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Biomedical subjects

E Ford

Publications and source records attributed to E Ford.

At least 19 recordsLinked to original sources
PubMed1998

The Oct-1 POU domain activates snRNA gene transcription by contacting a region in the SNAPc largest subunit that bears sequence similarities to the Oct-1 coactivator OBF-1.

The RNA polymerases II and III snRNA gene promoters contain an octamer sequence as part of the enhancer and a proximal sequence element (PSE) as part of the core promoter. The octamer and the PSE bind the POU domain activator Oct-1 and the basal transcription factor SNAPc, respectively. Oct-1, but not Oct-1 with a single E7R mutation within the POU domain, binds cooperatively with SNAPc and, in effect, recruits SNAPc to the PSE. Here, we show that SNAPc recruitment is mediated by an interaction between the Oct-1 POU domain and a small region of the largest subunit of SNAPc, SNAP190. This SNAP190 region is strikingly similar to a region in the B-cell-specific Oct-1 coactivator, OBF-1, that is required for interaction with octamer-bound Oct-1 POU domain. The Oct-1 POU domain-SNAP190 interaction is a direct protein-protein contact as determined by the isolation of a switched specificity SNAP190 mutant that interacts with Oct-1 POU E7R but not with wild-type Oct-1 POU. We also show that this direct protein-protein contact results in activation of transcription. Thus, we have identified an activation target of a human activator, Oct-1, within its cognate basal transcription complex.

Amino Acid Sequence↗
PubMed1998

Lung cancer deaths in the United States from 1979 to 1992: an analysis using multiple-cause mortality data.

BACKGROUND: We sought to describe trends in the presence of lung cancer at the time of death in the United States from 1979 to 1992. METHODS: We analysed death certificate reports in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics, searching for any mention of lung cancer, lung cancer as the underlying cause of death, and comorbid conditions. RESULTS: Of the 29,042,213 decedents in the study period, 1,892,129 (6.5%) had a diagnosis of lung cancer listed on their death certificates; of these 1,892,129 decedents, 1,734,767 (91.7%) had lung cancer listed as the underlying cause of death. Decedents with lung cancer listed as being present but not the underlying cause of death were more likely to be male (relative risk [RR] 1.16, 95% confidence interval [CI]: 1.15-1.17), and older (RR 4.61, 95% CI: 4.35-4.88 for decedents older than 85 compared to those aged less than 44), but less likely to be black than white (RR 0.88, 95% CI: 0.87-0.90). The mortality rate, age-adjusted to the 1980 population, increased 23.0%, from 47.9 per 100,000 in 1979 to 58.9 per 100,000 in 1992. Over the study period, black men had the highest mortality rates (117.3-125.2 per 100,000), followed by white men (81.7-88.7 per 100,000), men of other races (37.4-46.7 per 100,000), white women (22.1-39.1 per 100,000), black women (21.4-38.2 per 100,000), and women of other races (12.6-18.1 per 100,000). Age-adjusted, state specific rates varied threefold, from 30.4 per 100,000 in Utah to 93.9 per 100,000 in Nevada. CONCLUSIONS: We conclude that the underlying cause of death data base, which captures almost 92% of decedents with lung cancer present, accurately tracks lung cancer mortality trends in the US. Mortality rates of lung cancer, which are decreasing among men, continue to increase among women.

Adolescent↗
PubMed1997

Characterization of a trimeric complex containing Oct-1, SNAPc, and DNA.

