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[Histoplasma duboisii osteitis as an imported disease].

A case of imported Histoplasma duboisii osteitis in a visitor from Africa to Switzerland is described. The diagnosis was by histology confirmed by culture. Infection of other organs was ruled out. Amphotericin B therapy and its side effects are discussed.

Adult↗

Atypical Histoplasma capsulatum infection in a dog.

Disseminated histoplasmosis was diagnosed in a 10-year-old dog suspected of having hepatic carcinoma. Clinical abnormalities included diffuse hepatomegaly, gastrointestinal bleeding, thoracic and abdominal effusion, anemia, leukocytosis, and thrombocytopenia. Histoplasmosis characteristically is a disease of the mononuclear phagocyte system, but in this case was diagnosed by finding Histoplasma capsulatum organisms in neutrophils on the blood smear.

Adrenal Insufficiency↗

Red-pigmented Histoplasma capsulatum--an unusual variant.

An unusual variant of Histoplasma capsulatum was isolated from a canebrake. The mycelial form produced a red pigment that diffused into the medium and which was also present in the cell walls of the mycelium, microconidia and macroconidia. The yeast cells were not pigmented nor did they produce any pigment.

Cell Wall↗

Effects of Histoplasma capsulatum products on the functional activity of alveolar macrophages.

The possibility that Histoplasma capsulatum may affect the activities of alveolar macrophages through products of either secretion or lysis was examined. Varying amounts of histoplasmin (HP), the filtrate of cultures of H. capsulatum, were added to monolayer cultures of alveolar macrophages of Wistar rats, and the effects of the filtrate on viability, ingestion rate, random migration, adhesive properties and microbial killing capacity were evaluated. No clear cytotoxic or cytopathogenic effects were produced at any dose tested. The endocytic rate was enhanced when HP (0.2 micrograms) was added, the effect being due to the recruitment of non-phagocytosing cells. Alveolar macrophages that had remained nonadherent after 3 h of incubation adhered to glass slides after HP was added. Dose-dependent inhibition of random migration of macrophages was produced with the addition of HP. However, the microbial killing capacity was not modified significantly at any dose of the H. capsulatum product.

Animals↗

Comparative study of the effect of thiabendazole and fungizone on Histoplasma capsulatum in macrophages.

The antifungal properties of Fungizone (amphotericin B intravenous solution) and thiabendazole on Histoplasma capsulatum within guinea pig macrophages were compared using the staining method and a newly developed plating method to determine the viability of intracellular H. capsulatum. The two methods were compared to determine the effectiveness of Fungizone and thiabendazole on H. capsulatum within macrophages. Fungizone was fungicidal for intracellular H. capsulatum, killing 99.9% of the yeasts at a concentration of 0.5 microgram/ml. There was some indication that non-viable intracellular yeasts were stained which could result in misinterpretation of the effectiveness of Fungizone using the staining method unless the yeasts are very closely examined for staining abnormalities. There was a good correlation between the two methods to demonstrate suppression of the multiplication of intracellular H. capsulatum in macrophages treated with 50 microgram/ml of thiabendazole. Thiabendazole was lethal for some intracellular H. capsulatum.

Amphotericin B↗

[Immunology of histoplasmosis: isolation of a polysaccharide-protein complex with immuno-specific activity from Histoplasma capsulatum].

A polysaccharide protein complex (PPC) with a high specificity in immunodiffusion in gel (IDG) was isolated from a Histoplasma capsulatum strain. Although unaffected by proteolytic enzymes (pronase) and heat, the PPC antigen activity was destroyed by beta-glucosidase. These results suggest that the specificity of the PPC antigen might be located in the polysaccharide fraction. Polyacrylamide gel electrophoresis of the PPC antigen gave only one brand detected by Schiff's reagent (PAS).

Animals↗

[Study of yeast phase Histoplasma capsulatum antigens used for skin tests].

The results of skin tests with two antigens of the yeast phase of Histoplasma capsulatum are presented. Both antigens were able to fix complement and form precipitating bands in the presence of sera from patients with active histoplasmosis. Their sensitivity was lower than the metabolic antigen usually employed in serology. Results of skin tests obtained with both yeast phase antigens and a standard histoplasmin coincided in animals infected with H. capsulatum. Only one cross reaction was observed in animals inoculated with Paracoccidioides brasiliensis. Skin tests in humans were conducted on patients with and without mycotic disease. The percentages of positive reactions in patients with histoplasmosis were not significantly different between control histoplasmin and whole cell extracts. In the patients with non mycotic diseases the frequency of positive tests varied between 28.8% and 32%, which agrees with previous statistical data for the general population of the area. Equally the positive percentage of 55% and 68% in patients with paracoccidioidomycosis coincided with the results of previous studies. The histological patterns of these skin tests showed that they were produced by cell mediated hypersensitivity. The sensitivity of a whole yeast cell extract was similar to histoplasmin L48, but its preparation was quicker and easier to perform and it had no foreign substances from the culture medium, so we think that it would be easier to standardize it chemically.

