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Biomedical subjects

K M Leiferman

Publications and source records attributed to K M Leiferman.

At least 73 records · Page 4Linked to original sources
PubMed1989

Episodic angioedema with eosinophilia.

A 40-year-old woman had monthly episodes of angioedema, eruption of pruritic papules and plaques and fever. During acute episodes white blood cell counts increased to 31,000/mm3 with 75% eosinophils, body weight increased to 10% of baseline weight, and urine excretion decreased to 40 ml/24 hours. No evidence was found for cardiac or other visceral organ involvement. Extensive diagnostic evaluations revealed no evidence for parasitic infestation, connective tissue disease, or neoplastic disorders. Results of immunologic studies revealed increased serum IgM and IgE levels and showed elevated levels of circulating activated T-helper cells. Biopsy specimens of lesional skin showed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil granule major basic protein in the extracellular matrix within the dermis. Immunophenotyping of the dermal infiltrate with monoclonal antibodies revealed the predominance of T-helper cells, many of them expressing the human leukocyte antigen (HLA)-DR, suggesting that angioedema with eosinophilia may be a T-helper cell-mediated disease.

Adult↗
PubMed1989

Follicular mucinosis: clinical and histopathologic study.

Fifty-nine patients with the histologic diagnosis of follicular mucinosis (alopecia mucinosa) were evaluated retrospectively. Thirty-seven were male and 22 were female; ages ranged from 10 to 76 years. Of 19 patients with mycosis fungoides, 16 had initial lesions of follicular mucinosis on the trunk or extremities. Two patients had Hodgkin's disease and follicular mucinosis; both were younger than 20 years of age. Seven other patients were 20 years of age or younger. Two of the nine adolescent patients had persistent plaques of follicular mucinosis up to 18 years after diagnosis. Evaluation of biopsy specimens for lymphocytes, eosinophils, nonlymphoid cell infiltration, epidermal lymphocytic exocytosis, mucin deposition, and epidermal hyperplasia revealed no predominant feature that differentiated the group with benign disease from the group with mycosis fungoides. We conclude that no single clinical or histopathologic observation predicts which patients with follicular mucinosis will have a benign course and that evaluation of multiple clinical and histologic variables is necessary.

Adolescent↗
PubMed1989

Evidence for eosinophil degranulation with deposition of granule major basic protein in solar urticaria.

Multiple sequential biopsy specimens of wheals elicited by a solar simulator in four patients with severe solar urticaria were studied with the use of indirect immunofluorescence for eosinophil granule major basic protein. Examination of control biopsy specimens from normal, unstimulated skin did not show eosinophils or major basic protein deposition. Five minutes after solar simulation, eosinophils were observed in vessels in the dermis, and 2 hours later there was marked tissue eosinophilia. Extracellular major basic protein was extensively deposited in the dermis at 2 and 24 hours, suggesting eosinophil degranulation. Thus evolution of the solar urticaria wheal is accompanied by infiltration of eosinophils and neutrophils and by tissue deposition of the eosinophil major basic protein, suggesting eosinophil degranulation.

Blood Proteins↗
PubMed1989

Preferential differentiation of inflammatory cells by recombinant human interleukins.

The effects of recombinant human interleukins (IL) on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical cord blood and bone marrow cells. The results showed that IL-5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with IL-5, over 90% of nonadherent cells in both bone marrow cell and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with IL-4 resulted in the selective growth of OKT-3+ lymphocytes. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of IL-3, basophilic, eosinophilic, and neutrophilic myelocytes developed within 2 weeks. By 3 weeks, however, the majority of non-adherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither IL-3 nor combination of IL-3 and IL-4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.

Basophils↗
PubMed1989

Eosinophils and human disease.

The likely roles of the eosinophil leukocyte in human disease are reviewed. The eosinophil is richly endowed with toxic cationic proteins and is able to mount a respiratory burst. Thus, eosinophils have the capability to damage various targets, and evidence exists that they do so during helminth infections and during the course of many hypersensitivity diseases. Here we discuss the role of the eosinophil in human onchocerciasis with particular attention to the Mazzotti reaction. We also discuss other diseases where eosinophil degranulation is seen, especially cutaneous diseases. Finally, the possible role(s) of the granule major basic protein in human pregnancy is noted.

Animals↗
PubMed1989

Evidence for eosinophil degranulation in the pathogenesis of herpes gestationis.

Herpes gestationis is a pregnancy-related bullous dermatosis of unknown origin with associated tissue and peripheral blood eosinophilia. In this report, eosinophil degranulation in herpes gestationis was studied, and the role that the eosinophil may have as an effector cell that induces tissue damage through deposition of toxic cationic proteins is discussed. Using indirect immunofluorescence with antibody to human eosinophil granule major basic protein, major basic protein was observed both within tissue eosinophils and deposited extracellularly outside eosinophils in the dermis of eight patients with herpes gestationis. Possible mechanisms whereby eosinophils might be activated to degranulate in herpes gestationis are reviewed.

