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Biomedical subjects

P D Walzer

Publications and source records attributed to P D Walzer.

At least 73 records · Page 4Linked to original sources
PubMed1988

Blastogenic responses to Pneumocystis carinii among patients with human immunodeficiency (HIV) infection.

Proliferative responses by human peripheral blood mononuclear cells and rat spleen cells were measured to Pneumocystis carinii in a blastogenic assay using organisms obtained from rat lungs and propagated in tissue culture as the antigen. Responses occurred only in subjects with known prior exposure to P. carinii and the magnitude of the response varied with the number of organisms present in the antigen preparation and days in culture. Healthy human adults showed higher proliferative responses to P. carinii than did patients with Class II (asymptomatic) or Class III (lymphadenopathy) human immunodeficiency virus (HIV) infection. No responses to the preparation were found among Class IV HIV patients with the acquired immunodeficiency syndrome, including those with prior episodes of P. carinii pneumonia or those receiving azidothymidine. Overall, the blastogenic responses obtained with P. carinii were similar to those obtained with tetanus toxoid and phytohemagglutinin, and correlated well with the number of circulating CD4 cells. The data suggest that the blastogenic assay using tissue culture-derived rat P. carinii is specific for the organism and should be helpful in studying the cellular immune responses in pneumocystosis among different human patient populations.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Analysis of the developmental stages of Pneumocystis carinii, in vitro.

Rat derived Pneumocystis carinii cultured in vitro was analyzed by a variety of light microscopic and staining techniques for identification of developmental stages and changes in these populations over time in culture. Evaluation of culture dynamics based on a limited number of life cycle stages indicated that trophic replication contributed significantly to the observed growth in vitro. Identification of additional life cycle stages, particularly early cyst forms, suggested that the process of maturation from early precyst to mature cyst may also contribute to the net growth. All developmental stages identified from culture were verified by their presence in stained impression smears of infected rat lung. Based on these data, a tentative life cycle for P. carinii in vitro has been proposed.

Animals↗
PubMed1987

Strongyloidiasis in US veterans of the Vietnam and other wars.

The prevalence of strongyloidiasis among American veterans of the Vietnam and other wars was evaluated by testing several groups of veterans for serum IgG antibodies against Strongyloides stercoralis antigens, using an enzyme-linked immunosorbent assay. Of 493 Vietnam veterans, eight (1.6%) were seropositive. Of 60 patients with abdominal symptoms and/or elevated eosinophilia (greater than 0.08 [greater than 8%]) admitted to the Cincinnati Veterans Administration Medical Center, 12 (5%) were seropositive. Of 147 residents of a Veterans Administration-operated nursing home, six (4%) were seropositive. All infected patients in the latter two groups were World War II veterans. The usefulness of the enzyme-linked immunosorbent assay as a screening tool for at-risk groups is suggested by the finding that S stercoralis larvae were demonstrated in most seropositive patients when a sufficient number of fresh stools were examined.

Adult↗
PubMed1987

A comparison of the antigenic characteristics of rat and human Pneumocystis carinii by immunoblotting.

The antigenic characteristics of rat Pneumocystis carinii obtained from infected lungs and grown in tissue culture were compared with the properties of human P. carinii obtained from the lungs of AIDS and non-AIDS patients by the immunoblotting technique, using different sources of antibody. Major immunoreactive bands of 45, 50, and 116 kd were found in both lung and tissue culture-derived rat P. carinii, suggesting the organism retains its antigenic characteristics in short-term culture. The principal immunoreactive bands in human P. carinii included a band of 40 kd, and to a lesser extent, a band of 66 kd; these antigens were found in the lungs of six and seven AIDS patients but in only one of eight non-AIDS patients with pneumocystosis. The rat and human P. carinii antigens reacted with sera from immunized rabbits, from rats with pneumocystosis and prolonged environmental exposure to the organism, from AIDS and non-AIDS P. carinii patients, and from healthy blood donors. Reactivity of these antigens could be removed by adsorption of antisera with P. carinii-infected lungs but not with normal lungs or lungs infected with bacteria and fungi. We conclude that rat and human P. carinii have shared, as well as species-specific, antigenic determinants, which should be useful for a variety of studies with this organism.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pneumocystis carinii: immunoblotting and immunofluorescent analyses of serum antibodies during experimental rat infection and recovery.

