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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 73 records · Page 4Linked to original sources

Stereospecific N-methylation of the tetrahydroisoquinoline alkaloids isosalsoline and salsolidine by amine N-methyltransferase A from bovine liver.

Stereospecific N-methylation of the tetrahydroisoquinoline alkaloids isosalsoline (7-hydroxy-6-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) and salsolidine (6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) by amine N-methyltransferase A isolated from bovine liver is reported. Incubation with S-adenosylmethionine as cosubstrate revealed that in case of isosalsoline, an endogenous tetrahydroisoquinoline alkaloid, the (+)-(R)-enantiomer, is preferentially methylated, whereas in the case of salsolidine the (-)-(S)-enantiomer is preferentially methylated. The results were obtained by using two independent methods, namely a radioassay and HPLC following separate incubation experiments.

Animals↗

Greenhouse gases in cold water filaments in the arabian sea during the southwest monsoon

The distribution of partial pressure of carbon dioxide and the concentrations of nitrous oxide and methane were investigated in a cold water filament near the coastal upwelling region off Oman at the beginning of the southwest monsoon in 1997. The results suggest that such filaments are regions of intense biogeochemical activity which may affect the marine cycling of climatically relevant trace gases.http://link.springer. de/link/service/journals/00114/bibs/9086010/90860489.htm</HEA

Journal Article↗

Antibody titers to hepatitis B surface antigen among vaccinated emergency physicians: three years' experience with a wellness booth.

STUDY OBJECTIVE: To determine antibody titers to hepatitis B surface antigen (anti-HBsAg) among previously vaccinated emergency physicians and to assess the degree of compliance with Centers for Disease Control and Prevention (CDC) postvaccination guidelines. METHODS: A descriptive analysis was performed of anti-HBsAg titer determinations and vaccination surveys among a self-selected group of emergency physicians attending the annual scientific assembly of the American College of Emergency Physicians in 1995, 1996, or 1997. RESULTS: Of 943 participants, titer levels were found to be protective in 768 (81%), borderline in 45 (5%), and nonreactive in 130 (14%). A total of 337 participants (36%) had not obtained postvaccination titer determinations, as advised by the CDC. More than 50% reported an occupational exposure to blood products within the previous 2 years. CONCLUSION: Despite their high risk for exposure to blood products, many previously vaccinated emergency physicians were not in compliance with CDC postvaccination guidelines.

Centers for Disease Control and Prevention, U.S.↗

Expression of core binding factor Osf2/Cbfa-1 and bone sialoprotein in tooth development.

The transcription factor Osf2/Cbfa1 is a key regulator of osteogenic differentiation while BSP, a major non-collagenous protein, is a marker of osteoblastic differentiation. To determine the relationship between Osf2/Cbfa1 and the formation of mineralized tissues in tooth development we have studied the temporal expression of Osf2/Cbfa1 and BSP mRNA using in situ hybridization. These studies show that Osf2/Cbfa1 is expressed early in mesenchymal and epithelial tissues destined to form the mineralized tissues of the tooth and periodontal tissues, whereas BSP provides a specific marker for the differentiated cells in each of these tissues. Expression of Osf2/Cbfa1, but not BSP, was observed in the periodontal ligament indicating that expression of Osf2/Cbfa1 is not restricted to mineralizing tissues.

Age Factors↗

Stability and change in longitudinal water-level task performance.

Three longitudinal samples of children (N = 481), 8 to 16 years old, were assessed 3 times at yearly intervals on 8 water-level items. The within-child change in task performance over age is viewed as a stochastic process of the child changing or remaining in 1 of 3 latent (strategy) states: (a) bottom-parallel responders, (b) random responders, or (c) accurate responders. A random-effects binomial mixture distribution is used to model performance at each age. Change over age is gauged by a stochastic transition model. Although there was improvement in task performance over age, the more general finding is that strategy stability, not change, is most typical.

Adolescent↗

Moclobemide in the treatment of major depressive disorder (DSM-3) following traumatic brain injury.

Major depression (MDD) following traumatic brain injury (TBI) is a common phenomenon. There are no adequate studies in the literature defining optimum treatments for this condition following TBI. The opportunity arose to analyse a group of patients who were included in a larger study of an antidepressant (moclobemide). As the treatment, but not the delivery, was known, this has the status of an open study. Twenty-six patients with major depression of late onset (mean 4.67 years post-TBI) were identified (18 male, 8 female), with a mean age at injury 28.49 years. The group was moderately depressed with Hamilton Depression score (HAM-D) of 23.385 and moderately anxious with Hamilton Anxiety score (HAM-A) of 21.231. Mean HAM-D reduction was 81% and HAM-A reduction 81%. Of the 26 subjects 23 were defined as responders. Onset of action was rapid, with 17 responding by day 3. Irritability scores showed a mean reduction of 57% and pain scores a reduction of 39%. It is concluded that moclobemide may be an effective treatment for MDD following TBI, but properly controlled studies must be carried out to confirm this.

