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Biomedical subjects

G F Murphy

Publications and source records attributed to G F Murphy.

At least 163 records · Page 9Linked to original sources
PubMed1985

Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation.

Exercise-induced anaphylaxis (EIA) is a unique and an increasingly recognized syndrome consisting of premonitory symptoms and signs of generalized body warmth, pruritus, and erythema, which progresses on continued exertion to confluent urticaria, laryngeal edema with stridor or hoarseness, and gastrointestinal colic and frequently culminates in vascular collapse. Previous studies of five individuals with this condition have demonstrated significant elevations of serum histamine concurrent with the early clinical manifestations after experimental exercise. To assess relevant morphologic alterations in the skin of these patients, cutaneous mast cells were examined by light and transmission electron microscopy before and during the initial erythema elicited by exertion. The marked alterations observed in mast cells immediately after exercise consisted of (1) loss of electron density and internal substructure of granules, (2) fusion of granule membranes with those of adjacent granules and with mast cell membranes creating conduits to the extracellular space, and (3) an apparent decrease in the number of intact granules per cell. Biopsy specimens obtained before exercise from patients with EIA and from two normal individuals who served as control subjects were identical, and the control subjects had normal mast cell morphology after exercise. Serum histamine levels were significantly elevated in patients with EIA after exercise at the time of biopsy, whereas control subjects had normal levels. These observations provide evidence that EIA is a distinct form of physical allergy associated with mast cell degranulation similar in morphology to that of human pulmonary mast cell IgE-Fc-dependent activation secretion. Characterization of this disorder is important because its prevalence may be underestimated, and its clinical consequences, which may include some morbidity, are not fully known.

Adult↗
PubMed1985

Depletion and repopulation of epidermal dendritic cells after allogeneic bone marrow transplantation in humans.

We have observed marked depletion of epidermal dendritic cells, defined by monoclonal antibodies directed against HLA-DR (Ia-like) and T6 antigens, after allogeneic bone marrow transplantation. To more precisely characterize this observation, we examined a total of 39 sequential biopsies from 15 patients both before and after allogeneic bone marrow transplantation. Profound depletion of HLA-DR and T6-positive epidermal dendritic cells was observed early after transplantation (1-4 weeks), followed by gradual and variable repopulation. Transmission electron microscopy confirmed absence of dendritic cells in selected biopsies. Depletion of dendritic cells did not appear to be related to development of clinical or histologic evidence of graft-versus-host disease, suggesting that depletion may relate to pretransplant conditioning regimens. The rate of return of these cells, however, may be influenced by the presence or persistence of clinical disease. Repopulation of epidermal dendritic cells after initial depletion in bone marrow transplantation represents a human model relevant to studies concerned with the origin and kinetics of Langerhans cells.

Adolescent↗
PubMed1985

Expression of activation antigens by T cells infiltrating basal cell carcinomas.

The association of T lymphocytes and dendritic cells with the stromal mononuclear cell response to basal cell carcinomas has led to speculation that cellular immunity may, in part, regulate the growth and development of this neoplasm. It has not been established, however, whether these T cells are functionally competent, or simply coincidental bystanders. We examined the immunologic phenotypes of mononuclear cells in 32 lesions of basal cell carcinoma obtained from 26 patients. The majority of infiltrating mononuclear cells were T cells that were equally distributed between the helper/inducer (Leu 3a+) and cytotoxic/suppressor (Leu 2a+) subtypes; a minority of cells were dendritic and expressed Leu 6 antigen. Virtually all T cells and dendritic cells were HLA-DR+, and many (greater than 30%) of the T cells expressed antigens consistent with stages of ongoing activation (T9, T10). TS2/7, a novel monoclonal antibody recently documented to identify activation-specific subcomponents of 210/165/130 kD glycoprotein complex present on the surface of mitogen- or alloantigen-stimulated human T cells, was also used. Greater than 50% of the T cells observed were TS2/7+. These observations provide in situ immunomorphologic evidence of stromal T cell activation in association with basal cell carcinomas, and suggest a role for active and ongoing cellular immune mechanisms as a determinant of local biological behavior of this neoplasm.

Antibodies, Monoclonal↗
PubMed1985

Effects of cyclosporine on glucose tolerance in the rat.

In a study of prevention of spontaneous diabetes in BB rats by therapeutic doses of cyclosporine (10 mg/kg/day), the male control non-diabetes-prone rats showed glucose intolerance after a 0.25 g/kg glucose load by gavage, at 90 and 130 days of treatment. Non-BB male Wistar rats treated similarly showed glucose intolerance at 1 wk of treatment, with progressive worsening for 5 wk, then sustained up to 12 wk of treatment. Fasting euglycemia was maintained, but both pre- and postchallenge plasma insulin levels were significantly lower with cyclosporine at several time points. Total pancreatic insulin was decreased to one-third that of control after 5 wk. After withdrawal of cyclosporine, glucose tolerance returned to normal in 2 wk. Sprague-Dawley rats responded similarly and in both strains, an increase in the cyclosporine dose to 15 mg/kg/day augmented the glucose intolerance. These results demonstrate that therapeutic doses of this agent induce reversible glucose intolerance due, in part, to inhibition of insulin secretion and also possibly inhibition of synthesis, though a peripheral effect is not excluded. This hyperglycemic effect of cyclosporine has implications for its potential use in type I diabetes mellitus, transplantation, and other autoimmune disease.

Animals↗
PubMed1985

Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation.

A case of perianal and perineal extramammary Paget's disease in a male is reported. The presence of gross cystic disease fluid protein--a new marker of apocrine epithelia--in Paget's cells provides additional insight into the histopathogenesis of this condition. This marker may be a valuable diagnostic adjunct in evaluating intra-epithelial malignancies at a variety of anatomic sites.

