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Biomedical subjects

T M Scott

Publications and source records attributed to T M Scott.

At least 37 records · Page 2Linked to original sources

The L-name-resistant component of acetylcholine-induced relaxation of the rat superior mesenteric arterial bed is innervation-dependent.

Using L-NAME and the potassium channel blocker apamin we have investigated the component of acetylcholine-induced vascular relaxation lost when the mesenteric arterial bed is denervated. We have confirmed that vascular denervation produces a reduction of up to 35% in the ability of ACh to cause relaxation in the presence of the alpha agonists methoxamine and cirazoline. A single 30 minute exposure to L-NAME reduced the relaxation to ACh by up to 44% in control vascular preparations and by 85% in denervated preparations. In control preparations, prolonged exposure to L-NAME reduced the relaxation to ACh by up to 66% and by 77% in the presence of apamin. In denervated preparations prolonged exposure to L-NAME reduced the relaxation to ACh by 96%. The almost complete loss of acetylcholine-induced relaxation following prolonged exposure to L-NAME (96.6% in methoxamine and 93.9% in cirazoline) in denervated preparations suggests that innervation is involved in the expression of the L-NAME-resistant relaxation to acetylcholine in the superior mesenteric arterial bed of the rat.

Acetylcholine↗

Deficits in short-term memory in posttraumatic stress disorder.

OBJECTIVE: The purpose of this study was to compare the memory function of patients with posttraumatic stress disorder (PTSD) to that of matched comparison subjects. METHOD: Vietnam veterans with combat-related PTSD (N = 26) were compared to physically healthy comparison subjects (N = 15) matched for age, race, sex, years of education, handedness, socioeconomic status, and alcohol abuse. Memory and intelligence were assessed with a battery of neuropsychological tests, including the Russell revision of the Wechsler Memory Scale, the Selective Reminding Test, and subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). RESULTS: The PTSD patients scored significantly lower than the comparison subjects on the Wechsler Memory Scale logical memory measures for immediate recall (mean = 11.6, SD = 3.3 versus mean = 20.9, SD = 6.6) and delayed recall (mean = 8.0, SD = 3.3 versus mean = 17.8, SD = 6.4). The PTSD patients also scored significantly lower on the total recall, long-term storage, long-term retrieval, and delayed recall measures for the verbal component of the Selective Reminding Test and on the recall, long-term storage, long-term retrieval, and continuous long-term retrieval measures for the visual component of the Selective Reminding Test. There was no significant difference between the PTSD patients and comparison subjects in prorated full-scale IQ as measured by the WAIS-R. CONCLUSIONS: Patients with PTSD may have deficits in short-term memory. Counseling and rehabilitation that address these deficits may be of value for PTSD patients.

Humans↗

How we teach anatomy efficiently and effectively.

An anatomy course is presented which stresses the teaching of applied anatomy using lectures, laboratory workshops and problem-solving tutorials. Laboratory workshops include the use of prosected specimens and body imaging such as CT scan and ultrasound, but do not include dissection. The problem-solving tutorials make extensive use of clinical cases and the application of anatomical knowledge. The course is taught by anatomists and practising physicians, and needs only 98 hours of curriculum time. The performance of the students and the positive attitudes of both students and faculty are enhanced by the design of the course.

Anatomy↗

Quantitative magnetic resonance imaging in temporal lobe epilepsy: relationship to neuropathology and neuropsychological function.

Magnetic resonance images (MRIs) were obtained from 25 patients with medically refractory epilepsy of temporal lobe origin (12 on the left, 13 on the right) and 14 right-handed control subjects. The hippocampi and temporal lobes were traced by computer on successive coronal images and the resulting measurements of area were summed for each region. The left and right hippocampi were symmetrical in the control subjects; however, for patients the hippocampus was smaller on the side of the seizure focus. Moreover, the left-right hippocampal ratio significantly differentiated the control subjects from each patient group. The left temporal lobe was significantly smaller than the right in control subjects. The epileptics' temporal lobes were smaller on the side of the seizure focus, compared to the temporal lobes in the control subjects. MRI hippocampal measurements were compared to hippocampal neuronal densities obtained postoperatively. Significant correlations were obtained between the ratio (side ipsilateral to focus/side contralateral to focus) of MRI hippocampal measurements and neuronal densities in all hippocampal subfields except CA2. Prior to surgery, patients were administered the Wechsler Memory Scale and the verbal Selective Reminding Test. Significant correlations existed between MRI measurements of the left hippocampus and the Wechsler logical memory percent retention scores and between the left temporal lobe measurements and the verbal Selective Reminding Test scores for patients with seizure foci in the left temporal lobe.