Adolescent↗
PubMed1989

Eosinophils in atopic dermatitis.

The eosinophilic granulocyte is commonly associated with allergic inflammation. Although blood eosinophilia frequently accompanies atopic dermatitis, accumulation of tissue eosinophils is not prominent. Recent studies have elucidated the structure, content, and activities of the eosinophil. In addition, immunofluorescence localization of eosinophil granulate proteins has shown that eosinophils disrupt in tissue depositing toxic granule proteins in several diseases. Here, evidence for eosinophil degranulation in atopic dermatitis is presented and mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects in atopic dermatitis and related conditions are discussed.

Blood Proteins↗
PubMed1988

Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3+ lymphocytes. However, OKT3+ cells did not develop if the bone marrow cells were depleted of OKT3+/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.

Bone Marrow Cells↗
PubMed1987

Increases of plasma eosinophil major basic protein levels late in pregnancy predict onset of labor.

Major basic protein (MBP), the core of the eosinophil granule, is a potent toxin for parasites and mammalian cells; it also causes histamine release from mast cells and basophils. Plasma levels of MBP are increased in all pregnant women, and MBP has been localized by immunofluorescence to placental X cells and placental-site giant cells. Analyses of plasma MBP levels during pregnancy showed a striking correlation between increases late in the third trimester and spontaneous onset of labor. In one case with premature labor, the plasma MBP level also was increased coincidentally with labor. In contrast, in cases of prolonged gestation in which labor was induced, there were no late increases in MBP levels. Also, uterine contraction during spontaneous labor or oxytocin-induced labor did not cause elevations of plasma MBP. Measurement of plasma MBP levels in pregnancy may be useful for the prediction of labor and for the development of new means of intervention for premature labor and prolonged gestation.

Blood Proteins↗
PubMed1986

Differences between basophils and mast cells: failure to detect Charcot-Leyden crystal protein (lysophospholipase) and eosinophil granule major basic protein in human mast cells.

Human eosinophils contain several distinctive proteins including eosinophil granule MBP and the membrane-associated CLC protein (lysophospholipase). Human basophils also contain these proteins, indicating biochemical similarities between eosinophils and basophils. To determine whether MBP or CLC protein is present in connective tissue mast cells, we studied human lung and cutaneous mast cells by immunofluorescence by utilizing specific antibodies to CLC and MBP. Cytocentrifuge slides of enriched lung mast cells and mast cells in sections of formalin-fixed, paraffin-embedded cutaneous tissue from urticaria pigmentosa lesions were stained for CLC and MBP. Neither pulmonary nor cutaneous mast cells stained for CLC protein or MBP. In contrast, lung and cutaneous eosinophils in the same preparations showed bright staining for both proteins. The failure to find CLC protein and MBP in mast cells provides additional evidence of dissimilarity between mast cells and basophils, and an immunochemical means to distinguish between them.

Basophils↗
PubMed1986

Hypereosinophilia and recurrent angioneurotic edema in a 2 1/2-year-old girl.

A 2 1/2-year-old girl presented with monthly episodes of angioneurotic edema, eruption of pruritic papules, and fever. During acute episodes, white blood cell counts rose as high as 52,100/cu mm with 62% eosinophils, and body weights increased up to 20% of remission weight. Short courses of prednisone acetate caused rapid defervescence, resolution of angioneurotic edema, and lowering of eosinophil counts. In a one-year follow-up no evidence was found for cardiac or other visceral organ involvement. Findings of extensive diagnostic evaluations revealed no evidence for atopy, neoplasm, collagen-vascular disease, or parasitic infestation. Results of immunologic studies were essentially normal with the exception that this patient had a high level of circulating activated helper T cells. Biopsy specimens of the skin lesions revealed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil major basic protein in the extracellular matrix. Awareness of this clinical entity and its distinction from the hypereosinophilic syndrome is important because of its favorable prognosis and rapid response to corticosteroid therapy.

Angioedema↗
PubMed1986

The eosinophil and cutaneous edema.

Although eosinophils are readily identified in skin tissue, their role in cutaneous disease has been obscure. Recent studies have elucidated the structure, content, and several activities of the eosinophil. The eosinophil is a potent parasite-killer cell and probably mediates damage to respiratory epithelium in bronchial asthma. We review information showing an association between cutaneous edema and eosinophil degranulation in tissue. These studies show that eosinophils release and deposit toxic granule proteins extensively in the skin despite the existence of few intact eosinophils in tissue. The evidence suggests that the eosinophil functions not only as a parasite-killer cell but also as a proinflammatory cell that may be pathophysiologically related to the development of cutaneous edema.

Adult↗
PubMed1985

Dermal deposition of eosinophil-granule major basic protein in atopic dermatitis. Comparison with onchocerciasis.

