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Biomedical subjects

L D Gottlieb

Publications and source records attributed to L D Gottlieb.

At least 19 recordsLinked to original sources
PubMed1999

The status of Clarkia australis (Onagraceae).

Clarkia australis and C. virgata grow on the western slope of the central Sierra Nevada of California. Clarkia australis was established to accommodate populations of C. virgata from south of the Tuolumne River that could not be successfully hybridized to populations north of the river. Although the species is maintained in the new Jepson Manual, its validity has been questioned because only two populations were originally tested, and they had no useful morphological traits that distinguished them from C. virgata. We report here the results of a large program of interpopulation hybridizations that show that C. australis is distinct and that its reproductive isolation from C. virgata is complete and absolute and reflects a compatibility block that apparently causes abortion of hybrid seeds in early development. Both species include populations north and south of the Tuolumne River and, in general, those of C. australis occupy higher elevations. Morphologically, the species are extremely similar though the mean values of several dimensions of the petals are different. However, significant variation among their populations has the consequence that, at present, the only certain way to assign particular populations to species is to test their compatibility with previously tested populations.

Journal Article↗
PubMed1997

A recently silenced, duplicate PgiC locus in Clarkia.

Previous electrophoretic analysis showed that 17 diploid species of the wildflower Clarkia (Onagraceae) have two cytosolic isozymes of phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid species have a single PGIC. Molecular studies revealed that the two isozymes in the former species are encoded by duplicate genes, PgiC1 and PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1. Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was silenced four times independently in the genus. Here we describe a psi PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The discovery of the psi PgiC2 is significant because it confirms a formal prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039 nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the intervening introns and 3' nontranslated region. The absence of an increase of nucleotide substitutions in its "exons" suggests that the gene was silenced recently. The present study appears to be the first to establish that a specific duplicate gene locus regularly expressed in a group of related plant species has been silenced in one of them. The multiple independent silencings of PgiC2 suggest that it remained functional but inessential in ancestral lineages. We discuss the possibility that PgiC2 may have been preserved in these lineages by selection against mutants causing defective PGIC1-PGIC2 heterodimers.

Base Sequence↗
PubMed1997

A collaborative project in Connecticut to improve the care of patients with acute myocardial infarction.

BACKGROUND: State-based peer review organizations (PROs) and individual hospitals are challenged to achieve their quality improvement (QI) goals with shrinking resources. In 1993-1994 the Connecticut PRO and 15 local hospitals generated a comparative QI database on acute myocardial infarction (AMI) care for 1,202 Medicare and non-Medicare patients discharged in 1992 and 1993. METHODS: A steering committee composed of hospital and PRO representatives was assembled to provide oversight. PRO staff developed a chart abstraction tool and trained hospital abstracters who collected and submitted data to the PRO for comparative analyses. Written feedback was provided to all hospitals and supplemented with onsite presentations when requested. Each hospital prepared a written QI plan based on its unique data profile. RESULTS: Opportunities for improvement were identified at all hospitals. The most commonly targeted areas for improvement included the use of thrombolytics at presentation, aspirin at presentation and at discharge, and beta blockers at discharge. Improvement interventions included staff education sessions, development of AMI critical paths and standing orders, and storage of appropriate medications in emergency departments. Self-report data from the hospitals indicate improvements in care. DISCUSSION: PROs and hospitals can augment their individual QI activities by working together to share data, resources, and lessons learned. Twenty-three hospitals are now collaborating with the Connecticut PRO on a similarly designed QI project aimed at improving the care of patients hospitalized with atrial fibrillation. This project includes a more formal means of communicating QI interventions.

Aged↗
PubMed1996

A collaborative project in Connecticut to improve the care of patients with acute myocardial infarction.

