Biomedical subjects

D H Howard

Publications and source records attributed to D H Howard.

At least 55 records · Page 3Linked to original sources

PubMed1986

Isolation of Bipolaris australiensis from a lesion of viral vesicular dermatitis on the scalp.

Bipolaris australiensis is recorded as an opportunistic pathogen of humans. The fungus was recovered from a biopsy specimen of skin taken from an area of viral vesicular dermatitis on the scalp. Hyphal elements of B. australiensis were seen in the tissues. The taxonomy of the genera Bipolaris, Drechslera, Exserohilum and Helminthosporium is discussed with particular reference to published case reports.

Aged↗

PubMed1984

T-cell hybridoma-produced lymphokine that activates macrophages to suppress intracellular growth of Histoplasma capsulatum.

Supernatants from concanavalin A-stimulated T-cell hybridomas activated macrophages to suppress the intracellular growth of Histoplasma capsulatum and to kill tumor cells. The supernatants had high interferon activity and were pH 2 sensitive and heat resistant. Gamma interferon is suggested to be among the active substances in the supernatants. Neither alpha interferon nor beta interferon activated macrophages for the Histoplasma growth inhibitory activity.

Animals↗

PubMed1984

Heat shock and heat stroke proteins observed during germination of the blastoconidia of Candida albicans.

Cytoplasmic proteins extracted from germinating yeast cells of Candida albicans were analyzed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Similar extracts from a recently isolated nongerminating variant were compared with those from the parent. Five proteins (18, 22, 40, 68, and 70 kilodaltons [kd]) behaved as heat-shock proteins in that they appeared or were greatly increased in amount within 20 min of a temperature shift from 23 to 37 degrees C. Three of the five (40, 68, and 70 kd) were undetected in cells incubated at 23 degrees C, appeared within 20 min of temperature shift, and were no longer detected after 120 min at 37 degrees C, whereas two of the five (18 and 22 kd) were present in small amounts at 23 degrees C, increased greatly after shift, and persisted for 120 min at the elevated temperature. Two temperature-repressed (heat-stroke) proteins (30 and 88 kd) were also observed. The same heat-shock and heat-stroke proteins were also found in the nongerminating variant. The differences in proteins expressed by blastoconidia and by germlings appeared to be related to the heat-shock response.

Candida albicans↗

PubMed1984

Inhibition of growth of Histoplasma capsulatum by lymphokine-stimulated macrophages.

Peritoneal cells from mice immunized by sublethal infection inhibit the intracellular growth of Histoplasma capsulatum in vitro. Lymphokines generated in cultures of immune splenocytes stimulated with Histoplasma antigen activate normal macrophages to inhibit the intracellular growth of the fungus. Such lymphokines may inhibit the intracellular growth of H. capsulatum by 60 to 80% but have no direct effect on the viability of the fungus extracellularly. The lymphokine preparations have high interferon activity that is heat stable and acid labile. The cells in the spleen that are responsible for lymphokine production are T lymphocytes, but the help of other cells such as macrophages is essential for maximal production.

Animals↗

PubMed1984

The epidemiology and ecology of blastomycosis, coccidioidomycosis and histoplasmosis.

Blastomycosis, coccidioidomycosis and histoplasmosis are the major pulmonary mycoses of humans. Each is considered to be a primary pulmonary disease acquired by inhalation of infectious spores from the environment. Blastomycosis occurs predominantly in the Mississippi River Valley and Southeastern portions of the U.S.A. Clinical cases have also been noted from a few other areas of the world. The etiologic agent, Blastomyces dermatitidis, is not readily recoverable from nature, but the disease is not contagious and must be acquired from some exogenous source poorly defined at present. Blastomycosis is common in dogs but unusual in other species although a wide variety of animals can be infected experimentally. The disease is more common in middle age, in blacks, and in males. Coccidioidomycosis is restricted to the Western Hemisphere where most cases occur in the semiarid regions of Southwestern U.S. and contiguous areas of Mexico. Limited endemic foci are found in South and Central American locations. The arthroconidia of Coccidioides immitis occur in the soil of endemic areas from whence they are inhaled by humans and other animals. The disease is not customarily contagious. Handling cultures in the laboratory is a serious biohazard. The basis for an apparent racial predisposition to develop disseminated disease is unknown. Two clinical entities distinguishable by their etiologic agents are recognized to comprise histoplasmosis. Histoplasmosis caused by Histoplasma capsulatum var. capsulatum is a cosmopolitan disease with the greatest known concentration of cases located in the eastern half of the U.S. and most of Latin America.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1983