Serum antibodies to Pneumocystis carinii were measured in rats by the indirect fluorescent antibody and immunoblotting techniques. Serum IgG and IgM antibodies developed with environmental exposure to P. carinii, were low or absent during immunosuppression to induce P. carinii pneumonia, and rose when immunosuppression was withdrawn. The IgG and IgM antibodies formed at the same time, but the titers of each antibody varied in individual rats. Serum IgG antibodies by immunoblotting recognized bands of 45, 50, and 116 kDa as the major reactive moieties of P. carinii. The bands were detected with sera from all rat groups in a temporal pattern which closely paralleled antibody formation by indirect immunofluorescence. The pattern of immunoblotting reactivity varied among individual rats, particularly with immunosuppression. Additional bands were detected with prolonged exposure to P. carinii. Thus, the rat makes both IgG and IgM antibodies to P. carinii, and specific P. carinii antigens identified in this immune response might be targeted for future serologic studies.

Animals↗
PubMed1987

Comparison of histologic and quantitative techniques in evaluation of therapy for experimental Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia was induced in rats by the administration of corticosteroids, and histologic and quantitative techniques were compared in the evaluation of the severity of the disease and response to therapy. A highly significant correlation was found between the histologic score of the extent of alveolar involvement (the standard method of assessment) and the number of P. carinii cysts and nuclei in lung homogenates, lung weight, and lung weight/body weight ratio. Clear differences were noted between rats which responded well and rats which responded poorly to therapy by all techniques. Quantitation of P. carinii cysts and nuclei revealed a 10(4)-fold reduction in organism burden with successful treatment. Thus, these techniques should be helpful in the development of testing of new antimicrobial agents in the rat model of pneumocystosis.

Animals↗
PubMed1987

Seroepidemiologic study of giardiasis patients and high-risk groups in a midwestern city in the United States.

Serum antibodies to Giardia lamblia were measured in giardiasis patients, in groups at high risk for intestinal parasite infection, and in controls by an indirect fluorescent antibody (IFA) technique. Symptomatic patients had the highest antibody titers, and antibodies remained present for up to 18 months in persons with chronic infection. Indochinese refugees and male homosexuals with the acquired immunodeficiency syndrome (AIDS) and pre-AIDS had higher mean antibody levels than did healthy controls, whereas sewer and highway maintenance workers had levels similar to those of controls. Serum antibodies to Entamoeba histolytica measured by an indirect hemagglutination antibody technique were detected in only a few Indochinese refugees. We conclude that serology is a promising tool in G. lamblia epidemiology and that further population studies would be of interest.

Entamoeba histolytica↗
PubMed1986

Techniques for examining Pneumocystis carinii in fresh specimens.

Pneumocystis carinii was examined in fresh preparations of infected rat lung homogenates and tissue culture supernatants by a variety of light microscope techniques, vital dyes, and histologic stains. Phase-contrast microscopy, Nomarski interference-contrast microscopy, and bright-field microscopy with oblique illumination provided excellent views of P. carinii. Erythrosin B, and to a lesser extent trypan blue, were helpful in assessing organism viability. The use of Triton X-100-Giemsa stain permitted differentiation of the developmental stages in the P. carinii life cycle. The techniques developed here are easily adaptable to the microbiology laboratory and thus should have important clinical and research applications.

Animals↗
PubMed1986

Diagnostic implications of parasite-specific immune responses in immunocompromised patients with strongyloidiasis.

Parasite-specific humoral and cellular immune responses were evaluated in in nine immunosuppressed patients with Strongyloides stercoralis infection. Four patients had the disseminated form of the disease, and five had serious manifestations without evidence of hyperinfection. All patients had high levels of immunoglobulin G (IgG) antibodies directed against S. stercoralis larval antigens as detected by the enzyme-linked immunosorbent assay. Seven patients had both elevated total serum IgE and parasite-specific IgE antibodies detected by a modified radioimmunoassay. The hyperinfected patients differed significantly from the nonhyperinfected group in total and specific IgE levels and peripheral eosinophilia but not in specific IgG levels. None of the patients tested exhibited significant in vitro lymphoproliferative responses to parasite antigens. Our results indicated that the possibility of a protective role of IgE and eosinophils in strongyloidiasis deserves further investigation. In addition, we suggest that the enzyme-linked immunosorbent assay for specific IgG antibodies may have an important place in the diagnosis of strongyloidiasis in immunocompetent as well as in immunocompromised patients.

