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Biomedical subjects

S Spector

Publications and source records attributed to S Spector.

At least 91 records · Page 5Linked to original sources
PubMed1986

Vitamin D3 derivatives inhibit the differentiation of Friend erythroleukemia cells.

A number of vitamin D3 metabolites inhibit benzodiazepine- and dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. The inhibition is dose dependent and occurs at nM concentrations. The order of potency of these compounds is 1,25-dihydroxycholecalciferol greater than 1,25,26-trihydroxycholecalciferol greater than 1,24R,25-trihydroxycholecalciferol greater than 1 alpha-hydroxycholecalciferol greater than 24R,25-dihydroxycholecalciferol greater than 25S,26-dihydroxycholecalciferol. The inhibition is maximal when the vitamin D3 analogs are added together with the inducer, and becomes progressively decreased with delayed addition. These results suggest that the vitamin D3 metabolites may play a regulatory role in erythropoiesis.

Animals↗
PubMed1986

Intussusception.

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Child↗
PubMed1985

Peripheral-type benzodiazepines influence ornithine decarboxylase levels and neurite outgrowth in PC12 cells.

A number of the benzodiazepines (BZDs) inhibit nerve growth factor (NGF)-induced neurite outgrowth in a dose-dependent manner in PC12 cell cultures. The rank order of potency of a series of BZDs for inhibition of neurite outgrowth does not correlate with the order of their affinity constants for the so-called peripheral BZD sites present on PC12 cells. Whereas the inhibition of neurite extension is stereospecific, the binding to the peripheral site is not. The inhibition of neurite outgrowth is not attributable to a blockade of NGF binding to either its fast or slow receptors. Additionally, several other characteristics of NGF stimulation of PC12 cells, such as autoadhesion and the induction of ornithine decarboxylase (OrnDCase), remain unaltered in the presence of BZDs. Many BZDs increase OrnDCase levels in PC12 cells in the absence of NGF. The OrnDCase response to BZDs is blocked by actinomycin D. Furthermore, the structural requirements of BZDs for induction of OrnDCase activity is not identical to that for the inhibition of NGF-induced neurite extension. Thus, unlike attenuation of neurite extension, BZD induction of OrnDCase is not stereospecific. Also, some BZDs block neurite growth but do not induce OrnDCase. We propose that there are at least three sites of action of BZDs on PC12 cells. The first is the well-characterized high-affinity peripheral site. The second distinct locus of action results in a blockade of NGF-induced neurite outgrowth. The structural requirements for the latter effect are essentially indistinguishable from those for BZD induction of hemoglobin synthesis in Friend erythroleukemia cells. The third site of action results in an induction of OrnDCase. Structural requirements for this activity are not identical to those for either the differentiation of Friend cells or the inhibition of neurite outgrowth.

Animals↗
PubMed1985

Scintillation proximity radioimmunoassay utilizing 125I-labeled ligands.

A unique type of radioimmunoassay is described that does not require centrifugation or separation. Microbeads containing a fluorophor are covalently linked to antibody. When an 125I-labeled antigen is added it binds to the beads and, by its proximity, the emitted short-range electrons of the 125I excite the fluorophor in the beads. The light emitted can be measured in a standard scintillation counter. Addition of unlabeled antigen from tissue extracts displaces the labeled ligand and diminishes the fluorescent signal. Application of scintillation proximity immunoassay to tissue enkephalins, serum thyroxin, and urinary morphine is described. Applications of the principle to study the kinetics of interaction between receptors and ligands are discussed.

Chorionic Gonadotropin↗
PubMed1985

Isolation of morphine from toad skin.

A nonpeptide opioid was found in toad skin and purified to homogeneity by using HPLC with electrochemical detection. A nonpeptide opioid also was detected in bovine brain and adrenals as well as rabbit and rat skin, by reversed-phase HPLC following Sephadex G-15 column chromatography. The material in toad skin was identical to morphine by immunological, pharmacological, and physical chemical criteria.

Adrenal Glands↗
PubMed1985

Impaired in vitro interferon, blastogenic, and natural killer cell responses to viral stimulation in acquired immune deficiency syndrome.