Adolescent↗

Perivascular innervation is lost in experimental atherosclerosis.

Nerve fibers, immunohistochemically positive for neuropeptide Y, tyrosine hydroxylase, calcitonin gene-related peptide and substance P, form a perivascular network surrounding the carotid arteries of New Zealand White rabbits. Transmission electron microscopy demonstrates that the nerve fibers are primarily located at the adventitial-medial border. Placing a silastic collar around a carotid artery for 14 days, in rabbits fed a diet high in cholesterol, resulted in a focal, intimal thickening in 10 out of 12 rabbits. Contralateral sham-operated arteries showed no intimal thickening. At sites where intimal thickening occurred, there was a disappearance of the perivascular nerve network. The carotid arteries from rabbits that did not respond to the collar and the sham-operated carotid arteries showed an intact and normal perivascular nerve network. In the group of animals which responded to the collar with intimal thickening, there was evidence of a proliferative response proximal to the collar and in this same tissue there was evidence of degeneration of nerve fibers. In conclusion, it has been demonstrated for the first time that, in regions of the carotid artery where intimal thickening occurred, there was an associated degeneration of the perivascular nerve network. The cause of this degeneration and its functional consequences require further investigation.

Animals↗

Peptidergic nerve involvement in the control of endothelium-dependent vascular relaxation.

The ability of Acetylcholine (ACh) and A23187 to induce endothelium-dependent relaxation was compared in the isolated perfused mesenteric arterial bed of untreated adult rats, adult rats treated neonatally with capsaicin, and adult rats treated as adults with capsaicin. Following neonatal capsaicin treatment, the response to both agents was reduced. Following adult treatment, the response to both agents was reduced seven days following capsaicin treatment. The same results were obtained in the presence of L-arginine or indomethacin. Tissues from all rats responded equally to sodium nitroprusside. Following capsaicin treatment no change in the structural relationship of the arterial intima was detected but no perivascular nerve fibres immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP) could be demonstrated. It is suggested that the reduced response to ACh and A23187 does not involve a change in endothelial muscarinic receptors or a structural change in the arterial intima, but is directly related to the absence of immunohistochemically demonstrable CGRP/SP-containing perivascular innervation.

Acetylcholine↗

Capsaicin-sensitive nerves influence the release of atrial natriuretic factor by atrial stretch in the rat.

Although many factors may modulate the release of atrial natriuretic factor (ANF), the primary mechanism has been demonstrated to be atrial stretch. Recent studies have led to the suggestion that the peptidergic innervation of the heart, through the release of peptides, may be involved in the control of ANF secretion. We have examined the influence of chronic capsaicin treatment on three models of atrial stretch that release ANF. This treatment inhibited ANF released through in vivo blood volume expansion and through balloon inflation in the right atrium of in vitro isolated perfused hearts. Immunohistochemical and electron microscopical analysis confirmed the absence of innervation of the heart by calcitonin gene related peptide and substance P immunoreactive nerve fibres and apparent lack of effect on atrial granules in capsaicin treated rats. We conclude that capsaicin-sensitive cardiac innervation is a component modulating the release of ANF, stimulated by atrial stretch in the rat.

Animals↗

Interrelationships of heterozygosity, growth rate and heterozygote deficiencies in the coot clam, Mulinia lateralis.

