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Biomedical subjects

R F Schell

Publications and source records attributed to R F Schell.

At least 109 records · Page 6Linked to original sources

Immune serum confers protection against syphilitic infection on hamsters.

Pooled serum from hamsters immune to syphilitic infection conferred complete protection on recipient hamsters challenged with Treponema pallidum subsp. endemicum. Cutaneous lesions did not develop, and the recipients' lymph nodes weighed less than those of controls and contained no treponemes. Treponemicidal activity in the pooled immune serum was relatively high. When treponemes were incubated in immune serum and complement and the suspension was then inoculated into hamsters, recipients developed neither lesions nor enlarged lymph nodes teeming with treponemes. With hamsters already infected for several weeks, however, immune serum failed to impair or influence the progression of syphilis. Treponemes were eliminated only when immune serum was administered within a short time of syphilitic infection. These results demonstrate that hamsters develop an effective serum-mediated treponemicidal response, but this response is not sufficient to eliminate treponemes at the primary foci of infection.

Animals↗

Detection and quantitation of simulated anaerobic bacteremia by centrifugation and filtration.

Fresh human whole blood was inoculated with various anaerobic bacteria or with combinations of anaerobic, facultatively anaerobic, and aerobic microorganisms (3 to 28 microorganisms per ml). The seeded blood was then layered on a reduced Ficoll-Hypaque gradient (density, 1.093 g/ml) and centrifuged (400 X g) for 30 min at ambient temperature. The entire gradient (plasma, leukocytes, and Ficoll-Hypaque) was removed and filtered anaerobically through a 0.45-micron membrane filter. The filters were then placed on reduced chocolate Mueller-Hinton agar plates and incubated at 35 degrees C in humidified atmosphere containing 85% N2, 10% H, and 5% CO2 or in air containing 5% CO2. No statistically significant differences were detected between the numbers of microorganisms recovered (alone or in combination) by filtration and by direct culturing of the original inoculum. All organisms were detected within 30 h after filtration. This technique has excellent sensitivity.

Anaerobiosis↗

In vitro antimicrobial activity of ceftizoxime.

The antimicrobial activity of ceftizoxime was compared to cefamandole, cefoperazone, cefotaxime, cephalothin, and lamoxactam (moxalactam) against 549 bacteria. It had activity similar to cefotaxime and lamoxactam against most members of the Enterobacteriaceae. Ceftizoxime should prove useful against gram-negative bacteria except Pseudomonas aeruginosa and Acinetobacter spp.

Bacteria↗

Effect of local and systemic macrophage activation in hamsters on infection with Treponema pertenue and Treponema pallidum Bosnia A.

The role of nonspecific macrophage activation in the destruction of treponemes needs to be defined. Studies have been hindered by an inability to confirm that macrophages have enhanced bactericidal activity at the site of treponemal infection. We show that subcutaneous and intravenous vaccination with BCG (Mycobacterium bovis) induces macrophage activation in hamsters, as determined by an enhanced ability to suppress the growth of Listeria monocytogenes in the livers, spleens, and inguinal lymph nodes. However, hamsters challenged in the inguinal region with Treponema pertenue during periods of enhanced microbial resistance (3 to 8 weeks after BCG vaccination) developed lesions faster and with more necrosis. Increased numbers of treponemes were recovered from the regional lymph nodes of BCG-vaccinated hamsters than from nonvaccinated controls, although the differences were not statistically significant. No pathological differences were detected in BCG-vaccinated and non-vaccinated hamsters challenged with Treponema pallidum Bosnia A. These studies demonstrate that BCG vaccination influences the pathogenesis of some treponemal diseases without inducing macrophage-mediated treponemicidal activity.

Animals↗

Activity of nine antimicrobial agents against Lancefield group C and group G streptococci.

The activity of nine antimicrobial agents against 44 strains of group C and group G streptococci was studied using a microtiter broth dilution technique. Several antimicrobial agents, including third-generation cephalosporins, the newer semisynthetic penicillins, and erythromycin, exhibited good activity against the organisms. Occasional tolerance to various agents was observed. No cross-tolerance was observed in this study.