The in vitro immune response to herpes simplex virus (HSV), type 1, strain 539, HSV type 2, strain 316D, and cytomegalovirus was studied in 20 patients (14 with acquired immune deficiency syndrome, four with the acquired immune deficiency syndrome-related symptom complex, and two sexually active asymptomatic homosexuals) and 18 heterosexual healthy controls. Peripheral blood mononuclear cells were cultured with 2 X 10(5) plaque-forming units of heat-inactivated viruses, their lymphocyte blastogenic responses were measured after 5 days in culture by [3H]-thymidine incorporation, their interferon production was measured after 24 hr and 5 days, and natural killer (NK) cell activation was measured after 24 hr and 5 days of culture. Blastogenic responses to viruses were significantly low for only HSV, type 1:1.75 X 10(3) cpm in patients' cells compared to 6.36 for controls. Interferon responses to all three viruses were significantly low at both 24 hr and 5 days; e.g., HSV, type 1:139 IU/ml in patients' cells compared to 777 for controls at 24 hr. NK cell responses of patients were lower than those of controls when tested fresh and after 24 hr of incubation: 6.1 versus 11.7% and 9.2 versus 16.8% target cell lysis, respectively. Exposure to viruses boosted NK cell responses of both patients' and controls' cells, but boosting was generally greater among the normal rather than the patients' cells. The abnormalities of response were present in all three patient groups. Addition of interleukin-2 in vitro increased the patient and control blastogenic and NK responses but did not augment the interferon responses. The in vitro responses to both HSV, type 1, and HSV, type 2, correlated significantly with our conventional assays of the percentage and absolute level of T4+-helper lymphocytes in the blood and the blastogenic responses to mitogens, such as phytohemagglutinin, pokeweed mitogen, and concanavalin A. This system should be useful for the study of host defense in acquired immune deficiency syndrome patients and those in high-risk groups, and also for the in vitro evaluation of immunomodulators.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Differentiation of Friend erythroleukemia cells induced by benzodiazepines.

Many benzodiazepines of the type whose receptors are found in peripheral tissues cause the differentiation of cultured Friend erythroleukemia cells. The maximal level of induction of hemoglobin synthesis is 10-80% of the cells, depending on the compound tested. The induction is concentration and time dependent, requiring micromolar amounts of the drugs and about 5 days of treatment for full expression. The time course is very similar to that observed for a well-studied inducer, dimethyl sulfoxide. The affinities of the agents for the peripheral-type benzodiazepine binding site are not correlated with their capacity to induce differentiation. Also, the biological effect is stereospecific since the (3S) stereoisomer Ro11 -6896 is at least an order of magnitude more potent than its (3R) enantiomer, Ro11 -6893. The benzodiazepine effect exhibits definite structure-activity relationships. A 1-methyl group is an absolute requirement, although this is not sufficient in itself. Hydroxyl and methoxyl groups at the 4' position enhance the biological activity, but 4'-chloro decreases it. Substitutions at the 2', 6', and 4 positions also decrease the biological activity, as does the lack of a 2-carbonyl group. These data suggest that the benzodiazepines act in a specific manner to induce the differentiation of Friend erythroleukemia cells.

Animals↗
PubMed1984

Benzodiazepines that bind at peripheral sites inhibit cell proliferation.

[3H]Ro5-4864 binds to mouse thymoma cells in a specific, saturable, and reversible manner. Scatchard analysis shows a single class of binding sites with a Kd of 4.4 nM and a Bmax of 477 fmol per 10(6) cells. This benzodiazepine binding site is of the peripheral type, based on the relative potencies of Ro5-4864 and clonazepam in competing for [3H]diazepam binding. Fifteen benzodiazepines that bind to this site with affinities ranging from 6 nM to 1 microM also reversibly inhibit the proliferation of thymoma cells in culture at the micromolar dose range. There is a strong positive correlation (r = 0.85) between the binding constants of these compounds for the peripheral-type sites and their ED50 in inhibiting the uptake of [3H]thymidine into the cells. These sites may be involved in the regulation of thymoma cell proliferation.

Animals↗
PubMed1984

Interaction of calcium channel blockers with non-neuronal benzodiazepine binding sites.

The ability of calcium channel blockers to displace the binding of benzodiazepine ligands was investigated in rat heart, kidney, and brain. The dihydropyridine calcium channel blockers nifedipine and nitrendipine displaced the binding of the non-neuronal-site ligand [3H]Ro5-4864, but not that of the neuronal-site ligands [3H]flurazepam or [3H]clonazepam. The inhibition was competitive, with Ki values in the micromolar range. Other calcium channel blockers--i.e., verapamil and diltiazem--were inactive at both sites. Thus, non-neuronal benzodiazepines bind to a class of sites that also binds dihydropyridines. This implies a role for benzodiazepines in the mediation of calcium-dependent phenomena.

