Minding your manners.
Explore the source record for details and available documents.
Physician-Patient Relations↗
Biomedical subjects
J R Thomas
Publications and source records attributed to J R Thomas.
Influence of a steroid receptor DNA-binding domain on transcriptional regulatory functions.
We have isolated two independent mutations in the DNA-binding domain of the rat glucocorticoid receptor, P493R and S459A, that implicate DNA binding in the control of attached transcriptional activation domains, either that of the receptor itself or of VP16. The mutants are capable of activating transcription normally, but unlike wild-type receptors, they interfere with particular transcriptional activators in yeast and mammalian cells, and inhibit growth when overexpressed in yeast. The mutant residues reside at positions within the three-dimensional structure of the receptor that could, in principle, transduce structural changes from the DNA-binding surface of the receptor to other functional domains. These findings, together with the salt dependence of specific and nonspecific DNA binding by these receptors, suggest that specific DNA acts as an allosteric effector that directs the functional interaction of the receptor with targets of transcriptional activation and that the P493R and S459A mutants mimic the allosteric effect of specific DNA, allowing the receptor to interact with regulatory targets even in the absence of specific DNA binding.
Allosteric Regulation↗
Telomere fusion as a mechanism for the progressive loss of the short arm of chromosome 11 in an anaplastic Wilms' tumor.
Wilms' tumor (WT) is associated with chromosomal deletions and loss of heterozygosity (LOH) of alleles at 11p13. The authors report the youngest known patient with diffusely anaplastic WT and, to their knowledge, the first case to demonstrate telomeric fusions as a chromosomal mechanism for the loss of bands 11p13 and 11p15 in WT. Recurrent clonal telomeric association (tas) initiated breakage/fusion cycles that resulted in deletions of chromosome bands 11p15, 11p13, and, subsequently, the entire short arm of chromosome 11. In addition, tas involving the long arms of chromosomes 7 and 9 resulted in the subsequent deletion of the long arm of chromosome 7. This report expands the spectrum of chromosomal mechanisms that can account for the loss of alleles on the short arm of chromosome 11 in WT by providing evidence that the progressive loss of critical chromosome regions associated with tumor suppression may occur as a result of chromosomal instability initiated by tas.
Chromosome Deletion↗
Cold-induced perturbation of cutaneous blood flow in the rat tail: a model of nonfreezing cold injury.
Cold-induced alteration of cutaneous blood flow, measured with laser-Doppler flowmetry, was studied in a rat tail model of nonfreezing cold injury (NFCI). The NFCI-inducing condition consisted of prolonged tail immersion in 1 degree water. Before exposure to the injury condition, tail blood flow (laser Doppler flux) during brief 3 degrees immersion showed cold-induced cycles of vasoconstriction followed by cold-induced vasodilation (CIVD). Tail temperature exhibited cyclic patterns similar to blood flow in response to cold water immersion. Cold exposures to 1 degree for 1 or 3 hr induced no systematic change; however, cold exposures of 6 or 9 hr induced profound and long-lasting blood flow and temperature deviations. Following the cold injury condition, CIVD was completely absent and remained absent for several weeks, suggesting that CIVD loss is an important component in development of NFCI. Cold-induced disturbances of cutaneous blood flow in the rat tail consisted of a sequence of distinctive stages analogous to those described in human NFCI. These stages were evidenced initially by several days of reduced blood flow and thermal sensitivity, followed in a week by a hyperemia stage, and later by enhanced vascular and thermal sensitivity. The cutaneous blood flow alterations and sequence of variations following prolonged cold exposure suggest that the rat tail may be a valid model of human NFCI.
Animals↗
Gastrointestinal autonomic nerve tumor presenting as high-grade sarcoma. Case report and review of the literature.
Gastrointestinal autonomic nerve (GAN) tumors, also known as plexosarcomas, are a rare distinct subtype of the gastrointestinal stromal tumors. These tumors are usually histologically low-grade, epithelioid or spindle-cell neoplasms that can be distinguished from the other gastrointestinal stromal tumors on the basis of their unique ultrastructural features. A 66-year-old female presented with a histologically high-grade sarcoma of the small bowel. Ultrastructural studies showed features of a GAN tumor. The light microscopic and ultrastructural features are described. The tumor cells gave strong, diffuse staining for vimentin and synaptophysin, and weak focal staining for neuron-specific enolase and S100. While usually presenting as low-grade neoplasms on histologic examination, this case demonstrates that GAN tumors should be considered in the differential diagnosis of a histologically high-grade sarcoma of the gastrointestinal tract, especially when evidence of smooth muscle, peripheral nerve sheath, or neuroblastic origin is not forthcoming.
