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Biomedical subjects

T M Kelly

Publications and source records attributed to T M Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1996

Exercise testing and training of patients with malignant ventricular arrhythmias.

Malignant ventricular arrhythmias account for a significant number of deaths annually. Improved therapies have increased survival for this patient population. These patients, however, remain at high risk due to their history of sudden cardiac death and the preponderance of poor ventricular function in this population. This high risk status may have excluded them from participation in cardiac rehabilitation programs or from undergoing exercise testing in some medical centers. Although the risk of complications, especially arrhythmias, is quite real, the experience in some centers has indicated that it is manageable. This experience and some guidelines for exercise testing and training of patients with malignant ventricular arrhythmias are reviewed in this paper.

Arrhythmias, Cardiac↗
PubMed1996

Validity of DSM-III-R diagnosis by psychological autopsy: a comparison with clinician ante-mortem diagnosis.

Psychological autopsies are an important research tool in establishing risk factors associated with suicide. We report the results of a validity study comparing psychological autopsy-generated DSM-III-R diagnoses in suicides and non-suicides with chart diagnoses generated by clinicians who had treated the subjects prior to death. The Structured Clinical Interview for DSM-III-R Disorders (SCID-P) and the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) were used to make independent post-mortem diagnoses. Comparison of research diagnoses with clinician ante-mortem diagnoses generated kappa coefficients of 0.85 for Axis I diagnoses and 0.65 for Axis II conditions. These kappa coefficients compare favourably with direct patient interview reliability studies. This provides evidence for the validity of the psychological autopsy as a method of determining psychiatric diagnosis.

Accidents↗
PubMed1996

Insulin-resistant lipolysis in abdominally obese hypertensive individuals. Role of the renin-angiotensin system.

Resistance to the capacity of insulin to suppress lipolysis may be an important link in the association between abdominal obesity and hypertension. Furthermore, a more active renin-angiotensin system in adipose tissue may contribute to insulin-resistant lipolysis in abdominally obese hypertensive subjects. We determined nonesterified fatty acid concentrations and turnover as well as lipid oxidation under basal conditions and during steady-state euglycemia with two levels of insulinemia (72 and 287 pmol/L) in lean normotensive, abdominally obese normotensive, and abdominally obese hypertensive subjects. To assess the role of the renin-angiotensin system in determining non-esterified fatty acid turnover, we repeated studies in the abdominally obese hypertensive subjects after double-blind random assignment to placebo or enalapril for 1 month each. The main findings were the following: (1) Nonesterified fatty acid flux was significantly higher in abdominally obese hypertensive subjects at both levels of insulinemia than in either abdominally obese normotensive or lean normotensive subjects and correlated significantly with both mean blood pressure and total systemic resistance during the higher level of insulinemia. (2) Enalapril significantly improved insulin-resistant lipolysis in the abdominally obese hypertensive subjects. The improvement in insulin suppressibility of nonesterified fatty acid flux at the high hormonal concentrations correlated positively with the magnitude of reduction in blood pressure. (3) Basal lipid oxidation and suppression in response to insulin were similarly impaired in both obese groups. Resistance to the antilipolytic actions of insulin is thus a characteristic feature in abdominally obese hypertensive subjects and may be linked to the elevated blood pressure in these individuals. A more active renin-angiotensin system may partly explain the insulin-resistant lipolysis in this form of hypertension.

Adult↗
PubMed1995

Cardiac rehabilitation in the time of health-care reform.

Cardiac rehabilitation has evolved into a medically efficacious, cost-effective intervention for patients with ischemic heart disease. Most aspects of this therapy are well developed, and guidelines for programs exist. As the health-care delivery system undergoes scrutiny and evolution, it would be prudent for the practitioners of cardiac rehabilitation to evaluate the methods they use to deliver their services. Program administrators should reconsider traditional approaches that are largely based on reimbursement criteria. Goal-directed, patient-centered service delivery will allow individualization of care. A model for such an approach to cardiac rehabilitation is presented.

Cost-Benefit Analysis↗
PubMed1995

Glucose metabolism in abdominally obese hypertensive and normotensive subjects.