Animals↗

Inhibition of isolated yeast and mycelial phase RNA polymerases of Histoplasma capsulatum by rifamycin derivatives.

Various derivatives of rifamycin were shown to inhibit the RNA polymerases of the yeast and mycelial phases of Histoplasma capsulatum. The relative potency of each of the derivatives against the isolated polymerases was the same as the potency of each against the viable organism. RNA polymerase PC III from the yeast phase was more susceptible to the rifamycin derivatives than yeast phase polymerases PC I and PC II and the biggest differences in susceptibility were seen with the derivative AF/ABDP (2,6-dimethyl-4-benzyl-4-demethyl-rifamycin). The susceptibility pattern of the mycelial polymerase activity was identical to the yeast polymerase PC III.

Cell Differentiation↗

Comparative study of a new Chrysosporium species with Histoplasma capsulatum.

The Chrysosporium state of a new ascomycete, Renispora flavissima (Gymnoascaceae), resembles Histoplasma capsulatum in its macroconidial morphology. It was discovered growing in bat guano, from which it was readily isolated by direct plating of diluted soil, but only rarely from mice inoculated with soil suspensions. The fungus was consistently reisolated from tissues of mice inoculated intravenously and intraperitoneally with conidial and mycelial suspensions from cultures of the fungus. Nevertheless, there is no evidence that this species is pathogenic. Cultures grew at 37 degrees C, but did not convert to a yeast form on agar media or within cultured mouse peritoneal macrophages. Although the hyphae and conidia of this fungus fluoresce when stained with H. capsulatum fluorescent antibodies, exoantigens of the fungus produce neither H nor M precipitin bands, thus differentiating it from H. capsulatum. Both H. capsulatum and the new Chrysosporium sp. demonstrate isozyme polymorphism, and isozymic differences have been discussed between the two species.

Animals↗

Immune responsiveness following intratracheal inoculation with Histoplasma capsulatum yeast cells.

Splenic in vitro immune responses from C57B1/6 mice have been evaluated after intratracheal (i.t.) or intravenous (i.v.) inoculation with live Histoplasma capsulatum yeast cells. Significant (P less than 0.005) numbers of cells reactive to heat killed H. capsulatum (HK-Hc) were present 1 week after i.t. inoculation with 5 X 10(5) viable yeast cells. In contrast, blastogenic responses to HK-Hc were not detected until 3 weeks after i.v. H. capsulatum inoculation. Examination of non-specific immunity, i.e. mixed lymphocyte responses to alloantigens and antibody formation to sheep erythrocytes, revealed a significant (P less than 0.005) and transient depression of these responses 1 week following i.t. H. capsulatum inoculation. The non-specific decreases associated with early (1 week) i.t. infection were not mediated by suppressor cells but were related to the number of viable yeast administered.

Animals↗

Isolation of aminopeptidases from Histoplasma capsulatum.

Two aminopeptidases (arylamidases) were isolated and partially purified from Histoplasma capsulatum. The larger molecular weight enzyme was a proline iminopeptidase and hydrolyzed primarily a synthetic substrate, L-prolyl-beta-napthylamide. The other aminopeptidase was less substrate specific and hydrolyzed rapidly the following amino acid beta-napthylamides (beta NA): L-arginyl-beta NA greater than L-lysyl-beta NA greater than -L-4-methoxy-leucyl-beta NA greater than L-leucyl-beta NA greater than L-phenylalanyl-beta NA greater than L-alanyl-beta NA. The proline iminopeptidase was purified 1420 fold while the leucine aminopeptidase was purified 650 fold with good recovery.

Aminopeptidases↗

The use of Histolyn CYL in an enzyme immunoassay to detect Histoplasma capsulatum antibodies.

