Structure determination of 3 beta, 17-dihydroxy-17 alpha-pregn-5-ene-20-one.

The title compound was synthesized as part of an effort to determine the identity of an abnormal steroid metabolite present in the urine of a patient exhibiting pronounced gynecomastia. The X-ray investigation of the synthesized compound showed that the 20-carbonyl of the 17 alpha oriented side chain lies under the D ring, and does not participate in hydrogen bonding in the crystal lattice. This conformation appears to be stable and sufficiently shielded that it is unlikely to make a major contribution to possible protein interactions.

The development of tolerance to antilipolytic agents by isolated rat adipocytes.

Using an isolated rat epididymal adipocyte system we have studied the development of tolerance to and cross-tolerance between nicotinic acid, 5-methylpyrazole-3-carboxylic acid and pyridyl-3-tetrazole. Preincubating isolated adipocytes with any one of these compounds results in a reduction of the antilipolytic activity of that compound when the cells are exposed to a subsequent challenge dose. Furthermore, preincubation with nicotinic acid, 5-methylpyrazole-3-carboxylic acid or pyridyl-3-tetrazole results in a reduction of the antilipolytic response to challenge with either of the other two compounds.

The development of tolerance to antilipolytic agents in rats.

The development of tolerance to the action of certain antilipolytic agents has been investigated in vivo in rats. Tolerance to oral nicotinic acid developed during twice daily dosing for 4 days at 100 and 250 mg/kg but not at 10, 25 or 50 mg/kg. Tolerance induced by high doses of nicotinic acid was no longer detectable after a further week without treatment.

Molecular structures of metabolites and analogues of diethylstilbestrol and their relationship to receptor binding and biological activity.

A series of indanyl derivatives of diethylstilbestrol (DES) have recently been identified as inv vivo metabolites of DES. These compounds are of interest because they possess effective uterine estrogen receptor-binding affinity but poor biological activity. The X-ray crystal structures of three of these derivatives were determined and their conformations were compared with those of estradiol and DES.

Characterization of monoclonal antibodies against beta-bungarotoxin and their use as structural probes for related phospholipase A2 enzymes and presynaptic phospholipase neurotoxins.

Hybridoma lines secreting monoclonal antibodies against a phospholipase-inactive derivative of the presynaptic neurotoxin, beta-bungarotoxin, have been established. These antibodies, either of the IgG1 or IgG2b isotype with affinities in the range 1-2 X 10(8) 1/mol, recognized a single immunodominant region of native beta-bungarotoxin, most probably located on the A (phospholipase homologue) chain of the toxin. Using plate-adsorbed radioimmunoassay procedures, antibodies reacted with native beta-bungarotoxin and other beta-bungarotoxin isotoxins as well as with the non-toxic phospholipase A also present in Bungarus multicinctus venom.

Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate.

Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of the hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extracellular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by 14CO2 evolution from [1-14C]pyruvate and [3-14C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate.

Electrophysiological and neurochemical investigations of the action of presynaptic neurotoxins.

Previous experiments have suggested that hemicholinium-3 might directly antagonize certain actions of beta-bungarotoxin at the neuromuscular junction. Data presented here show that, on the contrary, hemicholinium-3 neither inhibits the phospholipase activity of beta-bungarotoxin nor does it affect the characteristic pattern of transmitter release observed at end plates exposed to the toxin. Lanthanum ions were found to promote the release of acetylcholine from sartorius nerve-muscle preparations that had been paralyzed by botulinum toxin.

Dipeptide-hydroxamates are good inhibitors of the angiotensin I-converting enzyme.

The inhibition constants (Ki) and modes of inhibition have been determined for a series of dipeptide-hydroxamate compounds with bovine lung parenchyma angiotensin I-converting enzyme (peptidyldipeptide carboxy-hydrolase, E.C. 3.

Quieting response training: predictors of long-term outcome.

Extensive personality, demographic, and symptom-related information from a heterogeneous group of more than 300 patients was examined for patterns that would discriminate between successful and unsuccessful outcomes in patients undergoing Quieting Response (QR) training, an 8-week program that integrated EMG and thermal biofeedback with a variety of relaxation exercises. Follow-up evaluations were at 3, 6, 12 and 24 months. Agreement between expected (from stepwise discriminant analyses) and observed outcomes was 65% (whole sample), 62% (headache only), and 70% (Raynaud's only).

Quieting response training: long-term evaluation of a clinical biofeedback practice.

Clinical evidence for the long-term effectiveness of biofeedback related relaxation training is accumulating. The purpose of this report is to describe the population, self-regulation procedure, outcome criteria, and final outcome for patients who received Quieting Response (QR) training. Data from 340 patients who completed at least the first follow-up at 3 months is presented.

High affinity binding of [125I]monoiodoapamin to isolated guinea-pig hepatocytes.

The bee venom neurotoxin apamin has been labelled with 125I and its binding to isolated guinea-pig hepatocytes measured under physiological conditions. A single saturable component of [125I]monoiodoapamin binding with a Kd of 350 pM and Bmax of 0.99 fmol/mg dry wt was identified.

Synthesis and characterization of the anomeric pair of 17 beta-glucuronides of ethynylestradiol.

The alpha- and beta-anomers of the 17 beta-D-glucuronide conjugate of ethynylestradiol were synthesized by the SnCl4-promoted reaction between beta-acetoxy GAM and the t-17 beta-hydroxyl group of EE2-3-acetate. The conjugates were resolved by crystallization and HPLC. Positive identification was established by u.

The molecular structure of (20R)-20-phenyl-5-pregnene-3 beta, 20-diol, an inhibitor of cholesterol conversion to pregnenolone.

The crystal and molecular structure of (20R)-20-phenyl-5-pregnene-3 beta, 20-diol hemihydrate has been determined by X-ray analysis in order to establish the configuration and conformation at C(20). Interest in this compound was stimulated by its high affinity inhibitory binding to cytochrome P-450SCC, the enzyme which catalyzes the biosynthesis of pregnenolone (3 beta-hydroxy-5-pregnen-20-one) from cholesterol. The results of the analysis suggest a possible conformation for the cholesterol side chain in the enzyme complex.

Quieting response training: treatment of psychophysiological disorders in psychiatric inpatients.

Self-regulation methods incorporating biofeedback are known to be useful in the treatment of psychophysiological disorders in psychologically normal patients. In this study, the effectiveness of Quieting Response (QR) training for the treatment of secondary psychophysiological complaints in psychiatric inpatients was assessed. Ten male and 27 female inpatients with a variety of secondary psychophysiological diagnoses were accepted into the study.

Antibodies to beta-bungarotoxin and its phospholipase inactive derivative.

Antisera were raised against the presynaptic neurotoxin beta-bungarotoxin and against its phospholipase-inactive derivative, modified by reaction with p-bromophenacyl bromide. The cross-reactivity of the antisera to other phospholipase A2 enzymes and polypeptide neurotoxins was examined. The antisera inhibited both the neurotoxic effects of beta-bungarotoxin at the frog motor endplate and the enzymatic activity of the toxin on model phospholipid membranes, although it is unlikely that the catalytic active centre is the locus of any major determinant.

Natural science and medicine: social science and medicine: some methodological controversies.

The paper is in five parts. A discussion of the flaws in social science as seen from the viewpoint of medical science is followed by a consideration of what they hold in common--the shared institutions and ideal programme of Science. The major differences that still remain are then characterized in two further sections; the first concentrates on the issues raised by the human species' distinctive place in evolution, while the second discusses the problems and advantages created for social science by its necessary closeness to lay thought.