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S Kaplan

Publications and source records attributed to S Kaplan.

At least 73 records · Page 4Linked to original sources
PubMed2000

Doppler-derived mitral deceleration time as an early predictor of left ventricular thrombus after first anterior acute myocardial infarction.

BACKGROUND: The relation between left ventricular (LV) diastolic function and LV thrombus has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict LV thrombus formation after acute myocardial infarction. METHODS AND RESULTS: Two-dimensional and Doppler echocardiographic examinations were performed in 98 consecutive patients (aged 57 +/- 12 years; 8 women) with first acute myocardial infarction. The patients were studied within 24 hours and at days 3, 7, 15, and 30 after arrival to the coronary care unit. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. LV thrombus was detected in 20 of 98 patients. Patients were divided into 2 groups according to LV thrombus formation: group 1 (n = 20) with thrombus and group 2 (n = 78) without thrombus. Mitral E-wave DT was significantly shorter in group 1 than group 2 (134 ms vs 175 ms; P <.001). Patients in group 1 had significantly larger LV end-diastolic and end-systolic volumes and a higher wall motion score index than patients in group 2 (133 +/- 39 mL vs 112 +/- 41 mL, P =.03; 83 +/- 34 mL vs 59 +/- 30 mL, P =.003; and 1.8 +/- 0.3 mL vs 1.5 +/- 0.3 mL, P =.007, respectively). The LV ejection fraction was significantly lower in group 1 than in group 2 (39% +/- 13% vs 48% +/- 12%; P =.004). In a multivariate regression analysis, mitral E-wave DT was identified as an independent variable related to development of LV thrombus (P =.04). CONCLUSIONS: Doppler-derived mitral DT is superior to conventional clinical and 2-dimensional echocardiographic assessment in estimating the risk of left ventricular thrombosis after myocardial infarction.

Aged↗
PubMed2000

Interacting regulatory circuits involved in orderly control of photosynthesis gene expression in Rhodobacter sphaeroides 2.4.1.

FnrL, the homolog of the global anaerobic regulator Fnr, is required for the induction of the photosynthetic apparatus in Rhodobacter sphaeroides 2.4.1. Thus, the precise role of FnrL in photosynthesis (PS) gene expression and its interaction(s) with other regulators of PS gene expression are of considerable importance to our understanding of the regulatory circuitry governing spectral complex formation. Using a CcoP and FnrL double mutant strain, we obtained results which suggested that FnrL is not involved in the transduction of the inhibitory signal, by which PS gene expression is "silenced," emanating from the cbb(3) oxidase encoded by the ccoNOQP operon under aerobic conditions. The dominant effect of the ccoP mutation in the FnrL mutant strain with respect to spectral complex formation under aerobic conditions and restoration of a PS-positive phenotype suggested that inactivation of the cbb(3) oxidase to some extent bypasses the requirement for FnrL in the formation of spectral complexes. Additional analyses revealed that anaerobic induction of the bchE, hemN, and hemZ genes, which are involved in the tetrapyrrole biosynthetic pathways, requires FnrL. Thus, FnrL appears to be involved at multiple loci involved in the regulation of PS gene expression. Additionally, bchE was also shown to be regulated by the PrrBA two-component system, in conjunction with hemN and hemZ. These and other results to be discussed permit us to more accurately describe the role of FnrL as well as the interactions between the FnrL, PrrBA, and other regulatory circuits in the regulation of PS gene expression.

Aerobiosis↗
PubMed2000

Genetic and phenotypic analyses of the rdx locus of Rhodobacter sphaeroides 2.4.1.

Previously, we reported that rdxB, encoding a likely membrane-bound two [4Fe-4S]-containing center, is involved in the aerobic regulation of photosystem gene expression in Rhodobacter sphaeroides 2.4.1. To further investigate the role of rdxB as well as other genes of the rdxBHIS operon on photosystem gene expression, we constructed a series of nonpolar, in-frame deletion mutations in each of the rdx genes. Using both puc and puf operon lacZ fusions to monitor photosystem gene expression, under aerobic conditions, in each of the mutant strains revealed significant increased photosynthesis gene expression. In the case of mutations in either rdxH, rdxI, or rdxS, the aerobic induction of photosystem gene expression is believed to be indirect by virtue of a posttranscriptional effect on cbb(3) cytochrome oxidase structure and integrity. For RdxB, we suggest that this redox protein has a more direct effect on photosystem gene expression by virtue of its interaction with the cbb(3) oxidase. An associated phenotype, involving the enhanced conversion of the carotenoid spheroidene to spheroidenone, is also observed in the RdxB, -H, -I, and -S mutant strains. This phenotype is also suggested to be the result of the role of the rdxBHIS locus in cbb(3) oxidase activity and/or structure. RdxI is suggested to be a new class of metal transporter of the CPx-type ATPases.

Aerobiosis↗
PubMed2000

Domain structure, oligomeric state, and mutational analysis of PpsR, the Rhodobacter sphaeroides repressor of photosystem gene expression.

