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Biomedical subjects

R J Hay

Publications and source records attributed to R J Hay.

At least 271 records · Page 15Linked to original sources
PubMed1979

Mycoses imported from the West Indies. A report of three cases.

There have been isolated case reports of deep fungal infections from the Caribbean area but little is known about the distribution of mycoses there. Three cases, one of mycetoma, one of chromomycosis, one of histoplasmosis, are described. Their management and the advantages and disadvantages of treatment outside the area of origin are discussed.

Adult↗
PubMed1979

Failure of treatment in chronic dermatophyte infections.

A proportion of dermatophyte infections fail to respond to normally adequate courses of griseofulvin and topical antifungal therapy. The organism Trichophyton rubrum was isolated from 96% of 50 patients studied, but no instances of in vitro resistance were seen. Of these patients, 57% had an underlying condition, commonly hay fever/asthma, atopic eczema, collagen disease or ichthyosis. Defective delayed type hypersensitivity responses and leucocyte migration inhibition to the specific antigen, trichophytin, were demonstrated. Immediate type hypersensitivity was seen in 58% and this was partially suppressible with chlorpheniramine and cimetidine. The relationship between these abnormalities and failure of treatment is discussed.

Adolescent↗
PubMed1978

Effects of cystine or glutamine restriction on human diploid fibroblasts in culture.

Amino-acid restriction was studied using a strain of human diploid fibroblasts (HDF) isolated from fetal skin. HDF populations were maintained at reduced proliferation rates by lowering cystine or glutamine concentrations of Eagle's MEM. Effects of this treatment on mean cell diameters, total cell protein and specific activity of acid phosphatase were assessed. Threshold levels of cystine required for maintenance were found to be markedly influenced by type and/or batch of serum used irrespective of their free cystine content. A 96-hr exposure of passage 25 cells to medium 0.01 or 0.005 mM in cystine resulted in an increased mean cell diameter and a greater heterogeneity of cell size. This was accompanied by an increase in the total cellular protein. A 48-hr exposure, followed by return to control serial cultivation, induced persistent change in mean cell diameter without affecting the total life span (49 passages over 165 days). The mean size of untreated cells increased with serial passage reaching a size similar to treated cells only at passage 44. Acid-phosphatase specific activities were higher in cells maintained under conditions restrictive in cystine. None of the above changes were observed when glutamine concentrations were reduced to 0.0025 mM, a level required to inhibit division rates. The possible relevance of these findings to the phenomenon of in vitro cell senescence is discussed.

Acid Phosphatase↗
PubMed1978

Delayed-type hypersensitivity responses in infected mice elicited by cytoplasmic fractions of Cryptococcus neoformans.

Four subcellular fractions of Cryptococcus neoformans prepared by differential centrifugation of disrupted whole yeast and a 3-day culture filtrate were examined for their ability to elicit delayed-type hypersensitivity in sensitized animals. The methods used to detect sensitization were (i) the footpad swelling test and inhibition of peritoneal macrophage migration in mice and (ii) skin testing in guinea pigs. Two entities, the post-mitochondrial supernatant and the culture filtrate, showed considerable activity in the footpad test, with 26- and 30-microliter 24-h swellings, respectively, at 6 weeks after infection. With the latter there was interference from a strong antibody-mediated 4-h skin reaction. The post-mitochondrial supernatant produced strong delayed-type hypersensitivity in guinea pigs at a dose of 69 microgram, and there was no demonstrable cross-reactivity in animals sensitized with heterologous fungi. The footpad swelling in mice correlated well with the macrophage migration inhibition test, with 71% inhibition in mice infected subcutaneously with C. neoformans at 6 weeks. However, mice infected intravenously developed poorer cell-mediated immunity than the subcutaneously infected mice. The post-mitochondrial supernatant was found to contain detectable amounts of cryptococcal capsular polysaccharide.

Animals↗
PubMed1978

Experimental paracoccidioidomycosis: cranial and nasal localization in mice.

An experimental mouse model for paracoccidioidomycosis (South American blastomycosis) is described. When distribution of cranial lesions following i.v. injection was investigated, invasion of the nasal mucosa with subsequent discharge of budding Paracoccidioides brasiliensis cells into the nasal cavity was noted. The possible significance of this finding in terms of the processes associated with naturally occurring paracoccidioidomycosis is discussed.

Animals↗
PubMed1976

The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition.

Seven patients from four families are reported who had an inherited condition of which the main features were ankyloblepharon, ectodermal defects and cleft lip and palate. The ectodermal defects were partial or complete hair loss, absent or dystrophic nails, pointed widely spaced teeth and partial anhidrosis. Associated anomalies included lacrimal duct atresia, supernumerary nipples, syndactyly and auricular deformities. The inheritance of this abnormality was consistent with that of an autosomal dominant trait. The relationship between this and similar syndromes is discussed.

Adult↗
PubMed1976

Proliferation and agglutinability of primary and transformed human epithelial cells in culture.

