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Biomedical subjects

C M Burns

Publications and source records attributed to C M Burns.

At least 19 recordsLinked to original sources

NusG is required to overcome a kinetic limitation to Rho function at an intragenic terminator.

Rho-dependent transcription termination at certain terminators in Escherichia coli also depends on the presence of NusG [Sullivan, S. L. & Gottesman, M. E. (1992) Cell 68, 989-994]. We have found that termination at the first intragenic terminator in lacZ (tiZ1) is strongly dependent on NusG when transcription is done in vitro with the concentrations of NTPs found in vivo. With a lower level of NTPs, and consequently a slower rate of RNA-chain growth, Rho causes some termination by itself that is enhanced with NusG. These results suggest that NusG serves to overcome a kinetic limitation of Rho to function at certain terminators. At a second intragenic terminator within the lacZ reading frame (tiZ2) the efficiency of Rho-mediated termination was unaffected by either NusG or by RNA polymerase elongation kinetics. Thus, using purified components and intracellular levels of NTPs, we have confirmed the in vivo finding that certain Rho-dependent terminators also depend on NusG, whereas others do not.

Bacterial Proteins

p53-dependent growth arrest of REF52 cells containing newly amplified DNA.

The rat cell line REF52 is not permissive for gene amplification. Simian virus 40 tumor (T) antigen converts these cells to a permissive state, as do dominant negative mutants of p53, suggesting that the effect of T antigen is due mainly to its ability to bind to p53. To manipulate permissivity, we introduced a temperature-sensitive mutant of T antigen (tsA58) into REF52 cells and selected for resistance to N-(phosphonacetyl)-L-aspartate (PALA). Most freshly isolated PALA-resistant colonies, each of approximately 200 cells, selected at a permissive temperature, arrested when shifted to a nonpermissive temperature. Growth arrest was stable, with no evidence of apoptosis, as long as T antigen was absent but was reversed when T antigen was restored. In contrast, PALA-resistant clones grown to approximately 10(7) cells at a permissive temperature did not arrest when shifted to a nonpermissive temperature. All PALA-resistant clones examined had amplified carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) genes, present in structures consistent with a mechanism involving bridge-breakage-fusion (BBF) cycles. We propose that p53-mediated growth arrest operates only early during the complex process of gene amplification, when newly formed PALA-resistant cells contain broken DNA, generated in BBF cycles. During propagation under permissive conditions, the broken DNA ends are healed, and, even though the p53-mediated pathway is still intact at a nonpermissive temperature and the cells contain amplified DNA, they are not arrested in the absence of broken DNA. The data support the hypothesis that BBF cycles are an important mechanism of amplification and that the broken DNA generated in each cycle is a key signal that regulates permissivity for gene amplification.

Animals

Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine.

RNA encoding the B subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (GluR-B) undergoes a posttranscriptional modification in which a genomically encoded adenosine is represented as a guanosine in the GluR-B complementary DNA. In vitro editing of GluR-B RNA transcripts with HeLa cell nuclear extracts was found to result from an activity that converts adenosine to inosine in regions of double-stranded RNA by enzymatic base modification. This activity is consistent with that of a double-stranded RNA-specific adenosine deaminase previously described in Xenopus oocytes and widely distributed in mammalian tissues.

Adenosine

ECT for OCD.

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Comorbidity

CD45 regulation of tyrosine phosphorylation and enzyme activity of src family kinases.

Previous analyses have suggested that the CD45 tyrosine phosphatase activates src family tyrosine kinases p56lck and p59fyn by dephosphorylating regulatory COOH-terminal residues. We have examined the status of p56lck and p59fyn in murine and human CD45- T cell lines. Surprisingly, despite the fact that p56lck and p59fyn were spontaneously hyperphosphorylated, the tyrosine kinase activity of both enzymes was increased in CD45- versus CD45+ cells. In vitro exposure of hyperphosphorylated p56lck to CD45 decreased enzyme activity to near-basal levels. Lck from CD45- cells was hyperphosphorylated on the cyanogen bromide digestion fragment that contains the negative regulatory residue Tyr-505, and the identity of this site of phosphorylation was confirmed by trypsin digestion followed by high performance liquid chromatography. Loss of CD45 results, therefore, in a paradoxical hyperphosphorylation of the COOH-terminal tyrosine and increased src family kinase enzymatic activity.

Amino Acid Sequence

Toward Healthy People 2000: the role of the nurse practitioner and health promotion.

The central purpose of Healthy People 2000 is to increase the proportion of Americans who live long and healthy lives. The best health promotion strategies are those related to individual lifestyle, and include personal choices made in a social context that have a significant influence over one's health. The primary lifestyle activities include: physical activity; nutrition; alcohol, tobacco, and other drug use; family planning; and violent and abusive behavior. Nurse practitioners play a significant role in promoting healthy lifestyle behaviors in their patients. This article presents an innovative teaching strategy used to teach health promotion concepts and intervention strategies to nurse practitioner students. The course design follows a clinical protocol format, which facilitates translation to clinical practice.

Adolescent

Early detection and intervention for the hidden alcoholic: assessment guideline for the clinical nurse specialist.

Among hospitalized patients, it is estimated that between 20% and 35% have significant alcohol problems that remain largely undetected. Alcohol abuse is a risk factor for a variety of disorders, including diabetes mellitus, gastrointestinal problems, hypertension, liver disease, and stroke. In an era of health care cost containment, early detection, intervention, and referral of alcohol-abusing or -dependent patients by the CNS may significantly impact the cost effectiveness of hospital care. In this article, a guideline is described that can be used by the CNS relative to the assessment, intervention, and referral of alcohol-abusing or -dependent patients in the general hospital setting.

