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Biomedical subjects

S J Friedman

Publications and source records attributed to S J Friedman.

At least 19 recordsLinked to original sources
PubMed1992

Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules.

Dolastatin 15, a seven-subunit depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent dolastatin 10, a five-subunit peptide obtained from the same organism. We have compared dolastatin 15 with dolastatin 10 for its effects on cells grown in culture and on biochemical properties of tubulin. The IC50 values for cell growth were obtained for dolastatin 15 with L1210 murine leukemia cells, human Burkitt lymphoma cells, and Chinese hamster ovary (CHO) cells (3, 3, and 5 nM with the three cell lines, respectively). For dolastatin 10, IC50 values of 0.4 and 0.5 nM were obtained with the L1210 and CHO cells, respectively. At toxic concentrations dolastatin 15 caused the leukemia and lymphoma cells to arrest in mitosis. In the CHO cells both dolastatin 15 and dolastatin 10 caused moderate loss of microtubules at the IC50 values and complete disappearance of microtubules at concentrations 10-fold higher. Despite its potency and the loss of microtubules in treated cells, the interaction of dolastatin 15 with tubulin in vitro was weak. Its IC50 value for inhibition of glutamate-induced polymerization of tubulin was 23 microM, as compared to values of 1.2 microM for dolastatin 10 and 1.5 microM for vinblastine. Dolastatin 10 noncompetitively inhibits the binding of vincristine to tubulin, inhibits nucleotide exchange, stabilizes the colchicine binding activity of tubulin, and inhibits tubulin-dependent GTP hydrolysis (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990; Bai et al. J Biol Chem 265: 17141-17149, 1990). Only the latter reaction was inhibited by dolastatin 15. Nevertheless, its structural similarity to dolastatin 10 indicates that dolastatin 15 may bind weakly in the "vinca domain" of tubulin (a region of the protein we postulate to be physically close to but not identical with the specific binding site of vinca alkaloids and maytansinoids), presumably in the same site as dolastatin 10 (the "peptide site").

Amino Acid Sequence↗
PubMed1992

Stabilization of intercellular contacts in MDCK cells during Ca2+ deprivation. Selective effects of monocarboxylic acids on desmosomes.

Short-chain monocarboxylic acids (MCAs) selectively protect desmosomal junctions of MDCK cells from disruption by chelating agents and low calcium medium. This effect occurs in the millimolar concentration range and increases inversely with carbon chain length (formate > acetate = propionate > butyrate > isobutyrate > isovalerate). The relative activity of MCAs does not correlate with their overall hydrophobicity or ability to chelate ions, or their effectiveness in lowering cytosolic pH. It exhibits chemical specificity and is dependent upon postconfluency culture age. MCAs also inhibit cell rounding produced by low concentrations of aminocarboxylate-chelating agents. Their effect on cell rounding, but not on desmosomes, can be antagonized by okadaic acid. The possibility is discussed that MCAs may produce their effects by binding specifically to protein(s) associated with the desmosome of mature, fully polarized MDCK monolayers.

Animals↗
PubMed1990

Lichen spinulosus. Clinicopathologic review of thirty-five cases.

Lichen spinulosus is a rare, idiopathic dermatosis characterized by follicular keratotic papules that are grouped into large patches. In this report the clinical and histologic data of 35 patients with lichen spinulosus are presented. The patients consisted of 14 males and 21 females, and their average age was 17.8 +/- 9.5 years. The average age at onset of disease was 16.2 +/- 10.1 years. Affected areas were symmetrically distributed and involved the extensor surfaces of the arms and legs, back, chest, face, and neck. Lesions were characterized by round or oval, 2 to 6 cm plaques composed of grouped punctate, "thorny," 1 to 3 mm, follicular keratotic papules. Microscopic examination revealed keratotic plugging of the follicular infundibulum and a perivascular and perifollicular mononuclear infiltrate. Although the cause is not yet known, lichen spinulosus probably represents a follicular reaction pattern of more than one origin.

