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E H Epstein

Publications and source records attributed to E H Epstein.

At least 55 records · Page 3Linked to original sources
PubMed1990

Topical carmustine (BCNU) for cutaneous T cell lymphoma: a 15-year experience in 143 patients.

One hundred forty-three patients with cutaneous T cell lymphoma were treated with topical carmustine (BCNU). A complete response was obtained in 86% of those with limited extent (less than 10%) plaques (T1 stage), in 48% of those with extensive (greater than or equal to 10%) plaques (T2 stage), and in 21% of those with erythroderma. The median time to achieve complete response was 11.5 weeks. Favorable results were obtained in patients with less than 5% involvement treated locally. Mild hematopoietic depression occurred in less than 10% of patients. Erythematous reactions were common, but no secondary cutaneous malignancies occurred. Differences in freedom from relapse or in survival between T2-stage patients with and those without clinical adenopathy were not statistically significant. The 5-year overall survival rate was 77%; the median survival time was 9.4 years.

Administration, Cutaneous↗
PubMed1990

Detection of carriers for X-linked ichthyosis by Southern blot analysis and identification of one family with a de novo mutation.

Scaling in patients with recessive X-linked ichthyosis is caused by lack of activity of the enzyme steroid sulfatase. In approximately 90% of kindreds, this lack is the result of a DNA deletion large enough to eliminate the coding region completely. We have used Southern blot hybridization of DNA isolated from peripheral blood leukocytes to measure gene dosage of the steroid sulfatase gene. This readily detects a half-normal dosage in women who are carriers and therefore can be used to diagnose the carrier status of female relatives of 90% of patients with the disease. We have found one family in whom the deletion arose on an allele inherited from the proband's clinically normal maternal grandfather.

Arylsulfatases↗
PubMed1989

Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides.

Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived. Therapy was well tolerated. No significant hematological toxicity occurred. Although total body X ray irradiation and total skin electron beam radiotherapy produced excellent palliation of patients with advanced stage mycosis fungoides, new strategies to provide more effective systemic treatment are needed.

Adult↗
PubMed1989

Low-dose methotrexate for the Sézary syndrome.

Seventeen patients with Sézary syndrome were treated with low-dose methotrexate for periods of up to 5 years (median follow-up 22 months). Seven patients (41%) achieved a complete response, and six patients (35%) achieved a partial response (more than 50% improvement). As of their latest evaluation, 10 of 17 (59%) were in a state of either complete or partial response. The estimated 5-year survival rate was 71% (standard error 13%). Toxicity was minor and self-limiting in only one patient. Clinical improvement was accompanied by a decrease in the circulating Sézary cell count.

Adolescent↗
PubMed1987

Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis.

A human steroid sulfatase (steryl-sulfatase; steryl-sulfate sulfohydrolase, EC 3.1.6.2) cDNA 2.4 kilobases long was isolated from a human placental lambda gt11 cDNA expression library. The library was screened with monospecific rabbit antibodies elicited by injection of steroid sulfatase protein purified from human placentas. Hybridization of the cDNA with EcoRI-digested genomic DNA indicated that patients from 14 of 15 apparently unrelated families have gross deletions of the gene for steroid sulfatase. One patient had genomic DNA fragments that were identical to those from normal individuals, indicating the absence of any major deletions as the cause of his lack of steroid sulfatase enzyme activity.

Chromosome Deletion↗
PubMed1987

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DNA↗
PubMed1985

Recessive X-linked ichthyosis: lack of immunologically detectable steroid sulfatase enzyme protein.

Patients with recessive X-linked ichthyosis (RXLI), one hereditary form of scaly skin, lack activity of the enzyme steroid sulfatase in all tissues studied. To investigate the molecular defect underlying the lack of enzyme activity, we prepared antisera against normal enzyme by injecting normal placental microsomal suspensions or partially purified steroid sulfatase into rabbits. Antibody activity was assessed by immunoprecipitation of detergent solubilized steroid sulfatase. In addition, we prepared rabbit antisera against RXLI placental microsomal suspensions. To detect immunologically cross-reactive material in patients' placentas, extracts were studied by immunoblot techniques and by competition with normal enzyme for antibody binding. Patients' extracts did not contain immunoreactive material co-migrating on electrophoresis with purified enzyme nor did they inhibit immunoprecipitation of normal enzyme. Sera from rabbits immunized with RXLI placental microsomes contain no antibodies to normal steroid sulfatase, as judged by their failure to immunoprecipitate normal enzyme or to react with normal steroid sulfatase on immunoblot. Thus the mutation in RXLI appears to reduce steroid sulfatase enzyme protein as well as enzyme activity.

