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Biomedical subjects

K M Leiferman

Publications and source records attributed to K M Leiferman.

At least 19 recordsLinked to original sources
PubMed1992

Elevated serum levels of interleukin-5 in patients with the syndrome of episodic angioedema and eosinophilia.

The syndrome of episodic angioedema and eosinophilia is characterized by cyclic edema, marked peripheral blood eosinophilia, and eosinophil degranulation in the dermis. Using a sensitive immunoenzymetric method, we measured serum interleukin (IL)-5 levels in four patients with this syndrome. We also determined the percentage of activated T cells in the peripheral blood of a new patient before and during an attack. In the patient presented, IL-5 levels peaked several days before maximal eosinophilia and then declined. This patient's lymphocytes showed an increased percentage, 28% (normal 2% to 3%), of activated T cells staining for both CD3 and HLA-DR 10 days before maximal eosinophilia, but no increase at the time of peak eosinophilia. In serum from three previously reported cases, elevated serum IL-5 levels were found during attacks. After glucocorticoid administration, IL-5 levels became undetectable in three of the four patients. Production of IL-5 is likely an important determinant of the pathophysiology of this syndrome.

Adult↗
PubMed1992

Pyoderma gangrenosum-like ulcer in a patient with large granular lymphocytic leukemia.

Large granular lymphocytic leukemia refers to a clonal expansion of lymphocytes that have abundant cytoplasm and azurophilic granules. The disease is characterized clinically by chronic neutropenia and it may be associated with recurrent pyogenic infections. Except for these infections, cutaneous manifestations of this disease have not been well characterized. We describe a patient with large granular lymphocytic leukemia, which was confirmed by molecular genetics studies, who had a pyoderma gangrenosum-like ulcer on his leg. Results of an evaluation of the histologic characteristics and the leukocytic immunophenotype of a skin biopsy specimen from the ulcer demonstrated large granular lymphocytes within the blood vessels. Cutaneous ulceration may be a manifestation of large granular lymphocytic leukemia, and this disease should be considered when diagnosing patients with otherwise unexplained pyoderma gangrenosum-like ulcers of the skin.

Complement C3↗
PubMed1992

Adhesion molecule expression in polymorphic light eruption.

Endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are cytokine-regulated cell-surface leukocyte adhesion molecules. We have investigated the in vivo kinetics and pattern of expression of these adhesion molecules in relation to tissue accumulation of leukocytes in the photodermatosis, polymorphic light eruption (PMLE), which is characterized by dense perivascular leukocytic infiltration. Immunohistology was performed on biopsies taken at varying time points from PMLE lesions induced in 11 subjects by suberythemal solar simulated irradiation. Vascular endothelial ELAM-1 expression was first observed at 5 h, maximal at 24 to 72 h, and remained elevated at 6 d. VCAM-1, minimally expressed in control skin, was induced above background levels on endothelium and some perivascular cells after 24 h and maintained at 6 d. Endothelial cell ICAM-1 expression was increased above control levels at 72 h and 6 d. Keratinocyte ICAM-1 expression, most marked overlying areas of dermal leukocytic infiltration, began at 5 h and was strong at 72 h and 6 d. In addition to lymphocytes, significant numbers of neutrophils but not eosinophils were detected in the dermal leukocytic infiltrate that appeared at 5 h and persisted at 6 d. The pattern of adhesion molecule expression that we have observed is similar to that seen in normal skin during a delayed hypersensitivity reaction. These observations support an immunologic basis for PMLE.

Biopsy↗
PubMed1992

Cutaneous reactions to granulocyte-monocyte colony-stimulating factor.

BACKGROUND AND DESIGN: Granulocyte-monocyte colony-stimulating factor (GMCSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophils, eosinophils, and monocytes. We reviewed the cutaneous reactions that developed in 26 patients who received GMCSF as part of a chemotherapeutic protocol. RESULTS: Fourteen patients developed immediate localized angioedematous reactions at the subcutaneous GMCSF injection site, and 21 developed generalized cutaneous reactions. Four biopsy specimens were obtained from three patients who had generalized erythrodermic reactions. All specimens showed perivascular and periadnexal lymphocytic inflammation in the dermis, and two showed perivascular and periadnexal eosinophilia. Staining for eosinophil granule major basic protein showed infiltration by eosinophils and extracellular deposition of major basic protein in three specimens from two patients with eosinophilia. Extracellular deposition of neutrophil elastase and mast cell tryptase was minimal. CONCLUSIONS: Cutaneous reactions are prominently associated with GMCSF administration. Eosinophils, known to release toxic products after being activated, may have a role in these skin reactions through stimulation by GMCSF.

Adult↗
PubMed1991

Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer.

Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL-4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.

Aged↗
PubMed1991

Eosinophil and neutrophil degranulation in ophthalmic lesions of Wegener's granulomatosis.

Although eosinophils and neutrophils have been identified in orbital and corneoscleral tissues in some patients with Wegener's granulomatosis, their role in the pathogenesis of the disorder is not completely understood. Nine specimens from six patients with Wegener's granulomatosis and autopsy controls from patients without ophthalmic disease were evaluated with indirect immunofluorescence for eosinophil granule major basic protein and neutrophil elastase. Extracellular deposition of both major basic protein and elastase was identified in orbital tissues from all the patients with Wegener's granulomatosis. Two of the specimens were from enucleated eyes with corneoscleral disease; extracellular deposition of eosinophil major basic protein was identified in one eye, and extracellular neutrophil elastase was deposited in both eyes in lesional areas. None of the control tissues showed major basic protein or elastase deposition. These findings suggest that both eosinophils and neutrophils participate in the pathogenesis of the orbital and corneoscleral manifestations of Wegener's granulomatosis.