Adolescent↗

Early changes in murine epidermal cell phenotype by contact sensitizers.

In order to develop an in vitro predictive assay for the detection of contact sensitizers, we investigated the possible modulation of the expression of cell-surface molecules in the early phases of treatment of murine epidermal cells (EC) with known contact sensitizers. After in vitro treatment of Balb/c EC with the strong contact sensitizer, TNBS, Langerhans cells (LCs) demonstrated a rapid up-regulation of CD45, CD40, CD32/16 (Fc gamma RII/III) and CD23 (Fc epsilon RII) molecules. CD45 and CD40 were also rapidly up-regulated on the dendritic epidermal T cells. Interestingly, after treatment with this severe sensitizer, a marked induction of CD40 expression was found on a CD45 negative population, most probably keratinocytes. In contrast to these cell-surface molecules, I-Ad/I-Ed and CD90.2 expression were unchanged. No change was observed on the expression of CD45 and CD40 after treatment with a mild or a weak contact sensitizer, citral and citronellal respectively. In contrast, like TNBS, they up-regulated the expression of CD32/16 and CD23 on LCs. The irritant sodium dodecyl sulfate had no effect on all these cell-surface molecules. Our results indicated that in vitro, chemicals with allergic potential induced early specific phenotype changes that may represent an early-activated state of the cells. This state may be responsible for initiating the afferent phase of contact sensitivity in vivo. Based on these findings, it might be possible to develop an in vitro assay to reduce the number of experimental animals for a fast screening of contact sensitizers and for discriminating between mild contact sensitizers and irritants.

Allergens↗

Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer. Scottish Gynaecological Cancer Trials Group.

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2)). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical governance and revalidation.

The quality agenda in the NHS has many parts. For the medical profession the means of enhancing standards and consistency will be revalidation. This article outlines progress to date in defining how doctors will demonstrate they are 'up to date' and 'fit to practice'.

Certification↗

Evidence of a role for plant proteases in the degradation of herbage proteins in the rumen of grazing cattle.

Protein breakdown in the rumen is generally regarded as a two-stage process in which proteases produced by rumen microorganisms cleave plant protein into peptides and amino acids. However, many of the fiber-degrading cellulolytic species in the rumen are not in fact proteolytic, and the proteolytic activity of the entire rumen microbial population is only moderate when compared to the gastric and pancreatic secretions in the abomasum. Moreover, plant cell walls remain largely intact after initial chewing (particularly in cattle), presenting a physical barrier that must be breached prior to their effective colonization. The present study considers the hypothesis that the plant enzymes are at least partly responsible for herbage protein degradation in grazing ruminants. Ryegrass, red clover, white clover, and bird's-foot trefoil were incubated in the presence and absence of rumen microorganisms. The production of volatile fatty acids indicated the level of microbial activity, whereas the relative disappearance of the large subunit of ribulose 1,5 bisphosphate carboxylase/oxygenase (Rubisco LSU) indicated proteolytic activity. In all incubations, the relative abundance of the Rubisco LSU decreased as the incubation progressed. When rumen microorganisms were absent, low molecular weight peptides (below 20 kDa) accumulated as the incubation progressed. This accumulation was not observed in the presence of rumen microorganisms. Therefore we suggest that the intrinsic plant proteases contribute to the initial stages of proteolysis of grazed herbage.

Animal Feed↗

Expression of the c-erbB-3/HER-3 and c-erbB-4/HER-4 growth factor receptors and their ligands, neuregulin-1 alpha, neuregulin-1 beta, and betacellulin, in normal endometrium and endometrial cancer.

The objective of this study was to determine the immunohistochemical expression of the c-erbB-3 and c-erbB-4 growth factor receptors and their principal ligands, the neuregulins and betacellulin, in normal endometrium and determine whether there was evidence of under- or overexpression in endometrial adenocarcinoma. Immunohistochemistry was performed using well-characterized antibodies against each of the five proteins analyzed on formalin-fixed, paraffin-embedded archival material. Forty-three normal endometrial samples (16 proliferative, 19 secretory, and 8 hyperplastic) and 41 endometrial adenocarcinoma cases were analyzed. There was variable expression of the growth factor receptors and the ligands in the two principal phases of the menstrual cycle as well as in endometrial adenocarcinoma. In normal endometrium, the c-erbB-3 receptor was weakly expressed in both phases. The c-erbB-4 receptor and all of the ligands examined, neuregulin alpha, neuregulin beta, and betacellulin, were expressed at significantly higher levels in the secretory as compared with the proliferative phase of the menstrual cycle, suggesting a role for these proteins in endometrial maturation. In endometrial adenocarcinoma, overexpression of c-erbB-3, c-erbB-4, and betacellulin with underexpression of neuregulin a as compared with normal controls was observed. Neuregulin beta expression was not found to be significantly different in the two groups. These results suggest that signaling through the c-erbB-3 and c-erbB-4 receptors and the ligands neuregulin alpha, neuregulin beta, and betacellulin are important in endometrial carcinogenesis.