Chromatography, Agarose↗
PubMed1985

Lamellar body-enriched fractions from neonatal mice: preparative techniques and partial characterization.

Several problems have frustrated the isolation of lamellar bodies (LB) from mammalian epidermis. We obtained pellets enriched in intact LB by utilizing the staphylococcal epidermolytic toxin to provide intact, outer epidermal sheets, by controlled homogenization in a cell disrupter, and by passage of homogenates through a graded series of nuclepore filters (Science 221:962, 1983). Such preparations contained more intact LB than did fractions prepared by a variety of differential or sucrose/metrizamide discontinuous centrifugation methods. Initial characterization of the enzymatic content of this fraction revealed it to be enriched in certain hydrolytic enzymes (acid phosphatase, carboxypeptidase, cathepsin B, acid lipase, sphingomyelinase, and phospholipase A), but strikingly depleted in all sulfatases, beta-glucuronidase, and the non-lysosomal protease, plasminogen activator. Thus, LB show some properties of lysosomes, although certain characteristic lysosomal enzymes are strikingly absent. Lamellar body fractions contained 2-3 times more lipid per unit weight than did homogenates, and were enriched in phospholipids, free sterols, and glycosphingolipids, but not in other neutral lipids or ceramides. In summary, whereas some of the enzymes in LB could participate in the metabolism of LB lipid precursors to hydrophobic barrier constituents, others may attack intercellular constituents, ultimately resulting in desquamation. The lipid profile of these organelles suggests that they deliver precursors of permeability barrier lipids to intercellular domains.

Acid Phosphatase↗
PubMed1985

Topical carmustine therapy for lymphomatoid papulosis.

Seven patients with lymphomatoid papulosis were treated with solutions of topical carmustine, a nitrosourea compound. Recently used schedules have employed 10 mg of carmustine in dilute alcohol applied to the total skin surface daily for four to 17 weeks (total dosage, 280 to 1,180 mg). All patients experienced a rapid reduction in the number and size of lesions. Maintenance therapy consisted of local applications of carmustine (2 to 4 mg/mL of 95% ethanol) to individual new papules. This method was effective in suppressing disease activity and reduced by half the average life cycle of individual lesions. However, long-term lesion-free remissions were not seen. Bone marrow depression did not occur.

Administration, Topical↗
PubMed1984

Cholesterol sulfotransferase of newborn mouse epidermis.

Recent studies of the epidermis in patients with recessive X-linked ichthyosis indicate that cholesterol sulfate is an important endogenous substrate for steroid sulfatase in the stratum corneum. We report here that cholesterol sulfotransferase, which converts cholesterol to cholesterol sulfate, is present in the lower living epidermis. Epidermal cytosol also sulfates phenols and some steroids, and such reactions may be important in defending against compounds absorbed percutaneously and in modulating the pharmacologic activity of topical medicaments. Sodium salicylate and sodium citrate inhibit the sulfotransferase activity noncompetitively, and inhibition of cholesterol sulfate formation may be important in the desquamative action of these topical "keratolytics."

Animals↗
PubMed1984

Lipids in the pathogenesis of ichthyosis: topical cholesterol sulfate-induced scaling in hairless mice.

Although several abnormalities of lipid metabolism have been associated with abnormal cornification in humans, evidence that these lipids directly provoke abnormal scale is lacking. One recently described example of a lipid abnormality in ichthyosis is absence of the enzyme steroid sulfatase in recessive X-linked ichthyosis (RXLI). This enzyme normally desulfates cholesterol sulfate (CS) and sulfated steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). As a result of this enzyme deficiency, patients with RXLI accumulate CS in their blood and skin. To determine whether sulfated sterols are the specific cause of increased scale, we applied CS, DHEAS, cholesterol, or vehicle alone to the backs of hairless mice. In animals treated with CS, but not with DHEAS or with vehicle, visible scale without erythema appeared after 1 week, peaked at 2 weeks, and then diminished. When the dose of CS was doubled, abnormal scale reappeared and then decreased again. CS-induced scale was reversible, clearing within 3 days of discontinuation of treatment. Because there was no acanthosis, dermal inflammation, abnormal transepidermal water loss, or increased labeling index, it appears that the 3-fold increase in thickness of the stratum corneum in CS-treated animals is due to a direct effect on this layer.