Anti-Bacterial Agents↗

Transfer of resistance with syphilitic immune cells: lack of correlation with mitogenic activity.

Hamsters infected intradermally with Treponema pallidum Bosnia A develop extensive chronic skin lesions, usually accompanied by metastatic lesions involving the paws, lips, and anal region and by lymph nodes teeming with treponemes. Throughout the course of syphilitic infection, cells from the inguinal lymph nodes responded poorly to stimulation with suboptimal, optimal, or supraoptimal concentrations of concanavalin A, phytohemagglutinin P, or lipopolysaccharide. The response of syphilitic spleen cells was variable. Depression of lymphocyte reactivity to mitogens preceded clinical signs of infection and correlated well with the chronicity of syphilitic infection. When syphilitic hamsters were treated with a curative dose of penicillin, their mitogenic responses returned to normal or were slightly elevated. No correlation existed between mitogenic activity and the ability of lymphoid cells to induce an effective immune response when transferred to normal recipients. No significant differences in protection were detected among recipients of immune cells with or without activity to mitogens. These results demonstrate that lymphocyte transformation by mitogens in vitro is not a measure of effective treponemicidal activity and so may not be a valid indicator of the protective immune status of syphilitic animals.

Animals↗

Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes.

Hamsters infected with Treponema pallidum Nichols (venereal syphilis), T. pallidum Bosnia A (endemic syphilis), or T. pertenue (frambesia, or yaws) developed substantial resistance to homologous reinfection. Hamsters infected for 10 weeks developed no lesions, and their lymph nodes contained fewer treponemes after reinfection with the same strain. The degree of cross-resistance among the treponemes correlated well with pathological changes occurring in infected hamsters and with the persistence of treponemal antigen during primary infection. Only hamsters infected with T. pallidum Bosnia A developed substantial resistance to heterologous reinfection. These animals also had extensive chronic skin lesions and lymph nodes containing measurable numbers of treponemes. Frambesial hamsters had less extensive lesions and were resistant to T. pallidum Nichols and, to a lesser extent, to T. pallidum Bosnia A. Hamsters infected with T. pallidum Nichols developed no cutaneous lesions and were resistant only to reinfection with T. pertenue. Confirmation of these results was obtained in normal hamsters infused with syphilitic (Nichols or Bosnia A) or frambesial immune cells and challenged with homologous or heterologous treponemes.

Animals↗

Solid-phase fluoroimmunoassay for treponemal antibody.

An objective, solid-phase fluoroimmunoassay for treponemal antibody was developed with a lysate of virulent Treponema pallidum (Nichols strain) adsorbed on cellulose acetate disks. A probe containing both the antigen and control disks is inserted successively into a serum specimen dilution, a buffer rinse, fluoroscein isothiocyanate-conjugated goat anti-human immunoglobulin G, and a second buffer rinse. Fluorescence signal units are measured with a fluorometer. To establish test calibration curves, the corrected fluorescence values (antigen disk minus control) of reference sera are plotted against indirect fluorescent treponemal antibody test titers. The corrected fluorescence values obtained for 62 sera reactive in the fluorescent treponemal antibody absorption test ranged from 64 to 178; values for 66 nonreactive sera ranged from 20 to 46. Thus, the solid-phase fluoroimmunoassay for treponemal antibody clearly separated specimens from patients with documented primary, secondary, or latent disease from fluorescent treponemal antibody absorption-nonreactive sera. The test is technically simple and produces an objective quantitative result.

Antibodies, Bacterial↗

Rapid detection of simulated bacteremia by centrifugation and filtration.

