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Biomedical subjects

W L Epstein

Publications and source records attributed to W L Epstein.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of two dipeptidases purified from hepatic schistosome egg granulomas in mice. Leukotriene D4 hydrolases of granulomatous tissue.

Extracts prepared from tissue with granulomatous inflammation experimentally produced in liver of CBA-strain mice showed increased hydrolysis of leukotriene D4 (LTD4), Leu-Leu and Ala-Gly as compared with normal hepatic cells. Two dipeptidases, Leu-Leu dipeptidase and Ala-Gly dipeptidase, were purified from hepatic granulomas, and quantitative conversion of LTD4 into leukotriene E4 (LTE4) by both enzymes was demonstrated. M(r) values of the purified enzymes were 178,000 for Leu-Leu dipeptidase and 183,000 for Ala-Gly dipeptidase. The enzymes showed homogeneity, appearing as a single band on SDS/PAGE, and the M(r) values of the subunits were 56,000 and 57,000 for Leu-Leu and Ala-Gly dipeptidase respectively. The amino acid compositions of the two enzymes differed considerably from each other. The activity of Leu-Leu dipeptidase was inhibited by bestatin and captopril and stabilized with MnCl2. The Km for LTD4 was 25 microM with a V(max.) of 49.0 mumols/min per mg. In contrast, the activity of Ala-Gly dipeptidase was inhibited by cilastatin, cytinylglycine, EDTA and dithiothreitol, and also by captopril. The Km for LTD4 was 5.3 microM with a V(max.) of 50.4 mumols/min per mg. The findings indicate that the conversion of LTD4 into LTE4 by microsomal dipeptidases is elevated during granulomatous tissue reaction. This enzyme activity may become useful for biochemical quantification of the pathological tissue reaction that occurs in organized granulomas.

Amino Acid Sequence↗
PubMed1992

Prolyl endopeptidase purified from granulomatous inflammation in mice.

Activity of prolyl endopeptidase (EC 3.4.21.26) which hydrolyses the Pro7-Phe8 bond in angiotensin II has been found to elevate in experimentally produced granulomatous inflammation in liver and skin. We purified the enzyme 1,536-fold by 6 steps from murine hepatic granulomas. The purified enzyme has a molecular weight of 79 kDa and physicochemical properties equivalent to those previously reported for prolyl endopeptidase purified from other sources. By HPLC analysis, the cleavage of Phe8-Leu10 and Phe8 from angiotensin I and II, respectively, was detected and quantified. Monospecific IgG was prepared from serum of rabbits injected with purified enzyme. Concentration of the enzyme was immunohistochemically detected in cells which form granulomatous organization, but not in inflammatory cells surrounding the foci. The antibody, however, cross reacted with the enzyme in adjacent liver cells and weakly stained their cytoplasm. The findings indicate that this enzyme, in addition to angiotensin converting enzyme, may serve as a useful biochemical marker for granulomatous tissue reactions.

Angiotensin I↗
PubMed1992

Direct inactivation of herpes simplex virus type-2 by rat epidermal protein.

Proteins were extracted from corneocytes of skin of 2-day-old rats and fractionated by gel filtration and cation exchange column chromatography. The different protein fractions were tested for direct inactivation of herpes simplex virus infectivity as determined by reduction of plaque formation. The most effective protein fractions against herpes simplex virus were a neutral pH buffer soluble and mol. wts. ranging from 20 K to 30 K. Amino acid composition of the proteins were virtually identical to epidermal histidine-rich proteins. The activity was significantly (P less than 0.001) stronger against type-2 than type-1. The activity was most stable at pH 7.2 and the rate of inhibition increased in a time-dependent manner up to 4 h. The 50% effective dose was estimated as 1.1 micrograms protein/ml.

Amino Acids↗
PubMed1992

Molluscum contagiosum.

This in-depth review considers the known virological and molecular biological aspects of the molluscum contagiosum virus. Furthermore, the epidemiology of its infection of human skin is detailed, and the clinical, histological, and therapeutic information available at this time are cataloged. It is concluded that molluscum contagiosum has become an almost common skin disease that can prove very difficult to eradicate from an infected patient.

Humans↗
PubMed1992

Isolation and characterization of granuloma initiation factor.