The transcription factor PpsR from the facultative photoheterotroph Rhodobacter sphaeroides is involved in repression of photosystem gene expression under aerobic growth conditions. We have isolated a number of spontaneous mutations as well as constructed directed mutations and deletions in ppsR. Repressor activities and the oligomeric state of the wild-type and mutant proteins were assayed. Our results suggest that the wild-type PpsR exists in cell extracts as a tetramer. Analysis of the PpsR mutants confirmed that the carboxy-terminal region of PpsR (residues 400 to 464) is involved in DNA binding. The central region of the protein (residues 150 to 400) was found to contain two PAS domains (residues 161 to 259 and 279 to 367). PAS domains are ubiquitous protein modules involved in sensory transduction as well as in protein-protein interactions. All spontaneously isolated mutations, which significantly impaired repressor activity and which mapped outside the DNA binding region, were positioned in the PAS domains. None of these, however, affected the overall oligomeric state. This implies that the conformation of the PAS domains within the tetramer is critical for repressor activity. Upstream of the first PAS domain resides a putative glutamine-rich hinge (residues 127 to 136) that connects the first PAS domain to the amino-terminal region (residues 1 to 135). The role of the amino terminus of PpsR is not obvious; however, extended deletions within this region abolish repressor activity, thus suggesting that the amino terminus is essential for structural integrity of the protein. We present a model of the domain architecture of the PpsR protein according to which PpsR is comprised of three regions: the carboxy terminus responsible for DNA binding, the central region primarily involved in protein oligomerization and possibly signal sensing, and the amino terminus of unknown function. This model may prove useful for determining the mode of PpsR action.

Amino Acid Sequence↗
PubMed2000

Ticlopidine, Alka-Seltzer, or a combination of citric acid with aspirin: effects on platelet aggregation in individuals with an insufficient response to aspirin alone.

Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASA's antiaggregation effect, completed a sequential trial of ticlopidine, Alka-Seltzer, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease.

Adult↗
PubMed1999

A novel mechanism for the regulation of photosynthesis gene expression by the TspO outer membrane protein of Rhodobacter sphaeroides 2.4.1.

A bacterial homolog of the mammalian mitochondrial benzodiazepine receptor, the tryptophan-rich sensory protein (TspO) has been previously demonstrated to negatively affect the transcriptional expression of several photosynthesis genes of Rhodobacter sphaeroides. To identify components of the signal transduction pathway from the outer membrane-localized TspO to the DNA-active transcription factor(s), we examined the involvement of TspO in the regulation of tetrapyrrole metabolism in R. sphaeroides. By analyzing the tetrapyrrole pigments accumulated by resting cell suspensions of R. sphaeroides, we demonstrated that TspO negatively regulates the activity of coproporphyrinogen III oxidase in this bacterium. hemN, encoding one of the isoenzymes of coproporphyrinogen III oxidase of R. sphaeroides, provided in trans to the wild type strain, produced a TSPO1 mutant phenotype by abolishing the negative effect of TspO on the transcription of the photosynthesis genes, crtI and puc. It is proposed that TspO, by regulating the exit of certain tetrapyrrole intermediates of the heme/bacteriochlorophyll biosynthetic pathways in R. sphaeroides in response to the availability of molecular oxygen, causes the accumulation of a biosynthetic intermediate that serves as a corepressor for both specific pigment gene transcription and the puc operon. The relationship between the bacterial TspO and the mitochondrial peripheral benzodiazepine receptor is discussed.

Animals↗
PubMed1999

Zebrafish genetic map with 2000 microsatellite markers.

The zebrafish is the first vertebrate organism used for large-scale genetic screens seeking genes critical to development. These screens have been quite successful, with more than 1800 recessive mutations discovered that speak to morphogenesis of the vertebrate embryo. The cloning of the mutant genes depends on a dense genetic map. The 2000 markers we present here, using microsatellite (CA) repeats, provides 1.2-cM average resolution. One centimorgan in zebrafish is about 0. 74 megabase, so, for many mutations, these markers are close enough to begin positional cloning by YAC walks.

Animals↗
PubMed1999

Topological analysis of the membrane-localized redox-responsive sensor kinase PrrB from Rhodobacter sphaeroides 2.4.1.

Photosynthesis gene expression in Rhodobacter sphaeroides is controlled in part by the two-component (Prr) regulatory system composed of a membrane-bound sensor kinase (PrrB) and a response regulator (PrrA). Hydropathy profile-based computer analysis predicted that the PrrB polypeptide could contain six membrane-spanning domains at its amino terminus and a hydrophilic, cytoplasmic carboxyl terminus. Both the localization and the topology of the PrrB sensor kinase have been studied by generating a series of gene fusions with the Escherichia coli periplasmically localized alkaline phosphatase and the cytoplasmic beta-galactosidase. Eighteen prrB-phoA and five prrB-lacZ fusions were constructed and expressed in both E. coli and R. sphaeroides. Enzymatic activity assays and immunoblot analyses were performed to identify and to localize the different segments of PrrB in the membrane. The data obtained in E. coli generally correlated with the data obtained in R. sphaeroides and support the computer predictions. On the basis of the theoretical model and the results provided by these studies, a topological model for the membrane localization of the PrrB polypeptide is proposed.

