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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 235 records · Page 13Linked to original sources

Translation of the chloroplast psbA mRNA requires the nuclear-encoded poly(A)-binding protein, RB47.

A set of nuclear mutants of C. reinhardtii were identified that specifically lack translation of the chloroplast-encoded psbA mRNA, which encodes the photosystem II reaction center polypeptide D1. Two of these mutants are deficient in the 47-kD member (RB47) of the psbA RNA-binding complex, which has previously been identified both genetically and biochemically as a putative translational activator of the chloroplast psbA mRNA. RB47 is a member of the poly(A)-binding protein family, and binds with high affinity and specificity to the 5' untranslated region of the psbA mRNA. The results presented here confirm RB47's role as a message-specific translational activator in the chloroplast, and bring together genetic and biochemical data to form a cohesive model for light- activated translational regulation in the chloroplast.

Animals↗

Cleanup and analysis of sugar phosphates in biological extracts by using solid-phase extraction and anion-exchange chromatography with pulsed amperometric detection.

A cleanup method based on anion-exchange solid-phase extraction (SPE) was developed to render biological extracts suitable for the analysis of hexose phosphates with a modified anion-exchange chromatography method and pulsed amperometric detection. The method was applied to cell extracts of Saccharomyces cerevisiae obtained by using cold methanol as quenching agent and chloroform as extraction solvent. It was shown that pretreatment of the cell extract with SPE markedly improved the quality of the liquid chromatography analysis with recoveries of the sugar phosphates close to 100%. Furthermore, the method allowed for sample enrichment and the original extraction procedure could be simplified by implementing SPE early in the extraction protocol.

Cell Fractionation↗

A multi-center safety trial of the oral iron chelator deferiprone.

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.

Administration, Oral↗

Heteroduplex joint formation in Escherichia coli recombination is initiated by pairing of a 3'-ending strand.

The formation of heteroduplex joints in Escherichia coli recombination is initiated by invasion of double-stranded DNA by a single-stranded homologue. To determine the polarity of the invasive strand, linear molecules with direct terminal repeats were released by in vivo restriction of infecting chimeric phage DNA and heteroduplex products of intramolecular recombination were analyzed. With this substrate, the invasive strand is expected to be incorporated into the circular crossover product and the complementary strand is expected to be incorporated into the reciprocal linear product. Strands of both polarities were incorporated into heteroduplex structures, but only strands ending 3' at the break were incorporated into circular products. This result indicates that invasion of the 3'-ending strand initiates the heteroduplex joint formation and that the complementary 5'-ending strand is incorporated into heteroduplex structures in the process of reciprocal strand exchange. The polarity of the invasive strand was not affected by recD, recJ, or xonA mutations. However, xonA and recJ mutations increased the proportion of heteroduplexes containing 5'-ending strands. This observation suggests that RecJ exonuclease and exonuclease I may enhance recombination by degrading the displaced strands during branch migration and thereby causing strand exchange to be unidirectional.

DNA, Bacterial↗

House calls.

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House Calls↗

A poly(A) binding protein functions in the chloroplast as a message-specific translation factor.

High-affinity binding of a set of proteins with specificity for the 5' untranslated region (UTR) of the Chlamydomonas reinhardtii chloroplast psbA mRNA correlates with light-regulated translational activation of this message. We have isolated a cDNA encoding the main psbA RNA binding protein, RB47, and identified this protein as a member of the poly(A) binding protein family. Poly(A) binding proteins are a family of eukaryotic, cytoplasmic proteins thought to bind poly(A) tails of mRNAs and play a role in translational regulation. In vitro translation of RNA transcribed from the RB47 cDNA produces a precursor protein that is efficiently transported into the chloroplast and processed to the mature 47-kDa protein. RB47 expressed and purified from Escherichia coli binds to the psbA 5' UTR with similar specificity and affinity as RB47 isolated from C. reinhardtii chloroplasts. The identification of a normally cytoplasmic translation factor in the chloroplast suggests that the prokaryotic-like chloroplast translation machinery utilizes a eukaryotic-like initiation factor to regulate the translation of a key chloroplast mRNA. These data also suggest that poly(A) binding proteins may play a wider role in translation regulation than previously appreciated.

Amino Acid Sequence↗

[Cardiac ultrasonography in the diagnosis and monitoring of infectious endocarditis].

Transthoracic and transoesophageal doppler echocardiography has become an essential tool for the diagnosis of infective endocarditis. It detects valvular vegetations and destructions, evaluates regurgitations, and appreciates haemodynamic tolerance. Recognition of endocarditis, early identification of high-risk patients, and detection of mechanical complications are the most accurate informations derived from this technique. Transoesophageal echocardiography has the potential to avoid the difficulties encountered using the transthoracic approach, and it must be used particularly in the presence of non diagnostic transthoracic examination when clinical suspicion is high.

