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Biomedical subjects

T H Williams

Publications and source records attributed to T H Williams.

At least 55 records · Page 3Linked to original sources

The distribution and ultrastructure of VIP-immunoreactivity in the central nucleus of the rat amygdala.

Vasoactive intestinal polypeptide (VIP) neurons within the central nucleus of the rat amygdala were examined using light and electron microscopic immunocytochemical techniques. Vasoactive intestinal polypeptide-immunoreactive neurons were located in the ventral part and less frequently in the central part of the central nucleus. Vasoactive intestinal polypeptide positive terminals were distributed throughout the medial part of a cytoarchitectonically distinct central zone of the central nucleus. Three types of terminals formed synaptic contacts on VIP-immunoreactive neurons: type A containing round vesicles, type B containing many pleomorphic vesicles and type C containing fewer pleomorphic vesicles. All VIP-immunoreactive boutons observed were of type A variety, and made asymmetrical and symmetrical synaptic contacts on both VIP-immunoreactive and nonreactive neurons within the central nucleus.

Amygdala↗

Computer software design for pediatric practice. A modular approach.

Practical applications for using computers in everyday medical practice have not kept pace with the technical developments that now make this tool available to the pediatric practitioner. A modular approach to user-developed applications software is presented as a model for computerizing the pediatric office. Benefits have included lower cost, greater data reliability and validity, standardization of office and medical procedures, and automation of jobs formerly requiring much personnel time. Some patient services have improved, and other new services have become possible, through the application of computer software designed in accordance with our practice philosophy.

Computers↗

Ultrastructural identification of substance P cells and processes in the rat myenteric plexus.

Substance P containing perikarya and processes were identified by electron microscopic immunocytochemistry in the rat small intestine. The labelled perikarya possessed a cytoplasm of high electron density rich in organelles most of which contained numerous 80 to 130 nm large granulated vesicles. Labelled processes were found in pre- and postsynaptic positions. The presynaptic terminals contained 80 to 130 nm granular vesicles and 30 to 40 nm clear vesicles. These findings provide a morphological basis for the assumption that the peptide substance P may act as a transmitter and exerts postsynaptic effect on other intrinsic neurons and that the labelled cell bodies are links to a local neuronal circuit in the small intestine.

Animals↗

Stereospecific synthesis of 3 beta-hydroxylated bile alcohols.

This paper describes the synthesis of 5 beta-cholestane-3 beta, 7 alpha,25-triol and 5 beta-cholestane-3 beta, 7 alpha, 12 alpha, 25-tetrol from their corresponding 3 alpha-analogs. The method consists of refluxing a mixture of a steroid alcohol, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as formic acid. The sterically pure ester (3 beta-formate) so formed after saponification then allows an easy access to the epimer of the starting alcohol. Differentiation of these 3 beta-hydroxy bile alcohols from their corresponding 3 alpha-epimeric analogs was made possible on the basis of proton, 13C-NMR, and mass spectra as well as chromatographic mobility. Steric requirements of sterols and nucleophilicity of attacking acidic components played an important role for the success of this synthesis. Only equatorial hydroxyl groups in these bile alcohols reacted under mild conditions and epimerization, as well as protection of the alcoholic group, was achieved in one step. Formic acid was the acid of choice since the axial formate ester formed is sufficiently reactive to be hydrolyzed (KHCO3/aq X MeOH) under mild conditions.

Bile Acids and Salts↗

ACTH-immunoreactive boutons form synaptic contacts in the hypothalamic arcuate nucleus of rat: evidence for local opiocortin connections.

ACTH-like immunoreactive structures were localized in rat hypothalamic arcuate nucleus using the unlabeled antibody, peroxidase-antiperoxidase method. At the ultrastructural level, immunoreactive presynaptic nerve terminals were observed forming symmetrical synaptic contacts with unlabeled dendrites and with ACTH-like immunoreactive perikarya. The results obtained are consistent with the hypothesis that ACTH in the brain acts as a synaptic regulator or transmitter, contributing not only to long projection pathways but also to a local circuit in the arcuate nucleus where ACTH cell bodies are localized.

Adrenocorticotropic Hormone↗

Biotransformation of cibenzoline to 2-(2,2-diphenylcyclopropyl)-1H-imidazole.

A microsomal metabolite of cibenzoline, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole butanedioate, was identified by n.m.r. as the 4,5-dehydro analogue, 2-(2,2-diphenylcyclopropyl)-1H-imidazole. Three dogs dosed orally with 13.8 mg/kg 14C-cibenzoline base excreted 1.8-3.5% of the dose as this metabolite in the urine. Mean plasma concentrations of cibenzoline reached a peak of 1.5 micrograms/ml at 2 h while mean concentrations of the metabolite of 0.4-0.5 micrograms/ml were found between 2 and 7 h. The metabolite was synthesized and found to decrease the frequency of ventricular premature depolarizations in conscious dogs having a two-stage occlusion of the left anterior descending coronary artery performed 48 h before. It did not inhibit ventricular arrhythmia in rats induced by i.v. infusion of aconitine. Thus, in contrast to cibenzoline, the metabolite does not appear to be a true antiarrhythmic agent.

Animals↗

Metabolites of an antipsychotic chiral pyrroloisoquinoline and their effect on prolactin secretion in the rat.

