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Biomedical subjects

P D Walzer

Publications and source records attributed to P D Walzer.

At least 91 records · Page 5Linked to original sources
PubMed1984

Growth and serial passage of Pneumocystis carinii in the A549 cell line.

Pneumocystis carinii obtained from infected rats and patients was cultured in the A549 cell line, a presumptive alveolar type 2 cell line derived from a human lung carcinoma. Standard criteria were established for organism sampling, quantitation, and growth. The trophozoite form of P. carinii was a more sensitive indicator of growth than was the cyst. Rat P. carinii increased 10-fold in primary culture and could be serially passed three additional times to new cultures; success in growing human P. carinii was limited and appeared to be related to the quality of the specimen received for culture. Growth pattern experiments suggested that close interaction of P. carinii with the cell monolayer is an important step in the life cycle of the organism. Thus, the A549 culture system should be useful for in vitro studies of the immunobiology of P. carinii.

Animals↗
PubMed1984

Predisposing factors in Pneumocystis carinii pneumonia: effects of tetracycline, protein malnutrition, and corticosteroids on hosts.

Components of the immunosuppressive regimen used to reactivate latent Pneumocystis carinii infection were analyzed for their effects on the growth, nutrition, and lymphoid system of hosts. Rats that were administered either tetracycline or a low-protein (8%) diet alone for 7 weeks developed few abnormalities, but animals on the combined regimen developed lower body and lymphoid organ weights, lower serum albumin levels, and fewer circulating lymphocytes. Rats that were administered corticosteroids and tetracycline experienced severe wasting, debilitation, and generalized lymphocyte depletion; the low-protein diet increased the magnitude of these changes. Alterations in the frequency of occurrence of specific lymphocyte subsets occurred only in rats given corticosteroids and consisted mainly of a greater decline in peripheral blood T helper cells than in T suppressor cells. The data suggest that long-term tetracycline administration and a low-protein diet have a variety of adverse effects on the host which enhance the immunosuppressive properties of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1984

The effect of corticosteroid treatment on the cell surface glycocalyx of the rat pulmonary alveolus: relevance to the host-parasite relationship in pneumocystis carinii infection.

Pneumocystis carinii infection is characterized by the attachment of P. Carinii to host alveolar type I cell and propagation of the organism with corticosteroid administration. We have examined the effects of corticosteroids on the cell surface glycocalyx of the pulmonary alveolus in rats by ultrastructural histochemistry using cationized ferritin, ruthenium red and concanavalin A-horseradish peroxidase techniques. In rats treated for 4 and 6 weeks, the amount of the alveolar cell surface glycocalyx was markedly decreased by all three techniques. The changes were most pronounced at the cell surface of the type I pneumocyte, and this may be important in the pathogenesis of P. carinii pneumonia.

Animals↗
PubMed1984

Lymphocyte changes during chronic administration of and withdrawal from corticosteroids: relation to Pneumocystis carinii pneumonia.

Corticosteroids were administered for up to 8 wk in adult Lewis rats to provoke Pneumocystis carinii pneumonia, and lymphocyte subsets were analyzed at different body sites with monoclonal antibodies by flow microfluorometry in a fluorescence activated cell sorter. The rats became chronically ill, debilitated, and exhibited marked involution of all lymphoid tissues. The lymphocytopenia was characterized in peripheral blood by a large fall in the frequency of T helper cells, and in the lungs by a fall in T helper (Th) cells and a rise in T suppressor (Ts) cells; at both sites there was reversal of the Th to Ts ratio. These changes were not found in the thymus, spleen, or bone marrow. When corticosteroids were withdrawn, the rats gained weight, cleared P. carinii from the lungs, and regenerated their lymphoid tissues. The lymphocyte subpopulations exhibited variation in their frequencies at different body sites, but gradually returned to baseline levels. Thus, in this model chronic corticosteroid administration results in profound generalized lymphocyte depletion and changes in the proportions of circulating and pulmonary T cell subsets. These abnormalities may be an important immunologic mechanism in the development of P. carinii pneumonia.

Adrenal Cortex Hormones↗
PubMed1983

Immunologic alterations in bronchoalveolar lavage fluid in the acquired immunodeficiency syndrome (AIDS).