Animals↗
PubMed1984

Melatonin in serum and the pineal of spontaneously hypertensive rats.

Involvement of melatonin in the blood pressure regulation as an endogenous central hypotensive factor has been suggested in rats and in man. We studied the relationship between melatonin and the development of hypertension in 5- and 15-week-old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, by measuring serum and the pineal concentrations with a sensitive and specific radioimmunoassay coupled with a novel extraction method. Serum melatonin concentration at midnight in young SHR rats was significantly higher than that in age-matched WKY rats (P less than 0.01), whereas it was decreased in the adult SHR (P less than 0.01). No such differences were observed at noon. Pineal content of melatonin at midnight in 5-week-old SHR rats was lower than in age-matched WKY rats (P less than 0.01). These data demonstrate that melatonin in the nocturnal serum of SHR rats is elevated at prehypertensive stage while it is decreased after the development of hypertension. The role of melatonin in the hypertensive process in SHR rats requires further study.

Aging↗
PubMed1984

[Not Available].

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Death↗
PubMed1984

Structural requirements for the binding of benzodiazepines to their peripheral-type sites.

The DS19 Friend erythroleukemia cells possess peripheral-type benzodiazepine recognition sites that are similar to those characterized in other tissues and cells. These sites recognize only specific and well-defined ligand structures. In order for the benzodiazepines to bind to these sites, an alkyl group of 3 carbons or less is required at position 1, together with a carbonyl group at position 2. In addition, the binding affinity is enhanced by 4'-halogen or 4'-methoxy substituents, and by 7- or 2'-halogens. However, the affinity is decreased by substitutions at position 3 or 4. Central-type benzodiazepine binding in brain, on the other hand, is not affected by 1-alkyl groups and is inhibited by 4'-substitutions. Furthermore, unlike the peripheral-type site, the brain receptor is stereo-selective. These results demonstrate that the two binding sites are fundamentally different in their recognition of benzodiazepine ligands.

Animals↗
PubMed1983

Structure-activity requirements for hypotension and alpha-adrenergic receptor blockade by analogues of atropine.

The hypotensive action of various antimuscarinic compounds structurally related to atropine was studied in conscious, unanesthetized rats. The alpha-adrenolytic activity of these agents was assessed both in vivo (blockade of norepinephrine-induced pressor response) and in vitro (displacement of [3H]WB-4101 binding). Benztropine, homatropine and hyoscyamine caused hypotension and produced alpha-adrenergic receptor blockade similar to atropine. Other analogues were either inactive (atroscine, scopolamine, tropic acid and tropine) or evoked nonspecific changes in blood pressure and lacked alpha-adrenolytic activity (benactyzine, eucatropine, methylatropine, methylhomatropine and methylscopolamine). Based on these data, we propose the following structure-activity relationship for hypotension and alpha-adrenolytic activity: (a) the tropine moiety is inactive unless it is attached to another group by an ester linkage, (b) chemical modification of the tropine moiety, including quaternization, decreases potency, (c) the d-stereoisomer appears to be more potent than the corresponding 1-form.

Acetylcholine↗
PubMed1983

The binding of [3H]-diazepam to guinea-pig ileal longitudinal muscle and the in vitro inhibition of contraction by benzodiazepines.

1--The longitudinal muscle-myenteric plexus strip preparation of the guinea-pig ileum was used to study the binding of [3H]-diazepam and the effect of benzodiazepines on its contraction. 2--Scatchard analysis of binding indicated a single class of binding sites with KD = 43 nM and Bmax = 229 fmol/mg prótein. Binding was of peripheral type based on the much greater binding affinity of Ro5-4864 as compared to clonazepam. Binding of [3H]-diazepam reached equilibrium at 10 min and dissociated rapidly (T1/2 = 1.3 min). The KD derived from the rate constants agreed with that from the Scatchard analysis. 3--Benzodiazepines produced a dose-dependent decrease in the electrically induced contractions of the longitudinal muscle strip, but their potencies in this effect did not correlate with their binding affinities. 4--Diazepam antagonized the contractions of the longitudinal muscle strip induced by K+, Ca2+, histamine and carbachol. The inhibition of Ca2+-induced contractions was reversed by increasing the concentration of Ca2+ in the medium.

Animals↗