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Biomedical subjects

J M Hanifin

Publications and source records attributed to J M Hanifin.

At least 127 records · Page 7Linked to original sources
PubMed1984

Inhalational anesthesia and histamine release during bronchospasm.

The influence of inhalational anesthetics on histamine released during bronchospasm induced by Ascaris antigen aerosol was studied in Basenji-Greyhound (BG) dogs. Five BG dogs were anesthetized with thiopental and halothane on separate occasions and challenged with Ascaris antigen aerosol for five minutes. Pulmonary resistance (RL), dynamic compliance (Cdyn), and arterial plasma histamine levels were measured over 30 min following antigen exposure. Prior to antigen challenge, RL, Cdyn, and histamine levels were similar in thiopental- and halothane-anesthetized dogs. The peak change in RL and Cdyn occurred 10 min after the start of antigen challenge. RL increased 3.0 +/- 0.4-fold (mean +/- SEM) in thiopental-anesthetized dogs as compared with 1.6 +/- 0.2-fold in halothane-anesthetized dogs (P less than 0.05). Cdyn decreased to a similar extent in both groups, with maximal decreases of 0.53 +/- 0.08 and 0.53 +/- 0.09 times the prechallenge value for thiopental- and halothane-anesthetized dogs, respectively. Plasma histamine levels peaked at 5 min. Plasma histamine increased to 8.0 +/- 5.0 ng/ml in thiopental-anesthetized dogs compared with 10.7 +/- 4.7 ng/ml in halothane-anesthetized dogs. Histamine levels were not significantly different during or after antigen challenge between thiopental- and halothane-anesthetized dogs. Halothane, but not thiopental, significantly attenuated the increase in RL provoked by antigen challenge. However, arterial plasma histamine levels were similar during both anesthetics. Therefore, the authors conclude that the protective effect of halothane on airways was not due to an inhibition of release of histamine from mast cells.

Anesthesia, Inhalation↗
PubMed1984

Direct depletion and purification of monoclonal antibody defined cells from unfractionated human mononuclear leukocytes using antibody coated polystyrene Petri dishes.

Human peripheral blood mononuclear leukocytes were depleted or enriched in various monoclonal antibody-defined subsets using a simplification of the indirect " panning " technique. Unfractionated mononuclear leukocytes (MNL) were sensitized with appropriate dilutions of monoclonal antibodies to human Lyt3 , OKT4 and OKT8 antigens, and to a monocyte-myeloid line antigen. The sensitized cells were then placed on polystyrene Petri dishes coated with goat antimouse IgG to obtain a population of cells depleted and a population of cells enriched in each cell type. Direct separation of surface immunoglobulin-bearing cells was similarly achieved by coating the Petri dish with goat antihuman immunoglobulins. Results showed that MNL could be depleted to greater than 95% purity with these methods and that positively selected adherent cells could be enriched to at least 85% purity. The relative proportions of MNL subpopulations in various sorted cell populations is reported. Cells obtained by panning are functionally intact. As compared to complement lysis both marker positive and marker negative cells can be obtained and the technique requires less technical expertise than using fluorescence activated cell sorting. The modification reported here is simpler and less time consuming for human T cell subpopulation separations than previously reported panning methods since an initial sheep erythrocyte rosetting step was not used.

Animals↗
PubMed1983

Increased leukocyte histamine release with elevated cyclic AMP-phosphodiesterase activity in atopic dermatitis.

Maximal leukocyte histamine release in response to concanavalin A was significantly higher in a group of 16 adult patients with moderate to severe atopic dermatitis when compared to 13 adult nonatopic, normal subjects. In a further four atopic dermatitis patients, histamine release was similar to that in the normal group suggesting the existence of "high-releaser" and "low-releaser" subsets within the atopic dermatitis group. Leukocyte cAMP phosphodiesterase activity was significantly higher in the high-releaser group than in the low-releaser and normal groups. High and low histamine release responses showed strong correlations with high and low phosphodiesterase activities. Pretreatment with the experimental cAMP phosphodiesterase inhibitor Ro-20-1724 in high releasers reduced the histamine release to normal levels. These findings suggest that increased histamine "releasability" in atopic dermatitis is related to abnormalities in cyclic nucleotide regulation. Basophil percentages within the leukocyte preparation and the histamine content per basophil were not significantly different between the atopics and normals. Histamine release did not correlate significantly with serum IgE levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Pruritic dermatitis in asthmatic basenji-greyhound dogs: a model for human atopic dermatitis.