The association of Pneumocystis carinii pneumonia and cytomegalovirus infection in apparently healthy intravenous drug abusers or homosexual males recently has been described. Two patients with this syndrome were seen recently at our institution. Bronchoalveolar lavage samples from these two patients, taken at the time of bronchoscopy, were analyzed. In both patients a significant increase in inflammatory cells (polymorphonuclear cells) and evidence for polyclonal B cell activation, as measured by a reverse hemolytic plaque assay was seen compared to normal persons (p less than 0.01 both comparisons). IgM and IgG anti-Pneumocystis carinii antibody titers were elevated in the lavage fluid of one patient each. One patient, originally diagnosed as having "Hamman-Rich Syndrome," demonstrated unequivocal chest X-ray improvement with prednisone therapy alone. These observations suggest that the lungs of these two patients were the site of an intense inflammatory response, which was not reflected in studies with peripheral blood.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Cellular responses in human strongyloidiasis.

Peripheral lymphocytes from 16 patients with chronic uncomplicated strongyloidiasis and 15 non-infected controls were stimulated in vitro with Strongyloides stercoralis larval antigens, other non-parasite antigens and the T cell mitogen phytohemagglutinin (PHA). In the presence of autologous plasma the patients' responses to Strongyloides antigens were similar to those of controls. When lymphocytes from nine patients were cultured in the presence of normal human serum, responses to parasite antigens were enhanced, while responses to other antigens and to PHA were unaffected. Lymphoproliferative responses to PHA were significantly lower in the patients' group than in the controls. These findings suggest that in chronic strongyloidiasis, in addition to a depression of T cell activity, factors are present in the patients' serum that inhibit parasite-specific cellular responses in vitro.

Cells, Cultured↗
PubMed1983

Experimental Pneumocystis carinii pneumonia in C3H/HeJ and C3HeB/FeJ mice.

C3H mice develop heavier degrees of Pneumocystis carinii pneumonia than other mouse strains tested. We have compared P. carinii pneumonia in two strains of C3H mice: C3H/HeJ mice, which are unresponsive to the effects of bacterial lipopolysaccharide (LPS), have defects in macrophage function, and have increased antibody responses to orally administered T-dependent antigens; and C3HeB/FeJ mice, which are immunologically normal. P. carinii pneumonia was induced by corticosteroids, and the intensity of the infection was judged by a semiquantitative histopathologic scoring system. Heavier degrees of infection were found in C3H/HeJ mice than in C3HeB/FeJ mice. Serum antibodies to P. carinii, measured by an indirect fluorescent antibody technique, were mainly of the IgG class in both strains of mice and varied inversely with the intensity of P. carinii infection in the lungs. Antibody levels were significantly higher in C3H/HeJ mice than in C3HeB/FeJ mice. These data suggest that C3H/HeJ have increased susceptibility to the effects of steroids of host defenses against P. carinii, and heightened serum antibody responses to the organism.

Adrenal Cortex Hormones↗
PubMed1982

Serum antibody responses to Pneumocystis carinii among different strains of normal and athymic mice.

Pneumocystis carinii infection was produced in normal mice by the administration of corticosteroids and in athymic mice by the transmission of exogenous mouse- or rat-derived organisms. Serum antibodies to P. carinii, measured by an indirect fluorescent-antibody technique, were found in five of six strains of normal mice. Although antibody titers varied widely among the control and steroid-treated mice, they were inversely proportional to the intensity of P. carinii infection in the lungs. In sequential studies, antibody titers were low during steroid administration but rose with steroid withdrawal. Antibodies were mainly of the immunoglobulin G (IgG) class; IgM antibodies also occurred, but IgA antibodies were rare. nu/nu mice rarely produced serum antibodies to P. carinii despite the fact that one strain was sensitive and the other was resistant to exogenous infection. nu/+ mice produced specific antibodies to rat and mouse P. carinii which were primarily IgG. Thus, the host produces antibodies to P. carinii which are mainly IgG and T-cell dependent; yet, these antibodies do not appear to be important in susceptibility or resistance to P. carinii infection.

Animals↗
PubMed1982

Epidemiologic features of Strongyloides stercoralis infection in an endemic area of the United States.

