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Biomedical subjects

L E Cohen

Publications and source records attributed to L E Cohen.

32 records · Page 2Linked to original sources

High- and low-affinity receptors regulate platelet responses to phorbol diesters and teleocidin.

We examined binding of 3H-phorbol dibutyrate (3H-PDBu) to gel filtered human platelets (GFP) and discovered that GFP possess two classes of receptors for phorbol diesters (PDE). High-affinity (HA) receptors, approximately 5000/GFP, bound 3H-PDBu with an apparent dissociation constant (KD) of approximately 12 nM. Low-affinity receptors were approximately 5 times more numerous (2.4 X 10(4)/GFP) and had a 10-fold lower affinity for 3H-PDBu (apparent KD = 115 nM). The potencies of phorbol myristate acetate (PMA) and PDBu paralleled their binding affinities to the PDE receptors. Teleocidin (Tel), although structurally distinct from PDE, competed with 3H-PDBu for its HA-receptors (KI Tel = 1.9 nM). Binding of PDE to HA- or LA- receptors was rapid, reversible, saturable and stereospecific. The HA- and LA-receptors modulated different platelet responses. HA-receptors regulated the secretion of beta-thromboglobulin from alpha-granules and the release of N-acetyl-beta-D-hexosaminidases from lysosomes. LA-receptors mediated both platelet aggregation and the release of serotonin from dense granules. This is the first demonstration of two physiologically active classes of PDE/Tel receptors in human platelets, and demonstrates that particular platelet responses may be directed by distinct classes of receptors for specific agonists.

Binding, Competitive↗

The dermatologic exam.

This article provides a comprehensive approach to the patient presenting with dermatologic concerns. Emphasis is placed on the unique aspects of skin disease with regard to history and physical exam. Illustrations to demonstrate primary and secondary lesions, shape and configuration of the lesion, and regional distribution or pattern of involvement have been included. In addition, aids to diagnosis and instructions for slide preparations, patch testing, and performing skin biopsies are presented.

Biopsy↗

Common and uncommon cutaneous findings in patients with ataxia-telangiectasia.

This series describes some common and uncommon cutaneous findings in twelve patients with ataxia-telangiectasia (A-T). All patients had the characteristic telangiectasia as described previously. However, the telangiectases did not conform to a classic photodistribution . Our series did include one patient with a pathologic reaction to light-simulating hydroa aestivale or vacciniforme . In addition, there were three patients with acanthosis nigricans in two unrelated families. Vitiligo, impetigo, recurrent herpetic gingivostomatitis, hirsutism, lipoatrophy, gray hair, progeroid changes and hyper- and hypopigmented macules were noted in our patients. Many of our patients had one or more caf'e au lait like-lesions in a dermatomal distribution. In addition, several of the family members showed one or more café au lait-like lesions, suggesting the possibility that this finding may represent a phenotypic expression in the skin of carriers of this cancer-prone syndrome.

Acanthosis Nigricans↗

Specific binding of [3H]phorbol dibutyrate to phorbol diester-responsive and -resistant clones of a human myeloid leukemia (KG-1) line 1.

Phorbol diesters induce macrophage-like differentiation in KG-1 and HL-60 human acute myelogenous leukemia cell lines. We developed a cloned subline of KG-1, known as KG-1a, that does not differentiate when exposed to phorbol diesters. Both KG-1 and KG-1a cells have a single class of specific high-affinity receptors for labeled phorbol-12,13-dibutyrate with a mean Kd of 1.47 +/- 0.10 (S.E.) X 10(-8) M and 0.85 +/- 0.20 X 10(-8) M for the sensitive parental KG-1 line and the resistant KG-1a subline, respectively (p less than 0.025). The number of [3H]phorbol-12,13-dibutyrate binding sites (mean +/- S.E.) per cell was 3.85 +/- 0.98 X 10(5) and 3.94 +/- 0.31 X 10(5) on KG-1 and resistant KG-1a cells, respectively. We observed no significant decrease of specific binding with time (down regulation) in either KG-1, KG-1a, or HL-60 cells, suggesting that down regulation of specific phorbol-12,13-dibutyrate binding is not critical to induction of differentiation. Our data also confirm that the presence of specific high-affinity phorbol receptors on leukemic cells does not assure that phorbol diesters can trigger their differentiation.

Cell Differentiation↗

Development and learning in the offspring of rats fed an alcohol diet on a short- or long-term basis.

The offspring of rats fed a diet containing 12.5% (v/v) ethanol prior to, and during, gestation (LTE) were compared to the offspring of rats fed the same diet during gestation only (STE) in three studies. In Study I the neonates were tested on a variety of neuroreflex tasks, in Study II the offspring were tested in an activity wheel and open field, and in Study III the offspring were trained in a runway under partial or consistent reward conditions. Results indicated that STE offspring were delayed in developing fur and in opening their eyes, they righted more rapidly, and were slower in developing a reaction to and habituating to an auditory stimulus than their controls (STC) and the LTE offspring. Generally, movement was greater for ethanol exposed offspring and the LTE offspring showed more persistent fear-related responses than the STE offspring. No statistically reliable differences in learning or extinction were found among the groups, although a trend towards better learning and less resistance to extinction was noted in the LTE animals. Long-term alcohol use seems to attenuate the effects of gestational alcohol in rats.

Animals↗

Effects of gestational alcohol on the development of neonatal reflexes in the rat.

The offspring of rats fed a diet containing 10% (v/v) of ethanol were tested for developmental differences from controls on a variety of maturational events and reflexes. Results indicated slower development of fur onset and ear (pinnae) opening, more rapid and vigorous righting responses and shorter dowel-grasping times in the offspring of ethanol-fed dams. No differences in rooting reflex, Babinski reflex, or in the visual placing response were found. These findings were seen as consistent with the interpretation that gestational alcohol exposure results in reduction in the ability of subjects to inhibit responses. The reduction in inhibition is not inconsistent with damage to the hippocampal area of the brain.

Animals↗