Search PubMed⌕ Search

Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 181 records · Page 10Linked to original sources
PubMed1995

Core RNA polymerase and promoter DNA interactions of purified domains of sigma N: bipartite functions.

The sigma N class of sigma factors confer upon RNA polymerase the requirement for enhancer-binding activator proteins. The sigma-N (sigma N) protein of Klebsiella pneumoniae was analysed by the assay of purified peptides comprising domains or regions of sigma N defined by proteolysis or by homology alignment, respectively. The NH2-terminal Region I is required for the correct interaction of holoenzyme with the promoter, and promoter complexes forming with a truncated sigma N lacking Region I are not activatable. The complexes lack the DNA structure believed to represent nucleated strand separation but still make close contacts with this promoter part. Determinants of specific DNA recognition by sigma N were shown to reside in a C-terminal 16 kDa peptide, and core RNA polymerase binding determinants in an adjacent peptide. The latter contacts and appears to pack against the DNA-binding domain. Thus the DNA-binding and core-binding domains are bipartite in function, consistent with core functioning as an allosteric effector of the sigma DNA-binding activity. The DNA-binding and core-binding domains together include Region III of sigma N. Although not the primary determinant of core or DNA recognition, the acidic Region II of sigma N influenced both activities. Regions I and II in combination with core RNA polymerase thus appear to control the activity of C-terminal DNA contacting surfaces to allow formation of a closed promoter complex that is susceptible to activation.

Allosteric Regulation↗
PubMed1995

No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study.

A possible association between body iron stores, measured as serum ferritin, and carotid arterial intima-media thickening was investigated in the Atherosclerosis Risk in Communities Study during 1990-1992 using a matched case-control design. For a 143-micrograms/liter greater serum ferritin concentration (the interquartile range), the odds ratio for cases with carotid intima-media thickening versus controls was 1.12 (95% confidence interval 0.97-1.30). However, there was no association (odds ratio = 1.00) after adjusting for major cardiovascular risk factors. This analysis of carotid arterial intima-media thickening, a measure of early atherosclerosis, in relation to serum ferritin does not support the hypothesis that increased body iron stores increase the risk of atherosclerotic cardiovascular disease.

Arteriosclerosis↗
PubMed1995

Identification of close contacts between the sigma N (sigma 54) protein and promoter DNA in closed promoter complexes.

The complexes forming between the alternative sigma factor protein sigma N (sigma 54), its holoenzyme and promoter DNA were analysed using the hydroxyl radical probe and by photochemical footprinting of bromouridine-substituted DNA. Close contacts between the promoter, sigma N and its holoenzyme appear to be restricted predominantly to one face of the DNA helix, extending from -31 to -5. They all appear attributable to sigma N and no extra close contacts from the core RNA polymerase subunits in the holoenzyme-promoter DNA complex were detected. We suggest that the apparent absence of close core RNA polymerase contacts in the region of the promoter DNA to be melted during open complex formation is important for maintaining the closed complex. Results of the hydroxyl radical footprinting imply that sigma N makes multiple DNA backbone contacts across and beyond the -12, -24 consensus promoter elements, and the photochemical footprints indicate that consensus thymidine residues contribute important major groove contacts to sigma N. Formation of the open complex is shown to involve a major structural transition in the DNA contacted by sigma N, establishing a direct role for sigma N in formation of the activated promoter complex.

Base Sequence↗
PubMed1995

Efficacy and pharmacokinetics of two formulations of cyclosporine A in patients with psoriasis.

The efficacy and pharmacokinetic profiles of two oral formulations of cyclosporine A (Sandimmune and Neoral; Sandoz Pharmaceuticals, East Hanover, NJ) were evaluated in 37 patients with moderate to severe plaque psoriasis in a randomized, double-blind, modified, crossover study. Cyclosporine A (150 mg twice daily), administered in either formulation, reduced the severity of plaque lesions: 94% of all patients reported at least moderate improvement and 70% reported complete clearing. Approximately 2 weeks of therapy were required for drug exposure to stabilize on either formulation. Cyclosporine A exposure from Neoral was significantly greater relative to that from Sandimmune across all study weeks. At the eighth week (before crossover), AUC and Cmax values for Neoral and Sandimmune were 5618 +/- 1705 versus 3202 +/- 596 ng.h/mL and 1283 +/- 337 versus 623 +/- 173 ng/mL, respectively. In crossover analysis at steady state, the relative oral bioavailability of cyclosporine from the Neoral formulation was 54% greater than that from Sandimmune. Some pharmacokinetic parameters showed less variability both between and within groups of patients taking Neoral versus Sandimmune. Both formulations were well tolerated, in that most adverse events were of mild severity.