Aged↗
Tyrosine reverses a cold-induced working memory deficit in humans.
Acute exposure to cold stress has been shown to impair short-term, or working, memory, which may be related to reduction in, or disruption of, sustained release of brain catecholamines. Administering a supplemental dose of the catecholamine precursor tyrosine may alleviate cold stress-induced memory impairments by preventing cold-induced deficits in brain catecholamine levels. The present experiment determined whether administration of tyrosine would prevent a cold-induced working memory deficit, using a computer-based delayed matching-to-sample (DMTS) memory task. Eight male volunteers performed the DMTS task for 30 min at an ambient temperature of either 4 degrees C (cold) or 22 degrees C following a 30-min preexposure period and 2 h after ingesting 150 mg/kg of L-tyrosine or placebo. Subjects demonstrated a decline in matching accuracy on the DMTS task as delay interval increased, such that matching accuracy following a 16-s delay between sample and comparison stimuli was lower than that following a delay of 2 or 8 s. Consistent with previous research, and relative to 22 degrees C exposure sessions, matching accuracy during 4 degrees C exposure sessions was reduced significantly following placebo administration, which is attributed to the effect of cold exposure on short-term, or working, memory. Administration of tyrosine significantly improved matching accuracy at the longest delay interval most affected by cold exposure, such that matching accuracy in the cold following tyrosine was at the same level as matching accuracy following placebo or tyrosine administration at 22 degrees C. Tyrosine administered prior to 22 degrees C exposure had no effect on DMTS performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of training on gender differences in overhand throwing: a brief quantitative literature analysis.
Explore the source record for details and available documents.
Child↗
"No one is sure what to expect".
Explore the source record for details and available documents.
Cost Control↗
Domestic violence: don't look away.
Explore the source record for details and available documents.
Domestic Violence↗
Quality care for individuals with dual diagnosis: the legal and ethical imperative to provide qualified staff.
An evaluation of the treatment and habilitation services being provided to individuals with dual diagnoses of mental retardation and mental illness was presented. The current status of service delivery is identified as unacceptable. Legal issues relating to the obligation to provide quality services were discussed as were ethical issues relating to where the responsibility for providing such service lies. General ethical principles of nonmaleficence and beneficence were defined, and the codes of ethics for two professional groups were invoked to bolster the position that administrators and supervisors are ultimately responsible for the quality of service provided by their organizations. Recommendations for staff competencies necessary to improve treatment for individuals with dual diagnosis were made.
Art Therapy↗
Health system reform, smoking, and you.
Explore the source record for details and available documents.
Health Care Reform↗
Health care reform, easier?
Explore the source record for details and available documents.
Government Agencies↗
Synthesis and tissue distribution of (m-[125I]iodobenzyl)trozamicol ([125I]MIBT): potential radioligand for mapping central cholinergic innervation.
Racemic (m-iodobenzyl)trozamicol (6, MIBT), a high-affinity vesamicol receptor ligand, was radiolabeled, resolved, and evaluated in rats. Following iv injection, (+)- and (-)-[125I]MIBT achieved initial brain levels of 0.57 and 0.92% dose/g of tissue, respectively. The level of (+)-[125I]MIBT subsequently declined by 74% within 3 h, while that of (-)-[125I]MIBT remained stable for the duration. Ex vivo autoradiographic mapping of (-)-[125I]MIBT distribution in rat brain revealed a pattern which was inconsistent with central cholinergic innervation. However, high levels of (+)-[125I]MIBT were observed over the amygdala, striatum, nucleus accumbens, olfactory tubercle, and nuclei of the fifth and seventh cranial nerves, while moderate to low levels were detected within the cortex, hippocampus, and cerebellum. Thus, the distribution of (+)-[125I]MIBT parallels that of other presynaptic cholinergic markers. Co-injection of (+)-[125I]MIBT with 4-aminobenzovesamicol (2b), a potent vesamicol receptor ligand, reduced the levels of radiotracer in the striatum, cortex, and cerebellum by 58, 35, and 9%, respectively. Thus, (+)-[125I]MIBT binds to vesamicol receptors in vivo. In contrast, coadministration of (+)-[125I]MIBT with haloperidol (0.5 mumol/kg), reduced radiotracer levels in the cortex and cerebellum by 34 and 59%, respectively, while increasing the levels in the striatum by 32%. We conclude that although the distribution of (+)-[125I]MIBT qualitatively reflects cholinergic innervation, a fraction of radiotracer in the cortex and cerebellum is bound to sigma receptors.