A soluble component that transfers granulomatous tissue reaction was fractionated from Schistosoma mansoni egg-induced hepatic granulomas (SMHG) by Sephacryl S-300 column chromatography. The fractions separately bound to inert, Affi-Gel agarose beads were inoculated subcutaneously in naive mice. The low molecular weight fraction, consisting of proteins 23 kd, 20 kd, and 16 kd, produced organized granulomas 6 to 7 weeks after inoculation. This fraction was further purified by high-pressure liquid chromatography (HPLC) gel filtration and gave three fractions eluting at retention times of 44, 46, and 48 minutes. Each fraction contained all low-molecular-weight proteins in varying amounts and induced skin granulomas when inoculated subcutaneously. Amino acid sequence of the major 20-kd protein showed 11 N-terminal residues identical to those of cyclophilin. Antisera raised to the protein with retention time of 46 minutes, reacted with cells in the granulomas but not surrounding liver tissue as detected by immunofluorescence microscopy. The findings indicate a low molecular weight soluble fraction of SMHG can induce new granuloma formation when injected in an immobilized form into skin of naive mice. The results suggest granuloma initiation factor is a homolog of the cyclophilin gene family.

Animals↗
PubMed1991

Macrophage chemotactic factor partially purified from granulomatous inflammation.

Pathophysiological roles of macrophage chemotactic factor (MCF) in granulomatous inflammation were investigated. MCF was extracted in 10 mM phosphate-buffered saline, pH 7.4, from experimentally produced epithelioid cell granulomas in the liver and skin of mice. MCF activity reached a peak in the lesions prior to the time when granulomatous inflammation became maximal. MCF was then purified from 10-week-old hepatic granulomas and 2-week-old skin lesions by gel filtration, ion exchange column chromatography, and HPLC gel filtration. MCF from either liver or skin had a molecular weight about 650 kDa. MCF from hepatic granulomas was coupled to Affi-Gel beads and transplanted subcutaneously into naive mice. In vivo macrophage chemotaxis was observed around the beads and the cells formed a sheet, but organization of macrophages into granulomas did not occur with the MCF-active fractions. Macrophage chemotaxis alone is insufficient to elicit granulomatous inflammation.

Animals↗
PubMed1991

An improved noninfectious murine skin model of organized granulomatous inflammation.

An improved model of granulomatous inflammation in skin was developed by second passage skin grafting of isolated, lyophilized skin granulomas, originally elicited in naive mice by inoculations of lyophilized hepatic schistosome egg granulomas. The tissue reaction is caused by a single exposure to a noninfectious, acellular granulomagenic stimulus and occurs in healthy mice free of systemic disease. The model should prove useful for isolation of granuloma initiation factor(s). Furthermore, because there is a time lag before new granuloma formation begins, a window exists for analytical dissection of the initiation process. In this study we described the responses of host cells by autoradiography, and light and electron microscopy. The activity of angiotensin-converting enzyme and proline-specific endopeptidase showed a modulation during granuloma formation. In addition we found that severe immunosuppression with high dose cyclosporine therapy did not alter granuloma formation, supporting the idea that initiation of organized granulomas is T-cell independent.

Animals↗
PubMed1991

Immunogenetic influences on skin granuloma formation in mice.

Genetic influence on the development of granulomatous tissue reaction was investigated in C57BL/6 mice. Granulomas developed in the skin of euthymic C57BL/6 mice by transplantation of lyophilized hepatic granulomas were excised and lyophilized. The tissue mass free of parasite egg antigen and living cells was grafted into the skin of euthymic, athymic (nu/nu), and beige (bg/bg) C57BL/6 mice. Histological changes at the skin sites were studied weekly by light microscopy, and cells in newly developed granulomas at 6 weeks after grafting were examined by electron microscopy. Granulomatous inflammation occurred in all the variants but morphometric analysis showed that granulomatous inflammation was the most extensive in beige mice and least in athymic mice. The differences in the degree of tissue reaction were also quantified by measuring angiotensin converting enzyme and prolyl endopeptidase. Statistically significant differences among the animals with varying genetic background were confirmed by the marker enzyme activity. The findings confirm that initiation of a granulomatous response does not require T cells but T cell function is important for full expression of the reaction, while NK cell activity seems to suppress granuloma formation.

Animals↗
PubMed1990

Glycoconjugate expression of cells of human anagen hair follicles during keratinization.

