Search PubMed⌕ Search

Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 289 records · Page 16Linked to original sources
PubMed1999

Seasonal variations in hepatic and ovarian zinc concentrations during the annual reproductive cycle in female channel catfish (Ictalurus punctatus).

Seasonal variations in hepatic and ovarian zinc concentrations were studied during the reproductive cycle in female channel catfish (Ictalurus punctatus). The gonadal somatic index (GSI) increased dramatically in April and peaked in June prior to spawning. Exogenous vitellogenesis was initiated in the fall as noted by increases in serum estradiol and testosterone and liver somatic index (LSI). Total hepatic zinc and zinc in the cytosolic high-molecular weight (HMW) and metallothionein-like (MT) fractions were elevated in March but decreased during rapid vitellogenic oocyte growth in April and May. Following spawning in July, total hepatic zinc and zinc in the HMW and MT-like fractions were again elevated. Total ovarian zinc and zinc associated with HMW and MT-like fractions increased with GSI, then decreased to a low after spawning. However, on a per g tissue basis, ovarian zinc concentrations in both cytosolic pools declined during rapid oocyte growth, indicating a different intracellular localization of the zinc binding proteins. Hepatic MT-like proteins exhibit UV absorption profiles similar to mammalian MT while the ovarian proteins appear to be different. Results give evidence for the homeostatic regulation of hepatic zinc by MT during exogenous vitellogenesis and a similar function for the ovarian MT-like protein during oocyte development.

Animals↗
PubMed1999

Survival of life on asteroids, comets and other small bodies.

The ability of living organisms to survive on the smaller bodies in our solar system is examined. The three most significant sterilizing effects include ionizing radiation, prolonged extreme vacuum, and relentless thermal inactivation. Each could be effectively lethal, and even more so in combination, if organisms at some time resided in the surfaces of airless small bodies located near or in the inner solar system. Deep within volatile-rich bodies, certain environments theoretically might provide protection of dormant organisms against these sterilizing factors. Sterility of surface materials to tens or hundreds of centimeters of depth appears inevitable, and to greater depths for bodies which have resided for long periods sunward of about 2 A.U.

Environment↗
PubMed1999

Educational portfolios in the assessment of general practice trainers: reliability of assessors.

OBJECTIVES: This paper reports a project that assessed a series of portfolios assembled by a cohort of participants attending a course for prospective general practice trainers. DESIGN: The reliability of judgements about individual 'components', together with an overall global judgement about performance were studied. SETTING: NHSE South & West, King Alfred's College, Winchester and Institute of Community Studies, Bournemouth University. SUBJECTS: Eight experienced general practice trainers recruited from around Wessex, which incorporates Hampshire, Dorset, Wiltshire and the Isle of Wight. RESULTS: The reliability of individual assessor's judgements (i.e. their consistency) was moderate, but inter-rater reliability did not reach a level which could support making a safe summative judgement. The levels of reliability reached were similar to other subjective assessments and perhaps reflected individuality of personal agendas of both the assessed and the assessors, and variations in portfolio structure and content. CONCLUSIONS: Suggestions for approaches in future are made.

Education, Medical, Continuing↗
PubMed1999

Subunit-selective modulation of GABAA receptors by the non-steroidal anti-inflammatory agent, mefenamic acid.