Echocardiography, Doppler↗

Usefulness of pulmonary regurgitation Doppler tracings in predicting in-hospital and long-term outcome in patients with inferior wall acute myocardial infarction.

Right ventricular (RV) involvement is frequent during inferior wall acute myocardial infarction (AMI) and has been reported as a risk factor for in-hospital morbidity and mortality. The objectives of the present study were: (1) to evaluate in-hospital events in patients with and without RV involvement as diagnosed by abnormal flow characteristics derived from pulmonary regurgitation (PR) analysis (pressure half-time of PR, PHT(PR) < or = 150 ms and the lowest mid-diastolic to peak early diastolic velocity ratio, Vmin/Vmax < or = 0.5); and (2) to determine the influence of RV involvement in complications at long-term follow-up. Among 126 consecutively admitted patients with inferior wall AMI (mean age, 58 +/- 13 years), 101 had PR. We determined the prognostic significance of in-hospital and long-term events for the following variables: age > or = 65 years, ST-segment elevation > or = 1 mm in lead V4R, RV dilation, PHT of PR < or = 150 ms and Vmin/Vmax < or = 0.5, thrombolytic therapy, 3-vessel disease, and diabetes mellitus. We found that the PR derived Doppler index (PHT of PR < or = 150 ms and Vmin/Vmax < or = 0.5) was the only predictor of overall in-hospital clinical events (hazards ratio, 2.7, 95% confidence interval, 1.2 to 6.1, p = 0.016). At long-term follow-up (mean: 20 +/- 12 months, range 12 to 69), event-free survival analysis showed that age > or = 65 years was the only predictor of any event (relative risk, 3.7, 95% confidence interval, 2.1 to 6.3, p < 0.0001). Thus, RV involvement diagnosed with the use of PR flow-derived variables is an accurate and independent predictor of in-hospital complications. However, RV involvement does not influence long-term prognosis.

Aged↗

Mechanisms of insulin resistance in experimental hyperinsulinemic dogs.

This study was undertaken to characterize the insulin resistance and the mechanism thereof caused by chronic hyperinsulinemia produced in dogs by surgically diverting the veins of the pancreas from the portal vein to the vena cava. Pancreatic venous diversion (PVD, n = 8) caused a sustained increase in arterial insulin and decrease in portal insulin concentration compared with the control group (n = 6). Hyperinsulinemic euglycemic clamps were conducted 4 wk after surgery. The increase in the glucose disposal rate (GDR) was significantly less in the PVD group (39.0+/-5.0 vs. 27.9+/-3.2 micromol/kg/min, P < 0.01) compared with the control group, but the suppression of hepatic glucose production by insulin was similar for both groups. Muscle insulin receptor tyrosine kinase activity (IR-TKA) increased from 6.2+/-0.4 to 20.3+/-2.7 in the control group, but from 5.8+/-0.5 to only 12.7+/-1.7 fmol P/fmol IR in the PVD group (P < 0.01). With respect to the periphery, the time to half-maximum response (t1/2a) for arterial insulin was the same for both groups, whereas the t1/2a for lymph insulin (30+/-3 vs. 40+/-4 min, P < 0.05) and GDR (29+/-3 vs. 66+/-10 min, P < 0.01) were greater for the PVD group. Chronic hyperinsulinemia led to marked peripheral insulin resistance characterized by decreased insulin-stimulated GDR, and impaired activation of GDR kinetics due, in part, to reduced IR-TKA. Transendothelial insulin transport was impeded and was responsible for one third of the kinetic defect in insulin-resistant animals, while slower intracellular mechanisms of GDR were responsible for the remaining two thirds.

Animals↗

A multidimensional evaluation of fire fighter training for hazardous materials response: first results from the IAFF Program.

The International Association of Fire Fighters (IAFF) course on hazardous materials training for first responders is described together with an evaluation plan that includes multiple levels of assessment. Trainee appraisals of the course, shifts in their ratings of task competencies, gains in knowledge quiz scores, and self-reports on actions reflecting lessons learned from the course are among the measures used. Evaluations of courses given in several city fire departments found more than 60% of trainee judgments of course quality and utility to be highly favorable, along with significant post-course improvements in their competency ratings and quiz scores. Follow-up interviews with samples of trainees also suggested more self-protective behaviors and preventive actions being taken with regard to alarms and risks of hazardous materials exposures. However, cross-comparing the results for the various evaluation measures gave only limited support to a popular evaluation model that hypothesized that they would be interdependent. Limitations in appreciating technical course subjects, the value of add-on or refresher instruction, and variable risk experiences are noted in explaining differences in some training results.

Analysis of Variance↗

Effects of oral and intravenous terazosin and head-up tilt on blood pressure responses in patients with hypertension.