Although blood eosinophilia is commonly present in atopic dermatitis, accumulation of tissue eosinophils is not prominent. To determine whether eosinophil degranulation occurs in lesions of atopic dermatitis, we analyzed tissues by immunofluorescence for the presence of the eosinophil-granule major basic protein. Twenty biopsy specimens from 18 patients with atopic dermatitis were studied, and all showed major basic protein staining outside eosinophils. In 18 specimens, the staining was fibrillar, was located in the upper half of the dermis, and was similar to the distribution of elastic fibers. Twelve specimens with fibrillar staining also showed major basic protein staining in the form of extracellular granules. One specimen from unaffected skin showed minimal faint, fine, fluorescing fibrils, but there was marked deposition of the protein in affected skin. The fibrillar pattern of major basic protein staining in atopic dermatitis was very similar to that seen in lichenified lesions of untreated onchocerciasis. These results suggest that eosinophils commonly release granule proteins in the dermis and that assessment of eosinophil involvement in disease cannot be based simply on numbers of eosinophils in tissue.

Adolescent↗
PubMed1984

Acne fulminans and myositis.

Acne fulminans is characterized by highly inflammatory ulcerative lesions and systemic manifestations. We report a case of acne fulminans and myositis. In addition to having typical skin changes, the patient was unable to walk and electromyographic studies showed significant changes.

Acne Vulgaris↗
PubMed1983

Characterization of the glucocorticoid receptor in human skin.

Because of the profound importance glucocorticoids have in dermatologic therapy, we studied the glucocorticoid receptor in human skin. A cytosol fraction was prepared from frozen skin by homogenization and centrifugation. When reacted with [3H]dexamethasone, this cytosol contained saturable, low-capacity binding. The glucocorticoid binding was stabilized by a protease inhibitor, phenylmethylsulfonylfluoride, and by sodium molybdate and was destroyed by trypsin. Sedimentation analysis of the glucocorticoid binding protein showed an 8S to 4S transition in high salt, a property of many known steroid hormone receptors. The binding was steroid specific, supporting the conclusion that this binding protein was a glucocorticoid receptor. The receptor molecule had a frictional ratio of 1.60 and a Mr of about 226,000 under low-salt conditions (0.05 M KCl) and a frictional ratio of 1.86 and a Mr of about 100,000 under high-salt conditions (0.3 M KCl) consistent with a nonglobular, elongated molecule. Isoelectric focusing showed that the receptor had 2 molecular species with isoelectric points of approximately 5.8 and 7.5. Quantitation of receptor in human skin showed 4-7 times more receptors in the epidermis and papillary dermis than in the lower dermis and nearly equal numbers in epidermis and papillary dermis. The concentration of receptors varied in different anatomic areas, with male foreskin showing the highest concentration, followed by female face, breast, and abdominal skin. Interestingly, the concentration of glucocorticoid receptors also varied with age; the highest levels were present at the extremes of life and a significantly lower level at midlife.

Aging↗
PubMed1982

Recurrent incapacitating mucosal ulcerations. A prodrome of the hypereosinophilic syndrome.

The hypereosinophilic syndrome is a multisystem disease characterized by infiltration of eosinophils in bone marrow, heart, and other organs. Cutaneous involvement occurs, but usually it appears late in the disease and is of less importance than the cardiac and other organ involvement. We describe two patients with the hypereosinophilic syndrome (HES) in whom the initial manifestations of the disease were recurrent, severe mucosal ulcers involving the mouth and genitalia. In both patients, the mucosal involvement antedated the cardiac manifestations of the disease, and in both, the disease was refractory to treatment.

Adult↗
PubMed1979

Measurement of the potency of pollen extract by radioimmunoprecipitation.

We describe a novel procedure for standardization of allergen extracts using radioiodinated crude extracts. Radiolabeled extracts were reacted with immunoglogulin E (IgE) antibody, and the resulting complexes precipitated by anti-IgE. Experiments with ragweed pollen, grass pollen, honeybee venom, and Alternaria extracts revealed that 1% to 14% of the radioactivity was precipitated, these percentages ranged from 2 to 20 times blank values. Binding of labeled ragweed extracts to IgE antibody could be inhibited by unlabeled extracts and linear inhibition responses could be derived. The potencies of 11 short ragweed extracts were ranked by their inhibitory capacities in such an IgE radioimmunoprecipitation (RIP) test and compared to potencies determined by radioallergosorbent test (RAST) inhibition; these were related, rs = +0.97 (p less than 0.001). Labeled extracts were also reacted with IgG antibodies, and the resulting complexes were precipitated by anti-IgG. From 1% to 34% of the radioactivity associated with the various extracts was precipitated by anti-IgG, and these percentages were from 2 to 20 times blank values. The reaction of IgG antibody with radiolabeled pollen extracts could be inhibited by unlabeled extract, and in the case of short ragweed the measurements of potencies using IgG and IgE antibodies were correlated, rs = +0.96 (p less than 0.001), suggesting that similar determinants were recognized by both IgG and IgE classes. The RIP procedure provides an alternative to the RAST for the standardization of allergy extracts and eliminates the need for affinity chromatography-purified antibody to IgE.

Allergens↗