Mefenamic acid (MFA) has anti-convulsant and pro-convulsant effects in vivo, and has been shown to potentiate and inhibit GABAA (gamma-aminobutyric acid) receptors in vitro. In this study, whole-cell currents were recorded from Xenopus oocytes and human embryonic kidney (HEK) cells expressing human recombinant GABAA receptors to resolve the molecular mechanisms by which MFA modulates GABAA receptor function. We demonstrate that MFA potentiated GABA-activated currents for alpha1beta2 gamma2S (EC50 = 3.2 +/- 0.5 microM), but not for alpha1beta1 gamma2S receptors. MFA also enhanced GABA-activated responses and directly activated alpha1beta2/beta3 GABAA receptors, but inhibited responses to GABA on alpha1beta1 constructs (IC50 = 40 +/- 7.2 microM). A comparison of beta1, beta2 and beta3 subunits suggested that the positive modulatory action of MFA involved asparagine (N) 290 in the second transmembrane domain (TM2) of the beta2 and beta3 subunits. Mutation of N290 to serine (S) markedly reduced modulation by MFA in alpha1beta2(N290S)gamma2S receptors, whereas alpha1beta1(S290N)gamma2S constructs revealed potentiated responses to GABA (EC50 = 7.8 +/- 1.7 microM) and direct activation by MFA. The potentiation by MFA displayed voltage sensitivity. The direct activation, potentiation and inhibitory aspects of MFA action were predominantly conferred by the beta subunits as the spontaneously active homomeric beta1 and beta3 receptors were susceptible to modulation by MFA. Molecular comparisons of MFA, loreclezole and etomidate, agents which exhibit similar selectivity for GABAA receptors, revealed their ability to adopt similar structural conformations. This study indicates that N290 in TM2 of beta2 and beta3 subunits is important for the regulation of GABAA receptor function by MFA. Our data provide a potential molecular mechanism for the complex central effects of MFA in vivo.

Amino Acid Sequence↗
PubMed1999

Distant lymph node metastases in esophageal cancer: impact of endoscopic ultrasound-guided biopsy.

BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to evaluate the impact of endoscopic ultrasound (EUS)-guided biopsy in patients with esophageal carcinoma where distant lymph nodes which were possibly metastatic were visualized using EUS. PATIENTS AND METHODS: Out of 198 patients (150 men, mean age 66 years) examined over a 4-year period by EUS for local staging of esophageal cancer (121 squamous cell carcinomas and 77 adenocarcinomas), there was EUS visualization of distant lymph nodes in 40 (20%). EUS-guided biopsy was carried out in the latter patients, of cervical nodes with mediastinal tumors (n = 19), of celiac nodes with cervical tumors (n = 2) or superior mediastinal tumors (n = 9), and upper mediastinal lymph nodes in the case of distal adenocarcinomas (n = 10). RESULTS: On EUS-guided biopsy, results were positive in 31 patients, eight were correctly negative (as confirmed by surgery), and in one patient there was a technical failure, with positive findings on subsequent surgery. The sensitivity and specificity of the diagnosis of malignant lymph nodes were therefore 97% and 100% respectively. The positive results of EUS-guided biopsy modified the tumor staging in 31 of these cases (77.5%), proving distant lymph node metastasis which is classified as stage M1. With regard to actual clinical management, surgery was withheld from 24 patients (60% of 40 cases) who were then treated with concomitant radiotherapy and chemotherapy. CONCLUSION: EUS-guided biopsy of distant lymph nodes was indicated in 20% of patients with esophageal cancers, and the biopsy results led to upgrading of the tumor stage in about 80% of cases and influenced the treatment decision in about 60%.

Adenocarcinoma↗
PubMed1999

A case of agitated catatonia.

Agitation is one of the diagnostic features of catatonia in the DSM IV classification, but permanent forms of agitated catatonia have occasionally been described. We report the case of a 43-year-old man who had already suffered from undifferentiated schizophrenia for 7 years, and in whom we diagnosed agitated catatonia. While our patient was being treated with a neuroleptic during a second episode of paranoia, a state of agitation was observed which persisted for a further 8 months. During this period, he was treated with several different neuroleptics and benzodiazepines, either alone or in association, without any improvement. No organic cause was found. He was then transferred to our electroconvulsive therapy (ECT) unit, with a diagnosis of schizophrenic agitation resistant to drug therapy. ECT was begun, and he was only given droperidol in case of agitation and alimemazine for insomnia, neither of which had any effect. In view of his persistent agitation without any purpose, echolalia and echopraxia, stereotyped movements with mannerisms and marked mimicking and grimacing, we diagnosed him as having agitated catatonia. After the fourth session of ECT, we decided to stop all treatment and gave him lorazepam at a dose of 12.5 mg daily. Twenty-four hours later, all symptoms of agitation had disappeared. In our opinion, permanent catatonic agitation is not rare. In our case, the neuroleptic treatment maintained and may even have worsened the symptomatology. Lorazepam can be used as a therapeutic test for this type of agitation, especially if it does not respond to neuroleptics. This also allows the patient to be sedated rapidly and effectively, thus preventing him from injuring himself further.

