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Biomedical subjects

T Lyon

Publications and source records attributed to T Lyon.

9 recordsLinked to original sources

Localization and pharmacological characterization of pigeon diazepam-insensitive GABAA receptors.

Transduction mechanisms associated with ligand binding at diazepam-insensitive subtypes of GABAA receptors remain largely unknown, but unique behavioral effects of ligands binding at these sites have been reported in pigeons. The present study further evaluated the pharmacological characteristics of diazepam-insensitive GABAA receptors in pigeon brain, using [3H]Ro 15-4513. Autoradiography detected diazepam-insensitive benzodiazepine sites on GABAA receptors in a number of brain regions, with the highest densities present in the olfactory bulb, hippocampus, thalamic nuclei and cerebellar granule cell layers, with densities of approximately 10-20% of total benzodiazepine receptor binding. Saturation analysis revealed significant densities (approximately 10% of total benzodiazepine receptor binding) of extracerebellar diazepam-insensitive benzodiazepine receptors in optic lobe, hippocampus, and brainstem compared to 27% in cerebellum. As reported for mammalian diazepam-sensitive benzodiazepine receptors, GABA (50 microM) generally increased the affinities of agonists and partial agonists, had little effect on the affinities of antagonists, and decreased the affinity of an inverse agonist for pigeon cerebellar diazepam-sensitive benzodiazepine receptors. GABA modulation of ligand binding to diazepam-insensitive benzodiazepine receptors was less than that observed for diazepam-sensitive sites, and no positive modulation was observed. These results demonstrate the presence of cerebellar and extracerebellar diazepam-insensitive benzodiazepine receptors in pigeon brain, with distribution patterns and pharmacology similar to those reported in mammals. The comparable central localization and pharmacological properties of drugs at diazepam-sensitive and -insensitive benzodiazepine receptors in pigeons and rats attests to the evolutionary conservation of GABAA systems.

Affinity Labels↗

Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines.

p21/WAF1/CIP1/SDI1 is an important cell-cycle mediator with tumor suppressor gene capabilities, and its inactivation could potentially lead to tumor progression. Because tumor suppressor genes are commonly inactivated by somatic and germline mutations, we analyzed a variety of human tumor cell lines for p21 mutations. We used single-strand conformational analysis and direct sequencing to identify possible mutations in the p21 coding region. Two base-alterations were observed in 41 immortalized human tumor cell lines. A previously reported polymorphism that results in a serine-to-arginine amino-acid substitution at codon 31 was found in 24% (10 of 41) of the tumor cell lines but was also found in 10% (six of 62) of normal parental DNAs tested and 7% (three of 43) of normal DNAs from patients with primary endometrial tumors. Another nucleotide substitution found at codon 80 resulted in the replacement of threonine with methionine. Codon 80 changes were found in 7% (three of 41) of the tumor cell lines (all endometrial) and in 2% (one of 62) of the normal parental DNAs. This change was not found in any of the primary endometrial tumors examined. The biological activity of these base changes was analyzed by using in vitro cyclin-dependent kinase 2-cyclin A kinase assays and calcium phosphate transfections. We observed that wild-type p21 and the p21 variants had similar growth-inhibitory abilities. Thus, our results suggest that mutation of the p21 gene is not prevalent in human tumor cell lines and is not a probable mechanism of inactivation of this gene.

Base Sequence↗

Patients with femoral neck and intertrochanteric fractures. Are they the same?

A prospective analysis was performed involving 680 geriatric patients with hip fractures to determine whether the demographic profile of patients with femoral neck fractures was similar to that of patients with intertrochanteric fractures. All patients were community dwelling, cognitively intact, previously ambulatory elderly with femoral neck or intertrochanteric fracture. Three hundred fifty-eight patients (52.6%) sustained a femoral neck fracture; 322 (47.4%), an intertrochanteric fracture. Patients with an intertrochanteric fracture were significantly older, more likely to be limited to home ambulation, and were more dependent regarding basic and instrumental activities of daily living. After stratification by gender and adjustment for age, these differences remained significant in women only. There were no differences in age, prefracture ambulatory ability, or dependence in activities of daily living in men with either type of fracture.

Activities of Daily Living↗

Chronic exposure to benzodiazepine receptor ligands uncouples the gamma-aminobutyric acid type A receptor in WSS-1 cells.

Chronic exposure to benzodiazepines can result in an "uncoupling" of gamma-aminobutyric acid (GABA) receptors and benzodiazepine receptors (BzR) both in primary neuronal cell cultures and in vivo. The effect of chronic exposure to BzR ligands was examined in an engineered cell line (WSS-1) stably expressing "type I" GABAA receptors. Chronic exposure to flurazepam produced a concentration- (EC50, approximately 1.1 microM after a 48-hr exposure) and time-dependent (t1/2, approximately 3 hr at 100 microM) reduction in the efficacy (Emax) of GABA to enhance [3H]flunitrazepam binding to BzR, a characteristic of uncoupling in native GABAA receptor isoforms. Uncoupling of GABAA receptors and BzR without concomitant changes in BzR density was also produced by chronic exposure to other, structurally diverse, BzR ligands, including Ro 15-1788 and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, but was not manifested after exposure to the 5-hydroxytryptamine reuptake blocker fluoxetine. Chronic (12-48-hr) exposure to flurazepam did not remarkably alter levels of alpha 1 and gamma 2 mRNAs, which constitute GABAA receptors in this cell line. Based on these findings, it is hypothesized that uncoupling of GABAA receptors and BzR in this engineered cell line can proceed without the elaboration of additional novel subunits and could involve either post-translational modification of GABAA receptor proteins or changes in subunit stoichiometry.

