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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 235 records · Page 13Linked to original sources
PubMed1993

Characterization of the cysteine proteinases of the common liver fluke Fasciola hepatica using novel, active-site directed affinity labels.

The excreted/secreted proteinases of adult and juvenile Fasciola hepatica maintained in vitro were found to hydrolyse the fluorogenic substrates Cbz-Phe-Arg- and Cbz-Arg-Arg-NHMec. This activity was demonstrated to have a classical cysteine proteinase inhibitor profile, with turn-over of both substrates being blocked by pre-incubation with E64 and peptidyl diazomethanes. The Cbz-Arg-Arg-NHMec hydrolysing activity of the mature fluke exhibited an alkaline stability not characteristic of its mammalian lysosomal counterparts. Further, the biotinylated affinity reagents biotin-Phe-Ala-CHN2 and biotin-Phe-Cys(SBzyl)-CHN2 were used to label and characterize these cysteine proteinases in terms of apparent molecular weight and subsite specificity. Adult fluke media were found to contain four species of molecular weights 66, 58, 50 and 25-26 kDa; juvenile media contained three species of molecular weights 66, 54 and 25-26 kDa. The major 25-26 kDa cysteine proteinase common to both stages was shown to have a subsite specificity similar to that of mammalian cathepsin B.

Affinity Labels↗
PubMed1993

Gain of function mutations in p53.

We report that the expression of murine or human mutant p53 proteins in cells with no endogenous p53 proteins confers new or additional phenotypes upon these cells. Mutant p53 proteins expressed in cell lines lacking p53 resulted in either enhanced tumorigenic potential in nude mice ((10)3 cells) or enhanced plating efficiency in agar cell culture (human SAOS-2 cells). Also, mutant human p53 alleles, unlike the wild-type p53 protein, could also enhance the expression of a test gene regulated by the multi-drug resistance enhancer-promoter element. These data demonstrate a gain of function associated with p53 mutations in addition to the loss of function shown previously to be associated with mutations in this tumour suppressor gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

A quantitative assay for trans-activation by HIV-1 Tat, using liposome-mediated DNA uptake and a parallel ELISA system.

A cellular assay is described in which transient high-level expression of a heterologous reporter gene (chloramphenicol acetyltransferase, CAT) driven by the HIV LTR is used to determine trans-activation in a cell line constitutively expressing Tat. The use of a parallel ELISA system to determine effects on expression of CAT and of the neomycin phosphotransferase (NPT) marker gene effectively eliminated sample variability caused by cumulative processing errors or cell culture conditions. In addition the use of cationic liposome-mediated transfection minimized delay between DNA treatment that initiates trans-activation and addition of inhibitors, thereby eliminating background expression levels in treated samples. The assay has the potential to discriminate between inhibition of trans-activation and nonspecific effects such as inhibition of transfection and cytotoxicity. It has been adapted to a 96-well format suitable for high-throughput screening of natural products and synthetic chemicals.

DNA, Recombinant↗
PubMed1993

Gemcitabine in advanced renal cell carcinoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) an anticancer agent with activity in preclinical models, was felt to be a promising new chemotherapy drug which warranted testing in patients with advanced renal cell carcinoma. METHODS: Eighteen patients with histologically proven metastatic or locally recurrent renal cell carcinoma and bidimensionally measurable disease were accrued to a phase II study of gemcitabine administered intravenously on days 1, 8 and 15 of a 28 day treatment cycle. Initial doses of gemcitabine were 800 mg/m2; doses in subsequent cycles were escalated to a maximum of 1250 mg/m2, toxicity permitting. RESULTS: One partial response was seen for a response rate of 6%. Hematologic toxicity was not severe with this dosing schedule; however, two patients developed dyspnea with bronchospasm after repeated injections of drug. CONCLUSIONS: The dose and schedule of gemcitabine employed results in only a modest response rate in patients with advanced renal carcinoma. Investigators should be aware of the possibility of dyspnea and bronchospasm developing shortly after gemcitabine administration.

Adult↗
PubMed1993

Multicenter phase II study of brequinar sodium in patients with advanced breast cancer.

