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Biomedical subjects

D Pappagianis

Publications and source records attributed to D Pappagianis.

At least 73 records · Page 4Linked to original sources

Comparison and diagnostic value of the coccidioidin heat-stable (HS and tube precipitin) antigens in immunodiffusion.

Coccidioides immitis produces two unrelated heat-stable antigens which are diagnostically useful in immunodiffusion tests. One, the tube precipitin antigen, is valuable for specifically detecting antibody and diagnosing early primary cases of coccidioidomycosis. The other heat-stable antigen, designated HS, is the most useful coccidioidin antigen for specifically immunoidentifying C. immitis cultures. Both of the antigens were compared and evaluated for their usefulness in exoantigen and serologic immunodiffusion tests. Our studies indicated that the detection of tube precipitin antigen is of limited value for immunoidentifying C. immitis isolates because the antigen is common to certain gymnoascaceous saprophytes, such as Arachniotus, Auxarthron, and Malbranchea species, that form alternate arthroconidia. Antibodies to HS antigens are infrequently found in human sera from patients with coccidioidomycosis and are thus of little serodiagnostic value.

Antibodies, Fungal↗

Immunologic responsiveness and safety associated with the Coccidioides immitis spherule vaccine in volunteers of white, black, and Filipino ancestry.

A trial of the killed Coccidioides immitis spherule vaccine was undertaken with 151 healthy skin test negative adult volunteers and controls to evaluate the safety of selected regimens, the induction of humoral and cell-mediated immune responses, and to determine if there were immunogenetic differences in these responses. The vaccine was given as three intra-deltoid doses over 8 weeks. No severe systemic symptoms were noted, although 3% of 3.5 mg doses (but no 1.75 mg doses) were associated with severe local reactions. Half the vaccinees had skin test conversions, which generally persisted greater than or equal to 6 months, two-thirds showed boosting of lymphocyte transformation in vitro, and 16% given three 3.5 mg doses developed antibody. There was an association between degree of local adverse vaccine reaction and immunostimulation, and a trend to immune response in persons of O blood type and with some HLA phenotypes. There was no evidence of deficient response to vaccination in subpopulations known to respond to coccidioidal infection poorly. A regimen of three 1.75 mg doses appears to be safe and without reduced immunogenicity, and there is no evidence dosage modification for certain subpopulations would be necessary in efficacy studies.

Adolescent↗

Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis.

Previously, it was shown that arthroconidia of Coccidioides immitis appear to inhibit phagosome-lysosome fusion and survive within normal mouse peritoneal macrophages. However, when these macrophages are exposed to antigen-stimulated T lymphocytes from immune mice, activation occurs, leading to enhanced phagosome-lysosome fusion and killing of C. immitis. Results indicate that the activation of macrophages can be effected after incubation with soluble lymphocyte product(s) (lymphokines). The activation of macrophages results if the macrophages are exposed to the lymphokine before, but not after, infection. The results indicate that the lymphocyte population responsible for the elaboration of the lymphokine is phenotypically Lyt1+2- and that activation of macrophages by the lymphokine can occur across H-2 histocompatibility barriers.

Animals↗

Inhibition of chitin synthesis in the cell wall of Coccidioides immitis by polyoxin D.

The cell walls of both growth phases of Coccidioides immitis were studied by light and electron microscopy and biochemical procedures in an effort to assess the role of chitin in the fungus. Inhibition of normal chitin synthesis in the spherule by exposure to several concentrations of polyoxin D (PD) led to multiple morphological effects. Exposure of the mycelial phase to significantly higher levels of the compound had no morphological effect, as determined by autoradiography and light and electron microscopy. However, when equal masses of both morphological phases were treated with PD and pulsed with labeled N-acetylglucosamine, there was a greater relative (percent) reduction of incorporation of label in PD-treated mycelia compared with that of spherules. Nevertheless, the treated and untreated mycelia incorporated severalfold more counts than did corresponding spherules. The results suggest that chitin is important in maintaining the structural integrity of the spherule phase, but the role of chitin in the mycelial phase is less clear.