The epidemiologic features of Strongyloides stercoralis infection in Kentucky were studied by an analysis of clinical cases at the University of Kentucky Medical Center (UKMC); by an analysis of parasitologic records of the Kentucky Bureau for Health Services (KBHS); and by a prospective stool survey of school children in Clay County, located in southeastern Kentucky, an area of the state previously found to be highly endemic for intestinal parasites. S. stercoralis was the most common parasitic infection diagnosed at UKMC. The patients were predominantly white male adults who were over 50 years old, had an associated chronic or debilitating medical illness, were of low socioeconomic background, and resided in southeastern Kentucky. S. stercoralis was a common parasitic infection at KBHS ad the patients showed a similar geographic distribution. Of 561 Clay County children surveyed, 23.7% harbored one or more intestinal parasite pathogens and 3.0% had S. stercoralis. Thus, S. stercoralis remains highly endemic in Kentucky and may cause disease even in geriatric patients.

Adolescent↗
PubMed1981

Mechanism of pulmonary alveolar injury in experimental Pneumocystis carinii pneumonia in the rat.

Pneumocystis carinii pneumonia was produced in rats by the administration of corticosteroids and the permeability of the alveolar-capillary membrane was studied, using horseradish peroxidase (HRP) as an ultrastructural marker. The alveolar-capillary membrane was impermeable to HRP at 4 weeks of corticosteroid treatment as well as in control rats. However, by 7 weeks, when the Type I pneumocyte started to show degenerative changes, HRP leaked through the capillary endothelium, indicating changes in the permeability of the alveolar-capillary membrane. We conclude that this increased permeability is the first change which triggers the subsequent degeneration of the Type I pneumocyte. The possible pathogenesis of this increased permeability of the alveolar-capillary membrane is discussed in relation to the organism's attachment to the alveolar epithelium.

Animals↗
PubMed1981

Humoral immunity in experimental Pneumocystis carinii infection. I. Serum and bronchial lavage fluid antibody responses in rats.

Humoral immune responses to Pneumocystis carinii were studied in rats by an IFA technique. Serum IgG antibody titers to the organism were diminished in rats administered corticosteroids to produce P. carinii infection but rose with steroid tapering and clearance of the organism from the lungs. A similar pattern of changes occurred in total serum IgG and IgM but not IgA levels by single radial diffusion. Serum antibody titers developed in control rats housed in the same room for greater than or equal to 10 weeks with P. carinii--infected rats and in old but not young rats obtained from commercial breeders. Antibody titers in bronchial lavage fluid supernatants paralleled those in serum, but albumin levels were low and IgA was the only immunoglobulin detected. By contrast, P. carinii organisms in lavage fluid sediments had IgG, IgA, and IgM detected by IFA on their surface. We conclude that the host develops systemic and local antibodies to P. carinii with both active infection and prolonged environmental exposure.

Animals↗
PubMed1981

Effect of proteolytic enzymes on Pneumocystis carinii in rat lung tissue.

Rat lung homogenates heavily infected with Pneumocystis carinii were digested with trypsin and pronase. Pneumocystis carinii cysts were examined by light and electron microscopy, and by an indirect fluorescent antibody (IFA) technique. Cysts digested with trypsin exhibited swelling of their cell wall but stained brightly by IFA; cysts digested with pronase lost their cell wall and ability to stain by IFA. These effects were related to the concentration of the enzyme and duration of exposure. The data suggest that the antigenic determinants of P. carinii cysts reside in the cell wall.

Animals↗
PubMed1981

Clinical features of Strongyloides stercoralis infection in an endemic area of the United States.

Infection with Strongyloides stercoralis, the most common intestinal parasite at our hospital, was encountered in 56 patients over a 3-yr period. The majority of the patients were male adults over 50 years old who had a chronic debilitating associated illness; about half the patients were immunocompromised. Strongyloidiasis was usually a chronic relapsing illness of mild to moderate severity characterized by gastrointestinal complaints (diarrhea, pain, tenderness, nausea, vomiting) and peripheral eosinophilia. Hypoalbuminemia also occurred. Stool examination for larvae was an effective method of diagnosing the parasite, and treatment with thiabendazole was usually successful. The frequent occurrence of S. stercoralis in geriatric patients with other medical problems and the delays in making the diagnosis suggest that the clinical spectrum of strongyloidiasis is greater than generally appreciated by the medical profession. Increased awareness of S. stercoralis is important to prevent the hyperinfection syndrome, which was estimated to occur in 1.5-2.5% of our patients.

Adolescent↗