Allozyme surveys of marine invertebrates commonly report heterozygote deficiencies, a correlation between multiple locus heterozygosity and size, or both. Hypotheses advanced to account for these phenomena include inbreeding, null alleles, selection, spatial or temporal Wahlund effects, aneuploidy and molecular imprinting. Previous studies have been unable to clearly distinguish among these alternative hypotheses. This report analyzes a large data set (1906 individuals, 15 allozyme loci) from a single field collection of the coot clam Mulinia lateralis and demonstrates (1) significant heterozygote deficiencies at 13 of 15 loci, (2) a correlation between the magnitude of heterozygote deficiency at a locus and the effect of heterozygosity at that locus on shell length, and (3) a distribution of multilocus heterozygosity which deviates from that predicted by observed single-locus heterozygosities. A critical examination of the abovementioned hypotheses as sources of these findings rules out inbreeding, null alleles, aneuploidy, population mixing and imprinting as sole causes. The pooling of larval subpopulations subjected to varying degrees of selection, aneuploidy or imprinting could account for the patterns observed in this study.

Alleles↗

The effect of perivascular denervation on endothelium-dependent relaxation to acetylcholine.

We have examined the effect of perivascular denervation on the ability of acetylcholine to produce endothelium-dependent relaxation in the isolated perfused mesenteric arterial bed. Treatment with capsaicin prevented the development of substance P and calcitonin gene-related peptide containing perivascular nerve fibres. Treatment with 6-hydroxydopamine prevented the development of catecholaminergic perivascular nerve fibres. In the arterial beds from capsaicin treated rats there was a depression of the ability of Acetylcholine to produce endothelium dependent relaxation. No change in endothelium-dependent relaxation to ACh was found in 6-hydroxydopamine treated rats.

Acetylcholine↗

The peptidergic innervation of the developing mesenteric vascular bed in the rat.

We have followed the development of perivascular nerve fibres using antisera to substance P, calcitonin gene related peptide, neuropeptide Y and vasoactive intestinal polypeptide in the mesenteric vascular bed of developing Sprague-Dawley rats. The pattern and density of innervation appeared to be determined by one week of age. The pattern of innervation by SP- and CGRP-positive fibres was similar. The pattern of innervation by neuropeptide Y-containing fibres was distinct from that of SP and CGRP. The VIP-positive fibre plexus was sparse and irregular compared with the others examined. The density of innervation by all fibre types was highest in the jejunal arteries.

Animals↗

The interaction between catecholaminergic and peptidergic perivascular nerve fibres in the innervation of the rat mesenteric vascular bed.

The interaction between catecholaminergic and peptidergic fibres innervating the rat mesenteric vascular bed was investigated by independently inhibiting the development of one or other system. Through examination of electron microscopic and immunohistochemical preparations it was determined that an increased density of catecholaminergic innervation occurred in the absence of peptidergic innervation, but that a decreased density of peptidergic innervation occurred in the absence of catecholaminergic innervation. These results indicate an interaction between the two systems which may take place directly, indirectly through a third factor, or in the case of a decrease in density directly through the loss of mixed fibre bundles normally formed predominantly by one fibre type.

Animals↗

The relationship between innervation and arterial structure in late prenatal and early postnatal development of the rat jejunal artery.

The peripheral nervous system exerts a trophic influence on target tissues. We have examined the development of the perivascular innervation of the rat jejunal artery and correlated the simultaneous development of the endothelium and medial smooth muscle. Before birth a close relationship exists between endothelial cells and the first layer of differentiating medial smooth muscle, whereas the nerve fibres at this stage are formed into large remote bundles. After birth the differentiation of the media continues and the endothelial cells become separated from the smooth muscle by a thick internal elastic lamina. The nerve fibres grow from the large peripheral bundles to reach the smooth muscle as small bundles or individual fibres, with those immunoreactive to anti-calcitonin gene-related peptide being best developed by birth. From these studies it would seem that it is unlikely that perivascular nerve fibres influence the early development of the arterial wall, but they suggest that endothelial cells are more likely to be involved.

