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Biomedical subjects

T H Williams

Publications and source records attributed to T H Williams.

At least 91 records · Page 5Linked to original sources
PubMed1979

Enzymatic and immunological evidence for two forms of carnosinase in the mouse.

Carnosinase (aminoacyl-L-histidine hydrolase, EC 3.4.13.3) hydrolyzes the dipeptide carnosine (beta-alanyl-L-histidine), which is thought to play a role in cerebral and skeletal muscular function and has been implicated as a neuroaffector in the olfactory bulb. Carnosinase activity is present in many tissues of the mouse including heart, liver and lung, but it is most active in kidney, uterus and nasal olfactory mucosa. Kinetic measurements with 1H-NMR spectroscopy indicate that the enzyme is stereospecific and can hydrolyze L-but not D-carnosine. Anserine is a poorer substrate, while homocarnosine is essentially a non-substrate. However, these two dipeptides are effective inhibitors of the hydrolysis of L-carnosine. Carnosinase activity is unaffected when assayed in 2H2O at 99% isotopic purity. From considerations of the effect of Mn2+ on (1) substrate concentration velocity curves; (2) thermostability, and (3) inhibitor behavior, tissues with carnosinase can be divided into two groups. Kidney, uterus and olfactory mucosa represent one group, while central nervous system, muscle, spleen, etc. represent the second. The validity of this classification is confirmed by immunological evidence. Antiserum prepared against carnosinase purified from kidney cross-reacts with and inhibits the activity of olfactory mucosa, kidney and uterus but not that from central nervous system, heart or liver.

Animals↗
PubMed1979

Ultrastructural evidence for remodelling in a central noradrenergic pathway following electrolytic lesioning.

Electrolytic lesions were carried out in the medial hypothalamus of adult rats to study remodelling responses in a central noradrenergic pathway, the medial forebrain bundle. Four days, two weeks, 4 weeks and 8 weeks post-lesion, the animals were perfused and processed for correlated fluorescence microscopic (FM) and electron microscopic (EM) study. FM evaluation 4 days post-lesion showed that, compared with control preparations, catecholaminergic fibers became thick, distorted and intensely fluorescent. With increasing survival times the caliber of these fibers became finer and fluorescence intensity was gradually diminished. Some of the small blood vessels in the vicinity of the lesion acquired an intense perivascular fluorescence. Electron microscopic examination of the lesion site 4 days post-lesion disclosed many degenerating axons and increased extracellular space. No increased extracellular space was discerned by 8 weeks post-lesion. After all survival periods greatly enlarged axonal profiles were seen, and these resembled 'growth cones' described in earlier tissue culture, developmental and peripheral nervous system studies.

Adrenergic Fibers↗
PubMed1979

Age as a factor in 6-hydroxydopamine-induced plasticity in the hypothalamus.

The question of age as a possible factor influencing the regenerative response of catecholaminergic varicosities in the hypothalamus was investigated in the supraoptic commissure and the paraventricular, periventricular, and dorsomedial hypothalamic nuclei of rats that had received intraventricular injections of the neurotoxin 6-hydroxydopamine when they were (1) neonates, (2) young adults, or (3) senescent adults. After post-neurotoxin survival for 4, 21, 56, or 180 days, the animals were perfused, and the hypothalamic tissue sections were cut and processed using a glyoxylic acid method for localizing catecholamines. Four days following neurotoxin administration, counts of fluorescent varicosities showed a significant loss of catecholamine varicosities in each of the four areas. Subsequently, at least partial restoration of numbers of catecholamine varicosities occurred in all hypothalamic areas in all three age groups. It is concluded that, following selective lesions induced by the neurotoxin 6-OH-DA, catecholamine varicosities were restored both in immature and mature groups. According to the evidence obtained experimentally, the rate of restoration was greater in the neonate group, whereas the percentage restoration attained varies according to the hypothalamic area studied and the age of the animal.

Age Factors↗
PubMed1979

Novel application of proton nuclear magnetic resonance spectroscopy in the identification of 2'-chloronordiazepam metabolites in the dog.