Terazosin is a selective alpha1-adrenoceptor antagonist. A double-blind, randomized, placebo-controlled, two-period study evaluated the effects of posture and of oral and intravenous administration of terazosin on blood pressure and heart rate in patients with hypertension. At least one week after withdrawal of all antihypertensive medications, 31 patients with sitting diastolic blood pressure of 95 to 114 mmHg were enrolled in the study. After a 24-hour, single-blind, placebo lead-in phase, the patients were randomized to receive either oral terazosin (1 mg on day 1, 2 mg on day 2, and 5 mg on days 3 and 4), a 12-hour intravenous infusion of terazosin (2.5 mg, 5 mg, or 7.5 mg), or placebo for 4 consecutive days. Head-up tilt (60 degrees for 20 minutes) evaluations were performed before and 0.5, 1.5, 2.5, 6, 12, and 16 hours after start of administration during the placebo lead-in phase and on each of the 4 days of the double-blind treatment phase. Blood pressure and heart rate were monitored every 2 minutes during the 20-minute tilt. Statistically significantly larger mean changes in blood pressure and heart rate were observed with the 7.5-mg intravenous dose of terazosin compared with those after oral terazosin or placebo. With respect to intravenous terazosin, the orthostatic changes were maximal on the first day of the 4-day treatment and increased with increasing doses of terazosin. Maximum orthostatic changes in blood pressure after oral administration of terazosin were not significantly different from those observed with placebo. The most common treatment-emergent adverse events during tilt were dizziness and nausea. Dizziness occurred more frequently with intravenous terazosin than with oral terazosin. The results of this study indicate that oral dose titration of terazosin rather than a slower rate of terazosin infusion minimized the postural effects on blood pressure and associated symptoms during head-up tilt.

Administration, Oral↗

Response channel activation and the temporoparietal junction.

When we learn to make one motor response to one visual stimulus and a different motor response to another, representations of these stimulus-response associations must be maintained to efficiently transduce perception into action. When an irrelevant distractor is presented adjacent to a target stimulus, interference is observed when the two stimuli are associated with conflicting responses, presumably due to response channel activation by the incompatible information. We have explored the neural bases of these interference effects. In a previous study, patients with hemispatial neglect showed normal interference from contralesional flankers. In another study, patients with lesions of the lateral prefrontal cortex were found not to show interference from distractors presented in the contralesional hemifield. The current study provided a more anatomically detailed investigation of the effects of posterior association cortex lesions on flanker interference. Patients with chronic, unilateral lesions involving the temporoparietal junction (TPJ), two of whom had hemispatial neglect, were compared with patients with lesions of the posterior association cortex not involving the TPJ. All patients performed a color discrimination task at fixation while a congruent or incongruent colored flanker was briefly presented (16.7 ms) in the adjacent contralesional or ipsilesional hemifield. Patients with TPJ lesions showed no interference effects from the contralesional flankers. These results suggest that the TPJ, in combination with the dorsolateral prefrontal cortex, is involved in transducing perception into action.

Aged↗

Trial of labor after cesarean delivery: the effect of previous vaginal delivery.

OBJECTIVE: This study examined the effects of order of previous modes of delivery on the rate of cesarean delivery and duration of a trial of labor among women with a history of 1 previous cesarean delivery and 1 previous vaginal delivery. STUDY DESIGN: The medical records of 4393 women at our institution who were seen June 1984-July 1996 for a trial of labor after a previous cesarean delivery were abstracted. The 800 women with a history of 1 previous cesarean and 1 previous vaginal delivery were included in this analysis. They were split into 2 groups by obstetric history: (1) 1 cesarean delivery followed by 1 vaginal delivery (vaginal last) and (2) 1 vaginal delivery followed by 1 cesarean delivery (cesarean last). Patient characteristics, durations of labor, and rates of cesarean delivery were compared with chi2 analysis, the Student t test, and the Wilcoxon rank sum test. Possible confounding variables were controlled for with multivariate logistic regression. RESULTS: The rates of cesarean delivery for the vaginal last and cesarean last groups were 7.2% and 14.7%, respectively (P = .002). The median durations of labor for the vaginal last and cesarean last groups were 5.6 and 7.0 hours, respectively (P = .01). The differences in cesarean rates and durations of labor were seen regardless of the indication for the previous cesarean delivery. CONCLUSIONS: Among women with 1 previous cesarean and 1 previous vaginal delivery, those whose most recent delivery was vaginal had a lower rate of cesarean delivery and shorter duration of labor than did those whose most recent delivery was cesarean.

Adult↗

Assessing the role of case mix in cesarean delivery rates.