To determine whether the combination of obesity and hypertension results in additive defects in oxidative and nonoxidative glucose metabolism and the association of these changes with altered hemodynamic actions of insulin, we studied 11 abdominally obese hypertensive, 6 abdominally obese normotensive, and 7 lean normotensive nondiabetic subjects. Endogenous glucose production and glucose metabolized were calculated from a euglycemic clamp at 72 and 287 pmol insulin/m2 per minute. Glucose metabolized divided by insulin was lower at 72 pmol/m2 per minute in both obese groups than in lean normotensive subjects, at 148 +/- 14, 144 +/- 33, and 373 +/- 69 (mumol/m2 per minute)/(pmol/L), respectively (P < .01). Similar results were obtained during the higher insulin dose. Nonoxidative and oxidative glucose disposals by indirect calorimetry were lower in both abdominally obese groups (P < .05). Hepatic glucose production was completely suppressed in lean subjects at the lower insulin dose and in all three groups at the higher insulin dose. Hemodynamic responses during the clamp were not significantly different among the three groups. Abdominal obesity is associated with defects in insulin-regulated oxidative and nonoxidative glucose disposal as well as in insulin suppression of hepatic glucose production. Mild hypertension does not exacerbate these defects. Whereas the global impairment in glucose metabolism suggests the presence of an early defect or defects, including reduced tissue perfusion, systemic and regional hemodynamic responses to insulin were not altered. These findings do not support a direct role for insulin resistance in the pathogenesis of the hypertension associated with abdominal obesity.

Abdomen↗
PubMed1995

Idiotypic and anti-idiotypic antibodies interfere in a standard radioimmunoassay for beta-endorphin.

Human anti-beta-endorphin and anti-idiotypic antibodies competitively inhibited the binding of rabbit anti-beta-endorphin antibodies to beta-endorphin. Furthermore, human and rabbit antibodies demonstrated cross-reactive idiotypic binding interactions. Competition for binding to beta-endorphin and idiotypic binding between human and commercially produced rabbit antibodies interfered in a standard radioimmunoassay to detect beta-endorphin. Purified human anti-beta-endorphin antibodies falsely elevated the calculated concentrations of samples with standardized concentrations of beta-endorphin. Anti-beta-endorphin antibodies were also falsely measured as beta-endorphin in samples that did not contain beta-endorphin. In contrast, anti-idiotypic antibodies lowered the calculated concentrations. These data suggest the occurrence of complex competition between several competitors rather than inhibition by a single competitor (i.e., unlabeled peptide) in subjects that produce specific antibody. Competitive and idiotypic binding interactions between human and animal antibodies may affect radioimmunoassay for other substances in subjects that produce specific antibodies.

Animals↗
PubMed1994

An Escherichia coli gene (FabZ) encoding (3R)-hydroxymyristoyl acyl carrier protein dehydrase. Relation to fabA and suppression of mutations in lipid A biosynthesis.

Escherichia coli strain SM101 harbors a temperature-sensitive allele (lpxA2) of the gene encoding UDP-Glc-NAc acyltransferase (the first enzyme of the lipid A pathway). SM101 is temperature-sensitive for lipid A biosynthesis and growth. To determine whether or not E. coli mutants lacking lipid A can be isolated, we examined temperature-resistant revertants of SM101. All regained the ability to synthesize lipid A. However, some were not true revertants but had acquired mutations in a neighboring gene (orf17), while retaining the original lpxA2 lesion. Cell extracts of such revertants displayed 2-5 fold reductions in the specific activity of (3R)-hydroxymyristoyl-ACP dehydrase. Wild-type cells that overproduced the protein encoded by orf17 overproduced (3R)-hydroxymyristoyl-ACP dehydrase activity as much as 170-fold, suggesting that orf17 is the structural gene for the dehydrase. The proposed function of orf17 is further supported by its sequence similarity to fabA, the structural gene for (3R)-hydroxydecanoyl dehydrase of E. coli. We suggest that bypass of the lpxA2 phenotype by mutations in orf17 may be due to an increased (3R)-hydroxymyristoyl-ACP pool. The orf17 gene (which we now designate fabZ) is not regulated by fadR. However, orf17 may be related to sefA, a suppressor of certain lesions in the cell division/lipid A biosynthesis gene, envA.

Amino Acid Sequence↗
PubMed1994

Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection.

Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.

Adult↗
PubMed1994

Maxillofacial prosthetics: a preliminary analysis of Resource Based Relative Value Scale.