Adult↗
PubMed1999

Excision repair defect in Rothmund Thomson syndrome.

Rothmund Thomson syndrome is a rare autosomal recessive skin disorder. The main clinical feature is poikiloderma appearing in early childhood associated with skeletal abnormalities. Early occurrence of malignancies is another relevant feature. Here we describe the clinical features of 2 patients with Rothmund Thomson syndrome who were investigated for the in vitro DNA repair capacities of blood cells following UVC radiation exposure. DNA excision repair, assessed with unscheduled DNA synthesis following UVC exposure, was decreased in both patients. Such a defect might explain the patients' sensitivity to sunlight and the relatively high risk of cancer associated with this syndrome.

Adolescent↗
PubMed1999

Radiation processing to improve the quality of fishery products.

Extensive investigations, worldwide, in the last 4 decades have shown the benefits of radiation processing for the preservation and microbial quality improvement of seafoods. In the present review, the various factors determining the quality of seafoods are first presented. The basic principles underlying the effects of ionizing radiation and specific effects on food constituents such as proteins, amino acids, lipids, vitamins, and tissue enzymes are discussed. Data on radiation processing of seafoods are reported and discussed with respect to shelf life enhancement under refrigeration by control of bacteria causing spoilage, radiation sensitivity of pathogenic microorganisms and parasites of public health significance and their elimination in fresh and frozen fishery products, control of insect disinfestation in dried fishery products, influence of irradiation on nutritional and sensory quality attributes, detection of irradiation treatment, economics, and international status.

Animals↗
PubMed1999

Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin.

We detected an interaction of the N-terminus of huntingtin (htt171) with the C-terminal region of the nuclear receptor co-repressor (N-CoR) using the yeast two-hybrid system. This interaction was repeat length dependent and specific to htt171; the co-repressor did not interact with the repeat carrying a section of atrophin 1 nor with the androgen receptor or polyglutamine alone. The interaction was confirmed using His-tagged Escherichia coli -expressed C-terminal human and rat co-repressor protein which pulled full-length huntingtin out of homogenized rat brain and in pull-down assays. The N-CoR represses transcription from sequence-specific ligand-activated receptors such as the retinoid X-thyroid hormone receptor dimers and other nuclear receptors including Mad-Max receptor dimers. The mechanism of this repression appears to be through the formation of a complex of repressor proteins including the N-CoR, mSin3 and histone deacetylases. We have used N-CoR and mSin3A antibodies in immunohistochemical studies and find that in Huntington's disease (HD) cortex and caudate, the cellular localization of these proteins is exclusively cytoplasmic whilst in control brain they are localized in the nucleus as well as the cytoplasm; mSin3A immunoreactivity also occurred in a subset of huntingtin positive intranuclear inclusions. The relocalization of repressor proteins in HD brain may alter transcription and be involved in the pathology of the disease.

Acetyltransferases↗
PubMed1999

Binding characteristics of estrogen receptor (ER) in Atlantic croaker (Micropogonias undulatus) testis: different affinity for estrogens and xenobiotics from that of hepatic ER.

An estrogen receptor (ER) was identified in cytosolic and nuclear fractions of the testis in a marine teleost, Atlantic croaker (Micropogonias undulatus). A single class of high affinity, low capacity, and displaceable binding sites was identified by saturation analysis, with a Kd of 0.40 nM in cytosolic extracts and a Kd of 0.33 nM in nuclear extracts. Competition studies demonstrated that the receptor was highly specific for estrogens (diethylstilbestrol > estradiol >> estriol = estrone) and also bound several antiestrogens. Testosterone and 5alpha-dihydrotestosterone had much lower affinities for the receptor, whereas no displacement of specific binding occurred with 11-ketotestosterone or any of the C21 maturation-inducing steroids. A variety of xenoestrogens, including o,p'-dichlorodiphenyltrichloroethane (DDT), chlordecone (Kepone), nonylphenol, hydroxylated polychlorinated biphenyls (PCBs), and the mycotoxin zearalenone, bound to the receptor with relatively low binding affinities, 10(-3) to 10(-5) that of estradiol. A comparison of the binding affinities of various ligands for the testicular ER and the hepatic ER in this species revealed that the testicular ER was saturated at a lower [3H]estradiol concentration (1 nM vs. 4 nM). The binding affinities of several compounds, including testosterone and nafoxidine, exhibited marked differences for the two ERs; and most of the estrogens and xenoestrogens tested had higher binding affinities for the testicular receptor. Minor amounts of estradiol (0.12 ng/g tissue/h) were produced by testicular tissue fragments incubated in vitro, and estradiol was detected in male Atlantic croaker plasma. The identification of a testicular ER and evidence that estradiol is produced by the testes in croaker suggest that estrogens participate in the hormonal control of testicular function in teleosts.