Alkaline Phosphatase↗
PubMed1999

The cbb3 terminal oxidase of Rhodobacter sphaeroides 2.4.1: structural and functional implications for the regulation of spectral complex formation.

We have previously shown that the flow of reductant through the cbb3 terminal cytochrome c oxidase of Rhodobacter sphaeroides is essential to the repression of photosynthesis (PS) gene expression in the presence of oxygen by inhibiting the functional activity of the Prr two-component activation system. To gain further insight into the role of the cbb3 oxidase and the cognate ccoNOQP operon in the oxygen regulation of PS gene expression, we constructed nonpolar, in-frame deletions within the ccoN and ccoQ genes. Whereas mutations in ccoN, ccoQ, and ccoP resulted in PS gene expression in the presence of oxygen, only the ccoQ mutation showed both the normal flow of reductant through the cbb3 oxidase and the absence of any alteration in the relative levels of spheroidene and spheroidenone, as is observed for those mutations in the cco operon that result in the loss of terminal oxidase activity. Consistent with these findings is the observation that extra copies of the ccoNOQP operon in trans resulted in the decreased formation of both the B800-850 and B875 spectral complexes under anaerobic growth conditions. These results in conjunction with our earlier findings indicate that (1) the flow of reductant through the cbb3 terminal oxidase is a prerequisite to the regulation of PS gene expression by the Prr two-component regulatory system, (2) the CcoQ protein is involved in conveying the signal derived from reductant flow through the cbb3 terminal oxidase to the Prr regulatory pathway, (3) there is reductant flow through this terminal oxidase under anaerobic conditions, and as a result, the activity of the Prr system is still subject to cbb3 regulation, and (4) the acceptor for reductant flow through cbb3 under anaerobic conditions is in whole or in part involved in the conversion of spheroidene to spheroidenone.

Carotenoids↗
PubMed1999

RsGDB, the Rhodobacter sphaeroides Genome Database.

This report provides a summary of the sequencing project of the small chromosome (CII) of Rhodobacter sphaeroides 2.4.1(T),and introduces the first version of the genome database of this bacterium. The database organizes and describes diverse sets of biological information. The main role of the R.sphaeroides genome database (RsGDB) is to provide public access to the collected genomic information for R.sphaeroides via the World-Wide Web at http://utmmg.med.uth.tmc.edu/sphaeroides. The database allows the user access to hundreds of low redundancy R.sphaeroides sequences for further database searching, a summary of our current search results, and other allied information pertaining to this bacterium.

Databases, Factual↗
PubMed1999

Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis.

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2-L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 +/- 0.08 g/cm2 versus 0.98 +/- 0.14 g/cm2, respectively; P = 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 +/- 0.08 g/cm2 versus 0.76 +/- 0.15 g/cm2, respectively; P = 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss.

Antirheumatic Agents↗
PubMed1999

Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group.

OBJECTIVES: Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS: Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS: The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS: Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.

Acute Disease↗
PubMed1999

Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart.

OBJECTIVES: Morbidity and mortality patterns were characterized in adults with the Eisenmenger syndrome when two ventricles with a ventricular septal defect (VSD) joined two great arteries or one great artery, or when one ventricle joined two great arteries. BACKGROUND: Although afterload in these disorders differs, clinical differences have not been defined. METHODS: Seventy-seven patients were studied. Group A comprised 47 patients with VSD, aged 23 to 69 years (mean 39.5+/-10.2), follow-up 5 to 18 years (mean 7.2+/-4.9); group B, 14 patients with truncus arteriosus, aged 27 to 50 years (mean 33.7+/-7.3), follow-up 6 to 18 years (mean 7.7+/-5.1), and group C, 16 patients with univentricular heart, aged 18 to 44 years (mean 30.6+/-8.4), follow-up 5 to 15 years (mean 4.4+/-4.2). Echocardiography established the diagnoses and anatomic and hemodynamic features. Data were compiled on tachyarrhythmias, pregnancy, infective endocarditis, noncardiac surgery and the multisystem disorders of cyanotic adults. RESULTS: Thirty-five percent of the patients died. Sixty-three percent of deaths were sudden, and resulted from intrapulmonary hemorrhage, rupture of either the pulmonary trunk, ascending aorta or a bronchial artery, or vasospastic cerebral infarction, or the cause was unestablished. There were no documented tachyarrhythmic sudden deaths. CONCLUSIONS: Medical management of coexisting cardiac disease, multisystem systemic disorders, noncardiac surgery and pregnancy has reduced morbidity. Increased longevity exposed patients to proximal pulmonary arterial aneurysms, thromboses and calcification; to truncal valve stenosis and regurgitation; to semilunar and atrioventricular valve regurgitation, and to major risks of nontachyarrhythmic sudden death.

Adult↗