Chemistry, Pharmaceutical↗
PubMed1995

Detection of interleukin-1 signal transduction inhibitors: action of protein kinase inhibitors.

The dysregulated production of IL-1 has been shown to play an important role in many pathological processes. Despite the apparent value of compounds able to inhibit either the secretion of IL-1 or its signal transduction pathway in a specific manner, there are no such compounds suitable for clinical use. A major problem in identifying novel and specific inhibitors of signal transduction is the lack of knowledge of the intracellular events which mediate the cellular actions of IL-1. In this study a simple cellular assay has been established to screen natural product and synthetic compound libraries for low molecular weight inhibitors of the cytokine signalling pathways of potential therapeutic value. In addition, we have studied the action of several known modulators of signal transduction on the actions of IL-1.

Cell Division↗
PubMed1995

Reasons for non-drinking among Israeli adolescents of four religions.

Adolescent abstainers have largely been ignored in the literature. This article describes the reasons for not drinking of 2366 Israeli Jewish, Moslem, Druze and Christian adolescents in the north of Israel in the winter of 1994. It analyzes the findings by religious group, religiosity (secular versus religious Jews), location and gender of Jews, and school grade of Jews and Moslems. Harmful health consequences of alcohol use and religious injunction are the most prevalent reasons for abstinence among Moslems and Druze. Jews abstain mainly because of disliking the taste and/or smell of alcohol and because they 'do not care for it'. Christians abstain mainly because of the harmful effects of alcohol on health and dislike of its taste and/or smell. The implications of the results for prevention are discussed.

Adolescent↗
PubMed1995

Oxidation and glucose conjugation of synthetic abietane diterpenes by Cunninghamella sp. II. Novel routes to the family of diterpenes from Tripterygium wilfordii.

Abietane diterpenes from the perennial herb, Tripterygium wilfordii, have been shown to possess antiinflammatory activity. To obtain novel analogues of these diterpenes, two synthetic diterpenes, isotriptophenolide [1] (12,19-dihydroxy-18(4-->3)abeo-abieta-3,8,11,13-tetraen++ +-18-oic acid lactone) and triptophenolide [3] (14,19-dihydroxy-18(4-->3)abeo-abieta-3,8,11,13-tetraen++ +-18-oic acid lactone) were incubated with the filamentous fungi, Cunningbamella echinulata and C. elegans. The structures of the metabolites were then determined by spectroscopic methods. Both species of Cunninghamella glucosidated 1 at C-12 to yield 2. When incubated with triptophenolide [3], C. elegans and C. echinulata produced hydroxylated [6] and glucosylated [7] metabolites. In addition to B-ring hydroxylation, aromatic hydroxylation at ring C was also observed. Both species hydroxylated 3 to yield the dihydrodiol 4 which autooxidized to the quinone 5.

Biotransformation↗
PubMed1995

Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine.

Adult↗
PubMed1995

Do birth plans empower women? Evaluation of a hospital birth plan.

In early 1993 a birth plan for the South Western Sydney (Australia) Area Health Service was introduced in two district hospitals. Its ease of use and effectiveness were evaluated from May to July 1993, using a questionnaire that was completed postnatally by the first 100 women who had completed a prenatal birth plan. All women were asked to complete the questionnaire regardless of whether they had used the written birth plan during labor. Ninety-five percent of women said that they would encourage other women to use the plan. It increased their own understanding about the processes of labor and birth, and the hospital options open to them. Women said it was helpful, enabled them to express their needs and preferences, enhanced their confidence, and improved communication between them and staff. Birth plans show the commitment of health caregivers to recognizing and supporting diversity, allow for critical reappraisal of existing hospital policies and practices, and provide an opportunity for quality improvement in the context of client rights and preferences. They empower women by increasing their knowledge and understanding of birth practices, and helping them make informed choices.

Adult↗
PubMed1995

The oxidation of pyrene and benzo[a]pyrene by nonbasidiomycete soil fungi.