The only metabolite of 2'-chloronordiazepam, 7-chloro-1,3-dihydro-5-(2'-chlorophenyl)-2H-1,4-benzodiazepin-2-one (1), previously identified in the dog is lorazepam (2), which is a product of 3-hydroxylation. Two phenolic metabolites (3 and 4) in the dog corresponding to 4'-hydroxylation of the 5-phenyl ring and 9-hydroxylation of the fused benzene ring, respectively, have now been identified. The structure of the 9-hydroxy isomer 4 is deduced simply from the observed NMR spectral AB (J meta = 2.5 Hz) pattern of the protons of the fused benzene ring. In contrast, since a 2'-chloro substituent is present on the 5-phenyl ring of the parent drug, the usual method of recognizing 4'-hydroxylation of this ring by observation of AA'BB' multiplets in the proton nuclear magnetic resonance (1H NMR) spectra is inapplicable. Hence, a novel method is introduced to identify the 4'-hydroxy isomer 3, based on attributing different sets of NMR substituent effect parameters to hydroxyl groups, depending on whether these groups are meta or para to the benzodiazepinimine function. The urinary plus fecal excretion of 2-4 by one dog given in a single oral 10 mg/kg dose of 14C-labeled 1 amounted to 20, 5, and 7% of the dose, respectively; the urinary metabolites were excreted predominantly as conjugates of glucuronic acid and/or sulfate.

Animals↗
PubMed1979

Evidence for autonomic paraneurons in sympathetic ganglia of a shrew (Tupaia glis).

The morphological relationships between blood vessels and the small monoamine-storing cells have been studied in the superior sympathetic ganglia of Tupaia. Substantial clusters of these cells were found to be associated anatomically with vascular loops or glomeruli. Blood from these glomeruli enters the capillary bed that supplies principal ganglionic neurons. Thus the vascular path for catecholamine transportation is rather clearly defined in Tupaia, providing new morphological evidence for the existence of a portal system for conveying catecholamine from clusters of paraneurons to principal ganglionic neurons. On the basis of vesicle criteria, two populations of small, granule-containing cell were distinguished, and both were encountered in the same cluster. On the basis of fluorescence microscopy, the relatively small number (14.3%) of solitary SIF cells may be true interneurons because, although there has been no electron microscopic identification of efferent synapses, their processes are much longer than those of the paraneurons.

Animals↗
PubMed1978

SIF cells, cyclic AMP responses, and catecholamines of the guinea pig superior cervical ganglion.

The superior cervical ganglion (SCG) of the guinea pig has been investigated by a multidisciplinary approach. Dopamine (50 micron) produced no increase in cyclic AMP levels above control values of 27.9 pmole/mg protein, but 50 micron isoproterenol produced cyclic AMP levels of 210 pmole/mg protein, indicating the existence of a beta-adrenergic receptor-adenylate cyclase complex. The SIF cells were studied by fluorescence histochemistry, which indicated that two morphological types were present. A few Type I cells of the guinea pig SCG were solitary, but most were present in clusters containing many Type II cells. Immunohistochemical localization of antibodies to dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) demonstrated that types of SIF cell localize antibodies to DBH but not PNMT, providing strong evidence that norepinephrine is the neurotransmitter for all the SIF cells of the guinea pig SCG. Determination of the ratio of norepinephrine to dopamine confirmed that no other dopamine pools exist in the guinea pig SCG.

Adenylyl Cyclases↗
PubMed1978

Electronmicroscopic identification of type C particles in cultured murine neuroblastoma.

Monolayer of murine neuroblastoma were treated with dexamethasone and examined by electronmicroscopy. Most of the treated cells were morphologically differentiated and exhibited type C virus particles which were budding from the cell surface. This in vitro system may be of great value for exploring the oncogenic potential of the virus, and its possible role in cell differentiation.

Animals↗
PubMed1978

Interneurons of sympathetic ganglia: divergent cyclic AMP responses and morphology in cat and cow.

The biochemical properties of the small, intensely fluorescent (SIF) cells of bovine and feline superior cervical ganglia were determined by studying the cyclic AMP responses to incubation in vitro with adrenergic agonists: the morphological properties were studied by fluorescence histochemistry and electron microscopy. Incubation with 50 micron dopamine elicited cyclic AMP levels 524% of control values in the bovine ganglion, but only 152% in the feline ganglion (a value which is not statistically significant). Incubation with 50 micron isoproterenol produced an increase of 356% of control values in the cow, but no increase in the cat. SIF cells were classified into two types by fluorescence histochemistry. The bovine ganglion contained 23.7% Type I (solitary) SIF cells, and 76.3% Type II (clustered) cells, whereas the feline ganglion contained 99.5% Type II cells. Thus the feline ganglion lacks both Type I SIF cells and a dopamine receptor-adenylate cyclase complex. On the basis of biochemical and morphological evidence, we hypothesize that the Type I SIF cell is an interneuron, and infer that the lack of a response to dopamine stimulation in the feline ganglion is caused by a scarcity of interneurons in this species.

Animals↗