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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
PubMed2000

Treatment of severe atopic dermatitis by topical immune modulation using dinitrochlorobenzene.

We present the results of a small uncontrolled pilot trial which suggest that contact sensitization to dinitrochlorobenzene and repeated weekly applications significantly improve the clinical status of severe atopic dermatitis in adults. Although no changes were noted in circulating levels of either lymphocyte subset populations or the serum cytokines assayed in this trial, our observations may be due to topical immune modulation by dinitrochlorobenzene. Larger controlled studies of dinitrochlorobenzene treatment in atopic dermatitis are warranted.

Administration, Topical↗
PubMed1998

Colorimetric determination of citrulline residues in proteins.

A method is described for the direct colorimetric determination of citrulline residues in proteins based on the reaction with diacetylmonoxime in the presence of lower concentrations of sulfuric acid. The reduced sensitivity due to the lower acid concentration was overcome by the addition of ferric chloride which also contributed to the color stabilization. Insoluble proteins or proteins resulting in turbidity can be analyzed following partial hydrolysis of those with enzyme or acid. The molar absorption coefficient (epsilon) for citrulline at 464 nm was 2.8 x 10(4). The method enabled us to determine low levels of protein-bound citrulline which are beyond the limitations of conventional methods using an amino acid analyzer. We determined the citrulline contents in the cornified cells of the epidermis of newborn rats, as well as soybean trypsin inhibitor.

Amino Acids↗
PubMed1998

Thrombomodulin expression on dermal cells in normal and psoriatic skin.

The various subsets of dermal cells with a dendritic appearance can be identified by phenotypic differences in cell markers. We report on the morphology and tissue distribution of dermal cells detected with a monoclonal antibody against thrombomodulin in histological sections of normal arm and scalp skin and psoriatic skin. Double staining with antibodies to factor XIIIa, CD34 and CD68 was also employed in scalp biopsies to elucidate the relationship between thrombomodulin+ dermal cells and dermal dendrocytes and macrophages described by others. Thrombomodulin+ dermal cells in normal arm skin had little cytoplasm with fine branched dendrites and tended to be localized just beneath the epidermis. In scalp skin these cells had longer, more numerous dendrites and were distributed in the papillae and perivascular adventitial dermis primarily in the upper and central reticular dermis. In psoriatic skin, thrombomodulin+ dermal cells had an increased cytoplasmic volume with stout, less branched dendrites and appeared in the papillae and among inflammatory cells. Dermal cells detectable by thrombomodulin expression were factor XIIIa-, CD34- and CD68-, and seemed to represent a distinct subset of dermal cells which may function in tissue repair. However, thrombomodulin+ dermal cells and factor XIIIa+ dendrocytes were frequently seen close together and could act cooperatively to regulate extravascular thrombin homeostasis in both normal and pathological dermal environments.

Antigens, CD↗
PubMed1997

Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization.

Granuloma initiation factor (GIF), which elicits a granulomatous reaction in naive murine skin, contains low-molecular-weight proteins partially purified from organized granulomas developed in livers of mice with schistosomiasis. In this study, we found that 10- and 14-kDa proteins in the GIF are highly homologous to mouse migration inhibitory factor-related protein (MRP) 8 and MRP 14. Compared with the N-terminal amino acid sequence deduced from each corresponding cDNA, the 10-kDa protein from the granuloma lacks the first methionine, whereas the 14 kDa misses methionine, alanine, and asparagine. Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated blood vessels and at the edge of granulomas. The staining of differentiated macrophages and epithelioid cells located in the center of the granulomas was negative. Immunoreactivity of peritoneal exudate cells also was found to gradually disappear with time in cell culture. Furthermore, in vivo effects of the recombinant proteins in murine skin were described histologically. Both MRPs caused severe infiltration of neutrophils and monocytes during 7-14 days. The reaction resulting from individual MRP implantation became minimal after 50 days but inoculation of the Ca2+-dependent heterodimers showed an extensive eosinophil accumulation.

Amino Acid Sequence↗
PubMed1997

Topical immune modulation (TIM): a novel approach to the immunotherapy of systemic disease.

In this article, we present the concept of topical immune modulation, or TIM. TIM is based on the observation that skin contact sensitizing agents such as poison ivy, poison oak and dinitrochlorobenzene (DNCB) are potent stimulants of the cellular immune system that combats viruses and other pathogens. We discuss the evolution of DNCB as a therapeutic modality in the acquired immunodeficiency syndrome (AIDS) and we explore the mechanism by which DNCB directs the immune response. The potential use of topical immune modulators in autoimmune disease and vaccine development is also delineated. TIM represents a novel approach to immunotherapy that should have widespread application for immunologic diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Resorcinols and catechols: a clinical study of cross-sensitivity.