The human small nuclear (sn) RNA promoters contain a proximal sequence element (PSE), which recruits the basal transcription factor SNAPc, and a distal sequence element characterized by an octamer sequence, which recruits the POU domain transcription factor Oct-1. The Oct-1 POU domain and SNAPc bind cooperatively to probes containing a PSE and an octamer sequence, and this effect contributes to efficient transcription in vitro. In vivo, however, Oct-1 regions outside of the POU domain can activate snRNA gene transcription. Here, we have examined whether the role of these regions is to contribute to cooperative binding with SNAPc. We find that they indeed improve cooperative binding, but most of the effect is nevertheless mediated by just the POU domain. This suggests that Oct-1 activates transcription of snRNA genes in at least two steps, recruitment of SNAPc mediated primarily by the POU domain, and a later step mediated by regions outside of the POU domain. We also show that a PSE-binding complex observed in nuclear extracts consists of Oct-1 and SNAPc. Although Oct-1 cannot bind effectively to the PSE probe on its own, in the complex it contacts DNA. Thus, in a nuclear extract, SNAPc can recruit Oct-1 to a probe to which Oct-1 cannot bind on its own.

Base Sequence↗
PubMed1997

Development of tolerance in mice to the sedative effects of the neuroactive steroid minaxolone following chronic exposure.

Minaxolone is a potent ligand for the neurosteroid binding site of the GABAA, receptor. In radioligand binding studies to rat brain membranes, minaxolone caused a 69% increase in [3H]muscimol binding and a 25% increase in [3H]flunitrazepam binding and inhibited the binding of [3H]TBOB with an IC50 of 1 microM. In mice, minaxolone (100 mg/kg, orally) had marked sedative effects as indicated by a reduction in locomotor activity. Chronic dosing with minaxolone (100 mg/kg, orally, once daily for 7 days) resulted in a loss of sedative response to an acute dose of the drug, indicating development of tolerance. Chronic dosing with temazepam (10 mg/kg, orally, once daily for 7 days) resulted in the development of tolerance to an acute dose of temazepam; however, the two drugs did not appear to be cross-tolerant, indicating that they may have a different mechanism of action at the level of the GABAA receptor.

Anesthetics↗
PubMed1997

The role of the IsK protein in the specific pharmacological properties of the IKs channel complex.

IKs channels are composed of IsK and KvLQT1 subunits and underly the slowly activating, voltage-dependent IKs conductance in heart. Although it appears clear that the IsK protein affects both the biophysical properties and regulation of IKs channels, its role in channel pharmacology is unclear. In the present study we demonstrate that KvLQT1 homopolymeric K+ channels are inhibited by the IKs blockers 293B, azimilide and 17-beta-oestradiol. However, IKs channels induced by the coexpression of IsK and KvLQT1 subunits have a 6-100 fold higher affinity for these blockers. Moreover, the IKs activators mefenamic acid and DIDS had little effect on KvLQT1 homopolymeric channels, although they dramatically enhanced steady-state currents through heteropolymeric IKs channels by arresting them in an open state. In summary, the IsK protein modulates the effects of both blockers and activators of IKs channels. This finding is important for the action and specificity of these drugs as IsK protein expression in heart and other tissues is regulated during development and by hormones.

Animals↗
PubMed1995

Visual attention and perception in patients with Huntington's disease: comparisons with other subcortical and cortical dementias.

Shifts in attention were examined in patients with Huntington's disease (HD) using a divided attention paradigm that involved the presentation of global-local stimuli. The HD patients' pattern of performance was compared to the previously reported results of groups of patients with Alzheimer's disease (AD; Filoteo et al., 1992) or Parkinson's disease (PD; Filoteo et al., 1994). Across consecutive trials of the divided attention task, a visual target could appear at either the same global-local level or at a different level. When the target changed levels across consecutive trials, the AD patients demonstrated an impairment in disengaging attention from the level at which the last target appeared, whereas the PD patients were impaired in maintaining their attention at the previously attended level. In contrast to these patterns of performances, the HD patients did not demonstrate a significant impairment in shifting attention between hierarchical levels. Both the AD and the PD patients' abnormal shifting ability was significantly related to the number of errors they made in identifying target stimuli; however, the pattern of the relationship was qualitatively distinct. These results suggest that different attentional mechanisms may underlie AD and PD patients' visual-perceptual deficits. The HD patients' shifting ability was not related to the number of errors they made in identifying target stimuli, suggesting that a different mechanism may account for the visual-perceptual impairments exhibited by these patients.

Aged↗
PubMed1995

Education needs in palliative care.