Studies on the catalase of Histoplasma capsulatum.

Factors which control the levels of catalase within yeast cells of Histoplasma capsulatum were studied. Only a small fraction of the total catalase activity could be detected in whole cells. The bulk of the activity was revealed in cell-free extracts or in cells permeabilized with acetone. The formation of the enzyme was regulated by glucose and by oxygen. There were large, consistent differences in the levels of catalase among strains of H. capsulatum. The sensitivity of the strains to H2O2 toxicity also varied remarkably. Peroxidase activity could not be detected in cell-free extracts of the strains. Resistance to H2O2 did not correspond to levels of catalase. There was no obvious correlation of H2O2 sensitivity and virulence among the strains.

Catalase↗

PubMed1981

Proline uptake in Candida albicans.

L-Proline entered both mycelial and yeast cells of Candida albicans by an active transport system of high specificity at low (less than 0.1 mM) external concentrations of substrate. The apparent Km value of this system was 0.1 mM for both types of cells, while the V value was 4 nmol min-1 (mg dry wt)-1 for mycelial cells and 1.4 nmol min-1 (mg dry wt)-1 for yeast cells. At L-proline concentrations greater than 0.1 mM, the amino acid appeared to enter both morphological forms by diffusion as well as active transport. As saturation was approached diffusion became increasingly important. The higher uptake rate of mycelial cells seemed not to be the result of an inducible system. The optimal pH and temperature for transport of L-proline were 7.0 and 37 degrees C, respectively. Sodium azide and the proline analogues sarcosine and L-azetidine-2-carboxylic acid inhibited L-proline uptake, while L-thiazolidine-4-carboxylic acid was less effective. The active transport system was highly specific for L-proline since neither ammonium ions, which inhibit the general amino acid transport system of fungi, nor 16 different amino acids interfered substantially with uptake.

Amino Acids↗

PubMed1981

Comparative sensitivity of Histoplasma capsulatum conidiospores and blastospores to oxidative antifungal systems.

The comparative sensitivity of blastospores and conidiospores of Histoplasma capsulatum to hydrogen peroxide, to hydrogen peroxide and halides, and to a combination of hydrogen peroxide and halide with the enzyme myeloperoxidase was studied. Blastospores of different strains of H. capsulatum varied in their sensitivity to hydrogen peroxide. This variation correlated with the amount of catalase in cell-free extracts from the strains. Blastospores and conidiospores of a single isolate were about equally susceptible to hydrogen peroxide, but this sensitivity could obviously vary with the catalase content of the two types of spores. Halides augmented the antifungal activity of hydrogen peroxide for both types of spores. Iodide was far more efficient in this regard than was chloride. A crude granule lysate from guinea pig polymorphonuclear leukocytes was quite inhibitory to blastospore but not to conidiospore germination. A study of the myeloperoxidase activity of such preparations against blastospores was thus precluded. A sample of a very highly purified human myeloperoxidase functioned in the presence of hydrogen peroxide and either iodide or chloride to prevent germination of both blastospores and conidiospores. The preparation had no toxicity for spores apart from its interaction with hydrogen peroxide and halides.

Animals↗

PubMed1980

Isolation and characterization of arginine auxotrophs of Cryptococcus neoformans.