Adolescent↗
PubMed1989

Subcutaneous fat necrosis of the newborn: light, ultrastructural and histochemical microscopic studies.

Multiple subcutaneous plaques and nodules appeared on the back and the dorsal proximal area of the extremities of a 9-day-old male infant after a complicated prenatal period necessitating cesarean section. The clinical and histological features were diagnostic of subcutaneous fat necrosis of the newborn. Light microscopy revealed adipocyte necrosis, a lymphohistiocytic infiltrate, and needle-shaped clefts within adipocytes and macrophages. Ultrastructurally, there were aggregations of electron-lucent spaces in the form of spindles and needles arranged in parallel within the altered adipocytes; macrophages surrounded these cells or their fragments and invaded the fat lobules. Enzyme histochemical staining, not previously reported in the literature, showed that acid phosphatase, leucine aminopeptidase, and indoxyl and non-specific esterases were present in the areas of fat necrosis.

Acid Phosphatase↗
PubMed1989

Chronic inhibition of hypothalamic-pituitary-ovarian axis and body weight gain by brain-directed delivery of estradiol-17 beta in female rats.

The effect of preferential delivery of estradiol (E2) into the brain on both the hypothalamic-pituitary-ovarian axis and weight gain was studied in female rats. When E2 was coupled to a lipoidal dihydropyridine-pyridinium carrier, the resulting carrier E2 complex (CE), upon a single intravenous administration to cycling female rats, caused a dose-dependent inhibition of ovulation which lasted 3 times longer than with uncoupled E2. The dose of CE that delayed ovulation for 4 days was one twentieth the amount of E2 needed to produce the same effect. Studies in ovariectomized (OVEX) rats indicated that the prolonged ovulation-blocking action of CE appeared to be related to a sustained storage and release of E2 in the brain, which in turn suppressed the release of hypothalamic luteinizing hormone-releasing hormone (LHRH) and pituitary luteinizing hormone (LH). Upon single intravenous administration in pubertal female rats, CE caused a dose-dependent reduction of body weight gain for a minimum period of 28 days. The inhibitory action of CE on body weight gain was more potent and longer lasting than that of E2 in pubertal rats. When administered in OVEX rats, CE produced a loss of body weight that lasted significantly longer than that produced by uncoupled E2 in these rats. These results suggest that the biological action of E2 can be potentiated by this novel chemical delivery system.

Animals↗
PubMed1988

Studies on the mechanism of activation of human natural killer function by interferon and inhibitors of thymidylate synthesis.

Previous publications from this laboratory have demonstrated that agents such as methotrexate (MTX), 5-fluorodeoxyuridine (FUdR), trimethoprim, and D-glucosamine (D-GlcN), which are known to inhibit thymidylate synthesis, can augment human NK activity in vitro. Furthermore, this augmentation was inhibited by exogenous thymidine (TdR) at concentrations of 10(-6) to 10(-7) M. In this report, underlying mechanisms of action of FUdR, D-GlcN, and IFN are compared. Each of these agents increased the lytic activity of effector cells bound to targets but did not increase the percentage of conjugates formed. The augmentation could be induced in a population highly enriched for NK cells (Leu-1 lb positive in phenotype). FUdR and D-GlcN could not induce any augmentation in a Leu-1 lb-negative subpopulation whereas IFN could induce significant lytic activity. alpha-Amanitin, an inhibitor of RNA polymerase II, blocked the activation of NK activity by all three reagents; hence gene expression was required. Comparison of [35S]methionine-labeled proteins by two-dimensional gel electrophoresis revealed that six new proteins were induced in IFN-treated cells. Three of these were similar in pI and molecular weight to the newly synthesized proteins in the D-GlcN-treated cells. One protein was synthesized in increased amounts in the FuDR-treated cells and it was not common to either of the other treatments. Evidence to date is consistent with the hypothesis that separate mechanisms underlie the activation of NK cells by IFN and thymidylate synthesis inhibitors, although the existence of a final common pathway for all NK response modulators cannot be excluded at the present time.

