Search PubMed⌕ Search

Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 757 records · Page 42Linked to original sources
PubMed1993

The Drosophila neuralized gene encodes a C3HC4 zinc finger.

The neurogenic genes of Drosophila are required for cell-cell communication that determines the choice between neuronal and epidermal cell fate. Here we report the molecular characterization of the neurogenic gene neuralized (neu) and show that it encodes a protein containing a C3HC4 zinc finger DNA-binding motif. This motif has been previously characterized in a variety of regulatory proteins, including transcription factors, locus-specific Drosophila chromosomal proteins, and oncoproteins. These results suggest a nuclear function for neu in the cell-cell signalling process responsible for inhibiting neuronal determination.

Amino Acid Sequence↗
PubMed1993

Expression of the class III beta-tubulin gene during axonal regeneration of rat dorsal root ganglion neurons.

The effect of peripheral axotomy on the expression of the class III beta-tubulin gene in adult dorsal root ganglion (DRG) neurons was examined. Of the 5 isotypic classes of beta-tubulin expressed in the mammalian nervous system, only the class III beta-tubulin is neuron specific. While information about the expression of several of the tubulin genes during neuronal development and regeneration has become available recently, very little is known about the expression of beta III-tubulin during axonal regeneration. To explore this issue, we examined axotomy-induced changes in beta III-tubulin mRNA levels in adult rat lumbar dorsal root ganglion (DRG) neurons at different times (1-28 days) after unilateral sciatic nerve crush using northern blotting of total RNA and quantitative in situ hybridization. These studies showed an initial decrease in beta III-tubulin mRNA levels in axotomized DRG neurons as compared to contralateral controls at 1 day after injury followed by robust increases in beta III-tubulin mRNA levels relative to contralateral controls from 1 to 4 weeks after injury. We postulate that beta III-tubulin may play an essential role in axonal growth because of its unique neuron-specific pattern of expression and its substantial increase in neurons that have been stimulated to regrow their axons.

Animals↗
PubMed1993

Molecular and genetic characterization of the Drosophila tartan gene.

Here we report the discovery and characterization of the Drosophila tartan gene. tartan is transcribed in an unusual embryonic pattern of intersecting stripes which are generated in response to the anterior-posterior and dorsal-ventral regulatory systems. tartan encodes a putative transmembrane protein containing extracellular leucine-rich repeats characteristic of numerous cell surface receptors and adhesion proteins. Its expression is correlated with aspects of segmentation and neurogenesis, including the formation of neuroblasts, sensory mother cells, and peripheral nerves. Mutants homozygous for a recessive lethal tartan loss-function allele exhibit defects in the position and number of cells within peripheral sense organs, the routing of peripheral nerves, and the organization of commissures within the central nervous system. Mutants are also defective in muscle organization. These results suggest that tartan is required for cell surface interactions important for normal organization of epidermal and subepidermal structures.

Amino Acid Sequence↗
PubMed1993

Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q.

We have used the polymerase chain reaction to map the gene encoding human flavin-containing monooxygenase (FMO) form II (N. Lomri, Q. Gu, and J. R. Cashman, 1992, Proc. Natl. Acad. Sci. USA 89: 1685-1689) to chromosome 1. We propose the designation FMO3 for this gene as it is the third FMO gene to be mapped. The two other human FMO genes identified to date, FMO1 and FMO2, are also located on chromosome 1 (C. Dolphin, E. A. Shephard, S. Povey, C. N. A. Palmer, D. M. Ziegler, R. Ayesh, R. L. Smith, and I. R. Phillips, 1991, J. Biol. Chem. 266: 12379-12385; C. Dolphin, E. A. Shephard, S. F. Povey, R. L. Smith, and I. R. Phillips, 1992, Biochem. J. 286: 261-267). The localization of FMO1, FMO2, and FMO3 has been refined to the long arm of chromosome 1. Analysis of human metaphase chromosomes by in situ hybridization confirmed the mapping of FMO1 and localized this gene more precisely to 1q23-q25.

Base Sequence↗
PubMed1993

Spine and total body bone mineral density and serum testosterone levels in male athletes.