Cell Line↗

The Neer classification system for proximal humeral fractures. An assessment of interobserver reliability and intraobserver reproducibility.

The radiographs of fifty fractures of the proximal part of the humerus were used to assess the interobserver reliability and intraobserver reproducibility of the Neer classification system. A trauma series consisting of scapular anteroposterior, scapular lateral, and axillary radiographs was available for each fracture. The radiographs were reviewed by an orthopaedic shoulder specialist, an orthopaedic traumatologist, a skeletal radiologist, and two orthopaedic residents, in their fifth and second years of postgraduate training. The radiographs were reviewed on two different occasions, six months apart. Interobserver reliability was assessed by comparison of the fracture classifications determined by the five observers. Intraobserver reproducibility was evaluated by comparison of the classifications determined by each observer on the first and second viewings. Kappa (kappa) reliability coefficients were used. All five observers agreed on the final classification for 32 and 30 per cent of the fractures on the first and second viewings, respectively. Paired comparisons between the five observers showed a mean reliability coefficient of 0.48 (range, 0.43 to 0.58) for the first viewing and 0.52 (range, 0.37 to 0.62) for the second viewing. The attending physicians obtained a slightly higher kappa value than the orthopaedic residents (0.52 compared with 0.48). Reproducibility ranged from 0.83 (the shoulder specialist) to 0.50 (the skeletal radiologist), with a mean of 0.66. Simplification of the Neer classification system, from sixteen categories to six more general categories based on fracture type, did not significantly improve either interobserver reliability or intraobserver reproducibility.

Evaluation Studies as Topic↗

Pudendal nerve palsy induced by fracture table.

There are 23 cases in the literature of fracture table-induced pudendal nerve palsy. The majority of these patients had full sensory return; however, return of sexual function was unpredictable. The relevant anatomy, etiology, and incidence of this complication are discussed, and suggestions are made for its prevention.

Female↗

Effects of soft tissue mobilization (Rolfing pelvic lift) on parasympathetic tone in two age groups.

The effects of a soft tissue mobilization procedure, the Rolfing pelvic lift, on parasympathetic tone was studied in healthy adult men. Parasympathetic tone was assessed 1) by quantifying the amplitude of the respiratory sinus arrhythmia from the heart rate pattern and 2) by measuring heart rate. Heart rate patterns were assessed during the pelvic lift and during the durational touch and baseline control conditions. Two groups of healthy subjects were tested: Group 1 contained 20 subjects aged 26 to 41 years, and Group 2 contained 10 subjects aged 55 to 68 years. In Group 1, the pelvic lift elicited a somatovisceral-parasympathetic reflex characterized by a significant increase in parasympathetic tone relative to durational touch and baseline conditions. Group 2 did not exhibit a parasympathetic change during the pelvic lift. The results of this study contribute to our understanding of pelvic mobilization techniques and may help to explain why these techniques have been clinically successful in treating myofascial pain syndromes and other musculoskeletal dysfunctions characterized by reduced parasympathetic tone and excessive sympathetic activity.

Adult↗

The influence of acromioclavicular joint morphology on rotator cuff tears.

A detailed anatomic study of 123 shoulders was performed to define the location of the acromioclavicular (AC) joint within the supraspinatus outlet and to determine the correlation of AC joint morphologic characteristics with the presence of full-thickness rotator cuff tears (RCTs). The presence, location, and extent of RCTs were first documented for each shoulder, and 2 anatomic landmarks consisting of the anterolateral acromial corner and the inferior midpoint of the AC joint were identified and their positions digitized in 3 dimensions to calculate outlet space and clearance and AC joint locations. High resolution x-ray films were then obtained to determine the extent of degenerative changes including the location and size of inferior osteophytes and joint space. These specimens were cleaned of all soft tissues, and additional measurements were made. All data were entered into a computerized database and analyzed with respect to age, sex, and the presence of RCT. Comparison of age-matched RCT versus non-RCT groups revealed no significant differences in the position of the AC joint within the supraspinatus outlet. When AC joint morphologic characteristics were compared with those of a nontear, age-matched group, no significant differences with regard to joint space narrowing were found, but significantly larger and greater number of osteophytes were identified on both sides of the joint in the RCT group. In conclusion, the position of the AC joint is fairly constant within the supraspinatus outlet and does not appear to predispose to RCTs. The morphology of the AC joint contribution of the tears seems to be acquired in nature rather than inherent in its location within the outlet.

Acromioclavicular Joint↗