Animals↗
PubMed1999

Gonadal stage-dependent effects of gonadal steroids on gonadotropin II secretion in the Atlantic croaker (Micropogonias undulatus).

Involvement of gonadal steroids in the control of gonadotropin II (GTH II) (homologous to LH) secretion was investigated in the Atlantic croaker (Micropogonias undulatus) using gonadectomy (Gx) and steroid replacement paradigms. Gonadectomy in males and females during the late gonadal recrudescence phase elicited significant increases in the gonadotropin response to stimulation by an LHRH analog (LHRHa), without altering basal GTH II secretion. Slow-release silicone elastomer implants of testosterone or estradiol significantly inhibited LHRHa-induced GTH II secretion in gonad-intact and Gx males, and in Gx females, whereas 5alpha-dihydrotestosterone, a nonaromatizable androgen, was ineffective. Pretreatment of fish with an aromatase inhibitor, 1,4, 6-androstatrien-3,17-dione, 2 days before the administration of testosterone implants, completely blocked the negative effect of testosterone on LHRHa-induced GTH II secretion in males, but only partially restored it in females. This suggests that the negative feedback of testosterone in males is primarily mediated by its conversion to estradiol at the level of the hypothalamus and/or pituitary gland, while in females the androgen may also exert a direct inhibitory effect on GTH II secretion, probably mediated via an androgen receptor. In addition, estradiol and testosterone exerted positive effects on basal and LHRHa-induced GTH II secretion during the early-recrudescence phase of the gonadal cycle. The steroids switched to a negative effect on LHRHa-induced GTH II secretion once the fish had fully developed gonads, possibly as a mechanism that prevents a precocious surge in GTH II secretion and final gamete maturation until gametogenesis is complete and the environmental conditions are appropriate for spawning.

Animals↗
PubMed1999

Identification of two nuclear androgen receptors in kelp bass (Paralabrax clathratus) and their binding affinities for xenobiotics: comparison with Atlantic croaker (Micropogonias undulatus) androgen receptors.

Two distinct nuclear androgen receptors (ARs) were identified in brain and ovarian tissues of kelp bass, Paralabrax clathratus, termed kbAR1 and kbAR2, which correspond to the two nuclear ARs we have previously characterized in Atlantic croaker, Micropogonias undulatus, termed acAR1 and acAR2. Scatchard analysis of nuclear fractions of whole brain tissue demonstrated that kbAR1 had a single class of high-affinity binding sites for testosterone (T; K(d) of 1. 8 nM and B(max) of 1.0 pmol/g tissue), whereas cytosolic fractions of kbAR2 ovarian tissue had a single class of high-affinity binding sites for dihydrotestosterone (DHT; K(d) of 0.1 nM and B(max) of 0.5 pmol/g tissue). Competition studies showed that both kbAR1 and kbAR2 were specific for androgens. However, kbAR1 bound only T with high affinity, whereas kbAR2 bound DHT, mibolerone, 17alpha-methyl-testosterone, T, and 11-ketotestosterone with high affinity. In addition, we examined the binding affinities of dichlorodiphenyltrichloroethane and its derivatives, several hydroxylated polychlorinated biphenyl (PCB) congeners, PCB mixtures, and the fungicide vinclozolin and its two metabolites M1 and M2 for the two ARs in Atlantic croaker ovarian, testicular, and brain tissues and in kelp bass ovarian and brain tissues. Only 4, 4'-PCB-3-OH and 2',5'-PCB-3-OH demonstrated greater than 50% displacement of [(3)H]testosterone from either acAR1 or kbAR1. In contrast, with the exception of vinclozolin, all of the xenobiotics examined demonstrated binding to acAR2 in testicular and ovarian tissues. The binding affinities were highest in the testicular tissue with M2, 2,2'5'-PCB-4-OH, and o,p'-DDD all binding with EC(50)s less than 10 microM. The binding affinities of xenobiotics to kbAR2 in ovarian tissue were similar to their binding affinities for ovarian acAR2. The finding that AR1 and AR2 possess different binding affinities for natural androgens and synthetic steroids, as well as for xenobiotics, suggests that the activities of androgens and of certain xenobiotics will depend upon the type of AR present within the target tissue.