A literature review confirms a need for improved medical education on death, dying, terminal illness, and bereavement, and so palliative care, from 1900 until the present time in the UK, Australia, New Zealand, USA, and Canada. The origins of the hospice movement and its influence are also discussed. Current palliative care teaching is recorded in a table of the courses initiated in medical schools which demonstrates a lack of formal courses. An appreciation of the issues surrounding these topics is required for the appropriate provision of palliative care, most importantly good communication and symptom control. These together with the issues of development of attitudes towards death, delivering bad news of serious illness, recognition of palliative care as a philosophy, psychosocial aspects of care and counselling the bereaved are included in the recommendations for co-ordinated interdepartmental teaching. This acquisition of knowledge, development of attitudes, and improvement of skills in palliative care can be achieved through the use of small group work and role-play exercises as well as formal lectures and experience at a hospice. Rectification of these curricula omissions will provide future doctors in a caring and competent manner with the ability to permit a dignified and 'good' death for the terminally ill.

Australia↗
PubMed1995

Dealing with dying.

Explore the source record for details and available documents.

Attitude to Death↗
PubMed1994

Synthesis of circular RNA in bacteria and yeast using RNA cyclase ribozymes derived from a group I intron of phage T4.

Studies on the function of circular RNA and RNA topology in vivo have been limited by the difficulty in expressing circular RNA of desired sequence. To overcome this, the group I intron from the phage T4 td gene was split in a peripheral loop (L6a) and rearranged so that the 3' half intron and 3' splice site are upstream and a 5' splice site and 5' half intron are downstream of a single exon. The group I splicing reactions excise the internal exon RNA as a circle (RNA cyclase ribozyme activity). We show that foreign sequences can be placed in the exon and made circular in vitro. Expression of such constructs (RNA cyclase ribozymes) in Escherichia coli and yeast results in the accumulation of circular RNA in these organisms. In yeast, RNA cyclase ribozymes can be expressed from a regulated promoter like an mRNA, containing 5' leader and 3' trailer regions, and a nuclear pre-mRNA intron. RNA cyclase ribozymes have broad application to questions of RNA structure and function including end requirements for RNA transport or function, RNA topology, efficacy of antisense or ribozyme gene control elements, and the biosynthesis of extremely long polypeptides.

Bacteriophage T4↗
PubMed1992

Proximal and distal cannulation of the internal jugular vein for ECMO in a primate.

Extracorporeal membrane oxygenation (ECMO) is lifesaving for infants with severe respiratory distress but is complicated by severe intracranial hemorrhage in 10% to 30% of patients. Intracranial venous hypertension, as a result of ligation of the internal jugular vein (IJV), has been hypothesized as a contributing factor to cerebral edema and subsequent hemorrhage. Accessory cephalad IJV cannulation may serve as a means of additional venous drainage to the pump as well as protection against intracranial venous hypertension. Proximal and distal cannulation of the IJV were studied in a primate model. The parameters monitored included sagittal sinus, right and left ventricular pressures as well as venous pressure in the ECMO circuit. The cephalad venous cannula was clamped and unclamped at 30-minute intervals. There was no significant difference in sagittal sinus or intracranial pressures during periods of cephalad cannula clamping or unclamping. Venous return was augmented when the cephalad cannula was unclamped. Cephalad cannulation has no demonstrable protective effect on intracranial, subarachnoid or venous pressures but does improve venous return to the ECMO circuit. It is concluded that cephalad venous cannulation is not necessary in all cases and should be reserved for those patients requiring additional venous drainage to support pump flow.

Animals↗
PubMed1992

Comparability of risk factors for coronary heart disease among blacks and whites in the NHANES-I Epidemiologic Follow-up Study.

