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Biomedical subjects

B A Weissman

Publications and source records attributed to B A Weissman.

139 records · Page 8Linked to original sources

Diethylstilbestrol potentiation of the dopamine-elicited formation of adenosine 3',5'-monophosphate in incubated male rat hypothalamus.

Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA.

Adenosine Deaminase↗

Experience with the lathe cut Bausch & Lomb SOFLENS: Part 1--Clinical study.

This study consists of clinical experience with the recently produced lathe cut Bausch & lomb SOFTLENS. Sixteen patients were fitted with the spin cast and then lathe cut lens. Visual acuities were better with the lathe cut lens. Comfort was good with both lenses. Some degree of circum-corneal injection was noted with the larger lathe cut design.

Adolescent↗

Experience with the lathe cut Bausch & Lomb Soflens: Part II--Power and optics study.

Ten familiar spin cast and ten lathe cut Bausch & Lomb SOFLENS contact lenses were measured as to their power on a lensometer and on an eye. Both quality of the optics and quantitative measurements were considered. Lens flexure and the presence of a fluid lens between the posterior surface of the contact lens and the anterior cornea is indicated for both lenses to explain differences between power of the lens in air and on the eye. The spin cast lens design appears to create a quantitatively larger fluid lens, and one which will add positive optical power to the lens/eye system. Either from this and/or additional factors, the lathe cut lens appears to give improved optical performance both in air and on the eye.

Contact Lenses, Hydrophilic↗

Differentiation and activity of mast cells following immunization in cultures of lymph-node cells.

An extensive clonal differentiation into mast cells from primitive blast cell precursors occurred when lymph node cells obtained from mice immunized with horse serum were cultured on mouse embryonic skin monolayers. Horse serum was always present in the culture as a constituent of the nutritional medium. Mast cells developed to lesser extent also in cultures prepared from non-immunized mice. However, a clear difference in mast cell-granule ultrastructure and in histamine content was noted between the two. In cultures of lymph nodes cells from non-immunized mice the granules were tiny and uniform in size and in staining density; whereas granules in the immune cultures were larger and non-uniform in size and in staining density, and the intragranular organization manifested alterations of various forms. The content of intracellular histamine per 10(6) mast cells was about equal in both cultures. However, much more free histamine (per 10(6) mast cells) gradually accumulated in cultures of the immune lymph node cells, indicating higher rates of synthesis and release of histamine. The mast cells were readily degranulated by heat-inactivated (IgG1) sera of the mice used as donors of the lymph node cells. 92% of the mast cells were degranulated and as much as 80% of the histamine was released. The degranulation was accompanied by an immediate (albeit reversible) response of the fibroblast cells in the monolayer. A shift of the well-stretched cytoplasm of the fibroblasts opened numerous 'window' over the whole monolayer. The degranulated mast cells survived the process and could be maintained further in the cultures. Moreover, they were capable of repeated degranulation, releasing 50% of their histamine, even after four degranulation cycles performed over a 7 days' period of culture. No cytotoxic effect on the mast cells was noted and the histamine content in culture, 3 days after degranulation, seemed to be higher than in the undergranulated control cultures--suggesting an intensified rate of histamine synthesis.

Animals↗

Use of the Bausch & Lomb Soflens Plano T contact lens as a bandage.

Twenty patients with corneal disease were treated with a recently released soft lens specifically designed for use as a bandage. Patients wore their lenses continuously 24 hr a day. The results were similar to those of previous studies conducted with other lens designs. Improvement was frequent (10 of 12 cases) for bullous keratopathy and corneal graft, burn, or neuroparalytic lesion; limited (1 of 4 cases) for dry-eye syndrome; and absent (4 cases) for irregular cornea and vernal keratoconjunctivitis. No difficulties were found with the concurrent use of medication.

Adolescent↗

Possible role of dopamine in diethylstilbestrol-elicited accumulation of cyclic AMP in incubated male rat hypothalamus.

Pimozide and haloperidol, the dopaminergic antagonists, have been shown to effectively block diethylstilbestrol (DES)-elicited [3H] adenosine 3', 5'-monophosphate (cAMP) accumulation in incubated hypothalami from immature male rats. Several noradrenergic antagonists (i.e. propranolol, MJ-1999 and phenoxybenzamine) failed to reduce [3H]cAMP levels significantly. Pimozide was found to be more specific than haloperidol as it did not effect norepinephrine (NE)-elicited formation of [3H]cAMP, while the latter blocker caused a 48% reduction of the stimulation by NE. Pimozide was also more potent than haloperidol in inhibiting DES-stimulated [3H]cAMP formation. It can be inferred from these data that as a result of DES-receptor interaction dopamine (DA) is released and in turn activates DA-sensitive adenylate cyclase in the hypothalamus.