Animals↗
PubMed1999

Predicting the difficult neuraxial block: a prospective study.

UNLABELLED: Anticipated technical difficulty is one factor that can influence the anesthesiologist's decision to perform neuraxial (spinal or epidural) blockade. Problems during the procedure may be associated with patient dissatisfaction, neurologic sequelae, or hematoma. We designed this study of 595 neuraxial blocks to determine whether any patient characteristics would be useful in predicting a difficult neuraxial block. Before the procedure, the following data were noted: demographic data, body habitus (normal, thin, muscular, obese), spinal landmarks (good = easily palpable spinous processes, poor = difficult to palpate spinous processes, none = unable to positively identify spinous processes), and spinal anatomy (assessed by inspection and examination as normal or deformed). We noted the technique, approach, needle type, needle gauge, etc. We also recorded whether the procedure was completed at the first (first-level success) or second spinal level and the total number of new skin punctures (attempts) necessary to complete the procedure. Of all the factors considered, the quality of landmarks best correlated with technical difficulty as measured by both first-level success and number of attempts. Abnormal spinal anatomy correlated with difficulty as measured by number of attempts. Body habitus also correlated with difficulty, but only as measured by number of attempts. There was no association between either measure of difficulty and any of the following: age, sex, spinal versus epidural, approach, needle type, needle gauge, or training level of the provider. Thoracic epidurals were less difficult than lumbar epidurals by both measures of difficulty. We conclude that body habitus does not seem to be the best predictor of technical difficulty. An examination of the patient's back for the quality of landmarks and obvious anatomical deformity better predicts the ease or difficulty of neuraxial block. Other factors seem to have little or no influence on the difficulty of neuraxial block procedures. IMPLICATIONS: We studied a number of factors, including equipment, technique, and patient characteristics, that may indicate the ease or difficulty of performing neuraxial (spinal and epidural) blocks. Of these factors, only patient characteristics had significant predictive value. We found that an examination of the patient's back for the quality of landmarks and obvious anatomical deformity better predicts the ease or difficulty of neuraxial block than does body habitus.

Adolescent↗
PubMed1999

Fusibacter paucivorans gen. nov., sp. nov., an anaerobic, thiosulfate-reducing bacterium from an oil-producing well.

A strictly anaerobic, halotolerant, spindle-shaped rod, designated strain SEBR 4211T, was isolated from an African saline oil-producing well. Cells stain Gram-positive, which was confirmed by electron microscopy observations. Strain SEBR 4211T was motile by means of one to four peritrichous flagella, had a G+C content of 43 mol% and grew optimally at 37 degrees C, pH 7.3, with 0 to 3% (w/v) NaCl. It utilized a limited number of carbohydrates (cellobiose, glucose, fructose, mannitol and ribose) and produced acetate, butyrate, CO2 and H2 as end products from glucose fermentation. It reduced thiosulfate to sulfide. In the presence of thiosulfate, a decrease in butyrate and an increase in acetate production was observed. Phylogenetically, strain SEBR 4211T was related to members of the low G+C Clostridiales order with Clostridium halophilum as the closest relative (16S rDNA sequence similarity of 90%). On the basis of phenotypic, genotypic and phylogenetic characteristics of the isolate, it is proposed to designate it as a new species of a new genus, Fusibacter gen. nov., as Fusibacter paucivorans sp. nov. The type strain is SEBR 4211T (= DSM 12116T).

Bacteria, Anaerobic↗