Histolyn CYL, the yeast phase reagent, has been employed as the antigen in an enzyme immunoassay (ELISA) to detect antibody to Histoplasma capsulatum in sera from experimentally sensitized rabbits and from humans with histoplasmosis. Three different lots of Histolyn CYL were initially evaluated with respect to antibody detection in individual and pooled rabbit serum specimens. Optimal reactivity was obtained with 4.5 micrograms (total dry weight) per ml of lots 2 and 3 of the reagent. The optimally diluted pooled reagent detected antibody titers ranging from 1:16 to 1:8192 in 36 rabbit sera. In contrast, a marked decrease in sensitivity was evidenced when the same sera were assayed by complement fixation and immunodiffusion tests with commercially available reference reagents. Complement fixation titers ranged from 0 to 1:128 and immunodiffusion tests on undiluted sera were positive with only 5 specimens. Twenty-five sera from patients with acute, chronic and disseminated histoplasmosis were also assayed by the ELISA with the reagent described above. Titers ranged from less than 1:16 to 1:20,480 or greater. Complement fixation titers ranged from 0 to 1:1024 (mycelial antigen) and from 0 to 1:256 (whole yeast cell antigen). No antibody was detected in 7 specimens with mycelial antigen or in 3 specimens with the yeast cell antigen. Immunodiffusion tests on undiluted sera were positive with 9 of 11 specimens. Minimal cross reactivity was evidenced when Histolyn CYL was used in the ELISA to detect anti-Coccidioides immitis antibody in sera from infected animals and humans. These data encourage the continued development of this method for the serodiagnosis of human histoplasmal infection.

Animals↗

Histoplasmosis due to Histoplasma capsulatum var duboisii in a Canadian immigrant.

Histoplasmosis due to Histoplasma capsulatum var duboisii developed in a Canadian immigrant one year after his entry into Canada. He had lived in Guinea for two years prior to immigration. Lymphatic infection characterized the course of his illness. The clinical and pathologic features of this disease's distinctive skin and bone manifestations are outlined. The causal agent's mycologic features are compared with those of H capsulatum var capsulatum. Treatment with amphotericin B was successful.

Adult↗

Histoplasma capsulatum. Isolation from an Australian cave environment and from a patient.

The fungus Histoplasma capsulatum, although commonly found in bat-frequented caves in many countries, has not previously been isolated from that environment in Australia. This report describes the isolation of H. capsulatum from several sources, including cave soil, the organs of mice exposed to the cave environment, and the sputum of a patient clinically diagnosed as having acute pulmonary histoplasmosis after exposure to the cave environment.

Acute Disease↗

A case of histoplasma posthitis.

The present report describes a case of disseminated histoplasmosis with involvement of the prepuce. Phimosis resulting from histoplasma posthitis is exceedingly rare and hence being documented.

Adult↗

Distribution of the two mating types among Histoplasma capsulatum isolates obtained from an urban histoplasmosis outbreak.

The mating type distribution among the 28 Histoplasma capsulatum isolates obtained from the histoplasmosis outbreaks which occurred in Indianapolis in 1978-1979 and 1980-1981 was studied. The overall ratio of + and - types was 1:2.5. The isolates from disseminated patients showed a 1(+):1(-) ratio while the isolates from non-disseminated pulmonary cases showed a 1(+):4(-) ratio. The frequency of the + type in these outbreaks was three times higher than that of the previous study. This was due to an unusually high prevalence of the + type among the patients with disseminated histoplasmosis.

Animals↗

Sulfhydryl induced respiratory "shunt" pathways and their role in morphogenesis in the fungus, Histoplasma capsulatum.

When the mycelial to yeast transition of the dimorphic fungus Histoplasma capsulatum is induced by a temperature shift from 25 to 37 degrees C, the activities of the cytochrome system and the alternate oxidase decrease in parallel over the first 24 to 40 h (stage 1 of the transition). The decrease in activity of the cytochrome system is correlated with extensive decreases in the amounts of cytochromes b, c, and aa3, assayed spectrophotometrically. After 40 h, the cells enter a dormant phase (stage 2 of the transition) and cysteine or other sulfhydryl-containing compounds are required to reactivate mitochondrial respiration. This reactivation is due to the establishment of shunt pathways which bypass blocked segments of the electron transport system. The "shunt" pathways operate normally in mycelia grown at 25 degrees C, but are shut down during the transition, possibly because of depletion of intracellular cysteine. The longstanding observation that cysteine is required to progress beyond the initial stages of the morphological transition may be due, at least in part, to the reactivation of these "shunt" pathways.

Cytochromes↗

The mycelial status and reversibility in Histoplasma capsulatum.

The highly variable mycelial phase cultures of Histoplasma capsulatum are generally described as brown to albino colonies with the albino type overtaking the brown in a unidirectional and mainly irreversible process. In this study it was found that cultures could be reversed from albino to brown type by manipulation of substrates. As the cultural morphology and stability were shown to be essentially substrate-dependent, the mycelial status of this organism was reassessed. It is proposed that albino and intermediate variants are usually artificially induced by conventional refined carbohydrate media, while crude guano substrates tend to promote cultures of a brown wild type.

Animals↗