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H Thomas

Publications and source records attributed to H Thomas.

At least 199 records · Page 11Linked to original sources
PubMed1991

Regional mapping of 22 microclones around the adenomatous polyposis coli (APC) locus on chromosome 5q.

A previously described genomic library constructed from microdissected DNA has been used to generate a large number of probes around the adenomatous polyposis coli (APC) gene at 5q22. A total of 202 clones were hybridised directly onto a somatic cell hybrid panel containing two APC-related interstitial deletions. Of 75 microclones that gave clear hybridisation signals, 22 independent clones mapped into the region common to both deletions. In addition, 4/22 of the markers are conserved in rodent DNA. These clones should provide a valuable resource for screening cDNA libraries and cloning the DNA around the APC gene in yeast artificial chromosomes.

Adenomatous Polyposis Coli↗
PubMed1991

Tetrahydroisoquinoline alkaloids mimic direct but not receptor-mediated inhibitory effects of estrogens and phytoestrogens on testicular endocrine function. Possible significance for Leydig cell insufficiency in alcohol addiction.

Possible effects of various tetrahydroisoquinolines (TIQs) on rat testicular endocrine function were tested in vitro in order to prove whether these compounds, some of which have been claimed to accumulate in alcoholics, may be mediators of the development of Leydig cell insufficiency, a well-known side-effect of ethanol ingestion. TIQ effects on different levels of regulation of testis function were compared in vitro with estrogen effects, since both classes of compounds have structural similarities. Gonadotropin-stimulated testosterone production by testicular Leydig cells was inhibited by tetrahydropapaveroline and isosalsoline, the IC50 values (30 microM) being comparable to those of estradiol (3 microM), 2-hydroxyestradiol (10 microM), and the phytoestrogens, coumestrol (15 microM) and genistein (7 microM); salsolinol (85 microM) and salsoline (240 microM) were less effective, and salsolidine was ineffective. None of these TIQs interacted significantly with testicular estrogen receptor as analyzed by estradiol displacement. However, tetrahydropapaveroline, isosalsoline and salsolinol competitively inhibited (Ki 130-150 microM) substrate binding to cytochrome P450XVII, one key enzyme of androgen biosynthesis, with similar efficiency as the estrogens did (Ki 50-110 microM); salsoline and salsolidine were again much less effective. Since the efficient TIQ concentrations in this system are identical with those reported to generate central-nervous effects, it is concluded that certain TIQs may amplify peripheral inhibitory effects of ethanol on testicular endocrine function by their interaction with at least one enzyme of the androgen biosynthetic pathway.

Alcoholism↗
PubMed1991

Effects of interferons and other cytokines on tumors in animals: a review.

The term cytokine describes a group of protein cell regulators involved in the control of cell growth and differentiation in embryogenesis, immunity and inflammation. They are of low molecular weight, are produced locally, and act in an autocrine or paracrine manner. In the past decade their use as cancer therapy has become a reality. Thirty years ago mice were treated with the antiviral protein interferon (IFN) which not only produced a reduction in the incidence of virus-induced tumors but also slowed the development of transplantable tumors. This was one of the first indications that cytokines can be negative regulators of cell growth. Here we outline current knowledge of the actions of IFNs and other cytokines in animal models, and draw parallels with clinical trials to illustrate the invaluable nature of this preclinical and mechanistic work.

Animals↗
PubMed1991

Characterization and mapping of microdissected genomic clones from the adenomatous polyposis coli (APC) region.

The gene associated with adenomatous polyposis coli (APC) has been mapped to the long arm of chromosome 5. To saturate the APC region with DNA markers, two independent microdissection libraries with an emphasis on 5q21.2-21.3 and 5q22 have been constructed from GTG-banded human metaphase chromosomes. PCR-amplified insert DNA of the primary amplificate used as a probe in chromosomal in situ suppression (CISS) hybridization of human metaphase spreads revealed region-specific signals at the chromosomal site that was excised for cloning. One hundred forty-two inserts, derived from both libraries, have been characterized in more detail. Deletion mapping analysis was performed with 17 single-copy clones on a hamster-human hybrid cell panel. Seven of these clones were located within two interstitial deletions of 6-8 Mb from APC-affected individuals around chromosome bands 5q21-22. The identification of new microclones mapping into these deletions and their use in isolating YAC clones should contribute to the construction of a contiguous physical map of the APC region.