Antibodies, Monoclonal↗
PubMed1988

Perilesional linear atrophy and hypopigmentation after intralesional corticosteroid therapy. Report of two cases and review of the literature.

We report on the cases of two patients in whom linear perilesional hypopigmentation and atrophy developed after intralesional injection of corticosteroids for treatment of keloids. Evaluation of our patients and the previously reported cases showed that perilesional linear atrophy or hypopigmentation (or both) is a distinct complication after intralesional or intraarticular administration of corticosteroids and is probably due to lymphogenous spread of the steroid suspension.

Atrophy↗
PubMed1988

Punctuate porokeratotic keratoderma.

Two unrelated patients had numerous palmoplantar "music box spine" keratotic plugs and pits of 11 and 13 years' duration. Histologic examination revealed a compact column of parakeratosis resembling that of a cornoid lamella of porokeratotic conditions. Ultrastructurally in clinically affected skin, the stratum corneum contained numerous variable-sized pyknotic nuclei, and cells in the stratum granulosum contained fewer keratohyalin granules. The ultrastructural findings differed from those of porokeratosis of Mibelli and disseminated superficial actinic porokeratosis. The proper nosologic designation should be punctuate porokeratotic keratoderma.

Aged↗
PubMed1987

The regulation of sterol metabolism by cell interactions.

Total and free cholesterol levels in C6 glial cells are regulated by a cell interaction-dependent mechanism that operates independently of exogenous cholesterol and serum lipoproteins. This mechanism, which is activated by changes in culture density, coordinately regulates the activities of HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT). Both enzyme activities are low in sparse density cultures, rise as density increases from sparse to moderate, and decrease with further density increases. When culture density is abruptly elevated, both enzyme activities decay rapidly and with biphasic kinetics. Neither enzyme phosphorylation nor diffusible cytosolic factors appear to be directly involved in density suppression of HMG-CoA reductase. Studies with human fibroblasts that are defective in LDL receptor function demonstrate that density regulation does not require a functional LDL receptor. Extracellular matrix and soluble factors have also been ruled out as intercellular mediators. The specific growth rate of C6 cultures changes with density in the same manner as sterol metabolism. The possibility that growth and sterol metabolism are regulated by a common cell interaction-dependent mechanism is discussed.

Alkaline Phosphatase↗
PubMed1987

Seborrheic keratoses of penis.

A case is reported of a forty-nine-year-old black man in whom numerous skin-colored papules and verrucoid plaques had developed on his penis over the course of fifteen years. He did not seek medical attention, and some of the lesions had become quite large. The initial clinical impression was condyloma acuminatum, and prior to therapeutic intervention histologic evaluation revealed findings diagnostic of seborrheic keratosis. Seborrheic keratoses should be considered in the differential diagnosis of penile lesions especially because of clinical similarities to condylomata acuminata.

Condylomata Acuminata↗
PubMed1987

Omphalokeratolith.

A 69-year-old woman presented with a firm, black umbilical mass of unknown duration. It was easily removed with a warmed otic glycerin preparation. Histologic examination showed that it contained laminated keratin, amorphous material resembling sebum, numerous terminal hairs, and scattered collections of bacteria. Moderate amounts of argentaffin staining material were detected throughout the specimen, and the black color of the lesion was probably due to melanin and oxidized lipids, much like an open comedone. The mass is appropriately called an omphalokeratolith.

Aged↗
PubMed1987

Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythroderma.

A 3-year-old boy with nonbullous congenital ichthyosiform erythroderma with a four-month history of scabies was treated with a single dose of lindane cream. In a 48-hour period, he developed nausea and vomiting and also suffered from an epileptiform convulsion and muscular spasms. Seventy-two hours after application of the cream, his blood lindane level was 54 ng/mL. Caution should be exercised when using lindane in patients with compromised epidermal barrier function.

Child, Preschool↗