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At least 19 recordsLinked to original sources
PubMed1986

ADR1-mediated regulation of ADH2 requires an inverted repeat sequence.

DNA sequence analysis of wild-type and mutant ADH2 loci suggested that two unusual features 5' of the promoter, a 22-base-pair perfect dyad sequence and a (dA)20 tract, were important for regulation of this gene (D. W. Russell, M. Smith, D. Cox, V. M. Williamson, and E. T. Young, Nature [London] 304:652-654, 1983). Oligonucleotide-directed mutagenesis was used to construct ADH2 genes lacking the 22-base-pair dyad or the (dA)20 tract (V.-L. Chan and M. Smith, Nucleic Acids Res. 12:2407-2419, 1984). These mutant genes and other ADH2 deletions constructed by BAL 31 endonuclease digestion were studied after replacing the wild-type chromosomal locus with the altered alleles by the technique of gene transplacement (T. L. Orr-Weaver, J. W. Szostak, and R. S. Rothstein, Proc. Natl. Acad. Sci. USA 78:6354-6358, 1981), using canavanine resistance as the selectable marker. Deletions lacking the dyad failed to derepress normally and did not respond to mutations at the ADR1 locus, which encodes a protein necessary to activate ADH2. Deletions of the (dA)20 tract did not have a detectable phenotype. A small deletion located just 3' to the (dA)20 tract (between positions -164 and -146) had a low amount of ADR1-dependent transcription during repressed growth conditions, indicating that the regulatory protein encoded by ADR1 is present in a potentially active form during repression and that alterations of a DNA sequence in the promoter region can unmask its latent activity.

Alcohol Dehydrogenase↗
PubMed1997

Causing death or allowing to die? Developments in the law.

Several cases which have been considered by the courts in recent years have highlighted the legal dilemmas facing doctors whose decisions result in the ending of a patient's life. This paper considers the case of Dr Cox, who was convicted of attempting to murder one of his patients, and explores the roles of motive, diminished responsibility and consent in cases of "mercy killing". The Cox decision is compared to that of Tony Bland and Janet Johnstone, in which the patients were in a persistent vegetative state. In all three cases, the doctors believed that their patients' quality of life was so poor that their continued existence was of no benefit to them, and decided that their lives should not be unduly prolonged, yet the doctor who was prosecuted was the one whose dying patient had requested that her death be hastened. The paper examines the law's seemingly contradictory approaches to such cases.

Double Effect Principle↗
PubMed1987

An in vitro system for the study of tracheal epithelial cells.

Enzymatically dissociated hamster tracheal epithelial (HTE) cells were cultured on collagen coated Millicell filters. Within 3-5 days after being placed in culture large numbers of ciliated and mucus cells began to appear. By 1 week the HTE cells closely resembled those seen in vivo, i.e. columnar morphology and organelle polarity. After 4 weeks in vitro the HTE cultures were still able to maintain the polarity and overall columnar morphology found in in vivo tissue. There was, in addition, no apparent degradation of the collagen substrate. Auto-radiographic data indicated that there was an initial period of high DNA synthesis during the first 3 days in vitro. This was followed by a second phase in which, by day 6, the amount of DNA synthesis was greatly reduced. Analysis of the numbers of ciliated cells relative to non-ciliated cells demonstrated that between days 5 and 8 there was an increase in the percentage of ciliated cells, suggesting that cellular differentiation (i.e. ciliogenesis) follows cellular proliferation. The results of this study show that when HTE cells are grown on collagen-coated Millicell filters there is a significant improvement in cell growth and morphology yielding cells that are very similar to those present under in vivo conditions. Moreover, since there is no degradation of the collagen substrate, HTE cultures may be suitable for long-term studies of respiratory tract epithelia.

Animals↗
PubMed1996

Randomized investigation of antimicrobials for the prevention of preterm birth.

OBJECTIVE: Occult amniotic fluid infection has emerged as a possible cause of many heretofore unexplained preterm births. We sought to determine whether antimicrobial therapy is effective in preventing preterm delivery. STUDY DESIGN: A double-blind, placebo-controlled, randomized trial was conducted to study the efficacy of ampicillin-sulbactam and amoxicillin-clavulanic acid in women hospitalized for preterm labor between 24 and 34 weeks' gestation. During this investigation no tocolytics or steroids were used. RESULTS: Thirty-nine women with preterm labor received antimicrobial therapy and 39 received placebos. The mean gestational ages at study entry were 29.8 +/- 0.4 weeks (SEM) and 30.6 +/- 0.3 weeks in the antimicrobial and placebo groups, respectively (not significant). Similarly, the mean gestational ages at delivery were 34.2 +/- 0.7 and 34.1 +/- 0.6 weeks, respectively (not significant). Other index values of pregnancy outcome, for example, birth weight, neonatal morbidity, and prenatal death, were not significantly improved by antimicrobial therapy given to the mother in preterm labor. CONCLUSION: We find that antimicrobial therapy given to women in preterm labor is ineffective in the prevention of preterm birth.

Amoxicillin↗
PubMed1997

Mutations of CLCN5 in Japanese children with idiopathic low molecular weight proteinuria, hypercalciuria and nephrocalcinosis.

The annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis. The disorder has been observed in over 60 patients and has a familial predisposition. Mutations of a renal chloride channel gene, CLCN5, have been reported in four such families, and we have undertaken studies in additional patients from 10 unrelated, non-consanguineous Japanese families to further characterize such CLCN5 mutations and to ascertain their prevalence. CLCN5 abnormalities we identified in 7 of the 10 unrelated patients and consisted of 5 mutations (2 nonsense, 1 frameshift and 2 missense), 1 deletion and 1 silent polymorphism. A clustering of these mutations in CLCN5 exons 8 and 10 was observed. Over 80% of the CLCN5 mutations could be readily detected by single stranded conformational polymorphism (SSCP) analysis, thereby providing a useful mutation screening method. Our results, which indicate that over 70% of Japanese patients with this renal tubulopathy have CLCN5 mutations, will help in the genetic and clinical evaluation of children at risk from this disorder.

Adolescent↗
PubMed1985

Anion transporter: highly cell-type-specific expression of distinct polypeptides and transcripts in erythroid and nonerythroid cells.

Affinity-purified antibodies and cDNA probes specific for the chicken erythrocyte anion transporter (also referred to as band 3) have been used to demonstrate that this protein is expressed in a highly cell-type-specific manner in the avian kidney. Indirect immunofluorescence analysis indicates that this polypeptide is present in only a small subset of total kidney cells and is predominantly localized to the proximal convoluted tubule of this organ. Chicken erythrocytes synthesize and accumulate two structurally and serologically related band 3 polypeptides. The polypeptide that accumulates in kidney membranes has an apparent molecular weight greater than either of its erythroid counterparts. This diversity is also reflected at the RNA level, as the single band 3 mRNA species detected during various stages of erythroid development is distinct in size from that found in kidney cells. Genomic DNA blot analysis suggests that both the erythroid and kidney band 3 RNAs arise from a single gene. Furthermore, of the adult tissues we have examined that are known to express ankyrin and spectrin polypeptides, only kidney accumulates detectable levels of the band 3 mRNA and polypeptide. These observations suggest that a subset of kidney cells use an anion transport mechanism analogous to that of erythrocytes and that band 3 is expressed in a noncoordinate manner with other components of the erythroid membrane skeleton in nonerythroid cells.

Animals↗
PubMed1999

Pharmacists' job satisfaction and perceived utilization of skills.

The relationship between job satisfaction and perceived utilization of skills among pharmacists practicing in institutional and ambulatory care settings in Arizona was studied, and factors thought to influence pharmacists' perceived utilization of skills were evaluated. Questionnaires on job satisfaction and perceived utilization of skills were mailed to a random sample of 600 pharmacists. Information on workplace factors such as hours worked, practice setting, and job title was collected. A 4-item measure of general job satisfaction and a 10-item measure of perceived utilization of skills were used. Responses were measured on a five-point Likert scale ranging from "strongly disagree" to "strongly agree." The response rate was 35%. There was a significant positive relationship between job satisfaction and perceived utilization of skills and between job satisfaction and adequate staffing, where "staffing" referred to factors such as competence of coworkers and workload. Pharmacists with training beyond a B.S. degree in pharmacy were more satisfied with their job than those whose highest degree was a B.S. in pharmacy. Pharmacists practicing in institutional settings, pharmacists with management titles, and older pharmacists perceived that they were utilizing their skills to a greater extent than did pharmacists practicing in ambulatory care settings, pharmacists with a general staff title, and younger pharmacists. Among a sample of Arizona pharmacists in institutional and ambulatory care settings, job satisfaction was influenced by perceived utilization of skills, staffing, and education; practice setting, job title, and age were significantly related to perceived utilization of skills.

Adult↗
PubMed1992

Detection and staging of small cell lung carcinoma with a technetium-labeled monoclonal antibody. A comparison with standard staging methods.

Tumor-associated radiolabeled monoclonal antibodies (MoAb) can detect neoplasms in a variety of settings. The authors conducted a study comparing the ability to detect and stage small cell lung carcinoma by using a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp, Seattle, WA) with standard staging methods. Standard staging included a physical examination, chest x-ray, a battery of radionuclide scans and/or computerized tomographic studies (head, abdomen, and bone), and bone marrow examination. A total of 22 comparisons were performed in 17 patients (five patients had reevaluations after therapy). Fifty-four (74%) of the 73 lesions defined by standard staging were detected by the radiolabeled MoAb. Seven of eight patients (88%) classified by standard staging as having "limited stage" disease on presentation were concordantly "limited stage" by radioimmunoimaging. One patient deemed "limited stage" by standard staging was correctly upstaged (bone marrow involvement) as a result of the radiolabeled MoAb. Two patients found to have extensive disease at diagnosis were characterized as "limited stage" by the MoAb, for an overall staging accuracy of 0.88. Thirteen of 19 missed lesions were smaller than 2 cm (10 were smaller than 1 cm; 3 measured 1 to 2 cm). This comparative study shows that radioimmunoimaging by Tc-99m labeled NR-LU-10 Fab antibody is capable of complementing standard staging methods used in the evaluation of small cell lung carcinoma.

Carcinoma, Small Cell↗
PubMed1996

Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors.

OBJECTIVE: The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. METHODS: Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients), and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. RESULTS: Rolandic cortex was activated by tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electrocortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with > 2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. CONCLUSIONS: FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.

Adolescent↗
PubMed2002

Floods: some probabilistic and statistical approaches.

Some of the many statistical aspects of floods are discussed and some new results are given on a number of features. The probability theory of extreme values is briefly reviewed and its potential for applications outlined. The peaks-over-threshold method of estimation is compared with the direct use of annual maxima and some theoretical comparisons of efficiency are given. The effect of trend on the distribution of maxima is analysed in terms of a simple theoretical model distinguishing the effects of trend in mean level and of trend in dispersion. An empirical Bayes method for pooling information from a number of sources is described and illustrated, and related to the procedures recommended in the Flood estimation handbook. In the final section, a range of further issues is outlined.

Bayes Theorem↗