Adenomatous Polyposis Coli↗
PubMed1991

Faculty attrition among three specialties.

STUDY OBJECTIVES: To survey faculty attrition in emergency medicine and compare it with faculty attrition in the specialties of orthopedic surgery and cardiology. DESIGN: Chairmen of the three departments were surveyed regarding faculty attrition, work hours, and motivation for leaving. Those emergency physicians having left also were surveyed. MAIN RESULTS: Responses were obtained from 67 of 68 emergency medicine programs, 53 of 58 orthopedic programs, and 47 of 54 cardiology programs. Overall, there were 670 total faculty in emergency medicine, of which 67 (10%) left their positions during 1988-38 to enter private practice, 18 to take another academic position, and 11 to do something unidentified. There was no difference in faculty attrition among the three specialties or in what the physicians left to do (P = .75). Both the orthopedists and the cardiologists worked more total hours each week (P = .001) but fewer night hours (P = .03) than the emergency physicians. Among the 67 emergency medicine programs, 28 reported no attrition; 39 reported one or more physicians leaving the program. These two groups of programs did not differ in terms of faculty size, hours worked, or night hours worked.

Cardiology↗
PubMed1991

Treating the vaginal vault in carcinoma of the endometrium using the Buchler afterloading system.

The advent of high-dose-rate afterloading intracavitary radiotherapy has implications for both staff safety and the possibility of convenient, outpatient-based treatment for the patient. We have carried out a retrospective analysis of its use with high-activity iridium 192 and the Buchler machine to treat the vaginal valut in patients with adenocarcinoma of the endometrium, most of whom also received external-beam radiotherapy to the pelvis. We have compared the survival, complication and local control rates with a comparable group of historical controls treated with low-dose-rate intracavitary caesium ovoids. Complication rates, which included vaginal stenosis not volunteered by the patient, were 16% (95% confidence intervals 6-26%) in the study group and 28% (95% confidence intervals 17-41%) in the control group, with no serious complications requiring surgery. The actuarial survival was 92% at 5 years in the study group, and 94% at 5 years in the control group. Local control was 94% at 5 years in the control group and 98% at 5 years in the study group. The authors suggest that the use of high-dose-rate intracavitary radiotherapy, with the Buchler afterloading system, for vaginal vault irradiation in carcinoma of the endometrium is a convenient, safe and quick method, which does not necessitate admission or sedation of the patient. In addition it provides complete radiation protection for staff.

Adenocarcinoma↗
PubMed1991

New therapeutic modalities for cancer.

A review is given on new biological approaches to cancer therapy based on knowledge concerning interferons, interleukins. LAK-cells, tumour-infiltrating lymphocytes, tumour necrosis factor, colony-stimulating factors, monoclonal antibodies and oncogenes. There are many potential permutations for the application of biological therapy for cancer. One of the most important developments has been the increased understanding of the molecular mechanisms of malignancy through which biological manipulation can be tailored to an individual tumour. Although current clinical studies are not demonstrating high response rates they may well be analogous to the advances seen with chemotherapy in its early days. As yet only relatively small numbers of patients have had access to, or been suitable for, treatment. With further refinements in production, administration, and an increase in the specificity of treatment, the possibility of curing metastatic solid tumours may become a reality.

Antibodies, Monoclonal↗
PubMed1991

Surgical and chemotherapeutic treatment of hepatic metastases from carcinoma of the breast.

To date, no five year survival rates have been reported for patients with hepatic metastases (HM) from breast origin treated by chemotherapy or hormone therapy. This study was done to evaluate whether or not surgical excision of such metastatic disease associated with chemotherapy has any effect on such a poor prognosis. Between May 1985 and September 1988, 22 patients with a diagnosis of isolated (solitary or multiple) HM have been surgically treated. The therapeutic approach also included systemic preoperative and postoperative chemotherapy. Laparotomy findings for those 22 patients are presented. There were benign hepatic lesions in four patients (four different histologic types) and hepatectomy was done in two patients. Diffuse metastatic disease contraindicated any attempt at hepatic resection in six patients. Hepatectomy was possible in 12 patients. There was no postoperative mortality and minimal morbidity. One-half of the patients with metastases had one or more positive lymph nodes at the hepatic pedicule. Median survival time for 12 patients treated by hepatectomy was 37 +/- 9 months after hepatectomy and 42 +/- 3 months after the discovery of HM. Eleven patients had other metastases after an average period of 11.8 months after hepatectomy, and the liver was the first site of recurrence in eight. One patient underwent a hepatectomy twice. Two patients were free of disease 29 to 46 months postoperatively in spite of poor prognostic features on the excised specimen. Although the median survival time was two times better than with usual treatment, we believe this procedure is of doubtful benefit. In this situation, hepatectomy acts as cytoreductive surgical treatment, with the main limiting factor being the relatively low effectiveness of chemotherapy. This type of therapy can be applied only to a restricted number of patients, and if we decide to proceed with this study, we will have to modify the protocol of chemotherapy radically.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase.