The purpose of this study was to determine the ability of nonbasidiomycete soil fungi to oxidize pyrene (four rings) and benzo[a]pyrene (BaP) (five rings). Fungi were isolated from five different soils in which the polycyclic aromatic hydrocarbon content ranged from 0.8 to 80 micrograms/g dry soil. Approximately 50% of the isolates in all sites were able to oxidize pyrene. The pyrene-oxidizing species belonged to all fungal divisions except basidiomycetes. The most common were Penicillium spp. of the subgenus Furcatum and these dominated the more contaminated soils. Penicillium janthinellum and Syncephalastrum racemosum exhibited the most rapid rates of pyrene oxidation. The major pyrene metabolites were identified by proton NMR and mass spectrometry as 1-pyrenol, 1,6- and 1,8-pyrenediol, and the 1,6-and 1,8-pyrenequinones. A high correlation was found between the ability to oxidize pyrene and BaP. As with pyrene, approximately 50% of the fungal isolates tested oxidized BaP to 9-hydroxy-BaP. Eighty percent of the pyrene-oxidizing strains were also able to metabolize BaP.

Benzo(a)pyrene↗
PubMed1995

Stage I testicular seminoma: results of adjuvant irradiation and surveillance.

PURPOSE: To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance. PATIENTS AND METHODS: Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1). RESULTS: The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age. CONCLUSION: The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.

Actuarial Analysis↗
PubMed1995

Trends in the management of alcohol withdrawal syndrome.

Alcohol use among head and neck cancer patients is common. Alcohol withdrawal (especially delirium tremens) poses significant potential morbidity to postsurgical patients. Treatment with newer benzodiazepines (BZDs) such as lorazepam and midazolam has become more widespread, and mortality rates from severe alcohol withdrawal have decreased in recent years. The authors retrospectively studied 102 patients with a diagnosis of alcohol withdrawal, including 20 patients undergoing surgery for cancer of the head and neck. There were 81 men and 21 women, with a mean (+/- standard deviation [SD]) age of 52.3 (+/- 16.1) years. Many of these patients (46%) were treated with more than one BZD or other neuroleptic, while 49% received single agent therapy of either chlordiazepoxide (26%) or lorazepam (23%). Delirium tremens occurred in 12% of all patients undergoing withdrawal and in 10% of head and neck cancer patients, with a mortality rate of 9% and 0%, respectively. Single agent use was successful in greater than 95% when either lorazepam or chlordiazepoxide was used. Instances of combination treatment where older BZDs were used yielded a 69% success rate. The higher complication rate and lower treatment success with combination treatment was multifactorial. Optimal management of the alcohol withdrawal syndrome requires an understanding of its pathophysiology and the principles of its prevention along with a familiarity of BZD pharmacokinetic drug profiles. The authors present a treatment plan which is cost-effective, keeps morbidity low, and should allow a continued decreasing trend in mortality rates from delirium tremens.

Adult↗
PubMed1995

Sources of alcohol and drug information among Israeli urban adolescents.

This article describes a study which investigated sources of alcohol and drug information among Israeli urban adolescents in the north of Israel during the winter of 1993. Data were obtained from a sample of 1,346 students (50.9% males, 49.1% females), who were asked to indicate the amount of information (none, little, much) they had received from ten sources about eight categories of drugs. Among the findings: television is the primary source of information for all drugs, except inhalants, for which newspapers/magazines are the main source. Newspapers/magazines are of secondary importance for the rest of the seven categories of drugs. Teenagers are less likely to receive information from physicians/nurses and relatives than from other sources. Information based on personal experience is prominent concerning alcohol, cigarettes, inhalants and hashish/marijuana, and it prevails more among males than among females (p < .01). Females use school teachers as a source of information in all drug categories more than males (p < .01). There are differences in using various information sources among grades and types of places of living. Information based on personal experience with alcohol is notably correlated with that with cigarettes, whereas information based on personal experience with opiates is correlated with that with stimulants, hallucinogens and hashish/marijuana (p < .001). The mean number of sources of information used by the respondents is the highest concerning alcohol and the lowest concerning depressants. Implications for prevention are discussed.

Adolescent↗
PubMed1995

Reasons for abstinence among Moslem, Druze, and Christian adolescents in Israel.

This article describes reasons for abstinence of 1,066 Israeli Arab (Moslem, Druze, and Christian) adolescents in the north of Israel in winter 1994. It analyzes the results by religious group, gender, and location. "Alcohol damages health" and "Do not like the taste/smell" are the most prevalent reasons for not drinking among Christians. "Alcohol damages health" and "Religion intolerant of alcohol use" are most important among Moslems and Druze. "Do not care for it" and "Have seen bad examples of what alcohol can do" are also prominent reasons among Arab respondents. Implications of results for prevention are included.

Adolescent↗