BACKGROUND: State-based peer review organizations (PROs) and individual hospitals are challenged to achieve their quality improvement (QI) goals with shrinking resources. In 1993-1994 the Connecticut PRO and 15 local hospitals generated a comparative QI database on acute myocardial infarction (AMI) care for 1,202 Medicare and non-Medicare patients discharged in 1992 and 1993. METHODS: A steering committee composed of hospital and PRO representatives was assembled to provide oversight. PRO staff developed a chart abstraction tool and trained hospital abstractors who collected and submitted data to the PRO for comparative analyses. Written feedback was provided to all hospitals and supplemented with onsite presentations when requested. Each hospital prepared a written QI plan based on its unique data profile. RESULTS: Opportunities for improvement were identified at all hospitals. The most commonly targeted areas for improvement included the use of thrombolytics at presentation, aspirin at presentation and at discharge, and beta blockers at discharge. Improvement interventions included staff education sessions, development of AMI critical paths and standing orders, and storage of appropriate medications in emergency departments. Self-report data from the hospitals indicate improvements in care. DISCUSSION: PROs and hospitals can augment their individual QI activities by working together to share data, resources, and lessons learned. Twenty-three hospitals are now collaborating with the Connecticut PRO on a similarly designed QI project aimed at improving the care of patients hospitalized with atrial fibrillation. This project includes a more formal means of communicating QI interventions.

Aged↗
PubMed1993

Molecular characterization of duplicate cytosolic phosphoglucose isomerase genes in Clarkia and comparison to the single gene in Arabidopsis.

The nucleotide sequence of PgiC1-a which encodes a cytosolic isozymes of phosphoglucose isomerase (PGIC; EC 5.3.1.9) in Clarkia lewisii, a wildflower native to California, is described and compared to the previously published sequence of the duplicate PgiC2-a from the same genome. Both genes have the same structure of 23 exons and 22 introns located in identical positions, and they encode proteins of 569 amino acids. Exon and inferred protein sequences of the two genes are 96.4% and 97.2% identical, respectively. Intron sequences are 88.2% identical. The high nucleotide similarity of the two genes is consistent with previous genetic and biosystematic findings that suggest the duplication arose within Clarkia. A partial sequence of PgiC2-b was also obtained. It is 99.5% identical to PgiC2-a in exons and 99.7% in introns. The nucleotide sequence of the single PgiC from Arabidopsis thaliana was also determined for comparison to the Clarkia genes. The A. thaliana PgiC has 21 introns located at positions identical to those in Clarkia PgiC1 and PgiC2, but lacks the intron that divides Clarkia exons 21 and 22. The A. thaliana PGIC protein is shorter, with 560 amino acids, and differs by about 17% from the Clarkia PGICs. The PgiC in A. thaliana was mapped to a site 20 cM from restriction fragment length polymorphism marker 331 on chromosome 5.

Amino Acid Sequence↗
PubMed1992

Molecular analysis of the plant gene encoding cytosolic phosphoglucose isomerase.

The gene encoding a cytosolic isozyme of phosphoglucose isomerase (PGI, EC 5.3.1.9) was isolated from Clarkia lewisii, a wild flower native to California, and the structure and sequence of the entire coding region determined. PGI catalyzes an essential step in glycolysis and carbohydrate biosynthesis in plants. Spanning about 6 kb, the gene has 23 exons and 22 introns, the highest number yet reported in plants. The exons range in size from 43 to 156 nt and encode a protein of 569 amino acids. The protein is about 44-46% identical to the inferred protein sequences of pig, Escherichia coli and Saccharomyces cerevisiae. All of the introns are bordered with the consensus 5'-GT...AG-3' dinucleotides. The longest intron includes a large stem-loop structure bounded by a perfect 9 nt direct repeat. We cloned the PGI gene from a genomic library prepared from a single plant of known PGI genotype. The locus and allele of the clone were identified by matching restriction fragments to fragments from genetically defined genomic DNAs by Southern hybridization.

Amino Acid Sequence↗
PubMed1989

Decreased-activity mutants of phosphoglucose isomerase in the cytosol and chloroplast of Clarkia xantiana. Impact on mass-action ratios and fluxes to sucrose and starch, and estimation of Flux Control Coefficients and Elasticity Coefficients.