Blood Proteins↗
PubMed1991

A current perspective on the role of eosinophils in dermatologic diseases.

Eosinophils are frequently observed in cutaneous inflammation, but little is known of their significance in the pathophysiology of cutaneous disease. Recent studies of the structure, content, and activities of the eosinophil have shown that it has potent toxic proteins with the potential to mediate tissue damage. Furthermore, immunofluorescent localization of eosinophil granule proteins has shown that eosinophils disrupt in tissue and deposit toxic granule proteins. The deposition of granule proteins in several diseases is vastly out proportion to the number of identifiable cells and indicates that eosinophil involvement in cutaneous disease cannot be judged by the number of intact eosinophils in the tissue. Specifically, deposition of eosinophil granule proteins outside of eosinophils has been observed in eczematous lichenified disorders with elevated serum levels of immunoglobulin E, in urticarial and angioedematous disorders, and in bullous diseases. The structural, compositional, and functional characteristics of eosinophils are reviewed, and evidence of eosinophil degranulation in cutaneous diseases is presented. Mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects are also discussed.

Asthma↗
PubMed1991

Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor.

To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis.

Adolescent↗
PubMed1991

Extracellular deposition of eosinophil major basic protein in orbital histiocytosis X.

Although eosinophils are prominent in orbital lesions of patients with histiocytosis X (Langerhans' cell histiocytosis), little is known of their pathogenic significance in the disease. To determine whether eosinophils degranulate and deposit toxic proteins in orbital histiocytosis X, the authors examined lesions by indirect immunofluorescence for localization of the core granule protein (major basic protein) outside of eosinophils. Four patients with histiocytosis X were studied: three with eosinophilic granuloma and one with Hand-Schüller-Christian disease. Tissue eosinophilia was prominent in all specimens; striking extracellular deposition of eosinophil major basic protein was noted in three patients, and focal deposition was present in the fourth patient. Orbital specimens obtained at autopsy from patients without orbital disease were studied as control specimens; no tissue eosinophilia or deposition of eosinophil major basic protein was observed. These findings indicate that eosinophils likely degranulate in lesions of orbital histiocytosis X and may participate in the pathogenesis of the disease.

Adolescent↗
PubMed1991

Localization of eosinophil granule major basic protein in incontinentia pigmenti.

We report a case of incontinentia pigmenti and demonstrate the deposition and localization of eosinophil major basic protein (MBP) in the vesicular stage of this neurocutaneous syndrome. The initial stage of incontinentia pigmenti is histologically characterized by intraepidermal vesicles associated with eosinophilic spongiotic dermatitis. Pathologic examination of a lesional tissue specimen from our patient demonstrated epidermal necrosis, spongiosis, and vesicle formation. Indirect immunofluorescence with affinity-chromatography purified antibody to human eosinophil granule MBP demonstrated many intact eosinophils within vesicles and scattered throughout the epidermis and dermis, and extracellular deposition of granular MBP in the tissue. The characteristic finding of extensive tissue eosinophilia in incontinentia pigmenti, as well as the new finding of extracellular deposition of an eosinophil granule protein in lesional tissue, suggests the involvement of eosinophils in the pathogenesis of the disease.

Blood Proteins↗
PubMed1991

Neonatal lupus erythematosus syndrome.

Three cases of neonatal lupus erythematosus (NLE) syndrome are described. The key diagnostic sign is the erythematous and annular clinical appearance of lesions. The histopathologic findings may be subtle in NLE syndrome compared with discoid or subacute cutaneous lupus erythematosus. Direct immunofluorescence testing may be useful in supplementing the histopathologic evaluation. Detection of immunoglobulins, complement, or both at the basement membrane zone in lesional skin by immunofluorescence occurs in approximately half of cases; a negative study does not preclude the diagnosis of NLE syndrome. Clinical and serologic evaluation of both the infant and the mother are important in establishing a diagnosis of NLE syndrome, particularly when histopathologic findings are subtle.

Fluorescent Antibody Technique↗
PubMed1990

Sequestration of eosinophil major basic protein in human mast cells.

Previous studies showed that lung and skin mast cells do not contain eosinophil granule major basic protein (MBP). However, MBP has been localized by immunofluorescence to mast cells from a recently established human mast cell line. Analysis of MBP in human mast cell-1 cell lysates by radioimmunoassay showed immunochemical similarity to eosinophil MBP as judged by comparison of dose-response regression lines. Based on these findings and other new information about mast cell heterogeneity, we tested whether mast cells contain MBP. Mast cells were preserved in Carnoy's fixative and were identified by staining with rhodamine-conjugated avidin or for chloroacetate esterase or aminocaproate esterase activity. MBP was localized by immunofluorescence to mast cells in 6 of 7 nasal polyps, 4 of 4 ileal tissue specimens, and 12 of 14 cutaneous mastocytosis specimens. Furthermore, by immunoelectron microscopy MBP was localized to mast cell granules in cutaneous mastocytosis lesions. In contrast, normal skin mast cells preserved in Carnoy's fixative did not contain MBP. After injection of MBP into normal skin and fixation in Carnoy's fluid, mast cells became MBP-positive within 3 minutes, suggesting that endocytosis of MBP by mast cells had occurred. These results suggest that human mast cells in several tissues may sequester toxic eosinophil proteins by endocytosis.

Blood Proteins↗
PubMed1990

Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction.

Intradermal injection of allergens in sensitive subjects produces an IgE-dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed.

Administration, Cutaneous↗
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↗