BACKGROUND: All allergic contact dermatitis caused by Philodendron species is common in the Hawaiian islands, and Toxicodendron species are the most common causes of plant-induced allergic contact dermatitis in North America. OBJECTIVE: The purpose of this study was to determine the incidence of cross-sensitivity between these plant species. METHODS: Alkylresorcinols (pentadec[en]yl and heptadec[en]ylresorcinols) were isolated and purified from extracts of Hawaiian-grown Philodendron scandens subspecies scandens and Philodendron lacerum. Alkylcatechols (mixtures of pentadec[en]ylcatechols from an extract of Toxicodendron radicans (poison ivy) were obtained from the Division of Biologics Standards (National Institutes of Health, Bethesda, MD). Seventeen patients from Hawaii and 8 patients from northern California were skin tested with 5 microL (concentrations, 1 to .001 mg/mL) of each allergen applied to the flexor forearm. The test sites remained open and were graded at 72, 96, and 144 hours. All 8 patients from California were naive to Philodendron species, and 8 patients from Hawaii were naive to Toxicodendron species. RESULTS: No cross-reactivity occurred in patients who were Philodendron sensitive and Toxicodendron naive when tested to the homologous Toxicodendron catechols. Conversely, with one exception, no cross-reactivity occurred in patients who were Toxicodendron sensitive and Philodendron naive when tested to homologous Philodendron naive when tested to homologous Philodendron resorcinols. CONCLUSION: Patients who are sensitive to Philodendron species (or other resorcinol-containing plants) may not necessarily be cross-sensitive to Toxicodendron species and vice versa.

Adolescent↗
PubMed1995

Improved results of delayed-type hypersensitivity skin testing in HIV-infected patients treated with topical dinitrochlorobenzene.

BACKGROUND: Infection with HIV results in progressive deterioration of cell-mediated immunity, with consequent impairment of delayed-type hypersensitivity (DTH) skin reactivity. Topical dinitrochlorobenzene (DNCB) is thought to increase cellular immune function in HIV infection. OBJECTIVE: Our goal was to evaluate changes in DTH skin reactivity of HIV-infected patients who were given DNCB therapy. METHODS: DTH skin testing and lymphocyte subset analysis were performed in five HIV-infected patients before the start of DNCB treatment and after 3 months of therapy. Topical DNCB application was carried out by the patients according to a standardized protocol. RESULTS: DNCB therapy enhanced DTH skin test responses in four of five patients. Three patients who were anergic before the start of treatment reacted to skin test antigens while using DNCB. The skin test results did not correlate with lymphocyte subset changes. CONCLUSION: DNCB treatment improves DTH skin test responses in HIV-infected patients, indicating a positive effect on cellular immune function.

Administration, Cutaneous↗
PubMed1994

Clinical and immunologic evaluation of HIV-infected patients treated with dinitrochlorobenzene.

BACKGROUND: Promotion of cell-mediated immunity appears to be an important goal in the control of HIV infection. Topical dinitrochlorobenzene (DNCB) stimulates systemic cell-mediated immunity via the induction of cutaneous delayed-type hypersensitivity. OBJECTIVE: Our goal was to evaluate the clinical and immunologic effects of chronic DNCB application in a group of 24 HIV-infected patients. METHODS: We observed the patients for a mean of 28 months (range, 14 to 44 months). Of the 24 patients, 13 continued weekly DNCB application throughout the study (the compliant group), and 11 discontinued DNCB use after a mean of 10.9 months (the noncompliant group). RESULTS: Two of the 13 compliant patients progressed to AIDS; none of these patients died. In contrast, AIDS developed in 5 of the 11 noncompliant patients and four of these patients died. Analysis of lymphocyte subsets revealed significant increases in natural killer cells and activated/cytotoxic CD8 T-cell subsets in the compliant group. In contrast, these cellular immune-related lymphocyte subsets decreased in the noncompliant subjects. Although CD4 T-cell levels decreased in both groups, there was a significantly greater drop in the noncompliant patients. CD8+CD38+ T cells increased significantly in both groups. CONCLUSION: Chronic DNCB application appears to have a beneficial clinical and immunomodulatory effect in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation.

Alpha-tocopherol and gamma-tocopherol were monitored in human adipose by using needle biopsies in four subjects during a 1-y supplementation trial with 800 mg all-rac-alpha-tocopherol/d, and for 1 additional year after cessation of supplement. Some increase in adipose alpha-tocopherol (per milligram adipose cholesterol) and a more consistent decrease in gamma-tocopherol were observed during the supplementation period. The alpha-tocopherol/gamma-tocopherol ratio rose consistently during supplementation and fell only gradually after the supplement was stopped. We estimate that > or = 2 y are required for the alpha-tocopherol/gamma-tocopherol ratio to reach a new steady state after a change in alpha-tocopherol intake. In a cross-sectional measurement in five subjects who reported long-term use of alpha-tocopherol supplements (> or = 250 mg/d), and in five other subjects who reported no supplement use, the adipose alpha-tocopherol/gamma-tocopherol ratio clearly discriminated between the two groups (P < 0.002). This ratio may be of value in ranking individuals according to long-term alpha-tocopherol intake.

