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Biomedical subjects

W L Epstein

Publications and source records attributed to W L Epstein.

At least 145 records · Page 8Linked to original sources

Low molecular weight eosinophil chemotactic factor in granulomatous liver of murine schistosomiasis.

An acidic peptide, preferentially chemotactic for eosinophils, was extracted from livers of mice infected with Schistosoma mansoni. Sephadex G-25 column chromatography showed that the majority of the eosinophil chemotactic activity was detected in the fractions just after elution of the molecular marker vitamin B12 (m.w. 1355.4). This activity began to appear in the livers of some mice 5 weeks after infection. Peak activity was detected at 8 to 12 weeks after infection and persisted at least until 16 weeks. It was sensitive to carboxypeptidase-A. By Dowex-1 anion exchange chromatography, the activity eluted as a narrow peak at pH 3.1 TO 2.6 as shown for eosinophil chemotactic factor of anaphylaxis (ECF-A). The activity was also detected in a broad peak at pH 6.3 to 3.7. Unlike ECF-A, the activity was stable to boiling in both acid and alkali. These findings suggest that granulomatous liver of murine schistosomiasis-derived eosinophil chemotactic factor (ECF-G) may play a specific role in eosinophil accumulation in this chronic inflammation.

Acids↗

The regressing thin malignant melanoma: a distinctive lesion with metastatic potential.

To validate the supposition that thin malignant melanomas (less than 0.76 mm thick) of ordinarily low risk but with areas of regression may paradoxically metastasize, we observed 121 thin malignant melanomas over a six year period. Of these, 23 displayed readily apparent areas of regression, of which five (21.7%) metastasized. The incidence of metastases in their 98 counterparts without regression was 2.0% (2/98). The difference between the two is statistically significant (p = less than .01). Of the entire group of the two is statistically significant (p = less than .01). Of the entire group of thin melanomas, those with regression represented 19.0% (23/121) yet accounted for a disproportionate 71.4% (5/7) of all metastases. We conclude that regression is a relatively poor prognostic sign, whose occurrence within an otherwise thin melanoma represents a significant caveat to the current histologic staging system that equates thinness with low risk. We thus submit that patients whose malignant melanomas display regression be followed rigorously for evidence of metastases irrespective of the tumor's actual measured thickness or level of invasion.

Adult↗

Ultrastructural study of the nuclei in premitotic and repair DNA synthesis following UVB injury.

Ultrastructural changes in nuclei synthesizing DNA were studied by cytochemical technique. Guninea pigs ears were UVB irradiated and TdR-H3 was injected intradermally into the irradiated sites 1 hr before biopsy. Areas of the epidermis containing more than 80% of cells in DNA (repair or premitotic) synthesis identified by light microscopic autoradiography were selected and cut at 600 A. The glycolmethacrylate sections were stained with uranyl acetate and lead citrate, and consecutive sections were incubated with 0.01% pronase and 0.5% RNase before staining in order to observe DNA. In cells undergoing DNA repair, the zone of DNA became discontinuous and DNA was scattered throughout the entire karyoplasm as small aggregates and fine filaments. Nuclei in S-phase showed essentially the same change, but quantitatively the disappearance of DNA from the nuclear membrane and distribution in the karyoplasm became much greater. These changes were not seen in specimens treated without cytochemical technique.

Animals↗

Effects of 4-tertiary butyl catechol on tissue cultured melanocytes.

Depigmenting effects of 4-tertiary butyl catechol (TBC) were investigated using tissue cultured melanocytes of adult guinea pig. Black guinea pig ear epidermis was trypsinized, suspended in BME Eagle media (5 X 10(6) cells) supplemented with 10% calf serum, and seeded in Petri dishes (2 ml/ea). On the 5th day of culture, TBC dissolved in DMSO was added to the media, and the central area of Petri dishes with large numbers of melanocytes (but not keratinocytes) present were examined by light and electron microscopy. After 6 hr of treatment with 1.5 X 10(-3) mg TBC per ml of media, about 15 to 30% of melanocytes detached and about half of the remaining cells showed reversible changes in the cell shapes. An increase of TBC concentration to more than 2 X 10(-3) mg per ml of media resulted in larger numbers of melanocyte deaths. The surviving cells contained numerous, but ultrastructurally unusual premelanosomes and melanosomes. In addition, microfilaments showed a wavy appearance.