A study done by the American Academy of Maxillofacial Prosthetics to evaluate the Medicare Resource Based Relative Value Scale (RBRVS) as it relates to maxillofacial prosthetics. The method of RBRVS formulation is described. The degree of difficulty and treatment time were determined for nine Physicians' Current Procedural Terminology-edition 4 (CPT-4) codified maxillofacial procedures. A preliminary survey indicates that practice expense and malpractice expense ratios were 66% and 1%, respectively. Correlation of maxillofacial procedures to other medical procedures was not performed because an additional study with a greater sample size is needed.

Ear↗
PubMed1994

Biosynthesis of a structurally novel lipid A in Rhizobium leguminosarum: identification and characterization of six metabolic steps leading from UDP-GlcNAc to 3-deoxy-D-manno-2-octulosonic acid2-lipid IVA.

Lipopolysaccharides (LPSs) are prominent structural components of the outer membranes of gram-negative bacteria. In Rhizobium spp. LPS functions as a determinant of the nitrogen-fixing symbiosis with legumes. LPS is anchored to the outer surface of the outer membrane by the lipid A moiety, the principal lipid component of the outer bacterial surface. Several notable structural differences exist between the lipid A of Escherichia coli and that of Rhizobium leguminosarum, suggesting that diverse biosynthetic pathways may also exist. These differences include the lack of phosphate groups and the presence of a 4'-linked GalA residue in the latter. However, we now show that UDP-GlcNAc plays a key role in the biosynthesis of lipid A in R. leguminosarum, as it does in E. coli. 32P-labeled monosaccharide and disaccharide lipid A intermediates from E. coli were isolated and tested as substrates in cell extracts of R. leguminosarum biovars phaseoli and viciae. Six enzymes that catalyze the early steps of E. coli lipid A biosynthesis were also present in extracts of R. leguminosarum. Our results show that all the enzymes of the pathway leading to the formation of the intermediate 3-deoxy-D-manno-2-octulosonic acid (Kdo2)-lipid IVA are functional in both R. leguminosarum biovars. These enzymes include (i) UDP-GlcNAc 3-O-acyltransferase; (ii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase; (iii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcN N-acyltransferase; (iv) disaccharide synthase; (v) 4'-kinase; and (vi) Kdo transferase. Our data suggest that the early steps in lipid A biosynthesis are conserved and that the divergence leading to rhizobial lipid A may occur at a later stage in the pathway, presumably after the attachment of the Kdo residues.

Acetates↗
PubMed1994

Cloning, sequencing, and overexpression in Escherichia coli of the alpha-D-glucose-1-phosphate cytidylyltransferase gene isolated from Yersinia pseudotuberculosis.

A clone of Yersinia pseudotuberculosis DNA carrying the ascA gene was constructed, and the corresponding protein was successfully overexpressed in Escherichia coli. A protocol consisting of DEAE-cellulose and Sephadex G-100 column chromatography was developed and led to a nearly homogeneous purification of the ascA product. Initial characterization showed that the ascA-encoded protein is actually the alpha-D-glucose-1-phosphate cytidylyltransferase which catalyzes the first step of the biosynthesis of CDP-ascarylose (CDP-3,6-dideoxy-L-arabino-hexose), converting alpha-D-glucose-1-phosphate to CDP-D-glucose. In contrast to early studies suggesting that this enzyme was a monomeric protein of 111 kDa, the purified cytidylyltransferase from Y. pseudotuberculosis was found to consist of four identical subunits, each with a molecular mass of 29 kDa. This assignment is supported by the fact that the ascA gene, as a part of the ascarylose biosynthetic cluster, exhibits high sequence homology with other nucleotidylyltransferases, and its product shows high cytidylyltransferase activity. Subsequent amino acid comparison with other known nucleotidylyltransferases has allowed a definition of the important active-site residues within this essential catalyst. These comparisons have also afforded the inclusion of the cytidylyltransferase into the mechanistic convergence displayed by this fundamental class of enzyme.

Amino Acid Sequence↗
PubMed1993

UDP-N-acetylglucosamine acyltransferase of Escherichia coli. The first step of endotoxin biosynthesis is thermodynamically unfavorable.