A centrifugation-filtration procedure was developed to expedite the recovery of microorganisms from blood. Fresh whole human blood was inoculated with various aerobic and facultatively anaerobic microorganisms (3 to 18 per ml). The seeded blood was carefully overlaid on a Ficoll-Hypaque gradient (density, 1.114 g/ml) and centrifuged (400 x g) for 45 min at ambient temperature. The entire gradient (plasma, leukocytes, and Ficoll-Hypaque) was removed and filtered through a 0.22-micrometer membrane filter. The filters were then placed on chocolate agar and incubated at 35 degrees C in humidified air containing 5% CO2. No statistically significant differences were detected between the numbers of microorganisms recovered by filtration and by direct culture of the original inoculum. Most microorganisms were detected within 18 h after filtration. This system has excellent sensitivity and negligible toxicity.

Blood↗

Mitogenic responses of hamsters infected with Treponema pertenue Lack of correlation with passive transfer of resistance.

Infection of the CB/Ss Lak hamster with Treponema pertenue is characterised by chronic cutaneous lesions and lymph nodes teeming with treponemes. Throughout the course of infection lymph node and spleen cells responded poorly to the mitogens concanavalin A, phytohaemagglutinin, and lipopolysaccharide. This impairment preceded clinical signs of infection and correlated well with the chronicity of framboesial infection. High concentrations of antigen from T pertenue, but not from the non-pathogenic Treponema phagedenis, depressed the mitogenic response of normal lymphoid cells. After framboesial hamsters were treated with penicillin the mitogenic activities of their lymph node and spleen cells were similar to or slightly raised above those of controls. No significant differences were detected among recipients of framboesial immune cells with or without mitogenic activity. Recipients of immune lymph node and spleen cells from penicillin-treated or non-penicillin-treated animals had no cutaneous lesions 21 days after infection and had significantly lower lymph node weights and fewer treponemes per node than recipients of cells from normal penicillin-treated or non-penicillin-treated animals. Since lymphocyte transformation in vitro does not correlate with in-vivo treponemicidal activity, it is not a valid approach to assess the protective immune capacity of the framboesial host.

Animals↗

Cefoxitin therapy in aerobic, anaerobic, and mixed aerobic-anaerobic infections.

Cefoxitin, a new beta-lactamase-resistant cephamycin, was evaluated in 66 patients for clinical and bacteriological efficacy, serum levels, tolerance, and toxicity. Seventeen patients had soft tissue infections, 14 had pleuropulmonary infections, 14 had intraabdominal infections, 13 had pelvic infections, and 8 had urinary tract infections. Among the 66 patients, 62 were cured and 4 could not be evaluated. Twelve patients had hospital-acquired infections, 31 had underlying disease, and 45 required a surgical procedure. Isolates included 116 aerobic and 72 anaerobic bacteria. Cefoxitin was more active than cephalothin against facultative and obligate anaerobic gram-negative organisms isolated from these patients. Mean peak cefoxitin levels in sera were 52 micrograms/ml after a 2-g infusion and 30 micrograms/ml after a 1-g infusion. Phlebitis occurred in two patients, eosinophilia in one, rash in two, vasculitis in one, and transient rises in SGOT and SGPT in two. Cefoxitin appears to be a safe and effective drug for the treatment of many aerobic, anaerobic, and mixed aerobic-anaerobic infections.

Adult↗

Evidence for depletion of Ia+ macrophages and associated immunosuppression in African trypanosomiasis.

The percentage of Ia antigen-bearing (Ia+) macrophages was significantly lower in mice infected with Trypanosoma rhodesiense than in normal controls. The degree of difference varied with the source of macrophages and time course of infection. The percentage of Ia+ macrophages isolated from spleens 10 days after infection was 71% of that in the controls, and depletion continued until Ia+ macrophages were almost undetectable 30 days after infection. The rate of depletion was slower in the peritoneal cavity. In contrast, Ia+ macrophages were not significantly depleted from the lymph nodes until 30 days after infection. The ability of macrophages from trypanosome-infected mice to present listerial antigen to sensitized T cells was significantly lower than in controls. Immune T cells had significantly less ability (43% of controls) to incorporate thymidine when exposed to splenic macrophages from infected mice during the early stage of disease. This loss of antigen presentation increased during the course of infection. Peritoneal macrophages also exhibited an early loss of ability to present antigen, but no significant decline occurred thereafter. No significant loss of antigen had occurred in the lymph node macrophages 10 days after infection, but during the later stages of the disease a significant loss was detected. Treatment of macrophages from infected and control mice with anti-Iab serum and complement inhibited their ability to present antigen. Our results demonstrate that Ia+ macrophages and their distribution can influence the ability of infected animals to process antigens and may therefore account in part for the immunosuppression observed in trypanosomiasis.