Rat liver dihydrodiol dehydrogenase (DDH, EC 1.3.1.20) has been shown to reduce the mutagenicity of benz[a]anthracene (BA) in the bacterial Ames test. BA-3,4-dihydrodiol is a highly mutagenic and tumorigenic metabolite of BA. In order to test the hypothesis that this dihydrodiol may be a substrate of DDH, we established two novel assay systems for the NADP(+)-dependent oxidation of BA-3,4-dihydrodiol by rat liver DDH, an HPLC-based assay procedure and a radiometric assay with specifically labelled [3,4-3H]-BA-3,4-dihydrodiol as substrate. With the HPLC-based assay, the kinetic constants of the enzymatic catalysis were as follows: Km(app) = 21 microM for BA-3,4-dihydrodiol and Vmax = 20.0 nmol/min.mg enzyme. The reaction product was identified by cochromatography, fluorimetry and mass spectroscopy as BA-3,4-catechol, but interconversions between the catechol and the corresponding o-quinone during the analytical procedures were detected. With the radiolabelled substrate, a linear relationship between substrate concentration and reaction velocity was found. The V/K value for labelled substrate was 0.155 ml/min.mg enzyme and a (V/K)H/(V/K)T kinetic isotope effect of 6.7 was observed. The non-labelled substrate acted as a competitive inhibitor of the enzymatic oxidation of tritiated BA-3,4-dihydrodiol with a Ki value of 56.4 microM. The reaction rates determined in this study suggest an important role of DDH activity in the metabolism of BA.

Alcohol Oxidoreductases↗
PubMed1990

Isolation and characterization of a 60-70-kD plasma membrane glycoprotein involved in the contact-dependent inhibition of growth.

Previous studies have shown that plasma membrane compounds are involved in the contact-dependent inhibition of growth of human diploid fibroblasts. The purification of the active plasma membrane glycoprotein is described in this report. The glycoprotein has an apparent molecular mass of 60-70 kD and, due to differential sialylation, isoelectric points between pH 5.5. and 6.2. Treatment with sialidase yielded one spot in two-dimensional gel electrophoresis with an isoelectric point of 6.3. After removal of the N-glycosidically linked oligosaccharide chains, the apparent molecular mass is reduced by approximately 22 kD. Treatment was diluted NaOH, which removes the O-glycosidically linked portion of oligosaccharides, resulted in a reduction of the apparent molecular mass by approximately 5 kD. The addition of 50 ng/ml of this glycoprotein-for which the term "contactinhibin" is proposed-in immobilized form to sparsely seeded human fibroblasts resulted in a reversible 70-80% inhibition of growth. The inhibition was not confined to human fibroblasts as other cells were also inhibited, with the exclusion of transformed cells, which are refractory to contactinhibin. The inhibitory activity was abolished by treatment with beta-galactosidase or glycopeptidase F, indicating that the glycan moiety is the biologically active part of the molecule. Confluent cultures treated with antibodies raised against contactinhibin were released from the contact-dependent inhibition of growth. In addition to enhanced saturation density, these cultures exhibited a crisscross growth pattern and the formation of foci. Immunocytochemical studies showed that contactinhibin was associated with vimentin. Furthermore, contactinhibin was found to be not expressed in a species- or organ-specific manner.

Animals↗
PubMed1990

An assessment of a hospital-based pregnancy testing service.

A proposal to withdraw the hospital-based pregnancy testing service provoked a local debate in which a range of strongly held but conflicting opinions were expressed. It was agreed to seek more detailed information before making any final decision. The authors describe their investigations and findings about the use of the service and the views of its consumers. Subsequently, a solution was reached for a novel but more appropriate form of service provision. It is argued that when planning changes in service provision health authorities should obtain information from and consult widely with all consumers.

Female↗