Adipose Tissue↗
PubMed1994

Occupational poison ivy and oak dermatitis.

Among the growing and diverse groups of outdoor and environmental workers, poison ivy and poison oak continue to be the major cause of occupational contact dermatitis. This article reviews the practical and theoretic means to prevent poison ivy and poison oak dermatitis in workers occupationally exposed to these weeds.

Catechols↗
PubMed1993

Purification and characterization of NADPH-cytochrome P-450 reductase from rat epidermis.

NADPH-cytochrome P-450 oxidoreductase (P-450 red) transfers reducing equivalents from NADPH to cytochrome P-450 (P-450) in the monooxygenase system. Detergent solubilized proteins from the membrane fraction of neonatal rat epidermis were purified by 2',5'-ADP-agarose affinity column chromatography. The purified protein showed an apparent homogeneity on sodium dodecylsulfate-polyacrylamide gel electrophoresis and molecular weight was estimated to be 78 kDa. NADPH-cytochrome c reductase activity increased by 95-fold in the purified enzyme. Epidermal P-450 red in vitro reconstituted benzo(a)pyrene hydroxylase activity in a dose dependent manner with P-450 purified from either rat liver or epidermis. Western blot analysis demonstrated that epidermal P-450 red immunologically cross reacts to liver P-450 red. Immunohistochemical staining showed that the enzyme was predominantly localized in the epidermis. The intensity of immunohistochemical staining of rat skin sections and tissue distribution did not change in the skin treated with beta-naphthoflavone, which results in a substantial increase in P-450 1A1 activity. Quantitative assessment of P-450 red in treated and untreated epidermis also showed no change. These findings indicate that constitutive P-450 red, fully capable of supporting P-450, exists in rat epidermis, and can function in metabolism of endogenous and exogenous compounds.

Animals↗
PubMed1993

Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection.

Dendritic cells, the primary antigen presenting cells of the human immune system, are heavily infected with human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS). Dinitrochlorobenzene (DNCB) is a contact sensitizing agent that acts as a potent immune modulator of dendritic cells. In this pilot study, we examined the safety and efficacy of topical DNCB application in patients with early HIV disease. Topical DNCB was well tolerated by these patients, with an adverse reaction rate of 10%. CD4+ T-cell counts remained stable with repeated DNCB use. In contrast, CD8+ T-cell counts and natural killer cells increased significantly following DNCB sensitization. This increase in CD8+ T-cell and natural killer cell subsets was accompanied by a decrease in HIV replication, as measured by serum HIV RNA levels. Based on this pilot study, we conclude that topical DNCB is safe in early HIV disease and may decrease viral load via a systemic effect on dendritic cells, CD8+ T-cells and natural killer cells. These results require confirmation in larger controlled trials.

Administration, Cutaneous↗
PubMed1993

Desmosome differentiation during epidermal cornification: new observations obtained from intermediate voltage electron microscopy.

Human epidermis was examined under 400-kV intermediate voltage electron microscopy using epon sections cut 5-8 times thicker than usual ultrathin sections. Asymmetry of desmosomal structures occurred as cells became cornified. Electron-dense proteins deposited at the inner leaflet of the plasma membrane of corneocytes do not extend into the desmosomal area, which connects to granular cells. Stereo micrographs revealed the existence of two different cellular elements at the cell surface confirming that the plasma membrane first thickened in areas without desmosomes. Examination of the three-dimensional nature of desmosomes and keratin-filament aggregation without serial sectioning and/or selecting a strict angle of the tissues will allow us to extend our ultrastructural knowledge.

Cell Membrane↗
PubMed1993

Purification and immunohistochemical localization of aspartic proteinases in rat epidermis.

Investigation of skin cathepsin E (EC 3.4.23.-) has been totally ignored compared to skin cathepsin D (ED 3.4.23.5). In this study both cathepsins E and D were simultaneously purified to homogeneity up to 370 and 640 times, respectively, from 2-day-old rat epidermis. The total aspartic proteinase activity of rat epidermis detected after Q-Sepharose column chromatography was attributed to 27% cathepsin E, 63% cathepsin D, and 10% other enzymes. The purified enzymes showed that cathepsin E (90 kDa) is a dimer of 45 kDa subunits whereas cathepsin D is a monomer of 42 kDa. Other biochemical properties of epidermal cathepsins E and D were similar to those reported from other tissue sources. Immunologically cathepsins E and D were distinct from each other and localization of the two enzymes differed in both rat and human skin by immunohistochemistry. Cathepsin E was distributed diffusely in the cytoplasm of almost all epidermal cells, though its concentration increased above suprabasal cells, whereas cathepsin D appeared in particulate form only in cells of the granular layer. The findings indicate that two aspartic proteinases that have similar enzymatic properties exist in the epidermis. They are, however, differentially distributed in the organ, presumably for different functions during the process of keratinization.

Animals↗
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↗