A recurrent, nonseasonal pruritic dermatitis manifested as lichenified plaques and as inflammatory nodules and papules in each of fourteen basenji-greyhound (B-G) crossbreed dogs, all of which demonstrated both nonspecific and Ascaris-specific airway hyperreactivity, with changes in pulmonary mechanics of the same order as those seen in symptomatic human asthma. Other features analogous to human atopic disease included blunted cyclic adenosine monophosphate (cAMP) responsiveness to beta adrenergic agents and in vivo release of histamine and slow-reacting substance of anaphylaxis in response to antigen aerosol challenge. The dermatitis appears to be a manifestation of the atopic state in these dogs and may provide an animal model for the study of human atopic dermatitis.

Animals↗
PubMed1983

Thymopoietin pentapeptide (TP-5) improves clinical parameters and lymphocyte subpopulations in atopic dermatitis.

In a double-blind prospective study, eighteen patients with atopic dermatitis (AD) were treated with thrice-weekly injections of 50 mg thymopoietin pentapeptide (TP-5) or placebo for 6 weeks. Clinical parameters, lymphocyte subsets defined by monoclonal antibodies, and serum IgE were modified. Younger patients (age less than 34) responded to TP-5 with much greater improvement in severity scores than TP-5-treated patients of age greater than 34 or than placebo-treated patients of either age group (p less than 0.05). Both absolute lymphocytes and OKT8+ cytotoxic/suppressor cells were significantly increased (p less than 0.05) in the TP-5 group, whereas they were not significantly increased in the placebo group (p greater than 0.05). Conversely, Ia+ cells were significantly increased in the placebo group (p less than 0.05), but remained the same in the TP-5 group (p greater than 0.05). Serum IgE levels were not significantly altered in either group. Thus, TP-5 had a beneficial clinical effect in AD, especially in younger patients, and increased the reduced OKT8+ cytotoxic/suppressor T cells and prevented an increase of Ia+ cells during pollen season.

Adult↗
PubMed1983

Aleukemic leukemia cutis: juvenile chronic granulocytic leukemia presenting with figurate cutaneous lesions.

We report a 3 1/2-year-old girl who developed a figurate cutaneous eruption. Distinctive findings in her skin biopsies, as well as unusual red cell characteristics, in the presence of a normal peripheral smear and bone marrow biopsy, led us to suspect the diagnosis of preleukemic juvenile type chronic granulocytic leukemia. This is the first case we know of in which this diagnosis was suspected prior to abnormal findings in the peripheral smear or bone marrow.

Biopsy↗
PubMed1983

Atopic dermatitis. Special clinical complications.

Atopic dermatitis is a common disease of childhood that remits with age. Its pathogenesis is still uncertain; histamine seems important but the role of IgE is uncertain. The condition presents with several clinical features, none of which alone is pathognomonic. In some patients, particularly infants, several observations may be needed to discover the chronic nature of the disease. Most patients with atopic dermatitis have excessive skin dryness and hand dermatitis; many have superficial pustular staphylococcal infection. Management focuses on measures that reduce trigger factors, such as skin irritant exposure, emotional stress, and infection. Therapeutic agents include emollient creams, corticosteroid creams and ointments, and oral antihistamines. Exposure to summer sunshine is important in control.

Administration, Topical↗
PubMed1983

Immunoregulation in atopic dermatitis: functional analysis of T-B cell interactions and the enumeration of Fc receptor-bearing T cells.