Racemic-2, 6-dimethyl-3-ethyl- 4,4a,5,6,7,8,8a, 9-octahydro-4a,8a-trans-1H-pyrrolo[2, 3-g]isoquinoline-4-one hydrochloride (rac-l HCl) appeared to be equipotent to haloperidol in increasing serum prolactin levels in rats although only about one-twentieth as potent as haloperidol in reversing dopamine-inhibited prolactin release by rat anterior pituitary cells in vitro. The metabolism of 14C-labeled rac-l HCl was studied in rats and the activity of metabolites was evaluated in the in vitro prolactin release assay. Four metabolites, two C11-monohydroxy diastereomers and one C10-and one C12-monohydroxy metabolite, plus parent drug were isolated from the urine of rats administered [14C]rac-l HCl. These were shown to be optically active, indicating that the racemic drug was stereoselectively metabolized. All of the identified metabolites plus those in extracts of urine and feces proved inactive in the in vitro prolactin release assay. In addition, the brains of three rats removed 1 hr after single 3.6 mg/kg oral doses of [14C]rac-l HCl contained essentially only unchanged drug. We conclude that the potency of rac-l HCl in raising serum prolactin levels is not due to the formation of active metabolite(s) in vivo.

Animals↗

Cholecystokinin in the nucleus of the solitary tract of the rat: evidence for its vagal origin.

Nerve fibers and terminals immunoreactive for cholecystokinin (CCK) were demonstrated in the nucleus of the solitary tract (NTS) of the rat using light and electron microscopic immunocytochemistry. The following morphological and biochemical evidence suggests that CCK in the NTS seems to be of extrinsic, most probably vagal, origin: (1) axon fragments of the intracranial vagus were identified by immunostaining on their way to the solitary tract: (2) CCK-immunostaining could be localized in nerve terminals in the nucleus of the solitary tract, where only a very few immunopositive dendrites or cell bodies were present; and (3) transecting the major neuronal afferents (via solitary tract and/or more laterally) resulted in a complete disappearance of radioimmunoassayable CCK from the nucleus of the solitary tract.

Animals↗

Intrinsic vasoactive intestinal polypeptide (VIP)-containing neurons in the baroreceptor nucleus of the solitary tract in rat.

Vasoactive intestinal polypeptide (VIP)-immunoreactive cell bodies, dendrites and nerve terminals in the nucleus of the solitary tract have been identified with electron microscopic immunocytochemistry in rats. The relatively high concentration of VIP in this nucleus, which corresponds to the primary baroreceptor center, was depleted only insignificantly by uni- or bilateral transection of the solitary tract, which eliminates peripheral neuronal (via glossopharyngeal and vagal nerves) input to the nucleus. Both immunocytochemical and biochemical data suggest that the majority of VIP in the nucleus of the solitary tract is present in intrinsic neurons.

Animals↗

Simultaneous characterization of pre- and postsynaptic neuron contact sites in brain.

The combined application of electron microscopic study of nerve degeneration and immunocytochemical techniques enables both pre- and postsynaptic structures of central nervous system synapses to be characterized simultaneously. Information obtained from a model experiment is presented to indicate the usefulness of the method. After the surgical transection of the ventral noradrenergic bundle in rats, degenerating boutons of brainstem axons were demonstrated on luteinizing hormone-releasing hormone-positive and adrenocorticotropic hormone-positive neurons in the hypothalamic arcuate nucleus.

Animals↗

Microbial products. VI Five novel metabolites related to benz[a]anthracene from an unidentified actinomycete designated X-14881.

Five metabolites of actinomycete X-14881 were isolated from the fermentation broth and characterized. The major component was identified as [3R-(3 alpha,6a beta,7 beta,12 alpha,12a alpha)] or [3S-(3 beta,6a alpha, 7 alpha,12 beta,12a beta)]-6a, 7,12-trihydroxy-3,4,6a, 7,12, 12a-hexahydro-8-methoxy-3-methylbenz[a]-anthracen-1(2H)-one; the other four are closely related derivatives thereof.

Actinomycetales↗

Bradycardia following injection of 6-hydroxydopamine into the intermediate portion of nucleus tractus solitarius medialis.

Studies were carried out to determine the effects of selective destruction of the catecholamine innervation of the intermediate portion of the nucleus tractus solitarius medialis (NTSm) on mean arterial pressure and heart rate in conscious rats. Following bilateral injections of 6-hydroxydopamine into the intermediate portion of NTSm, animals demonstrated a prolonged bradycardia, but no changes in mean arterial pressure or mean arterial pressure lability, when compared with controls. Results indicate that the baroreceptor reflex loop which mediates bradycardia is sensitive to impulses from catecholamine axons entering the intermediate NTSm.

Animals↗

Acyltransferase activity and cytochemical localization in differentiating neuroblastoma.

Acyltransferase (AT) enzyme activity was assayed biochemically and localized cytochemically in neuroblastoma monolayers to investigate the possible role of the enzyme in neuroblastoma differentiation and neurite extension. Treatment of cultures for 1 day with serum-free medium or Ro20-1724, a cyclic AMP phosphodiesterase inhibitor, induced neurite outgrowth but did not alter acyltransferase activity. Treatment for 4 days with dexamethasone or Ro20-1724 induced neurite outgrowth and a doubling of enzyme activity per cell. Chromatographic separation of lipid classes indicated that dexamethasone enhanced triacylglyceride synthesis. Acyltransferase was localized in mitochondria of neuroblastoma cells. The results show that 1) dexamethasone stimulates the storage lipid metabolic pathway in neuroblastoma cells and 2) increased acyltransferase activity is concomitant with dexamethasone-induced morphological differentiation. However, AT activity and neurite extension may not be causally related.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