Arginine auxotrophs were isolated in both mating types of Cryptococcus neoformans. In both mutants, the auxotrophy was due to the lack of active argininosuccinate lyase. The virulence in mice of the mutants was compared with that of the wild type. One auxotroph displayed a loss of virulence which appeared to be related to the presence of another mutation, one which prevented normal cell separation after budding. The other auxotroph had reduced virulence compared with the wild type, but a variant isolated from it by mouse passage had virulence equivalent to that of the wild type while maintaining the auxotrophic requirements.

Animals↗

PubMed1980

Cysteine transport and sulfite reductase activity in a germination-defective mutant of Histoplasma capsulatum.

A mutant of the dimorphic, zoopathogenic fungus Histoplasma capsulatum, defective in the ability of its blastospores to germinate, was used to show that the nutritional requirement for cysteine and the expression of sulfite reductase activity are temperature dependent and not related to the growth form the fungus, whereas the kinetics of cysteine transport depend on both temperature and the form of the fungus.

Biological Transport↗

PubMed1979

Mutants of Arthroderma benhamiae.

The object of these studies was to isolate conditionally lethal mutants of Arthroderma benhamiae whose vegetative growth was temperature sensitive (ts). Three sorts of mutants were derived from nitrosoguanidine treatment of the microconidia of A. benhamiae: (i) ts "pleomorphic", (ii) ts "non-pleomorphic", and (iii) slow growers (sg) which were not temperature sensitive. The growth of wild type A. benhamiae, as measured by colony diameters, was 6 mm/day at 37 degrees C (chosen as non-permissive for screening mutants) and 5 mm/day at 25 degrees C (chosen as permissive for screening mutants). Growth of mutants of the first sort was virtually stopped at 37 degrees C but their growth at 25 degrees C was more rapid than that of wild type. The colony texture of these mutants was downy and their mycelium sterile. They failed to mate with parents of opposite mating type. These mutants were considered to be ts "pleomorphic". The second sort of mutants were ts "non-pleomorphic". Two isolates of this kind were recovered. They grew normally at 25 degrees C but their growth at 37 degrees C was reduced 50--70% of that of wild type. The nature of the temperature sensitive defect has not been identified. The third sort of mutant occurred very frequently. These isolates were slow growers (sg) regardless of temperature of incubation and their response to the respiratory inhibitors antimycin and salicyl hydroxamic acid suggested a defect in mitochondrial ribosome assembly and deficiencies in cytochromes not unlike those observed in the poky mutants of Neurospora. Two of the sg-mutants (sg 2 and sg3) produced abundant cleistothecia with asci and ascospores when back crossed to parents of opposite mating type. The sg 5 mutant produced cleistothecia but no ascospores. The ergosterol content of the sg 2 mutant was nearly the same as that of wild type while the ergosterol content of sg 3 was somewhat reduced and that of sg 5 was markedly reduced as compared to that of wild type. Thus the ergosterol content seems to play some role in sexual reproduction of A. benhamiae. The pattern of sensitivity to amphotericin B also reflected differences in the sterol content of the mutants, i.e., the two mutants with some alteration in their ergosterol content, sg 3 and sg 5 were more resistant to the antibiotic. During the course of these studies a number of variants were observed that produced different sorts and degrees of pigmentation of the reverse of their colonies. One stable variant of this kind gave rise to colonies with a red reverse when incubated at 37 degrees C and a yellow reverse when incubated at 25 degrees C. When plates were shifted from one temperature to another the next wave of growth was the color specified by the temperature.

Ascomycota↗

PubMed1978

Uptake of metabolites by germinating blastospores of Histoplasma capsulatum.

