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Biomedical subjects

J M Hanifin

Publications and source records attributed to J M Hanifin.

At least 145 records · Page 8Linked to original sources
PubMed1982

Functional desensitization due to stimulation of cyclic AMP-phosphodiesterase in human mononuclear leukocytes.

We have previously demonstrated heterologous desensitization of human mononuclear leukocytes (MNL) by incubation of low (e.g., 10(-6)M) concentrations of histamine, isoproterenol and prostaglandin E1. Subsequent exposure of the cells to stimulating (e.g., 10(-3) to 10(-5)M) concentrations of any one of the three agonists shows reduced cAMP responses. Possible mechanisms for the subnormal responsiveness include rapid degradation of cAMP. In this report we demonstrated time-dependent elevation of cAMP-phosphodiesterase (PDE) activity following agonist desensitization. The increased enzyme activity was accompanied by a mirror-image decrease in cAMP responsiveness. The effect was rapid and prolonged, with recovery time proportional to desensitization time. Cycloheximide failed to inhibit the increase of cAMP-PDE activity caused by short-term histamine exposure, but partially diminished the elevation as the result of chronic histamine desensitization. We observed three different kinetic forms of cAMP-PDE in MNL, designated as I, II and III, each with distinctive Km and Vmax. Histamine desensitization increased the activity of form II and drastically reduced that of form I. Also we observed a possible conversion of lymphocyte cAMP-PDE from form I to the form II more characteristic of monocytes. Agonist-induced increases in cAMP-PDE activity and changes in enzyme kinetic characteristics represent a potentially important mechanism of functional desensitization. This may have significant effects on biological regulation of cyclic nucleotides.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Heterologous desensitization of leukocytes: a possible mechanism of beta adrenergic blockade in atopic dermatitis.

Studies of mononuclear leukocytes from patients with atopic dermatitis showed depressed cyclic AMP (cAMP) responses after exposure to isoproterenol, histamine, and prostaglandin E1. Because plasma and tissue histamine levels are elevated in atopic dermatitis, we questioned whether histamine or other mediators might be responsible for cAMP abnormalities. We found that exposure of normal cells to low (10(-6)M) concentrations of histamine, isoproterenol, or prostaglandin E desensitized the cells to subsequent stimulatory concentrations of any of the agonists. This heterologous desensitization occurred within 15 min and persisted for days, with gradual recovery of cAMP responses roughly paralleling those of cells from patients with atopic dermatitis. These findings provide a possible explanation for Szentivanyi's beta adrenergic blockade theory and the depressed leukocyte cAMP response to multiple agonists in atopy.

Adrenergic beta-Antagonists↗
PubMed1980

Leukocyte adherence in atopic dermatitis: diminished responses to histamine and isoproterenol.

Leukocyte adherence was examined in atopic and normal subjects and the influence of histamine and the beta-adrenergic agonist, isoproterenol, evaluated. Atopics included patients with mild to severe atopic dermatitis and patients with asthma and hayfever. No inter-group differences in leukocyte adherence of untreated leukocytes could be demonstrated, but there was a significantly smaller histamine and isoproterenol effect on the adherence of cells from patients with atopic dermatitis and hayfever. The induced inhibition of leukocyte adherence by histamine could be blocked by the H-2 histamine receptor antagonist, metiamide, suggesting that this effect may be mediated via cAMP. Our findings support the hypothesis that atopic dermatitis patients may have a defect or blockade of their cellular response to histamine.

Dermatitis, Atopic↗
PubMed1980

Yellow mutant albinism: cytochemical, ultrastructural, and genetic characterization suggesting multiple allelism.

This report describes three sisters, including monozygotic (MZ) twins, with clinical, ultrastructural, and histochemical features typical of yellow mutant albinism; This form of albinism is clinically similar to the tyrosinase-positive type, but hair bulbs showed (1) organelles similar to red hair pheomelanosomes and (2) absence of tyrosinase activity. Classical tyrosinase-negative albinism was found in a maternal cousin of the probands. Pedigree analysis of this family suggests multiple alleles occupying a single locus.

Adult↗
PubMed1979

Athletic shoe dermatitis. Contact allergy to ethyl butyl thiourea.

Ten patients with severe foot dermatitis were found to be highly allergic to innersole material prepared by Spenco Medical Corporation and used in Nike athletic shoes. Contact allergy testing showed sensitivity to ethyl butyl thiourea, a chemical accelerator in some neoprene (polychioroprene) rubber products. The dermatitis was recalcitrant and in many cases persisted long after discontinuance of wearing Nike shoes, raising the concern that traces of ethyl butyl thiorea or cross-reacting chemicals may be present in other footwear.

Adult↗
PubMed1979

Beta adrenergic receptor binding on polymorphonuclear leukocytes in atopic dermatitis.