Adult↗
PubMed1986

Inhibition of polyamine biosynthesis by alpha-difluoromethylornithine in African trypanosomes and Pneumocystis carinii as a basis of chemotherapy: biochemical and clinical aspects.

The symposium provided dramatic evidence of the value of the use of polyamine inhibition via alpha-difluoromethylornithine (DFMO, eflornithine) for advances in chemotherapy of Trypanosoma brucei gambiense sleeping sickness and Pneumocystis carinii pneumonia in acquired immune deficiency syndrome (AIDS) and also for further understanding the metabolic importance of the ubiquitous polyamines in these organisms.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Specific IgE responses in human strongyloidiasis.

IgE antibodies directed against Strongyloides stercoralis larval antigens were measured by a newly developed radioallergosorbant test (RAST). One hundred and fifty-two samples of sera from patients with parasitologically proven S. stercoralis infection were tested. One hundred and thirty-six of these (89.5%) were positive for parasite-specific IgE. Of 50 presumably non-infected North American adult control sera, 49 (98%) were negative. All sera from patients with other parasites were negative, except for two sera from subjects with Ascaris lumbricoides, who exhibited low positivity. Of eight sera from non-infected patients with allergies and high IgE levels, one was weakly positive, and the other seven were negative. Considerable individual variability was present in the levels of specific IgE as measured by the RAST in the infected patients. Significant differences were also found among the three major demographic groups which composed our study population, with Asians having higher values than Latin Americans and the latter having higher values than North American patients. We conclude that the majority of patients with strongyloidiasis develop IgE antibodies directed against antigens from filariform larvae, the invasive form of the parasite. While the functional significance of this response remains to be defined, the RAST for IgE may be a useful adjunct in the immunological evaluation of these patients.

Adolescent↗
PubMed1985

Pneumocystis carinii: growth variables and estimates in the A549 and WI-38 VA13 human cell lines.

Recent studies indicate that rat Pneumocystis carinii can be propagated in the A549 cell line, an alveolar epithelioid cell line derived from human lung carcinoma. In the present study, growth of P. carinii was compared in the A549 cell line and the WI-38 VA13 subline 2RA, an SV40 transformed derivative of the human fetal fibroblast cell line with epithelioid morphology. Similar P. carinii growth occurred in both cell lines under optimal conditions, but the WI-38 VA13 cell line was usually more sensitive to changes in the culture system. Growth of P. carinii was affected by temperature, environmental gas mixture, motion of the cultures, and source and concentration of serum additives, but not by the presence of antibodies in the medium. A technique was developed for quantitating P. carinii in the lung inoculum which permitted analysis of P. carinii growth during the first 24 hr of culture. Inverted microscope and oil immersion phase-contrast microscopy were very helpful in monitoring the organism's stages of development and viability. Thus, this culture system should be helpful in establishing standard methodology for in vitro work with P. carinii.

Ammonium Chloride↗
PubMed1985

Method of testing the susceptibility of Pneumocystis carinii to antimicrobial agents in vitro.

Rat Pneumocystis carinii grown on lung-derived cell lines in tissue culture flasks and multiwell plates was tested for susceptibility to four antimicrobial agents currently being used in the treatment of human pneumocystosis. Standard criteria for organism quantitation, replication, viability, and inoculum size were established. Trimethoprim-sulfamethoxazole inhibited P. carinii growth at a concentration ratio of 1:19 microgram/ml, and pentamidine isethionate was active at 0.1 microgram/ml. alpha-Difluoromethylornithine, an inhibitor of polyamine biosynthesis, inhibited P. carinii at a concentration of 1 mM once erythrocytes (which are high in polyamine content) were removed from the inoculum; this effect could be overcome by the polyamine putrescine. Dapsone suppressed P. carinii replication at a dose of 0.1 microgram/ml, but this effect was lost after 72 h in culture. Overall, the reduction in P. carinii numbers with these drugs was relatively modest (45 to 84%), which is consistent with their lack of lethal effects on the organism in vivo. Thus, the system presented here should be helpful in developing new anti-P. carinii agents and in elucidating their mechanism of action.

Animals↗