Animals↗
Natural killer cell cytotoxicity and T-cell proliferation is enhanced by avoidance behavior.
Natural killer (NK) cell activity and mitogen-stimulated spleenocyte proliferation were measured in rats exposed to stress in the form of avoidable and unavoidable shock. Rats that could avoid shock exhibited higher NK activity than either unshocked controls or rats that could not avoid shock. The latter were yoked to the avoidance rats and thus received the same number and frequency of shocks as did the avoidance group. The increased NK activity in the avoidance group appears due to a higher number of NK cells in this group as compared with those in the control or unavoidable shock groups. Additionally, NK activity was found to be proportional to avoidance response rate, with a majority of animals exceeding the minimal temporal avoidance requirement. Mitogen-stimulated proliferation of spleenocytes was also increased several fold in the group that could avoid shock as compared with that which could not and controls. The difference in NK activity and mitogen-stimulated proliferation could not be ascribed to differences in cortisol levels. The results indicate that behavior which results in the avoidance of aversive stimuli can lead to significant enhancement of immune system competence.
Animals↗
Tyrosine ameliorates a cold-induced delayed matching-to-sample performance decrement in rats.
Exposure to cold stress has been shown to impair short-term, or working, memory which may be related to a reduction in brain catecholamines. Administration of the catecholamine precursor tyrosine may alleviate a cold-stress-induced memory impairment by preventing a deficit in brain catecholamine levels. To test this hypothesis, eight rats performed a delayed matching-to-sample (DMTS) task at an ambient temperature of either 2 degrees C (cold) or 22 degrees C, following intraperitoneal administration of saline or tyrosine (50, 100 or 200 mg/kg). Rats administered saline prior to 22 degrees C exposure demonstrated a characteristic delay gradient in which accuracy decreased as the delay interval between sample and comparison stimuli increased from 1 to 16 s. Consistent with previous research, and relative to 22 degrees C exposure sessions, matching accuracy during 2 degrees C exposure sessions was reduced, which is attributed to the effect of cold on short-term, or working, memory. In particular, during cold exposure sessions matching accuracy was significantly reduced at the longer delay intervals, relative to matching accuracy at 22 degrees C. Additional analysis of cumulative matching errors within sessions showed that during exposure to cold, errors occurred at a constant rate throughout the session, indicating rats' performance was equally debilitated by the stressor over the entire session. During cold exposure sessions, the higher doses of 100 and 200 mg/kg tyrosine significantly improved overall matching accuracy relative to saline, but did not completely reverse the effect of cold exposure, as overall matching accuracy did not increase entirely to levels obtained at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides.
Three iodinated benzamides, 5-7, analogues of the potent acetylcholinesterase inhibitor 1-benzyl-4-[N-[4'-(benzylsulfonyl) benzoyl-N-methylamino]ethyl]piperidine (2), were synthesized and evaluated as potential anticholinesterase agents. All three compounds were found to be three orders of magnitude less potent than the parent compound. However, receptor screening revealed that compounds 5-7 exhibit nanomolar affinity for the sigma binding site. Both [125I]5 and [125I]7 were synthesized and evaluated in rats. Following the intravenous administration of [125I]5 into rats, 1.59% of the injected dose was found in the rat brain within 5 min. The level of radioactivity in the brain remained steady for 2 h, the duration of the study. In contrast, 0.42% of the injected dose was detected in the rat brain following the i.v. injection of [125I]7. Coadministration of either [125I]5 or [125I]7 with 0.5 mumol/kg of haloperidol resulted in a 56-73% reduction in the level of radioactivity in the rat brain, suggesting that these compounds bind to the sigma binding site in vivo. Planar imaging studies with [123I]5 revealed significant accumulation of radioactivity within the monkey brain, with a half-life of 6 h. Compound [123I]5 may be potentially useful for studying sigma receptor distribution in the human brain.
Animals↗