1. Subcellular-compartment-specific decreased-activity mutants of phosphoglucose isomerase in Clarkia xantiana were used to analyse the control of sucrose and starch synthesis during photosynthesis. Mutants were available in which the plastid phosphoglucose isomerase complement is decreased to 75% or 50% of the wild-type level, and the cytosol complement to 64%, 36% or 18% of the wild-type level. 2. The effects on the [product]/[substrate] ratio and on fluxes to sucrose or starch and the rate of photosynthesis were studied with the use of saturating or limiting light intensity to impose a high or low flux through these pathways. 3. Removal of a small fraction of either phosphoglucose isomerase leads to a significant shift of the [product]/[substrate] ratio away, from equilibrium. We conclude that there is no 'excess' of enzyme over that needed to maintain its reactants reasonably close to equilibrium. 4. Decreased phosphoglucose isomerase activity can also alter the fluxes to starch or sucrose. However, the effect on flux does not correlate with the extent of disequilibrium, and also varies depending on the subcellular compartment and on the conditions. 5. The results were used to estimate Flux Control Coefficients for the chloroplast and cytosolic phosphoglucose isomerases. The chloroplast isoenzyme exerts control on the rate of starch synthesis and on photosynthesis in saturating light intensity and CO2, but not at low light intensity. The cytosolic enzyme only exerts significant control when its complement is decreased 3-5-fold, and differs from the plastid isoenzyme in exerting more control in low light intensity. It has a positive Control Coefficient for sucrose synthesis, and a negative Control Coefficient for starch synthesis. 6. The Elasticity Coefficients in vivo of the cytosolic phosphoglucose isomerase were estimated to lie between 5 and 8 in the wild-type. They decrease in mutants with a lowered complement of cytosolic phosphoglucose isomerase. 7. The implications of these results for regulation and for evolution are discussed.

Chloroplasts↗
PubMed1989

Isolation and characterization of the phosphoglucose isomerase gene from Escherichia coli.

The nucleotide sequence of the gene encoding the glycolytic enzyme phosphoglucose isomerase (PGI) from Escherichia coli is presented. The gene encodes a polypeptide of 549 amino acids. The transcriptional start point of the gene was determined and found to lie within a consensus promoter region. The amino acid sequence derived from the E. coli PGI gene can be aligned without insertions or deletions to the predicted amino acid sequence of a nuclear-encoded chloroplast isozyme of PGI from a higher plant, and the two sequences have a similarity of 87.6%. The amino acid sequence similarity between E. coli and that predicted from cDNA sequences for mouse and pig PGI is approximately 65%.

Amino Acid Sequence↗
PubMed1989

The efficacy of atenolol in the outpatient management of the alcohol withdrawal syndrome. Results of a randomized clinical trial.

We conducted a randomized, double-blind, clinical trial of atenolol compared with placebo in the outpatient management of patients with the alcohol withdrawal syndrome. In addition to receiving customary therapy, 88 patients were randomly assigned to receive atenolol and 92 to receive placebo. Outcome during the next 14 days was assessed using two main measures: the patient's clinical course as assessed by an alcohol withdrawal severity index; and the occurrence of treatment failure (composite measure including return to drinking, dropouts, and withdrawal lasting longer than 5 days). In addition, levels of craving for alcohol were assessed as an associated response variable. Overall, treatment failure occurred for 37% of the patients receiving atenolol and 52% of those receiving placebo. Among patients who had withdrawal symptoms at baseline, vital signs became normal more rapidly in the patients receiving atenolol, and their abnormal behavioral characteristics also resolved more rapidly. Levels of craving for alcohol were strongly associated with treatment failure; the group of patients who received atenolol included significantly fewer who reported high levels of craving 24 hours after treatment began (7% of patients receiving atenolol and 20% of those receiving placebo). We conclude that the outpatient management and treatment outcomes of the alcohol withdrawal syndrome are improved in patients who receive atenolol, and that the beneficial effects are associated with reduced levels of craving for alcohol. If these results are confirmed by other investigators, atenolol may prove to play an important role in the outpatient management of the alcohol withdrawal syndrome.

Adult↗
PubMed1988

The role of beta blockers in alcohol withdrawal syndrome.