Autoradiography↗

Comparison of immunodiffusion techniques with standard complement fixation assay for quantitation of coccidioidal antibodies.

Quantitative immunodiffusion (QID) and complement fixation (CF) methods were compared for their agreement in detecting coccidioidal antibodies. For these studies, we assayed 719 sera from 181 patients with coccidioidomycosis. Over 60% of the specimens had CF results of 1:2 to 1:256. A total of 43 patients had five or more specimens obtained over periods of between 1 and 8 years. The QID method, as originally performed, agreed within a twofold dilution of the CF titer in 191 of 267 sera (71.5%). Modification of QID by repeated filling of the antigen and serum wells improved agreement to 84.7% (383 of 452 sera). The degree of CF titer change in patients over time periods was more closely matched by the modified than by the original QID method. Discrepancies between the CF and QID methods appeared not to be due to a subpopulation of patients. QID measurement of coccidioidal antibodies may be a useful substitute for the CF assay in certain clinical laboratories.

Antibodies, Fungal↗

Dangerous dust.

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History, Modern 1601-↗

Coccidioidomycosis in the llama: case report and epidemiologic survey.

An 8-year-old nongravid female llama with a 1-month history of progressive posterior paresis was referred because of suspected degenerative myelopathy secondary to copper deficiency or plant poisoning. Neurologic examination revealed loss of conscious proprioception and slightly depressed bilateral patellar reflexes. Electromyographic examination of hindlimb flexors and extensors did not elicit evidence of lower motor neuron disease. Possible fragmentation and mottling of the 10th thoracic vertebral body were noted radiographically. Results of a lumbar CSF tap, complete blood count, and fecal flotation were not diagnostic. In the face of poor prognosis, the llama was euthanatized. Postmortem and histologic evaluation revealed, in addition to disseminated visceral granulomas, an extradural pyogranulomatous mass compressing the cord laterally at the level of T-10. Large numbers of Coccidioides immitis were dispersed throughout the granulomas. Complement fixing antibody tests in 11 other herd members showed evidence of C immitis infection in three.

Animals↗

Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro.

Peritoneal macrophages from normal mice phagocytized arthroconidia and endospores of Coccidioides immitis without affecting the viability of the spores within 4 h after infection. In contrast, macrophages, when infected in the presence of lymphocytes from immune mice, significantly reduced the viability of phagocytized endospores and arthroconidia. The inability of macrophages from normal mice to kill C. immitis may in part be explained by the observation that C. immitis appeared to inhibit fusion of the phagosomes containing fungal spores with the lysosomes within the macrophages. However, fusion of phagosomes containing spores and lysosomes was observed in macrophages infected in the presence of lymphocytes from immune mice.

Animals↗

Association of ABO blood group and outcome of coccidioidal infection.

Dissemination of fungal infection due to Coccidioides immitis has been previously shown to be related to hereditary factors. Two associations reported to date are race (e.g., Filipino and black ancestry) and HLA histocompatibility type (HLA-19). In the present study of 105 patients a significant association of blood group B and dissemination is demonstrated. C. immitis is known to possess antigens with blood group A activity. Previous epidemiologic studies have also shown HLA-A9 and blood group B are both more common in persons of black and Filipino ancestry. Further studies are needed to define whether these are independent variables, and may define subgroups at particularly high risk following coccidioidal infection.

ABO Blood-Group System↗

Development of resistance to amphotericin B in Candida lusitaniae infecting a human.

Candida lusitaniae associated with infection in a patient with acute myelogenous leukemia developed resistance to amphotericin B during systemic treatment of the patient. The organism, when isolated initially, was inhibited by 0.31 mug of amphotericin B per ml in yeast nitrogen base agar, but when isolated (20 days later) just antemortem and postmortem, required 100 and 50 mug/ml, respectively, for complete inhibition at 48 h.