The aim of this study was to compare the effects of intense endurance vs strengthening exercise on bone mass and serum testosterone levels in male athletes. Bone mineral density (BMD) of the total body and spine and serum testosterone levels were measured in male rowers (n = 12), triathletes (n = 8) and sedentary controls (n = 13). The total body scan also gave values for percentage body fat and regional bone densities. Calcium intake and physical activity levels were measured by questionnaire. The rowers had significantly higher BMD in the spine and total body than the triathletes (P < 0.01 and P < 0.05 respectively) and sedentary controls (P < 0.01 and P < 0.05). There were no differences between the triathletes and controls. Serum testosterone levels were significantly lower in the triathletes than in the controls (P < 0.05); there was no significant difference between the rowers and controls. All groups fell within the normal range for testosterone. In a step-wise multiple regression, including age, body mass, height, calcium intake and activity, no single factor had a significant effect on spine BMD. Body mass had a significant effect on total body BMD and could account for the differences between the groups. A significant positive correlation was found between calcium intake and total body BMD. The heavy weight training typical of rowing training seemed to result in significant bone accretion. The low testosterone levels in the triathletes may have negated any positive effect of the increased exercise on BMD.

Adolescent↗
PubMed1993

Neutrophil-mediated proteolysis. Differential roles for cathepsin G and elastase.

In this study, we assessed the underlying mechanisms by which proteinases released from activated neutrophils mediate fibronectin degradation. Purified human neutrophils (1 x 10(6)) were incubated for 1 hr with 1 microM PMA in the absence or presence of different proteinase inhibitors in 96-well microtiter plates that were coated with 125I-labeled fibronectin (FN). PMA-activated neutrophils caused 85% of FN to be degraded (versus 5% under control conditions). A selective inhibitor of elastase (L658,758), a monoclonal antibody directed against human neutrophilic elastase, and plasma all reduced the neutrophil-mediated FN degradation by 60%. A monoclonal antibody directed against the neutrophil adhesion glycoprotein CD11/CD18 increased the antiproteolytic effect of plasma to 70% but had no effect on the other anti-elastase agents, suggesting that the subjacent space formed by adherent neutrophils restricted to a small degree plasma derived antiproteinases. Agents that blocked cathepsin G or cathepsin G and elastase completely prevented the proteolysis associated with PMA-stimulated neutrophils, suggesting that the actions of elastase may be dependent on the presence of biologically active cathepsin G.

Amino Acid Chloromethyl Ketones↗
PubMed1993

A method for continuous monitoring of meconium in the amniotic fluid during labour.

In about 10% of pregnancies overall, the fetus discharges meconium (its bowel contents) into the amniotic fluid during labour. In about 10% of cases where meconium is passed, the fetus gasps, inhaling the sticky meconium into the upper respiratory tract. After birth, the meconium blocks the air passages in the lungs, impairing gas exchange--meconium aspiration syndrome (MAS). Up to 20% of infants suffering from MAS die and recently published studies have shown a long-term effect of MAS in causing cough and wheeze. The risk of meconium aspiration is thought to be increased by intrauterine hypoxia. At present, meconium is only noticed at birth or occasionally when amniotic fluid leaks past the presenting part of the fetus. A method has been developed which measures absolute meconium concentration with a 99% prediction interval of +/- 30 g l-1; allows monitoring of the rate of appearance of meconium linearly with a nonlinearity of 5%, and differentiates between meconium and blood. The method uses the ratio of the intensity of back-scattered light from the amniotic fluid at 700 and 415 nm, the latter being near the peak of light absorption by meconium and the former a reference value. The ratio is also affected by the presence of blood. However, blood has specific absorption peaks at 540 and 575 nm from which it can be detected (the presence of blood is also a significant abnormality, and is relatively uncommon). The measurement method could easily be integrated into an optical sensor mounted onto an intrauterine probe.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1993

Modulation of the intracellular survival of Brucella abortus by tuftsin and muramyl dipeptide.