Changes in the expression of glycoconjugates in cells of the inner root sheath (IRS) and outer root sheath (ORS) of human anagen hair follicles were investigated by lectin histochemistry. Concanavalin A (Con A) and Ricinus communis (RCA-I) stained hair follicle cells regardless of their differentiation stages. In IRS, Ulex europeaus-I (UEA-I) bound to the surface of the cells as soon as they were morphologically defined, and Glycine max (SBA) stained as their differentiation progressed. Innermost (IM) cells of ORS layers were reactive with UEA-I at the stage where Henle's cells were keratinized, while the reactivity of UEA-I was lost at the site of the completion of IRS keratinization where SBA reaction was detected. Staining of both UEA-I and SBA was prominent in other ORS cells at the levels where SBA binding in IM cells became strong. The staining intensity increased up to the position of the follicular isthmus. In addition, a sugar residue recognized by Dolichos biflorus (DBA) was detected in differentiated cells of ORS. In contrast, the DBA reaction was not found at all in cells of IRS, infundibulum, and epidermis. These findings identified a complexity of carbohydrate metabolism in the cells of different layers at various stages of keratinization. IM cells differentiate independently from other ORS cells but seem responsive to the degree of IRS keratinization. All ORS cells possess a unique sugar moiety not found in other keratinocytes either in the hair or epidermis.

Concanavalin A↗
PubMed1979

Immunochemical comparison of histidine-rich protein in keratohyalin granules and cornified cells.

(1) Combination of techniques for extraction and purification of histidine rich protein established by several investigators were employed for comparison of histidine-rich protein in granular cells and cornified cells of newborn rats. (2) Histidine-rich protein extracted from the same cell fraction by two different techniques either in 1 M potassium phosphate buffer (Ugel) or in 4 M urea (Dale) showed identical elution profiles on CM 52 cellulose ion exchange chromatography and the same SDS polyacrylamide gel electrophoretic patterns. (3) Histidine-rich protein from granular cells contained polypeptides of larger molecular sizes than those in histidine-rich protein from cornfield cells, although amino acid composition of the two histidine-rich protein was non-distinguishable (histidine residue was more than 7%). (4) Antibodies raised in rabbits by injection of histidine rich protein from granular cells and that from cornfield cells immunologically cross-reacted. Furthermore, the antisera were found to be reactive over both keratohyalin granules and cornified cells, but not epidermal cells of the lower strata.

Animals↗
PubMed1979

The thorax as the initial site for systemic relapse in malignant melanoma: a prospective survey of 324 patients.

Thirteen of 324 patients with malignant melanoma followed during a 24 month period experienced dissemination. The thorax was the initial site for relapse in 12, all of whom were asymptomatic. Ten gave no evidence of extrathoracic disease. Retrospective analysis of previous x-rays originally interpreted as negative revealed metastases in 33%. Life table analysis demonstrated a significantly longer survival for the subset with isolated intrathoracic metastases treated surgically than for their counterparts with metastases no longer amenable to surgery and treated by other modalities. We conclude that the thorax is the site of predilection for initial systemic relapse in malignant melanoma, that detection of early, surgically resectable metastases correlates with longer patient survival, and that routine chest roentgenography is inadequate in reliably uncovering such early disease. These data suggest the potential value of more vigorous radiographic surveillance (with either computed tomography or conventional full lung tomography) in patients at high risk for relapse.

Adult↗
PubMed1979

Granulomatous inflammation in normal and athymic mice infected with schistosoma mansoni: an ultrastructural study.

Inflammatory cell types and their interrelationships were studied in hepatic schistosome egg granulomas by correlated light and electron microscopy in thymus-intact and athymic mice. Intact animals developed large granulomas composed of phagocytes, stimulated macrophages, epithelioid cells, eosinophils and mast cells. The lesions peaked in size between 10--14 weeks after infection and tended to heal after 16 weeks. In athymic mice only phagocytes, stimulated macrophages and possible epithelioid cells appeared in the granulomas which were much smaller and less well organised than in intact mice. Virtually no eosinophils or mast cells entered the granulomas. These findings support the idea that development of granulomatous inflammation per se is not determined by CMI, but T cell co-operation seems to be required for its full expression in schistosomiasis. Since CMI closely regulates ingress of eosinophils and mast cells into the granuloma, the nature of T cell co-operation probably occurs at several levels in this complex infectious granuloma.

Animals↗
PubMed1979

Biological properties of human melanoma cells in culture.