Immune aberrations in atopic dermatitis (AD) are multiple and interrelated. We investigated immunoregulatory cell markers and functional interactions of purified T- and B-enriched cells in a pokeweed mitogen (PWM)-stimulated IgG production assay in patients with AD. Atopic mononuclear leukocytes and autologous recombinations of purified atopic T and B cells were hyporesponsive to PWM stimulation of IgG synthesis. When atopic B cells were cultured with normal T cells, they were still less responsive than normal B cells. Atopic T cells generated normal levels of suppression in three responder systems. Radioresistant T-cell help was also in the normal range whereas nonirradiated AD T cells produced slightly less help than normal T cells. We noted reduced levels of T lymphocytes with FcIgG receptors (T gamma) and found that T gamma reduction correlated inversely with log serum IgE. In the light of normal T suppression, we critically examined AD cell adherence and contamination at various steps in the T gamma assay to rule out technical causes of T gamma reduction in AD. Lowered T gamma cells in AD were not associated with circulating IgG immune complexes and subsequent blockade of the FcIgG receptors. Thus, we have identified defects in the numbers of an immunoregulatory T cell, and in the generation of PWM-responsive B cells. A model is proposed in which the alterations in atopic cyclic nucleotide metabolism of T-cell helpers could result in abnormalities of immunoregulatory T cells and PWM-recruitable B cells.

Adolescent↗
PubMed1983

Citric acid airway constriction in dogs with hyperreactive airways.

To understand the mechanisms underlying the bronchoconstrictor response to 10% citric acid administered for 5 min in Basenji-Greyhound (BG) dogs, we evaluated the protection afforded by atropine (0.2 and 0.4 mg/kg iv) and by aerosols of isoproterenol (1 mg/ml) and cromolyn sodium (20 mg/ml). In untreated dogs, citric acid increased pulmonary resistance by 4.6- to 11.5-fold and decreased dynamic compliance (Cdyn) to 45-55% of the control response. Isoproterenol and cromolyn sodium significantly reduced the response, whereas atropine did not. Moreover we have demonstrated in the arterial plasma of these dogs a slow-reacting substance (SRS) after, but not before, citric acid challenge. This SRS exhibits both pharmacologic properties and chemical characteristics similar to leukotrienes. We conclude that mediators of immediate-type hypersensitivity rather than reflex mechanisms play a dominant role in the production of airway constriction during citric acid (5-min) challenge in BG dogs.

Airway Resistance↗
PubMed1983

Role of mediators in allergic and nonallergic asthma in dogs with hyperreactive airways.

Basenji-Greyhound crossbreed dogs, with nonspecific airway hyperreactivity, release histamine into the plasma after aerosol challenge with Ascaris antigen and a slow reacting substance (SRS) after aerosol challenge with citric acid or Ascaris antigen. The appearance of SRS in the plasma after citric acid aerosol challenge, without an increase in histamine, closely parallels the changes in pulmonary mechanics. The pulmonary response to citric acid, in contrast to Ascaris antigen, is totally prevented in vivo by FPL 55712, an SRS antagonist. SRS exhibits both pharmacologic properties and chemical characteristics similar to leukotrienes. These studies suggest that SRS may be an important mediator in nonallergic airway constriction in vivo.

Airway Resistance↗
PubMed1983

Effects of thymopoietin pentapeptide (TP-5) on in vitro and in vivo IgE production by atopic dermatitis cell subsets.

Atopic dermatitis (AD) patients exhibit multiple immune abnormalities, including T-cell defects that may be partially correctable by the administration of thymic hormones. Our investigations confirmed that peripheral blood mononuclear leukocytes obtained from patients with AD spontaneously synthesized markedly elevated amounts of IgE in vitro. The thymic hormone thymopoietin pentapeptide (TP-5) greatly inhibited this synthesis. An antihuman pan-T cell monoclonal antibody (Lyt3) was used to separate T-cell marker-positive (T+) T cells from marker-negative (T-) B-enriched cells. TP-5 pretreatment of T+ cells resulted in significant reduction of in vitro IgE synthesis by recombined T+ and T- cells, whereas pretreatment of T- B-enriched cells resulted in a nonsignificant reduction in in vitro IgE synthesis. Thus, although pretreatment of both subsets resulted in some degree of reduction, TP-5-induced inhibition of in vitro IgE synthesis was primarily mediated via T cells. The majority of patients' untreated T+ and T4+ cells showed enhanced IgE synthesis, but only one patient's T8+ cells were capable of suppressing IgE synthesis. Thus TP-5 may either induce suppressor T-cell activity or reduce helper T-cell activity. A six-week double-blind clinical trial of TP-5 produced evidence of clinical improvement and alterations of abnormalities of OKT8+ cells, although no significant effects on serum IgE were seen.