It has been postulated that the patient with atopic dermatitis has defective beta adrenergic receptor function. However, a more generalized defect is suggested by the observation that cyclic AMP generation is diminished in these patients following stimulation with both isoproterenol and PGE1. To determine the nature of this abnormality, we measured beta adrenergic receptor binding directly on polymorphonuclear leukocyte membranes using the radiolabeled beta adrenergic antagonist (-) [3H]dihydroalprenolol (DHA). DHA binding was studied in 6 mild and 9 moderate-to-severe atopic dermatitis patients, and 8 normal controls using a subsaturating concentration of DHA (0.5 nM) to estimate receptor affinity and a saturating concentration of DHA (30 mM) to determine the total number of receptors per cell. No significant differences (p greater than .05) were found in the total number of receptors per PMN between the control population (805 +/- 95) and the mild atopic dermatitis patients (745 +/- 91) or the moderate to severe group (621 +/- 79). In addition, no significant differences in receptor affinity were found among any of the 3 study groups. These findings suggest that beta receptor binding in atopic dermatitis is normal. Reduced cyclic AMP generation in atopic dermatitis PMN leukocytes would appear to be due to a defect distal to the beta adrenergic receptor itself.

Adult↗
PubMed1979

Delayed cutaneous hypersensitivity and lymphocyte transformation: dissociation in atopic dermatitis.

Studies of cell mediated immunity (CMI) in atopic dermatitis have demonstrated various defects and frequently contradictory results. The true nature of immune dysfunction remains uncertain. We approached this question by concurrently examining two aspects of CMI: delayed cutaneous hypersensitivity and in vitro lymphocyte transformation. Responses were tested using the antigens Candida albicans and streptokinase-streptodornase (SKSD). Mean lymphocyte transformation was equal in atopic patients and controls, although a subgroup of severely dermatitic patients showed depressed responses. Cutaneous anergy was the rule in atopic patients (96% to candidin and 84% to SKSD). Although normal subjects showed good correlation between in vitro and cutaneous responses, atopic patients showed a significant lack of correlation. Many patients manifested cutaneous anergy in the face of normal lymphocyte transformation re sponses.

Adolescent↗
PubMed1979

Lymphocyte response to phytohemagglutinin in atopic dermatitis.

Studies of patients with atopic dermatitis (AD) have demonstrated several clinical and laboratory indications of immunity defects, but with frequently contradictory results. We have recently shown that many patients with negative cutaneous delayed type hypersensitivity to candidin and streptokinase-streptodornase may have normal in vitro lymphocyte transformation to the same antigens. We hypothesized that this represents recovery of immunocompetent cells when they are isolated in vitro. This report describes phytohemagglutinin-induced transformation of lymphocytes immediately after isolation and after four days in culture (precultured). Responses of lymphocytes from patients with AD were initially subnormal, but increased to normal levels after the preculture period. Our results suggest that defective immune function in AD is not due to a permanent intrinsic lymphocyte defect, but is more likely due to factors associated with disease activity and severity.

Adolescent↗
PubMed1978

The glucagonoma syndrome. A distinctive cutaneous marker of systemic disease.

The glucagonoma syndrome is a rare clinical condition characterized by a distinctive cutaneous eruption associated with a glucagon-secreting islet cell neoplasm of the pancreas. A 19-year-old woman manifested typical features of this condition: a polymorphous skin eruption with characteristic distribution of lesions in perioral and paragenital regions; lesions in sites of cutaneous trauma; a skin biopsy that showed epidermal cleavage; glossitis; weight loss; mild anemia; abnormal glucose tolerance test results. Plasma glucagon levels, determined by radioimmunoassay, were approximately five times normal. Angiography indicated a pancreatic tumor with liver metastases. Islet cell origin was confirmed histologically. It is hoped that wider recognition of the distinctive clinical features of this syndrome will result in earlier detection and possible surgical cure of the underlying malignancy.

Adenoma, Islet Cell↗
PubMed1978

Lack of functional immunoregulatory cells in a patient with mycosis fungoides and circulating Sézary cells.

Peripheral blood lymphocytes obtained at various intervals from normal individuals and from a patient with mycosis fungoides (MF) were cultured with phytohemagglutinin (PHA) for 3 days to activate suppressor cells. After being cultured, the PHA-treated cells were irradiated, washed, and then transferred to fresh medium with PHA. The PHA responsiveness of the cells from normal individuals was suppressed approximately 90% by autologous or normal allogeneic lymphocytes activated for 3 days with PHA, whereas the cells activated for 3 days with PHA from the patient with MF lacked the capacity to inhibit the mitogenic response of autologous or allogeneic lymphocytes. These data suggest that this patient lacked suppressor T-cells that have a specificity for helper T-cells.

Aged↗
PubMed1978

Levamisole therapy in atopic dermatitis: randomized double-blind evaluation.

A randomized double-blind study of levamisole hydrochloride therapy in atopic dermatitis is reported. No improvement was noted in any of several assessments, which included patients' subjective impressions; physicians' clinical impressions; comparison of clinical extent and severity scores; and incidence of cutaneous infections or lessening of serum IgE levels. A trend toward improvement was seen in a majority of cases, whether treatment was with a placebo or an active drug. This study emphasizes the need for double-blind techniques for therapeutic trial in the management of patients with atopic dermatitis.

Adolescent↗