Animals↗

Stimulation of Adenosine 3',5'-monophosphate formation in incubated rat hypothalamus by estrogenic compounds: relationship to biologic potency and blockade by anti-estrogens.

Several estrogenic compounds were examined for their abilities to stimulate the formation of adenosine 3',5'-monophosphate (cyclic AMP) in incubated hypothalami from immature (27-28 day old) female rats. 17-beta estradiol (E2) and diethylstilbestrol (DES) significantly increased the formation of cyclic AMP while estrone and estriol elicited small but not statistically significant increases in cyclic AMP formation. 17-alpha estradiol was ineffective in increasing cyclic AMP formation. The anti-estrogenic agent clomiphene was found to effectively antagonize the formation of cyclic AMP elicited by E2 and DES, while having no stimulatory effects on cyclic AMP formation itself. These data indicate that the binding of estrogenic compounds to cytoplasmic sites (receptors) in the hypothalamus is required for subsequent stimulation of cyclic AMP formations.

Animals↗

Diethylstilbestrol-elicited accumulation of cyclic AMP in incubated rat hypothalamus.

Diethylstilbestrol (DES) and 17beta-estradiol elicit significant increases in levels of endogenous and [14C]cyclic AMP in [14C]adeninelabeled hypothalami from immature female rats, but only after incubation of the hypothalami with these estrogenic agents for 40-50 min. Estriol has no effect. The 2-fold accumulation of cyclic AMP elicited by low concentrations (20 muM) of DES appears dependent on catecholamine-related mechanisms, since it is prevented by either alpha- or beta-adrenergic antagonists. Higher concentrations (100 muM) of DES elicit a 3-fold accumulation of [14C]cyclic AMP which is only partially blocked by adrenergic antagonists, haloperidol, or the adenosine antagonist, theophylline. These phenomena appear to be specific for the hypothalamus since incubation of cerebral cortical slabs with estrogens resulted in no significant increases in the levels of cyclic AMP. The slow time course in whole hypothalami and the complete lack of effects of low concentrations of estrogenic agents in chopped hypothalami suggest an indirect mechanism of action. Interaction of estrogens with receptors in cell bodies may result, after a latent period of 40-50 min, in enhanced release of catecholamines from distal synaptic terminals and in stimulation of catecholamine-sensitive adenylate cyclases at post-synaptic sites.

Adenylyl Cyclases↗

Preclinical pharmacology of buspirone hydrochloride.

Buspirone is an azaspirodecanedione that has anxiolytic actions in man and anticonflict actions in experimental animals. In contrast to many commonly used anxiolytic agents, buspirone does not appear to have significant sedative, muscle relaxant or anticonvulsant actions. Consequently, it has been termed an "anxioselective" agent. The effects of buspirone and related compounds have been examined in a number of neurotransmitter systems that have been linked to the actions of other anxiolytic agents. Buspirone has been shown to affect dopaminergic, serotonergic and noradrenergic pathways, as well as the GABA-benzodiazepine receptor chloride ionophore complex. Nonetheless, the doses (in vivo) and/or concentrations (in vitro) of buspirone (and related compounds) needed to affect these systems are not consistent with a causal relationship between the anxiolytic actions of buspirone and any of these systems. The neurochemical mechanism by which buspirone and related compounds exert both anticonflict and anxiolytic actions remains unknown.

Action Potentials↗

Aging does not alter the binding characteristics to voltage dependent calcium channels in the brain of CW1 mice.

Structural age-related changes in cholinergic regions within the central nervous system of CW1 mice have been described previously. Since elevated calcium concentration has been suggested to play a role in the brain aging processes, the possible involvement of voltage dependent calcium channels in this degeneration was investigated. The binding characteristics of the calcium channel antagonist [3H](+)PN 200-110 to brains of aged CW1 mice were studied. This ligand exhibited high affinity binding (Kd values in the range of 50-70 pM) to a single type of sites with a density (Bmax) of 150-200 fmol/mg protein. No significant differences were observed between the binding parameters measured in young (3 months), mid-aged (9 and 15 months) and old (20 months) mice. Autoradiographic study confirmed these results and extended them to specific brain regions. It is concluded that age-dependent degeneration processes, observed histologically in specific brain regions of these mice, are probably not related to alterations in voltage-dependent calcium channels.

Aging↗