Amphotericin B↗

Mechanisms of resistance to infection with Coccidioides immitis in mice.

Serum from vaccinated mice was ineffective in neutralizing the infectivity of arthrospores of Coccidioides immitis for recipient mice. However, a T-cell-enriched lymphocyte population was effective in preventing a lethal infection. Spleen cells from immune mice were passaged through nylon wool columns resulting in a T-cell enriched, B-cell-depleted population as shown by the susceptibility of the cell population to anti-theta serum and the inability of the cells to transfer adoptively an immune response to ovalbumin. Whereas transfer of 5 x 10(7) unfractionated immune spleen cells was required to protect 100% of the recipients against a lethal infection with C. immitis, 7 x 10(6) T-cell-enriched immune spleen cells were sufficient for the same level of protection. Thus, transfer of resistance to infection was achieved with fewer cells after the removal of B cells from the transferred spleen cells. The results confirm that T cells are crucial in transferring resistance against infection with C. immitis in mice.

Animals↗

Immunization of mice against coccidioidomycosis with a subcellular vaccine.

In vitro-cultivated spherules of Coccidioides immitis were disrupted in a Braun homogenizer. The resultant wall fragments were separated from cell sap and endospores by centrifugation. Extraction of the walls with phosphate-buffered saline yielded a subcellular fraction that was immunogenic in mice. This fraction, which contained polysaccharide and protein, gave substantial protection against intranasal challenge with a usually lethal dose (1,000) of arthrospores, provided that it was administered with adjuvant.

Adjuvants, Immunologic↗

Otomycosis due to coccidioidomycosis.

The course and treatment of two patients with otomycosis due to Coccidioides immitis, believed to be the first such cases reported, are described. Both infections appeared due to reactivation of hematogenously disseminated foci. Local and systemic chemotherapy plus surgery resulted in remission, and host immune response also appears to be an important factor. One patient, with systemic lupus erythematosus, required more extensive surgery, more chemotherapy, and reduction in steroid dose to arrest the disease. A combined surgical and chemotherapeutic approach appears necessary when otomycosis is due to invasive fungi such as C immitis.

Adult↗

Tempest from Tehachapi takes toll or Coccidioides conveyed aloft and afar.

New cases of acute primary coccidioidomycosis in large numbers resulted from a windstorm that blew through Kern County, California, on December 20, 1977. In most of these cases clinically apparent infections developed in early and mid-January 1978 and occurred not only in persons exposed directly to the dust raised by the windstorm but also among those in many areas to the north and west of Kern County. The exposure to the dustborne Coccidioides immitis was brief because of the arrival of drenching rains, but the continued heavy rainfall increased the potential for large numbers of cases of coccidioidomycosis to occur in the summer-fall season.

California↗

Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B.

The susceptibility of 12 strains of Coccidioides immitis to amphotericin B (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 mug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 mug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 mug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.

Amphotericin B↗

Significance of T cells in resistance to experimental murine coccidioidomycosis.

The resistance of mice to coccidioidomycosis was found to be dependent on lymphoid cells. Thus, spleen cells from mice immunized with killed spherules of Coccidioides immitis, when transferred to irradiated (500 R) recipients, conferred upon the recipient mice resistance to infection with C. immitis. Prior incubation of these spleen cells with anti-theta serum in the presence of complement abrogated their capacity to protect the recipients from infection with C. immitis. Adult thymectomized mice, which had been irradiated (800 R) and reconstituted with bone marrow from normal mice, were more susceptible to infection with arthrospores than were nonthymectomized, irradiated bone marrow-reconstituted controls. Genetically homozygous athymic ("nude") mice died after infection with a dose of arthrospores that was sublethal for their heterozygote counterparts possessing a thymus, or for normal mice. The results indicate that a functioning T-cell population is an essential component for effective immunity to C. immitis.

Animals↗