OBJECTIVE: Implicit in comparisons of unadjusted cesarean rates for hospitals and providers is the assumption that differences result from management practices rather than differences in case mix. This study proposes a method for comparison of cesarean rates that takes the effect of case mix into account. METHODS: All women delivered of infants at our institution from December 1, 1994, through July 31, 1995, were classified according to whether they received care from community-based practitioners (N=3913) or from the hospital-based practice that serves a higher-risk population (N=1556). Women were categorized according to both obstetric history (nulliparas, multiparas without a previous cesarean, multiparas with a previous cesarean) and the presence of obstetric conditions influencing the risk of cesarean delivery (multiple birth, breech presentation or transverse lie, preterm, no trial of labor for a medical indication). We determined the percent of women in each parity-obstetric condition subgroup and calculated a standardized cesarean rate for the hospital-based practice using the case mix of the community-based practitioners as the standard. RESULTS: The crude cesarean rate was higher for the hospital-based practice (24.4%) than for the community-based practitioners (21.5%), a rate difference of 2.9% (95% confidence interval=0.4%, 5.4%; P=.02). However, the proportion of women falling into categories conferring a high risk of cesarean delivery (multiple pregnancy, breech presentation or transverse lie, preterm, no trial of labor permitted) was twice as high for the hospital-based practice (24.4% hospital, 12.1% community). The standardization indicates that if the hospital-based practitioners had the same case mix as community-based practitioners, their overall cesarean rate would be 20.1%, similar to the 21.5% rate of community providers (rate difference=-1.4%, 95% confidence interval =-3.1%, 0.3%; P=.11). CONCLUSION: Standardization for case mix provides a mechanism for distinguishing differences in cesarean rates resulting from case mix from those relating to differences in practice. The methodology is not complex and could be applied to facilitate fairer comparisons of rates among providers and across institutions.

Cesarean Section↗

The differences in health concerns between mothers and health care professionals in a preventive community set up.

To assess the degree to which mothers, nurses and pediatricians share common concerns regarding infants' health and well-being a cross-sectional survey with stratified demographic sampling was conducted. A 12-item questionnaire pertaining to health concerns was administered to 22 mothers of infants between 1 and 18 months of age, treated at six Well Baby community clinics with 36 nurses and 25 pediatricians. Mothers and health care professionals expressed significantly different concerns. Pediatricians and nurses shared a more similar order of concerns. However, they too differed on the degree of concern related to some of the health issues, i.e. nurses perceived the issues related to feeding, behaviour, skin, sleep and daily routines as significantly more important than did pediatricians. Additional efforts should be devoted to improve and clarify communication between mothers and health care professionals.

Adult↗

Psychosocial factors associated with the stages of change for condom use among women at risk for HIV and STDs: implications for intervention development.

This study examined the prevalence of consistent condom use among inner-city women at risk for HIV, measured the distribution of these women across the stages of change for condom use, determined psychosocial factors associated with the stages, and suggested intervention strategies based on the results. The 5-city sample of women aged 15-34 years consisted predominantly of African Americans. Only 18% reported consistent condom use with main partners and 45% with other partners. Logistic regressions compared women in each stage of change with those in higher stages for each partner type. Results indicated that women who practice or intend to practice consistent condom use were more likely to talk with others about condoms, acknowledge the advantages of condoms, have higher self-efficacy for condom use, and indicate that people important to them favored condom use. Intervention approaches are suggested for women in different stages of change for condom use.

Adolescent↗

Comparison of irbesartan vs felodipine in the regression after 1 year of left ventricular hypertrophy in hypertensive patients (the SILVER trial). Study of Irbesartan in Left VEntricular hypertrophy Regression.

The SILVER (Study of Irbesartan in Left VEntricular hypertrophy Regression) trial is designed to test the hypothesis that the newly developed angiontensin-II receptor antagonist, irbesartan, will produce a greater reduction in left ventricular (LV) mass than felodipine ER, in a population of hypertensive patients defined by seated diastolic blood pressure (SeDBP) in the range 95-115 mmHg or seated systolic blood pressure (SeSBP) in the range 160-200 mm Hg. A population of 360 men and women of non-childbearing potential, >18 years of age, with hypertension, newly diagnosed or after a 3-week washout from previous anti-hypertensive or vasodilator therapies, will be randomised at approximately 80-90 European sites. Add-on therapy with hydrochlorothiazide and atenolol will be allowed for blood pressure control. Patients will be studied by two-dimensional and M-mode echocardiography at baseline (central validation of LV hypertrophy), on randomisation day, and after 6 and 12 months randomised therapy. Blinded analysis of echocardiograms will be performed at a central laboratory, which will provide measurements of the LV mass index (LVMI), determined by M-mode readings according to Devereux formula and using the Penn convention. The primary end-point of the study will be the change in LVMI from baseline to 12 months. The study power is 90% to detect differences between groups from baseline of approximately 8 g/m2.

Adolescent↗