Actin Cytoskeleton↗

The differential contribution by individual enzymes of glycolysis and protein catabolism to the relationship between heterozygosity and growth rate in the coot clam, Mulinia lateralis.

The locus-specific effects of heterozygosity upon individual growth rate were determined for 15 polymorphic enzymes among 1906 individuals from a single cohort sample of the marine bivalve Mulinia lateralis. Two measures of individual growth rate (total wet weight and shell length) were made at collection and after a period of growth in the laboratory. The correlation between heterozygosity and growth rate was independently determined for each locus using multiple linear regression, thereby providing a rank of individual locus effects; these differed significantly. The four estimated rankings of relative locus effects (initial length, initial weight, length added in the laboratory, and added weight) were not statistically different. That is, a locus with a large effect of heterozygosity on growth rate in nature had a similarly large effect on laboratory growth rate. The effect of a locus was not related to heterozygosity per se; some highly heterozygous loci had no detectable correlation with growth rate. The data contained two pairs of relatively tightly linked loci; in both cases one locus of a pair had significant effects on growth rate, while the other had no effect. Loci with large and significant correlations with growth rate synthesize enzymes which function in protein catabolism or glycolysis; heterozygosity in enzymes of the pentose shunt, redox balance, or other miscellaneous metabolic roles was not correlated with growth rate. Since the metabolic basis for the correlation is known to derive from individual differences in net energy status, particularly energetic costs of whole-body protein turnover, these data indicate that phenotypic effects (e.g., variation in growth rate) are determined by heterozygosity at the studied genes, not other linked loci.

Animals↗

Parallel expression of the MB19 genetic polymorphism in apoprotein B-100 and apoprotein B-48. Evidence that both apoproteins are products of the same gene.

Immunochemical studies have demonstrated that apoprotein B-100 and apoprotein B-48 share some antigenic determinants, but whether they are products of the same gene has remained uncertain. Utilizing a specific mouse monoclonal antibody, MB19, we recently characterized a common form of genetic polymorphism that was expressed in apo-B-100 (Young, S. G., Bertics, S. J., Curtiss, L. K., Casal, D. C., and Witztum, J.L. (1985) Proc. Natl. Acad. Sci. U.S.A., in press). Antibody MB19 binds different allotypes of apo-B-100 (MB19(1) and MB19(2] with high and low affinities, respectively. Compared to a rabbit antiserum against human low density lipoprotein, which detects 100% of apo-B mass in all individuals, antibody MB19 detects 100% of apo-B with allotype MB19(1) but less than 10% of apo-B with allotype MB19(2). Western blots demonstrate that MB19 binds to both apo-B-100 and apo-B-48. To determine if apo-B-48 and apo-B-100 from the same individual express the same polymorphism, chylomicrons and very low density lipoproteins were isolated from 23 subjects in whom the allotypes of apo-B-100 were known. Delipidated apoproteins were separated electrophoretically and then transferred to nitrocellulose membranes. Nitrocellulose membranes were incubated with 125I-MB19 (to detect the polymorphism) and 131I-antiserum to human apo-B (to quantitate total apo-B transferred to nitrocellulose membranes). Apo-B-100 and apo-B-48 bands were removed and the ratio of 125/131 counts in each band was calculated. In all 23 subjects studied, the same MB19 polymorphism was present in both apo-B-100 and apo-B-48. This observation provides strong evidence that both apoproteins are products of the same gene.

Adult↗

Vascular and neural changes in the rat optic nerve following induction of diabetes with streptozotocin.

This study was undertaken to determine whether or not changes occur in blood vessels, axons or glia of the optic nerve as the result of streptozotocin-induced diabetes. Diabetes was induced in 4 weeks old Sprague-Dawley rats. At 12 and 16 weeks of age, the rats were killed and the optic nerves prepared for examination. The number and density of blood vessels was found to be significantly increased in the diabetic rats. No alteration in the structure of the blood vessels was noted. A decrease in the percentage volume of axons and an increase in the percentage volume of glial elements accompanied the increase in blood vessels in the diabetic rats. No difference was found in the spectrum of fibre diameters.

Animals↗