Antigens, Ly↗
PubMed1982

Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness.

Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Atopic dermatitis.

Atopic dermatitis is a chronically relapsing inflammatory skin disease with altered immune and pharmacologic responses. Elevated serum IgE probably reflects defective immune regulation. Various other cellular immune defects rise and fall exacerbations and remissions of skin inflammation. Increased responsiveness to cholinergic and alpha adrenergic agents may relate to abnormalities of cyclic nucleotide regulation. Recent observations of abnormal cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity in atopic dermatitis may provide new insights into the pathogenesis and treatment of the disease.

Acetylcholine↗
PubMed1982

Ketoconazole in griseofulvin-resistant dermatophytosis.

The efficacy of ketoconazole was evaluated in twenty patients with chronic dermatophyte infections who had failed to clear with griseofulvin therapy. Trichophyton rubrum was the causative organism in nineteen of the patients, and Trichophyton mentagrophytes in one patient. Three of twelve organisms tested showed in vitro resistance to griseofulvin. Duration of infection ranged from 2 to 28 years. Patients received 200 to 400 mg of ketoconazole daily for periods up to 8 months. In addition, patients were followed for 5 months post-therapy to monitor recurrences. Clearing was seen clinically as early as 2 weeks, and by 18 weeks all patients showed marked improvement or clinical clearing, though only six achieved complete mycologic cure. Improvement followed a predictable sequence of sites, with lesions of the trunk healing first, followed by hands, feet, and finally, nails. After 8 months, though all patients showed proximal nail clearing, onychomycosis persisted in thirteen of twenty affected sites. By 5 months post-therapy, four of six patients who had achieved clearing of skin and nails showed recurrences. No significant side effects were observed during therapy, though rare, apparently idiosyncratic cases of hepatotoxicity have been reported. Ketoconazole is an affective therapeutic agent for griseofulvin-resistant dermatophytosis. Apparent cures may subsequently recur after discontinuation of therapy.

Adult↗
PubMed1982

Immunosuppression in a homosexual man with Kaposi's sarcoma.

The occurrence of Kaposi's sarcoma in young homosexual men is a recently reported condition. The same individuals are at risk for the development of Pneumocystis carinii pneumonia and other unusual infections. These associations suggest these persons are somehow immunocompromised. Evidence of current or prior cytomegalovirus (CMV) infection is seen in a high percentage of these and other homosexual men. CMV infections are known to induce alterations in the immunoregulatory suppressor and helper T lymphocyte populations. The CMV infection is suspect as the cause of immunosuppression in these individuals. We present a case of Kaposi's sarcoma in a homosexual men with CMV cultured from his urine and semen. He showed a marked increase in his suppressor/cytotoxic cell (OKT8-positive) population, as well as a marked decrease in his helper cell (OKT4-positive) population. Mitogen and antigen studies demonstrated absent or markedly diminished response both in vitro and in vivo. Pokeweed mitogen (PWM)-induced IgG synthesis appeared normal. This patient, as well as the majority of other reported patients with this disease, manifested the HLA-Dr5 phenotype. The immunosuppression in this patient and possibly other similar men appears to be mediated by abnormalities in the immunoregulatory T lymphocytes.

Adult↗
PubMed1982

FcIgG receptor-bearing lymphocytes and monoclonal antibody-defined T cell subsets in atopic dermatitis: effect of treatment with thymopoietin pentapeptide (TP-5).

Lymphocyte subpopulations were determined in the blood of patients with atopic dermatitis (AD) before and after treatment with the thymopoietin pentapeptide TP-5. The relative and absolute numbers of lymphocytes bearing suppressor/cytotoxic cell markers (FcIgG+E+ and T8+ cells) were significantly decreased in the untreated patients and the T4+/T8+ cell ratio was increased, indicating an imbalance between lymphocyte subpopulations in AD. Patients who had been treated for 6 weeks with TP-5 displayed no significant abnormality of any of the lymphocyte subsets studied and comparison of pre- and posttreatment values revealed that there was a statistically significant increase in T8+ cell numbers, that by contrast did not take place in placebo-treated AD patients. The treatment had no demonstrable effect on IgE serum levels or on the spontaneous in vitro production of IgE by cultured lymphocytes from the patients.

Antibodies, Monoclonal↗