The uptake of radioactive L-leucine, L-glutamic acid, and guanine was monitored during blastospore germination of Histoplasma capsulatum. Blastospores of H. capsulatum, grown in Salvin's medium at 37 degrees C for 48 h and shifted to 23 degrees C, germinated within 24 h. Metabolite uptake was faster in mycelial cells at 23 degrees C than it was in yeast cells at 37 degrees C. During the yeast to mold transition, the initial rate of uptake was first markedly depressed and then increased and achieved a level characteristic of the mycelial phase of growth. Estimates of macromolecular synthesis occurring during transitional morphological events might be influenced by these differences in the rate of uptake.

Culture Media↗

PubMed1977

Fungal endophthalmitis following intraocular lens implantation.

Endophthalmitis developed in a 61-year-pld man after an intraocular lens implantation. A whitish opacity developed, visual acuity decreased to light perception, and we enucleated the eye. Paecilomyces lilacinus (Thom) Samson, a saphrophyte that has contaminated laboratory solutions, was cultured.

Cataract Extraction↗

PubMed1977

Epidemiologic differences among serotypes of Cryptococcus neoformans.

In the USA, the most prevalent serotype of the fungus, Cryptococcus neoformans, was serotype A. The serotype constituted 203 of 272 isolates from infections and 85 of 89 isolates from the environment. Serotype B or C isolates were infrequent causes of infection, except in Southern California, and were infrequent causes of infecand were not isolated at all from environmental sources. In Southern California, the absence of serotypes B and C in 67 soil and pigeon dropping isolates was striking, considering that 25 of 49 isolates from infections were serotypes B or C. The site in nature where serotypes B and C exist is currently unknown but differs from that of serotypes A and D. Serotype D may be unusually prevalent in both environmental and patient isolates from Denmark and Italy. Of 24 isolates from those countries, 21 were serotype D.

Animals↗

PubMed1977

Experiments on lymphocyte-mediated cellular immunity in murine histoplasmosis.

Peritoneal exudate cells from immunized mice inhibit the intracellular growth of Histoplasma capsulatum. The lymphocyte is the mediator cell of this phenomenon. Lymphocytes from immunized animals are highly activated cells. Supernatants from cultures of immune lymphocytes or from cultures of mitogen-stimulated lymphocytes did not arm macrophages from normal animals to inhibit the intracellular growth of H. capsulatum.

Animals↗

PubMed1976

Germination of Candida albicans induced by proline.

Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts.

Amino Acids↗

PubMed1976

Further studies on the intracellular behavior of Torulopsis glabrata.

The growth of Torulopsis glabrata was inhibited in glucose-peptone broth containing 10 to 20% normal human serum. Addition of iron to the medium diminshed the fungistatic effect. The intracellular growth of T. glabrata was remarkably restricted within mouse macrophages maintained in vitro, but this growth restriction was not caused by the limitation of iron imposed by the serum in the medium. The intracellular growth of T. glabrata within a very small percentage of the macrophages was not obviously related to the failure of lysosomal fusion to the phagosomes in those cells. The studies did not permit definite conclusions regarding the viability of the inhibited yeasts, but results suggested that a large portion of them survived. Potentially misleading artifacts of the technique for assessment of the intracellular behavior of the fungus were detected and are discussed.

Acid Phosphatase↗

PubMed1976

Uptake of L-proline by Histoplasma capsulatum.

The uptake and incorporation of L-proline by yeast cells of the dimorphic zoopathogen Histoplasma capsulatum were studied. The amino acid was assimilated in at least two ways: by an active transport system with a Km of 1.7 X 10(-5) M and by simple diffusion. The active transport system was sterospecific and severely restricted to neutral aliphatic side-chain amino acids. Certain analogues inhibited L-proline uptake and prevented incorporation of the amino acid into cellular constituents. The inhibition of L-proline uptake by L-leucine was competitive. Since L-leucine and L-proline are seemingly transported by a system with similar characteristics, must be concluded, as originally postulated, that the buckled ring of L-proline, in solution, acts as an aliphatic side chain and that this cyclic amino acid is transported by a system more or less specific for amino acids with neutral aliphatic side chains.

Amino Acids↗