Primary epithelial populations (HAM) were obtained by dissociation of the amniotic membrane stripped from human placentae. Agglutinability of cells from such normal populations and of cells from the transformed epithelial line WISH was then compared using concavanalin A as mediator. Extensive similar studies have previously been reported with cell strains isolated from other species. Freshly dissociated HAM cells from primary cultures agglutinated much less readily than did cells from WISH populations. Furthermore, the former exhibited a drastic decline in agglutinability as a function of time in suspension culture after trypsinization. Short-term exposure (60 h) of HAM cells in monolayer culture to 5-bromodeoxyuridine (BrdU) elicited heightened agglutinability detectable through 22 days in vitro. Addition of the protease inhibitors n-tosyl-L-lysyl-chloromethyl ketone (TLCK) or p-tosyl-L-arginine-methyl ester (TAME) to the culture medium inhibited proliferation of the WISH line by 40--50% while effecting only a 10-15% inhibition of HAM cells. These results also confirm data with other cell species indicating that high proteolytic activity at the surface of transformed cells may be related to the rapid proliferation rate.

Agglutination↗
PubMed1975

Proliferative and functional impairment of pancreatic epithelial cells maintained in vitro.

Studies on the proliferative and functional properties of epithelial cells from human and guinea pig pancreatic tissue were presented and discussed. A novel technique for the isolation of epithelial cell groupings as colonial aggregates in two dimensional culture was utilized. More conventio;al clonal analyses were also performed. Irrespective of the methodology employed, epithelial cells from both species exhibited reduced proliferative activity with time in vitro. Total degeneration occurred in less than five months in every case studied. Aggregates and colonial aggregates, formed using fractionated suspensions containing up to 95% guinea pig acinar cells, were found to release amylase only during the first few days in vitro. Positive response to secretogogue stimulation was interpreted as evidence favoring the thesis that permanent cellular damage had not been sustained during tissue dissociation. These findings were discussed with reference to the phenomenon of human fibroblast degeneration with time in culture. Differences between fibroblast and epithelial cell behavior in vitro and in vivo were emphasized.

Amylases↗
PubMed1975

The pancreatic epithelial cell in vitro: a possible model system for studies in carcinogenesis.

A technique is described for the isolation and maintenance in culture of pancreatic epithelial cells from human embryos or neonatal guinea pigs. Dissociated cells from human material were essentially uncharacterized. Those obtained from guinea pig pancreas were subjected to centrifugal fractionation, and the resulting populations consisted of up to 95% exocrine cells. Suspensions of dissociated cells were incubated with gyration for 16 to 18 hr, and cell aggregated that formed were placed in stationary culture. Two-dimensional colonial aggregates developed on the plastic substratum. Cells comprising such colonies formed junctional complexes and could be maintained for 20 to 40 days in vitro. This system may provide a useful model for studies on pancreatic exocrine cell physiology and carcinogenesis.

Animals↗
PubMed1967

Factors influencing glucose flux and the effect of insulin in cultured human cells.

Uptake of glucose-(3)H into cultured HLM cells was measured. Equilibration of intracellular and extracellular pools occurred after 25 min. Glucose influx was determined subsequently by measuring the glucose-(3)H entering in precisely 1 min. Although saturation kinetics were demonstrated these were not of the simple Michaelis-Menten type. The K(m) of the glucose carrier system is probably about 60 mM glucose. Galactose did not compete with glucose. Insulin stimulated glucose flux without increasing the value of V(max). The stimulation was fully demonstrable after 10 min, could be elicited at concentrations of 10(-4) units/ml, and was absent 2-4 hr after removal. Increasing pH had little or no effect in stimulating glucose flux. Increasing osmotic pressure caused a marked increase and reduced the effect of insulin. Glucose influx was unaffected by anoxia. Glucose influx was increased and the effect of insulin abolished in the absence of K(+). Glucose influx was increased by mercuric chloride, iodoacetate, and fluoride which abolished the effect of insulin. Dinitrophenol decreased the rate of glucose uptake but did not alter the effect of insulin. Phlorizin reduced the rate of glucose uptake and abolished the effect of insulin. ATP and AMP enhanced the rate of glucose uptake. These findings are discussed in relation to the mode of action of insulin.

Adenine Nucleotides↗
PubMedDate not supplied

Further studies on the treatment of African histoplasmosis with ketoconazole.

Five patients with African histoplasmosis were treated with ketoconazole. Three of these were children with disseminated disease and 2 were adults with localized cutaneous disease. Both patients with cutaneous disease responded to treatment, although one was lost to follow-up. Of the 3 children with disseminated disease, one was apparently cured, one responded well but subsequently relapsed, and one failed to respond in spite of having blood levels of ketoconazole within the therapeutic range. Further studies are needed to determine the optimum dosage and duration of treatment with ketoconazole for this condition.

Administration, Oral↗