Alcoholism

Stimulus dose-titration in ECT: a 2-year clinical experience.

One hundred and thirty-four patients referred for electroconvulsive therapy (ECT) over a 2-year period underwent standardized stimulus dose-titration. No significant adverse events were associated with the dose-titration procedure. Our data demonstrate that seizure threshold increases with age (p = 0.0001) and is higher with bilateral electrode placement (p = 0.0001). Contrary to other studies, our data show the effect of gender is not statistically significant (p = 0.54). If consensus regarding optimal dosing strategies relative to seizure threshold can be achieved, dose-titration may be adopted as a clinically useful step in optimizing ECT technique.

Adult

The prevalence of obstructive sleep apnoea in an obese female population.

Obstructive sleep apnoea (OSA) has been estimated to affect between 1 and 4% of the total population. OSA may be more frequent among women than studies based on subjects presenting for treatment would indicate. The aim of this study was to determine the prevalence of OSA in an obese female population (BMI > 30 kg/m2, age > 18 years) who presented to a hospital-based obesity clinic. The women were screened by an overnight ambulatory sleep study (MESAM) to detect OSA. Subjective sleep quality and sleep disturbance were assessed by a 19-item questionnaire, the Pittsburg sleep quality index (PSQI). From a population of 108 women, 29 were screened by MESAM. OSA was determined on the basis of respiratory disturbance index (RDI). The prevalence of OSA, defined as five or more respiratory disturbances per hour, was 37.9%. The mean age of the women was 43.6 +/- 2.57 years (mean +/- s.e.m.) and they had a mean BMI of 40.7 +/- 1.40 kg/m2. There was a significant positive correlation for RDI and BMI (r = 0.71; P < 0.001). Our findings indicate that over one third of women had OSA, yet they did not complain of symptoms even though the PSQI questionnaire indicated that they were poor sleepers. Non-specific symptomatology of OSA may be important diagnostically, particularly in women, and obese women should be considered at risk of OSA.

Adult

Hepatotoxicity associated with angiotensin-converting enzyme inhibitors.

OBJECTIVE: To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury. DATA SOURCES: Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury. DATA SYNTHESIS: Nineteen cases of ACE-inhibitor-associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated. CONCLUSIONS: Hepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.

Angiotensin-Converting Enzyme Inhibitors

Assessment and screening for substance abuse: guidelines for the primary care nurse practitioner.

In ambulatory care settings, NPs can expect to encounter numerous patients who have had or currently have an alcohol and/or other drug problem. In addition, a large number of patients are estimated to have an undetected or undiagnosed problem. This article presents guidelines for the assessment and screening of patients abusing alcohol and other drugs. History-taking, screening instruments, physical examination, and commonly used biological markers/laboratory tests are described. Brief intervention techniques and referral resources are also discussed.

Decision Trees

The CD45 tyrosine phosphatase regulates phosphotyrosine homeostasis and its loss reveals a novel pattern of late T cell receptor-induced Ca2+ oscillations.

CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide hydrolysis. The Ca2+ response in these cells was altered in an unexpected fashion. Unlike wild-type cells, stimulated CD45- cell populations did not manifest an early increase in intracellular Ca2+, but did exhibit a delayed and gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging of individual cells revealed that CD45- cells experienced late Ca2+ oscillations that were not blocked by removal of extracellular Ca2+. CD45 revertants had the signaling properties of wild-type cells. Thus, CD45 has a profound influence on both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals a novel role for this tyrosine phosphatase in Ca2+ regulation.

Animals

High percentage of CD8+, Leu-7+ cells in rheumatoid arthritis synovial fluid.

OBJECTIVE: While analyzing the phenotype of the synovial fluid mononuclear cells (SFMC) clustered about dendritic cells in rheumatoid arthritis (RA) joint effusions, it was noted that most of the clustering cells were CD8+ and coexpressed Leu-7. Therefore, the present study was conducted to investigate the frequency of CD8+, Leu-7+ cells in RA SF: METHODS: SFMC from 13 patients with RA and from 12 patients with non-RA inflammatory arthritides were examined for CD8 and Leu-7 expression using 2-color immunofluorescence flow cytometry. RESULTS: RA SFMC had statistically significantly greater percentages of total CD8+ cells, total Leu-7+ cells, and CD8+, Leu-7+ cells, compared with SFMC from the non-RA patients. These RA CD8+, Leu-7+ SFMC had a distinctive electron microscopic appearance compared with CD8+, Leu-7- SFMC. When peripheral blood mononuclear cells (PBMC) from 31 RA patients (including 7 from the SFMC group) were compared with PBMC from 15 normal controls, the percentage of CD8+, Leu-7+ cells was not significantly greater in the RA patients. However, the combination of a modest increase in CD8+, Leu-7+ cells and a decrease in total CD8 cells in RA PBMC altered the composition of the RA CD8 population compared with normal PBMC, such that over 40% of RA peripheral blood CD8 cells coexpressed Leu-7. CONCLUSION: The increased frequency of CD8+, Leu-7+ cells in RA SFMC may arise from the fact that a high percentage of the CD8+ PBMC in RA patients are also Leu-7+. This altered composition of CD8 cells in RA SF may have a role in the pathogenesis of the disease.

Antigens, Differentiation