Three human melanoma cell lines derived from one primary and two metastatic tumors from three different patients were characterized for growth properties usually associated with malignant transformation; these include cell morphology, growth rate, saturation density, growth in semisolid media, colony-forming ability on contact-inhibited monolayers of normal fibroblasts and epithelial cells, and tumorigenicity in immunosuppressed mice. Variations in expression of aberrant properties were evident among the lines. One of the metastatic lines satisfied all the parameters of malignancy tested and the other showed a number of these properties, whereas the primary essentially fulfilled only one. These results suggest that cultured melanoma cells reflect the clinical variability often observed among melanoma patients and that metastatic melanoma seems to display a higher degree of malignant transformation than the primary.

Adult↗
PubMed1979

Transfer of contact sensitivity to beryllium using dialyzable leukocyte extracts (transfer factor).

Transfer factor derived from lymphocytes of donors with strong cellular immunity against beryllium was intradermally or subcutaneously injected into unprimed or subclinically primed human recipients who were patch test-negative. These recipients were challenged with beryllium at weekly intervals thereafter. Subjects who had been subclinically primed and received transfer factor either intradermally or subcutaneously showed transient patch test reactivity to the challenge. Subjects who received transfer factor but were not primed and subjects who had been primed but did not receive transfer factor showed no such conversion. This is the first demonstration of transfer of contact sensitivity in man using transfer factor, and it suggests that subclinical priming is necessary for such transfers.

Beryllium↗
PubMed1979

Fibrin deposition and clearance in chronic granulomatous inflammation: correlation with T-cell function and proteinase inhibitor activity in tissue.

Patterns of fibrin deposition were investigated by immunofluorescence microscopy in livers of thymus intact (TI) and athymic (AT) mice infected with Schistosoma mansoni. Thrombin and fibrinolysis inhibitor activity in tissue extracts also were measured. In TI mice fibrin was detected perivascularly by 6 weeks after infection and at 8 weeks it was found over the granulomas as they developed. Fibrin was cleared from the center of granulomas by 10 weeks. Thrombin inhibitor activity increased at 4 to 6 weeks but declined below control levels later as granulomas formed. Fibronolysis inhibitor activity, on the other hand, peaked at 9 to 12 weeks after infection. In AT mice extensive fibrin deposition was detected in the liver throughout the period when smaller and incomplete granulomas developed. Central clearing did not occur. Thrombin inhibitor activity greatly increased by 8 weeks after infection but fibrinolysis inhibitor activity remained unchanged. These findings suggest that fibrin deposition and firbinolysis are orderly events regulated in the lesions by proteinases and their inhibitors and this seems to be a general tissue reaction in the early stage of chronic granuloma formation. Since local clearance of fibrin in vivo and fibrinolysis inhibitor activity from tissue extracts studied in vitro are more evident in TI mice than in AT mice, it appears that T cell fu;ction is important in modulating the tissue response during granulomatous inflammation.

Animals↗
PubMed1979

Mangement of malignant melanomas: an overview.

This paper presents an overview of the management of malignant melanoma. It considers the value of wide reexcision relative to the depth of invasion of the melanoma. It considers the indications for elective lymphadenectomy and presents a critical review of chemotherapy, immunotherapy and other procedures, such as X ray. The conclusion is that surgery, wherever feasible, is still the best approach.

Humans↗
PubMed1979

In vitro studies of poison oak immunity. I. In vitro reaction of human lymphocytes to urushiol.

Poison oak, ivy, and sumac dermatitis is a T-cell-mediated reaction against urushiol, the oil found in the leaf of the plants. This hapten is extremely lipophilic and concentrates in cell membranes. A blastogenesis assay employing peripheral blood lymphocytes obtained from humans sensitized to urushiol is described. The reactivity appears 1--3 wk after exposure and persists from 6 wk to 2 mon. The dose-response range is narrow, with inhibition occurring at higher antigen concentrations. Urushiol introduced into the in vitro culture on autologous lymphocytes, erythrocytes and heterologous erythrocytes produces equal results as measured by the optimal urushiol dose, the intensity of reaction, and the frequency of positive reactors. This suggests that the urushiol is passed from introducer to some other presenter cell. Although the blastogenically reactive cell is a T cell, there is also a requirement for an accessory cell, found in the non-T-cell population, for reactivity. Evidence is presented that this cell is a macrophage.

Adolescent↗