In this study, 34 patients with advanced breast cancer were treated with brequinar sodium: 75% of the patients were postmenopausal, and 94% had received chemotherapy previously; 50% had previously received an anthracycline-containing regimen. Brequinar was administered intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 17 patients (50%) experiencing grade 3 or 4 toxicity. There were 33 patients evaluable for response: 4 patients (12%; 95% confidence interval, 3.4-28.2%) achieved partial responses, 10 patients (30%) were stable, and 19 patients (58%) had progressive disease. We conclude that, at this dose and schedule, brequinar has only modest activity in patients with advanced breast cancer.

Adult↗
PubMed1993

Rapid administration of multiple cycles of high-dose myelosuppressive chemotherapy in patients with metastatic breast cancer.

PURPOSE: To determine the feasibility and safety of a rapidly cycled sequence of high-dose myelosuppressive chemotherapy courses. PATIENTS AND METHODS: Seventeen patients with metastatic breast cancer were treated with two courses of cyclophosphamide (CPA; 3.0 g/m2) supported by granulocyte colony-stimulating factor (G-CSF). Following the first CPA treatment, peripheral-blood leukaphereses commenced when the leukocyte count recovered to 1.0 x 10(9)/L. After hematologic recovery from the second dose of CPA, patients were treated with carboplatin 1,500 mg/m2, etoposide 1,200 mg/m2, and CPA 5.0 g/m2 administered over 3 days. The peripheral-blood progenitors (PBPs) were reinfused 3 days later, and G-CSF was recommenced. RESULTS: All patients received the three courses. The median interval between treatments was 14 days (range, 13 to 21). Sixteen of the 34 courses of CPA resulted in admissions for fever. Following the third course, neutrophil counts recovered to 0.5 x 10(9)/L at a median of 9 days (range, 8 to 18) after PBP reinfusion and platelets recovered to 50 x 10(9)/L at a median of 12 days (range, 9 to 102). There were no treatment-related deaths. Flow-cytometric analysis was performed on the leukapheresis collections of eight patients. Seven patients with at least 2.0 x 10(6) CD34+ CD33- cells per kilogram body weight exhibited prompt hematologic recovery. One patient with 0.03 x 10(6) CD34+ CD33- cells was still cytopenic on day 21, and required reinfusion of her back-up marrow. Among seven patients with measurable or assessable disease, there were two complete responses (CRs) and four partial responses (PRs). CONCLUSION: These preliminary results suggest that multiple, rapidly cycled courses of high-dose myelosuppressive chemotherapy can be administered. PBPs, harvested during the G-CSF-augmented rebound from CPA-induced cytopenia, produce rapid hematologic recovery in patients undergoing high-dose chemotherapy (HDC). Further follow-up will be necessary to assess the efficacy of this specific regimen in the treatment of metastatic breast cancer.

Adult↗
PubMed1992

Structuring HIV prevention service delivery systems on the basis of social science theory.

In order to identify the optimal configuration of HIV prevention programs, it is necessary to examine different theoretical models of behavior change. Cognitive/decision-making theories of human behavior change are compared to social learning theories vis-a-vis their influence on the structure of service delivery systems. Cognitive/decision-making theories ascribe behavior change to the provision of new information and favor the development of homogeneous interventions providing clients with information about risk behaviors. These interventions are easily standardized across delivery sites and various target populations. Social learning theories view behavior change as a series of stages and recognize the influence of sociocultural variables. They favor multiple heterogeneous interventions in a variety of settings, with the provision of skills training as well as information. Ongoing HIV prevention research indicates that social learning theories provide a more accurate paradigm of human behavior change for the complex behaviors related to HIV risk. Public health agencies must therefore continue to strengthen organizational and referral relationships with community-based organizations that can provide the specialized prevention interventions called for by social learning theory. This will require ongoing collaboration and technical assistance.

Adolescent↗
PubMed1992

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

Adult↗
PubMed1992

Tumour-infiltrating lymphocytes in cervical carcinoma.