Aged↗
PubMed1985

Ultrastructural documentation of M241 glycoprotein on dendritic and endothelial cells in normal human skin.

M241 is a glycoprotein that recently has been demonstrated to be present in human thymus in a distribution similar to T6. Studies in skin, however, suggest that M241, in contrast to T6, is detected only on a subset of Langerhans cells and on a population of dendritic cells in the superficial dermis. We compared the reactivities of monoclonal antibodies to M241 and T6 with dendritic cells in normal human skin using immunoelectron microscopy. Our findings indicate that M241 is present on a minority of Langerhans cells and on a substantial number of other predominantly dermal dendritic cells with morphologic features of indeterminate cells. Anti-M241 reactivity was generally restricted to the cell membrane, although cytoplasmic reactivity was detected in some Langerhans cells. Dermal endothelial cells, which like dendritic cells are capable of antigen presentation, were also reactive with anti-M241 antibody. M241 is a glycoprotein, different from T6, with a tissue distribution potentially relevant to the understanding of antigen-presenting cells in the skin.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia.

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

Cytarabine↗
PubMed1984

Involucrin expression in normal and neoplastic human skin: a marker for keratinocyte differentiation.

Involucrin is a recently recognized structural component of mature squamous epithelial cells. We examined involucrin expression using an immunoperoxidase technique in normal skin and in a variety of epidermal hyperplasias and neoplasms to determine whether distinctive staining patterns existed within these lesions. Four patterns of reactivity were observed: diffuse intracellular staining typical of keratinocytes of the upper third of normal epidermis and epidermal hyperplasias and benign neoplasms; staining at cell borders, seen principally in benign epidermal neoplasms; patchy staining characteristic of squamous cell carcinoma in situ; and absence of staining in benign and neoplastic basaloid epithelium. Invasive nests of squamous cell carcinomas were negative for involucrin reactivity, whereas pseudoinvasive tongues of epithelium at the bases of keratoacanthomas were focally positive. These results suggest that immunoperoxidase staining for involucrin may be useful in distinguishing certain benign from malignant epidermal neoplasms as well as in understanding the altered maturation and kinetics of proliferative processes afflicting keratinocytes.

Cell Differentiation↗
PubMed1984

Demonstration of T200 on human Langerhans cell surface membranes.

We have demonstrated the presence of the glycoprotein T200 on the surface of human epidermal Langerhans and indeterminate cells by immunoelectron microscopy with the use of a monoclonal antibody. No other epidermal cells were positive. The presence of T200 on Langerhans cells confirms their hematopoietic origin because T200 is limited to hematopoietic cells and neoplasms. Although the function of T200 is not known, antibodies directed against T200 have been previously shown to inhibit accessory cell and natural killer cell activities. While the existence of a possible relationship between Langerhans cells and natural killer cells is unclear, Langerhans cells are important in cutaneous accessory cell functions; therefore. T200 may be important in understanding the biology of Langerhans cells and their relationship to other cells in the immune response.

Adult↗
PubMed1984

Linear IgA bullous dermatosis v dermatitis herpetiformis. Quantitative measurements of dermoepidermal alterations.

Linear IgA bullous dermatosis (LAD), also known as "atypical dermatitis herpetiformis," is a disorder that is distinct from classic dermatitis herpetiformis (DH). In eight patients with DH and six with LAD, quantitative assessment of a variety of histopathologic variables was made. The number of rete tips with neutrophils in basal vacuoles and the length of the epidermal basement membrane zone (BMZ) associated with these findings were greater in LAD than DH. The number of microabscesses of neutrophils in the dermal papillae and the length of epidermal BMZ associated with them were greater in DH than in LAD. By using the number of microabscesses and the number of rete tips with neutrophils in basal vacuoles in a probability model, we found by retrospective analysis that a correct diagnosis could be made for LAD in 75% of biopsy specimens with a probability of 97% and in all cases of DH with a probability of 92%. Using this model, we made no misdiagnoses. This is the first diagnostic probability model in dermatopathology that expresses a confidence level in diagnosis.

Adult↗
PubMed1983

Radiation therapy for primary lymphoma of bone.

The records of 30 patients with primary lymphoma of bone (PLB) who were treated with radiation therapy were reviewed. The probability of NED-survival and overall survival at five-year follow-up was 53 and 63%, respectively. There were three local failures following treatment. The cumulative incidence of local recurrence was 14% at five years. No local failures were observed when tumors received doses higher than 50 Gy, or equivalent to a TDF of 70 or greater. The number of failures was too small to examine for a correlation between histologic subclassification and local control frequency if doses higher than 50 Gy were utilized. Complications of treatment occurred in four patients. Functional results were excellent in all except two patients. These data provide guidelines for determination of a clinically appropriate radiation dose level for PLB.

Adolescent↗
PubMed1983

Biochemical studies of immune complexes. II. Purification of immune complexes from sera of patients with malignant melanoma.

Circulating immune complexes (CICs) from serum samples of patients with malignant melanoma were isolated in high yield utilizing a bifunctional chromatography matrix that binds all normal serum proteins except IgG-containing immune complexes (ICs), IgG, and transferrin. Protein fractions were subsequently analyzed by polyacrylamide gel electrophoresis (PAGE) and characterized by molecular weight. By this method, one common and several unique component nonimmunoglobulin proteins of the ICs were identified. These proteins possess similar molecular weights to several previously described human melanoma antigens. This technique should permit biochemical and immunological characterization of the component antigens of CICs in melanoma and other malignancies.

Antigen-Antibody Complex↗