Previous studies have suggested that beta blockers might be useful in the treatment of alcohol withdrawal syndrome. A randomized, double-blind clinical trial was therefore conducted to compare results with atenolol versus those with placebo in patients hospitalized with alcohol withdrawal syndrome. In addition to receiving customary therapy, patients were randomly assigned to receive atenolol (61 patients) or placebo (59 patients). Outcome was assessed daily by the measurement of nine features in three categories: vital signs, clinical signs (eg, tremor), and behavioral signs (eg, agitation). Among patients who had withdrawal symptoms at baseline, vital signs became normal more rapidly in the patients receiving atenolol; abnormal behavior and clinical characteristics also resolved more rapidly. On each treatment day, significantly fewer patients receiving atenolol required concomitant oxazepam therapy for agitation. Patients receiving placebo, however, required a significantly higher mean daily dose of oxazepam. The results indicate that atenolol is helpful in the treatment of patients with alcohol withdrawal syndrome.

Adolescent↗
PubMed1985

Randomized clinical trial of atenolol in patients with alcohol withdrawal.

We conducted a randomized, double-blind clinical trial of atenolol as compared with placebo in the treatment of patients hospitalized with the alcohol withdrawal syndrome. In addition to receiving customary therapy, 61 patients were randomly assigned to receive atenolol, and 59 to receive placebo. Outcome was assessed daily by the measurement of nine features in three categories: vital signs, clinical signs (e.g., tremor), and behavioral signs (e.g., agitation and anxiety). Compared with placebo patients, atenolol patients had a significant reduction in the mean length of hospital stay (four as compared with five days, P less than 0.02). On each treatment day, significantly fewer patients receiving atenolol required concomitant benzodiazepines, and patients receiving placebo required a significantly higher mean daily dose of benzodiazepines. Among patients who had withdrawal symptoms at base line, vital signs became normal more rapidly in the patients receiving atenolol, and their abnormal behavior and clinical characteristics also resolved more rapidly. We conclude that atenolol is helpful in the treatment of patients with the alcohol withdrawal syndrome.

Adult↗
PubMed1984

Nucleotide sequence of the triose phosphate isomerase gene of Escherichia coli.

We report here the complete nucleotide sequence of the E. coli triose phosphate isomerase gene. The gene encodes a polypeptide of 255 amino acids which is approximately 46% homologous to eukaryotic triose phosphate isomerases, and approximately 38% homologous to the enzyme from a thermophilic bacterium, Bacillus stearothermophilus. The nucleotide sequence is 55% homologous to that of the corresponding gene in the yeast Saccharomyces cerevisiae. To our knowledge, this is the first report of the sequence of a gene coding a glycolytic enzyme from a prokaryotic organism.

Amino Acid Sequence↗
PubMed1984

Subunit hybridization and immunological studies of duplicated phosphoglucose isomerase isozymes.

We examined structural and functional properties of the recently duplicated cytosolic isozymes of phosphoglucose isomerase (PGI) (EC 5.3.1.9) of the wild plant Clarkia xantiana and related species. A new purification protocol yielded PGIs with high specific activities. The duplicated PGI isozymes showed similar substrate affinities (apparent Km) in both catalytic directions. A newly devised competitive enzyme-linked immunosorbent assay (ELISA), using polyclonal antibodies, distinguished sodium dodecyl sulfate (SDS)-denatured PGIs coded by the duplicated loci but did not discriminate between allelic products of one of the loci. In vitro dissociation and reassociation experiments revealed that the duplicated subunits differed in their efficiency of reassociation. The difference was closely correlated with differences between the isozymes in their in vivo accumulation. In contrast, allelic subunits in species with or without the duplication were able to reassociate with similar efficiency. The duplicated PGI isozymes have diverged more in structural properties than kinetic ones. The total evidence suggests that mechanisms have evolved which reduce the potential consequences of the duplication.

Cytosol↗
PubMed1983

Adequacy of antitetanus prophylaxis in six hospital emergency rooms.