Tumour-infiltrating lymphocytes from cervical carcinomas were cultivated in the presence of interleukin-2. The majority of bulk cultures were cytotoxic against K562, Mel 1 and Caski cells. CD8+ cells were the predominant subset in over 50% of cultures, with varying numbers of CD56+ and CD25+ cells. T cell clones were established from six tumour-infiltrating lymphocyte cultures and the majority exhibited non-MHC-restricted cytotoxicity. However, in one case cytotoxicity of several derived clones was limited to the autologous tumour and in another, to the autologous tumour and Caski cells. This study indicates that tumour-infiltrating lymphocytes can be amplified and cloned from cervical carcinoma biopsies in the presence of rIL2. Although the predominant cytolytic function is non-MHC-restricted, low autotumour cytotoxicity can be demonstrated at the clonal level. The nature of the antigen(s) recognised by T cells on autologous cervical carcinoma cells in unknown; the candidacy of human papillomavirus-related products requires investigation.

Adult↗
PubMed1992

Multicenter phase II trial of brequinar sodium in patients with advanced melanoma.

Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.

Adult↗
PubMed1992

Circulatory responses during electroconvulsive therapy. The comparative effects of placebo, esmolol and nitroglycerin.

Electroconvulsive therapy is usually accompanied by activation of the autonomic nervous system, which may be harmful in patients with cerebrovascular or ischaemic heart disease. We have compared this haemodynamic response in a series of 82 electroconvulsive treatments randomly assigned to receive either nitroglycerin 3 micrograms.kg-1, esmolol 2 mg.kg-1 or placebo. These drugs were given shortly after the suxamethonium and 2 min before the electroconvulsive therapy in all cases. Heart rate was significantly lower with esmolol 1 min after therapy as was blood pressure (systolic and diastolic). The pulse rate was higher following nitroglycerin than placebo, which in turn was higher than esmolol. The three groups did not differ with regard to seizure duration. The results demonstrate that esmolol is more effective than nitroglycerin in controlling the haemodynamic response to electroconvulsive therapy. With recent emphasis on stabilisation of heart rate in preference to blood pressure in at-risk cardiac patients, our study suggests that, in the doses selected, esmolol is preferred to nitroglycerin to control the heart rate response to electroconvulsive therapy.

Adrenergic beta-Antagonists↗
PubMed1992

Third ventricle enlargement and lower heart rate levels in a high-risk sample.

Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18-year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity.

Adolescent↗
PubMed1992

p53 mutations are not selected for in simian virus 40 T-antigen-induced tumors from transgenic mice.

Many diverse tumors contain cells that select for mutations at the p53 gene locus. This appears to be the case because the p53 gene product can act as a negative regulator of cell division or a tumor suppressor. These mutations then eliminate this activity of the p53 gene product. The simian virus 40 (SV40) large T antigen binds to p53 and acts as an oncogene to promote cellular transformation and initiate tumors. If the binding of T antigen to the p53 protein inactivated its tumor suppressor activity, there would be no selection pressure for p53 mutants to appear in tumors. To test this idea, transgenic mice that carried and expressed the SV40 large T-antigen gene were created. Expression of the T antigen was directed to the liver, using the albumin promoter, and the choroid plexus, using the SV40 enhancer-promoter. A large number of papillomas (indicated in parentheses) of the choroid plexus (14), hepatocellular carcinomas (5), liver adenomas (10), and tumors of clear-cell foci (5) were examined for mutant and wild-type p53 genes and gene products. In all cases, the tumor extracts contained readily detectable T-antigen-p53 protein complexes. A monoclonal antibody specifically recognizing the wild-type p53 protein (PAb246) reacted with p53 in every tumor extract. A monoclonal antibody specifically recognizing mutant forms of the p53 protein (PAb240) failed to detect p53 antigens in these extracts. Finally, p53 partial cDNAs were sequenced across the regions of common mutations in this gene, and in every case only the wild-type sequence was detected. These results strongly support the hypothesis that T antigen inactivates the wild-type p53 tumor-suppressing activity and there is no need to select for mutations at the p53 locus.

Animals↗
PubMed1992

Perception of alcoholism among Jewish, Moslem and Christian teachers in Israel.

This article describes a survey which investigated perception of alcoholism among Jewish, Moslem and Christian teachers in the north of Israel during the spring of 1991. Data were obtained from a sample of 553 teachers. The teachers were asked to agree or disagree with items associated with the disease concept or with the moral concept of alcoholism. The findings indicate differences in the perception of alcoholism among teachers of different religions, education levels, gender, and drinking practices. No differences were found among teachers of different ages or among those working in different types of schools.

Alcohol Drinking↗