Animals↗

Two tris urea mercaptoethanol extractable polypeptides found uniquely in scales of patients with psoriasis.

This study was designed to chemically characterize the principal structural proteins of psoriatic scales. Cornified cells were obtained from 40 patients with psoriasis, 21 patients with other scaly diseases, and 13 normal individuals. Cells were washed with Tris-HCl buffer and incubated in 8 M urea containing 2-mercaptoethanol (pH 9.0) at 30 degrees C for 7 hr. Extracted proteins were subjected to SDS polyacrylamide gel electrophoresis and protein patterns from normal and diseased scales were compared. The 67,000 dalton constituent of normal cornified cells could not be identified in protein from psoriatic scale and instead, a pair of polypeptides of approximately 54,000 and 57,000 daltons appeared. These extra bands were not found in protein extractions from other skin diseases, uninvolved skin of psoriasis patients, or normal skin. In order to analyze further normal and psoriatic scale proteins, the immunoreaction of rabbit antisera to human 67,000 dalton polypeptide with extracted psoriasis protein and with frozen biopsy sections, was studied using immunoprecipitation tests and indirect immunofluorescence microscopy. Both techniques demonstrated the existence of the 67,000 dalton protein in psoriasis, but as a minor component. These results indicate that additional unique urea mercaptoethanol soluble proteins are formed in psoriatic lesions, and this unusual protein synthesis may reflect the morphological changes in this disease.

Humans↗

Divalent cation stimulation of in vitro fibre assembly from epidermal keratin protein.

Keratin was extracted from purified cornified cells of newborn rats in Tris-HCl-buffered 8 M urea containing beta-mercaptoethanol. Microfilaments were assembled in vitro by reducing the ionic strength of buffer and the urea concentration. One millimolar concentration of KCl and NaCl did not affect filament formation, but the same concentration of divalent cations greatly altered this process. CaCl2 and MgCl2 induced gelation of keratin by formation of bundles of birefringent macrofilaments. ZnCl2, CuSO4 and HgCl2 formed greater numbers of macrofilaments and the protein aggregated.

Amino Acids↗

Changes in nuclear DNA and RNA during epidermal keratinization.

The distribution of nucleic acids within nuclei of epidermal cells in skin from guinea-pig ear was investigated using an indirect enzyme digestion technique to observe both DNA and RNA, and a direct Schiff-Thallium reaction technique, to observe DNA alone. Similar results were obtained by both methods. The distribution of DNA and RNA change gradually in nuclei as epidermal cells differentiate. DNA in cells of the lower strata is localized in essentially the same areas in which electron-opaque components are seen by conventional electron microscopy. With the cytochemical treatments, however, we found that DNA is not present in all electron-opaque areas of nuclei in superficial granular cells. RNA is present in the nucleoli of cells in all layers, but its density is also lower in the upper granular cells. We postulate that nucleic acids in nuclei of granular cells gradually decrease and that the space is filled with newly synthesized electron-dense protein, as part of the differentiation process.

Animals↗

Topically applied antifungal agents. Percutaneous penetration and prophylactic activity against trichophyton mentagrophytes infection.

Penetration and prophylactic activity against Trichophyton mentagrophytes infection of topically applied antifungal agents were studied in human volunteers. The concentration and persistence of drug in the stratum corneum was determined after different treatment schedules and from different vehicles. Measurable levels of griseofulvin, clotrimazole, miconazole nitrate, and thiabendazole remained in the skin four days after discontinuation of topical applications. Griseofulvin, miconazole, and clotrimazole exhibited prophylactic activity against infection by T mentagrophytes spores in a standardized test. Griseofulvin was a significantly better prophylactic agent than either miconazole or clotrimazole.

Administration, Topical↗

Melanoma: value of early detection and treatment.

Recent studies confirm that the prognosis in patients with melanoma depends on the level of invasion by the tumor at diagnosis. Superficial spreading melanomas usually are detected during the initial radial growth phase, when simple excision usually effects a cure. Nodular melanomas extend vertically from inception and often are not detected until they have penetrated to relatively deep levels. Because the possibility of recurrence is higher with deeper tumors, lymph node dissection may also be necessary. Fortunately, superficial spreading melanomas are considerably more common than the nodular type. Therefore, increased efforts at earlier detection and diagnosis of melanoma will be rewarded by increased cure rates.