Animals↗

Use of cefamandole in the treatment of soft tissue and skeletal infections.

In review of our data, 12 of 38 patients (31.5 percent) had adverse drug reactions, a somewhat bothersome factor. Disturbing side effects of leukopenia and pancytopenia were seen in two patients, respectively, who were receiving cefamandole 12 g/d. Other cephalosporins, including cephalothin and cefazolin, have been reported to cause leukopenia. Eosinophilia and elevations of alkaline phosphatase and SGOT levels were noted with other cephalosporins. We observed no adverse clinical reactions associated with these findings. Although our study was able to demonstrate the therapeutic effectiveness of cefamandole in the treatment of soft tissue and skeletal infections, it should be reemphasized that cefamandole should be used only as an alternative treatment for the penicillin-allergic patient. In reality, a first-generation cephalosporin should be used for gram-positive organisms if one is required in soft tissue infections.

Abscess↗

Endemic syphilis: transfer of resistance to Treponema pallidum strain Bosnia A in hamsters with a cell suspension enriched in thymus-derived cells.

Direct evidence for involvement of thymus-derived (T) cells in host defense against syphilitic infection is presented. Irradiated, bone marrow-reconstituted hamsters receiving cells from hamsters immune to infection with Treponema pallidum strain Bosnia A had significantly lower weights and fewer treponemes per lymph node than animals that had received normal lymphoid cells or only normal bone marrow cells. Cell suspensions enriched in T cells from immune hamsters were obtained by sequential filtration of pooled spleen and lymph node cells through glass- and nylon-wool columns. The fractionated suspensions of cells responded poorly to stimulation by phytohemagglutinin, Escherichia coli lipopolysaccharide, and dextran sulfate, but responded relatively strongly to the T-cell mitogen, convanavalin A. After fractionation the proportion of cells susceptible to antithymocyte serum and complement increased significantly. These immune cell suspensions depleted of bone marrow-derived cells closely resembled unfractionated suspensions in their ability to confer resistance to challenge with T. pallidium.

Animals↗

LSH hamster model of syphilitic infection.

The inbred LSH/Se LAK strain of hamster can be infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis. When infected, this strain consistently produced extensive chronic skin lesions that persisted for 6 to 9 months, even in the presence of peak antitreponemal antibody titers. The lymph nodes increased in weight and contained measurable numbers of treponemes. This infection also gave the hamster cross-immunity to T. pallidum Nichols and Treponema pertenue, the causative agents of venereal syphilis and frambesia, respectively. LSH hamsters are thus an excellent model to study the immune response mechanisms to syphilitic infection.

Animals↗

Evaluation of ten anaerobic blood culture media.

Selection of an anaerobic blood culture based upon clinical findings that have compared the isolation rates of bacteremic agents from different blood culture media. No agreement has been reached as to which of the commercially available blood culture media is optimal for detection of bacteremia. The purpose of this study was to determine the rates of recovery of anaerobic microorganisms from various anaerobic blood culture media. The blood culture media were inoculated with a small inoculum of microorganisms in the presence or absence of an erythrocyte-serum mixture. The results demonstrated that the type of medium and the erythrocyte-serum mixture influenced the ability of blood culture media to support the growth of microorganisms. The majority of the media failed to support the growth of 87% or more of the microorganisms within four days after inoculation. Pre-reduced brain-heart infusion broth supported the growth of a larger proportion of microorganisms than the other types of blood culture media.

Anaerobiosis↗