We studied the adequacy of antitetanus prophylaxis given to 620 patients with open soft-tissue injuries by 169 physicians in six hospital emergency rooms. Twenty-three per cent of the patients were treated incorrectly (6 per cent were undertreated and 17 per cent were overtreated) with tetanus toxoid or human tetanus immunoglobulin. Undertreatment ranged from 4 to 11 per cent, and overtreatment from 5 to 38 per cent at the different hospitals (P less than 0.01). Patients at highest risk for tetanus (those with tetanus-prone wounds who had never been given a complete initial course of immunizations) had the lowest likelihood (27 per cent) of receiving correct antitetanus treatment. By following an immunization protocol based on time since injury, mechanism of injury, estimated bacterial contamination, presence of devitalized tissue, wound depth, and past immunizations, physicians can better protect the population against tetanus while lowering the risk of adverse drug reactions and not increasing the cost of care.

Emergency Medical Services↗
PubMed1981

Biochemical properties of duplicated isozymes of phosphoglucose isomerase in the plant Clarkia xantiana.

The structural gene locus specifying subunits of cytoplasmic isoenzymes of phosphoglucose isomerase (PGI) is present in duplicate in many diploid species of Clarkia (Onagraceae), a genus of annual plants native to California. We studied the kinetic properties and molecular weights of a large number of genetically defined and highly purified PGIs in C. xantiana, a number of species with the duplication, as a means of examining the biochemical consequences of the evolution of a new gene locus. This species is primarily outcrossing, but also includes several previously described predominantly self-pollinating populations. Both cytoplasmic PGI loci in the outcrossing populations are polymorphic and their enzyme products are readily separated by electrophoresis. The PGIs from the outcrossing populations were rated by electrophoresis. The PGIs from the outcrossing populations were generally closely similar in molecular weight, pH optimum, heat sensitivity, energy activation, and apparent Km (fructose-6-phosphate). The PGI loci in the selfing populations are monomorphic and specify enzymes having identical electrophoretic mobilities to those coded by the most frequent alleles of the outcrosser. The PGI isozymes in the selfers differed fivefold in Km, suggesting that they have a very different catalytic effectiveness. The high Km of the PGI-3A' isozyme (1.1mM) was anomalous among the PGIs examined and would likely be disadvantageous in a species which lacked other more normally functioning PGIs. But in the cytoplasm of the selfing plants, it is present with other PGIs that have low Km values. The PGI-3A' enzyme is a good candidate for a gene product coded by a "forbidden" mutation that could not have been established in the absence of the duplication. The rationale for this suggestion is described and it is also pointed out that the divergence of duplicated genes is influenced by many factors such as the breeding system and other population factors as well as the effect of particular mutations.

Catalysis↗
PubMed1980

Biochemical properties and level of expression of alcohol dehydrogenases in the allotetraploid plant Tragopogon miscellus and its diploid progenitors.

This study demonstrates that homoeologous genes in two diploid plant species that specify different amounts of an enzyme maintain the same relative level of expression in an allotetraploid derivative. The three predominant alcohol dehydrogenase (ADH) isozymes (DD, DP, PP) in seeds of the recently evolved allotetraploid plant Tragopogon miscellus (Compositae) are dimers specified by Adh3-D and Adh3-P genes derived from its diploid progenitors T. dubius and T. pratensis. Seeds of T. pratensis contain twice as much ADH activity as those of T. dubius, while T. miscellus is intermediate. The three isozymes were similar in a number of catalytic properties; the densitometric ratio of the isozymes purified from T. miscellus was 1 DD : 4DP : 4PP for both ADH activity and protein; and dissociation-reassociation of the DP enzyme gave a 1:2:1 ratio of the three isozymes. Therefore, the enzymes were similar in specific activity, but twice as many P as D subunits were present in active enzymes in T. miscellus, precisely the difference in activity between the parents. In T. miscellus, the specific activity of ADH and its activity per mg tissue are intermediate to those of the diploids, because relative expression of the Adh gene in each genome is not influenced by the presence of the other genome.

Alcohol Oxidoreductases↗