The incidence of new coronary events and the predictive strength of the major coronary risk factors were evaluated in a biracial sample drawn from the general U.S. population. In this cohort of 12,599 persons, free of reported coronary heart disease (CHD) at baseline, both hospitalizations and deaths coded to this cause were recorded prospectively. Based on CHD as the underlying cause of death, black men and women experienced higher age-adjusted mortality than their white counterparts (BM = 6.15, WM = 5.59, BW = 3.72 and WW = 2.58 [cumulative deaths, percent]), while having lower hospitalization rates than did whites. In a univariate logistic regression model, with all incident events as the endpoint, the predictive strength of the coronary risk factors was remarkably similar for the four sex-race groups. Notable exceptions included smoking, where the data from this study are problematic, and body mass index, where a relationship was noted only among white women. In a multivariate model, the beta coefficients were similar for age, systolic blood pressure, cholesterol, and income; the statistical significance varied among the groups. Within the power of this study to examine between-race differences, the predictive strength of the standard risk factors are very similar. None of the within-sex, between-race differences in the multivariate relationships were significant, although sizable percentage differences were noted. Blacks appeared to receive less hospital care for CHD, despite higher rates of fetal events.

Black or African American↗
PubMed1992

Racial differences in mortality from cardiovascular disease in Atlanta, 1979-1985.

Mortality from cardiovascular disease (CVD) for the period 1979 to 1985 in the Atlanta metropolitan population was reviewed for racial differences. About 28% of the population was black in 1980. Of 22,585 deaths from hypertension, stroke, ischemic heart disease, and atherosclerosis, 78.7% occurred among whites and 21.3% among blacks. Overall, ischemic heart disease accounted for 47.7% of these four types of CVD deaths for both races and sexes. Age-specific and age-adjusted rates were compared. Among these four causes of death, blacks have the greatest excess of deaths from hypertension over whites for both males and females; the excesses were more than 200% when the rates were age-adjusted. The excess risk of death from hypertension occurred for all ages in blacks, with an excess of about 10 times in 30- to 49-year-olds. An excess risk from stroke also occurred in blacks below the age of 75; the risk reversed afterward. The age-specific mortality rates revealed an excess from ischemic heart disease only between the ages of 30 and 59 years and from atherosclerosis between 40 and 59 years of age for black men. This age-related crossover in females did not occur until the age of 75 years for deaths attributed to these causes. These data suggest that blacks were at highest risk for all four causes at younger age groups.

Adult↗
PubMed1991

Assessing population-based programs to reduce blood cholesterol level and saturated fats.

This article reviews seven community-based programs for prevention of cardiovascular disease and their effects on blood cholesterol levels and saturated fat intake. In two programs, cholesterol levels were reduced more in the intervention area than in the reference area. In two other programs, cholesterol increased less in the intervention area than in the reference area. In one program, cholesterol levels initially fell in the intervention group and increased in the reference group; after the first 4 years, the levels also started to increase in the intervention group. The final two programs reduced cholesterol equally in both groups. Only two programs reported on the intake of saturated fats; in both, intake of saturated fat was reduced more in the intervention area than in the reference populations. In one program area, total intake of fat was reduced more than in the reference area. Published data do not allow us to draw conclusions regarding which components of the programs were most important. These studies show that the average blood cholesterol level can be affected in a general population.

Cardiovascular Diseases↗
PubMed1991

Genotypic identification of pathogenic Mycobacterium species by using a nonradioactive oligonucleotide probe.

Commercial DNA hybridization assays (Syngene, Inc., San Diego, Calif.) utilizing alkaline phosphatase-labeled oligonucleotide probes for the identification of Mycobacterium tuberculosis complex and M. avium complex (MAC) were evaluated with 261 isolates of mycobacteria. On the basis of biochemical criteria, the test for MAC was 98% specific and more sensitive (95 of 99, 95%) than Gen-Probe (88 of 99, 89% sensitivity); the major difference in sensitivity noted between the two systems was related to the hybridization of seven MAC strains to the SNAP X probe. The M. tuberculosis complex probe correctly identified all 62 isolates of M. tuberculosis and all 11 isolates of M. bovis, for a sensitivity of 100%. There were two discrepant reactions with mycobacteria other than M. tuberculosis complex isolates.

Bacteriological Techniques↗