Amino Acid Sequence↗

Multicentre study of preoxygenation practices by anaesthesia providers.

A total of 155 consecutive anaesthetics in three public Malaysian hospitals were prospectively studied to assess preoxygenation practices by their anaesthesia providers. Preoxygenation was practised in 96.1% of patients. Specialist and non-specialist anaesthesiologist did not preoxygenate 8.8% and 2.3% of their patients, respectively. Overall incidence of arterial oxygen desaturation during induction was 15.5%. Arterial oxygen desaturation occurred more frequently with emergency surgery (30.2%) in comparison to elective surgery (9.8%). Arterial oxygen desaturation occurred more frequently with non-specialist (18.9%) than specialist anaesthesia providers (3.0%).

Adolescent↗

Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model.

IL-12 treatment of a murine transplantable breast carcinoma (HTH-K) led to tumour regression and cure which was related to the duration of treatment. We studied the sequential molecular and phenotypic changes in IL-12-treated tumours. IFN-gamma mRNA was detected 8 hr after the first treatment. mRNA expression for the IFN-gamma-inducible genes beta 2-microglobulin and indoleamine dioxygenase (IDO) was induced subsequently, together with the chemokine IP-10. IL-12-treated tumours had an abundant cellular infiltrate, consisting mainly of CD8+ T cells. mRNA for granzyme B and perforin also could be detected, suggesting that those cells were activated. After 7 days of daily therapy, tumours in IL-12-treated mice had a significant reduction in vasculature. Finally, the number of apoptotic tumour cells increased throughout IL-12 treatment. We compared the anti-tumour effects of IL-12 to those induced by IFN-gamma therapy, which caused initial tumour stasis but subsequent tumour progression. IFN-gamma induced beta 2-microglobulin and IDO over a 7-day period, but IP-10 was induced only transiently. IFN-gamma caused a lesser cellular infiltrate, a minor anti-angiogenic effect and a transient apoptotic effect. The success of IL-12 may be due to its ability to produce a distinct sequence of molecular and phenotypic changes in tumours, leading to an anti-tumour immune response, toxicity against tumour cells and an anti-angiogenic effect. Other cytokines, such as IFN-gamma, induce some, but not all, of these actions. Comparison of IL-12 and IFN-gamma suggests that sustained induction of IP-10 and activation of a resulting cellular infiltrate may be key changes in regressing tumours.

Animals↗

[Mask induction and one-lung ventilation with sevoflurane].

The low blood/gas solubility, the rapid uptake and nonpungent odor permits mask induction with sevoflurane in adults. Depending on the induction techniques (tidal breathing, deep breaths or single-breath induction), the use of nitrous oxide and the concentration of inspired sevoflurane anesthesia can rapidly be induced within 41-178 s. Adverse effects like coughing, breath-holding or increased secretions occur with a low incidence of 2%-20%. Some 88 to 100% of the volunteers or patients would accept a mask induction again. Clinical experience shows that sevoflurane is well indicated for mask induction in adults. Acute severe bronchospasm is a feared complication of anesthesia with an incidence of 1.7%. Although halothane is often recommended as the agent of choice in patients with reactive airways, there is little evidence in humans that it is more effective than other volatile agents. The bronchodilating effects of sevoflurane are comparable to those of other volatile anesthetics, it produces minimal airway irritation and allows rapid adjustment of anesthetic depth. These properties and our clinical experience suggest that sevoflurane is a useful choice for patients with reactive airways. Hypoxemia during one-lung ventilation (OLV) occurs in 9-27% of patients and remains a clinical problem. Although hypoxic pulmonary vasoconstriction is directly inhibited by volatile anesthetics in in vitro studies, this effect is usually of minor clinical consequence. The use of volatile anesthetics may be advocated because of their salutory effects on bronchomotor tone, high potency (allowing high inspired concentration of oxygen while avoiding awareness) and rapid adjustment of anesthetic depth. Sevoflurane possesses these attributes and may be useful for OLV.

Anesthesia, Inhalation↗