Animals↗
PubMed1984

Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis.

The pathological scaling in recessive x-linked ichthyosis is associated with accumulation of abnormal quantities of cholesterol sulfate in stratum corneum (J. Clin. Invest. 68:1404-1410, 1981). To determine whether or not cholesterol sulfate accumulates in recessive x-linked ichthyosis as a direct result of the missing enzyme, steroid sulfatase, we quantitated both steroid sulfatase and its substrate, we quantitated both steroid sulfatase and its substrate, cholesterol sulfate, in different epidermal strata, as well as within stratum corneum subcellular fractions obtained from normal human and neonatal mouse epidermis and from patients with recessive x-linked ichthyosis. In normal human and mouse epidermis, steroid sulfatase activity peaked in the stratum granulosum and stratum corneum, and negligible activity was detectable in lower epidermal layers. In contrast, in recessive x-linked ichthyosis epidermis, enzyme levels were virtually undetectable at all levels. In normal human stratum corneum, up to 10 times more steroid sulfatase activity was present in purified peripheral membrane preparations than in the whole tissue. Whereas in normal human epidermis cholesterol sulfate levels were lowest in the basal/spinous layer, and highest in the stratum granulosum, in recessive x-linked ichthyosis the levels were only slightly higher in the lower epidermis, but continued to climb in the stratum corneum. In both normal and in recessive x-linked ichthyosis stratum corneum, cholesterol sulfate appeared primarily within membrane domains, paralleling the pattern of steroid sulfatase localization. Finally, the role of excess cholesterol sulfate in the pathogenesis of recessive x-linked ichthyosis was directly tested by topical applications of this substance, which produced visible scaling in hairless mice in parallel to an increased cholesterol sulfate content of the stratum corneum. These results demonstrate an intimate relationship between steroid sulfatase and cholesterol sulfate in normal epidermis: both are concentrated in the outer epidermis (stratum corneum and stratum granulosum), and both are localized to membrane domains. Presumably, as a result of this distribution pattern, continued enzymatic degradation of substrate occurs in normal epidermis, thereby preventing excessive accumulation of cholesterol sulfate. In contrast, in recessive x-linked ichthyosis, degradation of cholesterol sulfate does not occur and cholesterol sulfate accumulates specifically in the stratum corneum, where it produces visible scale.

Administration, Topical↗
PubMed1984

Clinical staging for cutaneous T-cell lymphoma.

The Mycosis Fungoides Cooperative Group has been following patients with cutaneous T-cell lymphoma, including mycosis fungoides and the Sézary syndrome variant. Previous analyses identified the extent of skin involvement and the number of sites of clinically enlarged lymph nodes as important prognostic variables. These two variables were used to classify 340 patients into four clinical stages. Repeat analysis based on additional followup data shows the usefulness of this clinical staging system for identifying patients with differing survival experience. An alternative grouping suggested by fitting a survival model to the data also has been studied. Staging systems based only on skin involvement and lymph nodes are recommended for general use because the information needed is readily available, requiring only physical examination.

Humans↗
PubMed1983

Topical carmustine (BCNU) for mycosis fungoides and related disorders: a 10-year experience.

A 10-year experience in eighty-six patients confirms the effectiveness of topical carmustine (BCNU) in mycosis fungoides (MF). Complete remission (CR) was achieved in 84% of those with less than 10% involvement (stage IA), median CR, 12 months, and in 52% with greater than 10% involvement (stage IB), median CR, 23 months. The probability of freedom from relapse for 1 year was 72% in stage IA and 37% in stage IB. No deaths in stages IA or IB were attributable to MF. Including all causes of death, the probability of 5-year survival for stage IA was 93% and for stage IB, 48%. Good results were obtained with only local BCNU in fourteen patients with mostly less than 5% involvement. Five of seven with poikilodermatous MF, two with parapsoriasis en plaques (PEP), and three with lymphomatoid papulosis did well. Persistent local therapy cleared deeply infiltrated lesions in some patients. With present schedules, the hazard of bone marrow depression is slight. Erythematous reactions and telangiectasia are troublesome but have not been accompanied by premalignant changes.

Administration, Topical↗