Tuftsin, a physiologic bioactive peptide of animal origin, and muramyl dipeptide, a synthetic bioactive glycopeptide of microbial origin, are known to enhance several recognized macrophage functions and increase non-specific resistance of the host against a number of pathogens. The influence of these two bioactive peptides was studied in permissive bovine mammary macrophages that were unable to control the intracellular replication of Brucella abortus and restrictive bovine mammary macrophages that were able to effectively reduce the intracellular survival of B. abortus. Addition of tuftsin (Thr-Lys-Pro-Arg) or muramyl dipeptide significantly (P < 0.03) enhanced the ability of the permissive macrophages to control the intracellular replication of B. abortus strain 2308 and resulted in the functional conversion of the permissive macrophages into restrictive macrophages. Addition of tripeptide tuftsin fragment (Lys-Pro-Arg), a natural inhibitor of tuftsin, to the medium completely abrogated the effect of tuftsin (P < 0.03). No additive effect on the ability of the macrophages to control the survival of B. abortus resulted from the combination of tuftsin and muramyl dipeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Correlation between susceptibility to demyelination and interferon-gamma induction of major histocompatibility complex class II antigens on murine cerebrovascular endothelial cells.

The induction of major histocompatibility complex (MHC) Class II expression was studied on cerebrovascular endothelial cells (CVE) obtained from strains of mice that are resistant (BALB/c) and susceptible (SJL and CBA) to Theiler's virus-induced demyelination (TVID). Following 24 h treatment with interferon (IFN)-gamma, MHC Class II was induced on CVE derived from susceptible but not resistant strains of mice. However, IFN-gamma induced the expression of MHC Class II on late passages of BALB/c CVE. These results demonstrate a correlation between susceptibility to demyelination and the ability of IFN-gamma to induce the expression of MHC Class II on CVE. In susceptible strains of mice, the presence of activated, IFN-gamma-secreting T cells, in the vicinity of CVE would increase the antigen-presenting capabilities of CVE and result in increased T cell traffic into the central nervous system.

Animals↗
PubMed1993

Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi.

The major proteolytic activity of Trypanosoma cruzi is a cathepsin L-like cysteine protease expressed in all stages of the parasite. As an initial step in identifying possible functions of this enzyme in the life cycle of T. cruzi, and examining its potential as a target for rational drug design, two fluoromethyl ketone-derivatized cysteine protease inhibitors were studied for their effects on T. cruzi infection of mammalian cells. Both inhibitors are irreversible substrate analogues with high specificity for cysteine proteases and minimal toxicity to mammalian cells. While micromolar concentrations of inhibitors had some effect on replication of all parasite stages, the most dramatic arrest of parasite replication occurred at the transformation of trypomastigote to amastigote, and also from amastigote to trypomastigote. It is therefore proposed that the enzyme functions in intracellular protein degradation in some stages of T. cruzi, but also in remodeling of the parasite during transformation between stages. Concentrations of inhibitors necessary to interrupt the parasite life cycle had no observable toxicity to macrophages, fibroblasts or epithelial cells in culture. Differential susceptibility of T. cruzi versus host cysteine proteases to fluoromethyl ketone protease inhibitors suggests that inhibition of the T. cruzi cysteine protease is a potential lead for new chemotherapy of Chagas' disease.

Amino Acid Chloromethyl Ketones↗
PubMed1993

Characterization of 11 beta-HSD1B gene expression and enzymatic activity.

Nuclease protection analysis has been used to study the distribution of an mRNA that has been predicted to give rise to a truncated form of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1B). The 11 beta-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with low amounts of the message in the cortex. Neither the renal papilla nor a range of peripheral and central tissues showed evidence of 11 beta-HSD1B mRNA. Expression of the whole (11 beta-HSD1A) and truncated enzymes in COS cells resulted in immunoreactive 34 kDa and 26 kDa proteins respectively, while kidney homogenates showed 34 kDa and 40 kDa species. The 11 beta-HSD1A enzyme converted corticosterone and cortisol to their respective 11-dehydro metabolites with an absolute dependence on NADP as co-factor, while the 26 kDa 11 beta-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11 beta-HSD1B mRNA is associated with a mechanism down-regulating production of 11 beta-HSD1 activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Randomized trial of intraoperative radiotherapy in carcinoma of the stomach.

