes observed in tumor cell numbers and was initially assumed to be associated with tumor cells . When lysosomal enzyme activity was expressed as a function of the number of tumor cells or cellular protein, an enhanced activity following C . parvum treatment but not following BCG treatment was demonstrated . Enzyme activity associated with tumor cells was maximal 2 days prior to the profound depression in tumor cell maximal 2 days prior to the profound depression in tumor cell yield and may be associated with tumor cell killing . It is concluded that a correlation may exist between lysosomal enzyme activity, tumor cell numbers and the protective effect of the immunostimulant C . parvum . Whether the correlation is direct or indirect remains to be resolved. J Immunopharmacol, 1981, 3(1), 29 - 47 Corynebacterium parvum treatment of P388 tumor-bearing mice . I . Lysosomal enzyme levels in adherent peritoneal cells and peritoneal lavage fluid; Astry CL et al.; BDF1 mice treated with Corynebacterium parvum (C . parvum) 2 days before an implant of 106 P388 leukemic cells had up to an 110% increase in survival time above control; Bacillus Calmette-Guerin (BCG) treatment was ineffective . Acid phosphatase and beta-glucuronidase were measured in adherent peritoneal lavage cells and beta-glucuronidase in peritoneal lavage fluid form mice treated with C . parvum or BCG 2 days before the implant of P388 cells . In the presence of the tumor, adherent peritoneal cells from C . parvum-treated animals had a 250-300% increased specific lysosomal enzyme activity above control values (cells form animals receiving tumor implant alone) . Peak enzyme activity which occurred on day 3 was not present in adherent cells from BCG-treated tumor-bearing animals or the control animals . The beta-glucuronidase activity in peritoneal lavage fluid was elevated by the tumor cells, BCG, or C . parvum . Peak levels occurred on day 5 regardless of the treatment with an additive effect present on day 5 in animals receiving the combination of tumor with C . parvum . The evidence indicated the development of a different pattern of enhanced lysosomal enzyme activity if the immunopotentiator protected against the P388 tumor vs one that did not . Protection was associated with an increase in lysosomal enzyme activity in adherent cells with no increase in lavage fluid in the presence of tumor cells . Changes in cellular enzyme activity may prove to be diagnostic for antitumor activity by an immunostimulant. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1981, 249(4), 527 - 37 Purification and some properties of exotoxin from Corynebacterium ulcerans strain ATCC 9015; Vertiev YuV et al.; Corynebacterium ulcerans strain ATCC 9015 develops during growth in environmental media an exotoxin which is lethal for guinea-pigs . The exotoxin has been purified by ion-exchange chromatography on DEAE-Sephadex A-50, affinity chromatography using immunosorbent techniques, and gel-filtration through Sephadex G-75 . The exotoxin is of a protein nature and consists perhaps of two subunits . The molecular weights of the exotoxin and its subunits as estimated by SDS-PAGE were 40 000, 25 000, and 15 000, respectively . The toxic properties of exotoxin were destroyed upon heating (60 degrees C, 30 min), treatment with trypsin (10 micrograms/ml, 37 degrees C, 30 min), and by the extremes of pH (pH 4.0 or 10;0 24 hrs) . Homologous antibodies readily neutralized the exotoxin while commercial diphtheria antitoxin had no effects . No immunological cross-reactivity was revealed between exotoxin of C . ulcerans and other bacterial toxins such as diphtheria toxin, enterotoxin from V . cholerae, and exotoxin A of P . aeruginosa. Curr Eye Res, 1981, 1(8), 479 - 85 Corneal ulcers in corneal transplants; Tuberville AW et al.; Twenty-nine eyes, representing an infection rate of 4.9%, developed corneal ulcers following corneal transplant surgery; 26 with available data are presented . All occurred in the graft or at the wound margin . The median postoperative time to ulcer development was 5.5 months . All eyes were on topical steroids when the ulcer developed . Other associated factors were: loose sutures, bandage lenses and eyes grafted for herpes simplex keratitis . Ninety percent of the ulcers had one or more of these factors . Positive cultures for organisms were obtained in 75% and positive gram stain in 68% of the ulcers . Nine genera of bacteria were cultured; S . epidermidis, S . pneumoniae, P . aeruginosa and Corynebacterium were the most common organisms . Ninety-five percent of the bacteria tested were sensitive to gentamicin . Visual reduction occurred in 46% of the cases overall; herpetic corneas had an 88% incidence of visual loss. Int J Immunopharmacol, 1981, 3(2), 115 - 22 Antitumor activity of intralesionally administered Nocardia opaca preparations in rat and mouse tumors: a comparison with BCG and Corynebacterium parvum; Barot-Ciorbaru R et al.; Three Nocardia products: delipidated cells, lysozyme digest and Nocardia Water Soluble Mitogen (NW SM), have been assayed in regression experiments and compared with living BCG and killed C . parvum in rat and mouse fibrosarcomas transplanted intradermally . Intratumor injection of these Nocardia products induced regression in the BCG sensitive McFiFi2 (S) tumor . These substances were active at a dose of 1 mg, the lysozyme extract and NW SM also being active at 0.1 mg . Association with mineral or vegetable oil increased the efficiency of delipidated cells, and under these conditions, regression of tumors implanted contralaterally to treated tumors was also obtained. Ann Biol Clin (Paris), 1981, 39(3), 127 - 30 {Characterisation of Corynebacterium vaginale by the fluorescent antibody technic (author's transl)}; Bourlioux P et al.; When using the serum of rabbits immunized against the reference vaginal strain 594 of Gardner and Dukes, the authors tried to find an antigenic identity between this strain and the usual strains that can ordinarily be detected in vaginal samples . The immunizing process that has been used is indirect immunofluorescence . Through these studies, it is possible to conclude that, besides usual strains identical to the reference strain, some specific strains can be detected that have the same microscopic and cultural characteristics as Corynebacterium vaginale but that are deprived of its antigenic characteristics. J Clin Microbiol, 1981 Jan, 13(1), 85 - 88 Detection of bacteriuria: manual screening test and early examination of agar plates; Murray PR et al.; We assessed two procedures for the initial processing of urine specimens: (i) manual screening of urine samples by inoculation into tryptic soy broth and incubation for 3 to 6 h, and (ii) examination of agar plates inoculated with urine and incubated for 4 to 6 h . Of the urine samples with greater than 10(5) colony-forming units per ml, 73.6 and 90.1% were detected with the broth cultures after 3 and 6 h of incubation, respectively . The organisms not detected at 6 h were Corynebacterium spp., Lactobacillus spp., and one of six isolates of yeasts . When inoculated plates were examined for growth, 53.3 and 80.0% of the specimens with greater than 10(5) colony-forming units per ml were detected after 4 and 6 h of incubation, respectively . Of the cultures with significant growth of Enterobacteriaceae or Pseudomonas spp., 95% were detected on the plates after 6 h of incubation. J Clin Microbiol, 1981 Jan, 13(1), 219 - 21 Comparison of three techniques for isolation of Rhodococcus (Corynebacterium) equi from contaminated sources; Barton MD et al.; Inoculation of a liquid medium comprised of Trypti