Humans↗

The role of sesquiterpene lactones in contact hypersensitivity to some North and South American species of feverfew (Parthenium-Compositae).

Sixteen taxa of the genus Parthenium from North and South America and 20 sesquiterpene lactones derived from plants of the Compositae family were used for patch testing six volunteers who were known to be contact sensitive to plants and lactones of this family. The patterns of cross-sensitivity and structure-activity relationships of the allergenic lactones are evaluated and the clinical and ecological relevance is discussed.

Cross Reactions↗

Immunochemical studies of proteins in epidermal cornified cells of human and newborn rat.

1. Proteins were extracted from cornified cells of newborn rats and human palm with 8 M urea containing 0.1 M beta-mercaptoethanol. Two fractions, rat FIIIa and human F5.5 were obtained by acid precipitation for further study. 2. Antibodies raised in rabbits by injection of rat FIIIa gave two precipitin lines by agarose diffusion against rat FIIIa, but only one line against human F5.5. One of the antigenic determinants of rat FIIIa was found to be a protein of approximately 66 000 daltons. The other seems to be formed with two polypeptides in the range of 60 000 and 66 000 daltons. The antigenic determinant of human F5.5 was a protein of approximately 64 000 daltons which immunologically cross-reacted only with the antiserum to a protein of 66 000 daltons in rat FIIIa. 3. The antisera also cross-reacted with proteins extracted from epidermis of guinea pig, hamster, hairless mouse, dog ear, dog snout and dog foot pad, but did not react with the epidermis of either rabbit immunized with rat FIIIa or non-treated normal rabbit. 4. Indirect immunofluorescence demonstrated a reaction of rabbit anti-rat FIIIa serum over cornified cells as well as over granular, spinous and basal cells of the epidermis of newborn rat and human.

Animals↗

Dibutyryl cyclic AMP-induced differentiation of epidermal cells in tissue culture.

Histochemical and biochemical techniques have been used to compare the effects of dibutyryl cyclic AMP on epidermal cells and dermal cells in primary tissue culture. Rhodamin B staining showed only scattered positive cells in nontreated epidermal cells and a few contaminating keratinizing cell foci in both nontreated and treated dermal cell cultures. In contrast, treated epidermal cells stained strongly and had many keratinizing cell foci. A significant increase in histidine, cystine, and arginine incorporation was noted in epidermal cells treated with dibutyryl cyclic AMP as compared to untreated epidermal cells and to dermal cell cultures both treated and untreated. Dibutyryl cyclic AMP had no significant effect on leucine and phenylalanine incorporation. These results seem to suggest that the intracellular level of cyclic AMP not only controls the synthesis of DNA by epidermal cells in culture but also induces the process of differentiation toward keratinization.

Arginine↗

Inhibition of the in vivo effects of concanavalin-A on mammalian epidermis by alpha-methyl-D-glucopyranoside.

Concanavalin-A (Con-A) injected intradermally into newborn rats produces inhibition of granular-cell formation, accumulation of spinous cells, glycogen deposition, and a decrease followed by an increase in the number of basal cells in DNA synthesis. These changes were maximal with a dose of 0.1 mg Con-A, although 0.005, 0.01, and 0.05 mg caused some epidermal changes. The Con-A effects were partially blocked when 0.1 ml of 0.3 or 0.1 M alpha-methyl-D-glucopyranoside (alphaMG) solution was injected 2 hr after 0.1 mg Con-A and completely inhibited by injection of 0.1 ml of 3.0 M alphaMG solution. The inhibitory effects were not seen after injection of 0.1 ml of 3.0 M N-acetyl-galactosamine saline solution, or 0.1 ml normal saline. Injection of alphaMG alone did not cause any changes in epidermal cells. These results indicate that specific sugar inhibits Con-A effects on mammalian epidermis in vivo.

Acetylglucosamine↗

The induction of human multinucleated monocytes in culture.

The formation of multinucleated giant cells in vitro has been studied using human monocyte cultures. Multinucleated monocytes appeared early in the course of the culture, indicating that they are not purely a phenomenon found only in aging cultures. In 4 of the 33 normal adults, more than 20% of multinucleated forms appeared in the cultures. Supernatants from early monocyte cultures of those subjects having a high incidence of multinucleated cells induced the formation of multinucleated cells in other cultures. This effect did not occur when supernatant from subjects with low counts of multinucleated cells were incubated with other monocyte cultures.

Cells, Cultured↗