A prospectively randomized controlled clinical trial was performed comparing surgical resection and intraoperative radiotherapy (IORT) with conventional therapy in adenocarcinoma of the stomach. Patients in the experimental group underwent gastrectomy, and IORT was administered to their gastric bed (20 Gy using 11 to 15 MeV electrons). Patients in the control group underwent gastrectomy alone for early-stage lesions confined to the stomach (stages I to II) or resection and postoperative external beam radiotherapy to the upper abdomen (50 Gy using 6 to 10 mV photons) for advanced-stage lesions extending beyond the gastric wall (stages III to IV). One hundred patients were screened for the study, of whom 60 were randomized and underwent exploratory surgery. Nineteen patients were excluded intraoperatively because of unresectability or metastatic disease, leaving 41 patients in the study. Seven patients (17%) died of complications. The median survival for patients with tumors of all stages was 25 months for the IORT group and 21 months for the control group (p = 0.99). Locoregional disease failures occurred in 7 of 16 (44%) IORT patients and in 23 of 25 (92%) control patients (p < 0.001). Complication rates were similar between IORT and control patients. Although IORT failed to afford a significant advantage over conventional therapy in overall survival, IORT did significantly improve control of locoregional disease.

Actuarial Analysis↗
PubMed1993

Combined laparoscopic and endoscopic management of cholelithiasis and choledocholithiasis.

With the advent of laparoscopic cholecystectomy, optimal management of common duct stones remains controversial. Seven hundred six patients underwent laparoscopic cholecystectomy in our institution from January 1990 through January 1992. From this group of patients, 50 were identified as having clinical or radiographic evidence of common duct stones. Thirty-one patients demonstrated preoperative risk factors for common duct stones and underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP). The risk factors included jaundice (19%), pancreatitis (23%), elevated liver function tests (52%), and ultrasound evidence of choledocholithiasis (6%). Preoperative ERCP was performed in 94% of patients. There were two failures due to periampullary diverticula. Common duct stones were identified in 18 patients (62%) and successfully removed by endoscopic sphincterotomy in all of these patients. Nineteen patients were found to have unsuspected common duct stones on intraoperative cholangiography. Eighteen patients (95%) underwent successful ERCP and endoscopic sphincterotomy with stone extraction. Overall, major morbidity was 2% and included one patient who experienced endoscopic sphincteroplasty. The three endoscopic failures were managed by open common duct exploration, laparoscopic duct exploration, and combined laparoscopic and open common duct exploration. We conclude that combined laparoscopic and endoscopic therapy is a viable option for the management of cholelithiasis with choledocholithiasis.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1993

Bone physiology and the osteoporotic process.

Bone continually undergoes modelling (during growth) or remodelling (during adult life), brought about by the co-ordinated action of osteoblasts and osteoclasts. Osteoblasts form new bone, whereas osteoclasts are responsible for bone resorption. Both types of cell are under hormonal regulation. Osteoporosis, a reduction in bone mass, predisposes to fracture. The most important cause of osteoporosis is oestrogen deficiency which results in increased bone turnover in which resorption exceeds formation. Corticosteroids can also induce osteoporosis in which trabecular bone is particularly affected. This mainly results from suppression of osteoblastic activity.

Bone Density↗
PubMed1993

Geriatric medicine: does teaching alter medical students' attitudes to elderly people?

The development of a questionnaire to assess the attitudes of medical students towards old people is described. Principal components analysis of the responses of 114 first-year medical students revealed two orthogonal factors, named negative attitudes and medical intervention. Scores on these factors were compared among three groups of medical students: first-year students, 64 clinical phase medical students prior to a geriatric medicine course, and 69 medical students who had completed a geriatric medicine course. Negative attitudes scores did not differ between first year and the clinical years, but were reduced after the geriatric medicine course. Scores on the medical intervention factor reduced significantly from first year to the clinical years and were not reduced further by the geriatric medicine course. Women tended to have lower scores on negative attitudes. Medical students appeared to change their attitudes concerning the degree to which medical intervention is appropriate as a result of preclinical or general medical experience. However, their reservations concerning the reward to be gained from working with elderly people were stable over the same periods, but were altered by a course in geriatric medicine.

Aged↗