UDP-N-acetylglucosamine acyltransferase of Escherichia coli catalyzes the reaction, UDP-GlcNAc + R-3-hydroxymyristoyl-ACP--> UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc + ACP. Using Matrex Gel Green A and heparin-agarose, we have purified the enzyme to near homogeneity from a strain that overproduces it 474-fold. The subunit molecular mass determined by SDS-gel electrophoresis is approximately 30 kDa, consistent with results of previous radiolabeling experiments in mini-cells. The amino-terminal sequence (Met-Ile-Asp-Lys-Ser-Ala-Phe-Val-His-Pro) and the amino acid composition of the purified protein are consistent with DNA sequencing (Coleman, J., and Raetz, C. R. H. (1988) J. Bacteriol. 170, 1268-1274). At saturating concentrations of the second substrate, the apparent Km values for UDP-GlcNAc and R-3-hydroxymyristoyl-ACP are 99 and 1.6 microM, respectively. There is an absolute requirement for the R-3-hydroxy moiety of the fatty acyl-ACP substrate; myristoyl-ACP binds effectively (IC50 = 2 microM) but is inactive (< 0.01%) as an alternate substrate. The most remarkable feature of the reaction is its unfavorable equilibrium constant, Keq approximately equal to 0.01, which is not predicted by model S-->O acyl transfer reactions. Thus, although UDP-GlcNAc acyltransferase catalyzes the first unique step of lipid A biosynthesis, it is the second enzyme (the deacetylase) that commits the substrates to this pathway. The specific activity of the deacetylase is elevated approximately 5-fold when lipid A synthesis is inhibited.

Acyltransferases↗
PubMed1993

The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. The third step of endotoxin biosynthesis.

The possibility that the firA gene of Escherichia coli (Dicker, I. B., and Seetharam, S. (1991) Mol. Microbiol. 6, 817-823) might function in lipid A biosynthesis was examined based on its homology to the lpxA gene, which encodes UDP-N-acetylglucosamine O-acyl-transferase, the first enzyme in lipid A formation. Extracts of a temperature-sensitive firA mutant, RL-25, were assayed for their ability to acylate UDP-GlcNAc, using a coupled assay. The results suggested that extracts of RL-25 might be defective in the third enzyme of this pathway, the UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. Living cells of RL-25 also displayed a 5-fold decreased rate of lipid A biosynthesis at the nonpermissive temperature as judged by a 32Pi incorporation assay. In order to examine N-acyltransferase activity directly, the substrate [alpha-32P]UDP-3-O-(R-3-hydroxymyristoyl)-GlcN was synthesized enzymatically. N-Acyltransferase specific activity in RL-25 extracts was reduced to less than 10% of wild-type. When the wild-type firA gene was cloned into a T7-based expression vector, N-acyltransferase specific activity increased almost 360-fold relative to wild-type extracts, demonstrating that firA is the structural gene for the enzyme. The N-acyltransferase displays absolute specificity for the R-3-OH moiety of R-3-hydroxymyristoyl-ACP, as does the O-acyltransferase, consistent with the placement of R-3-hydroxymyristate in E. coli lipid A.

Acyltransferases↗
PubMed1993

A predictive model for the combined effect of pH, sodium chloride and storage temperature on the growth of Brochothrix thermosphacta.

Growth of Brochothrix thermosphacta was observed under ranges of pH (5.6-6.8), NaCl (0.5-8.0% w/v) and incubation temperature (1-30 degrees C). In order to compare different approaches, two models were used to fit growth curves to viable count data, and to calculate parameters from those fitted curves. Growth responses as a function of pH, NaCl and temperature were described with a quadratic function which was then used to predict growth within the limits where growth was observed. The predictions of the model show good agreement with published observations from other laboratories.

Cell Division↗
PubMed1991

The effects of temperature, pH, sodium chloride and sodium nitrite on the growth of Listeria monocytogenes.

An automated turbidimetric system using multiwelled plates was used to examine the effects of different combinations of NaCl (0.5-8.0% w/v), NaNO2 (0-400 micrograms/ml) pH (4.6-7.4) and temperature (5-30 degrees C) on the growth of Listeria monocytogenes in tryptone soya broth. The data presented clearly illustrate the combinations that permit visible growth of the organism. The ability of L. monocytogenes to grow at low pH levels was strongly influenced by incubation temperature as well as NaNO2 concentration. At 20 degrees C and below, no visible growth was detected, even with 50 micrograms/ml NaNO2 at pH 5.3 (or below) within 21 days. At pH 6.0 and above, NaNO2 had little effect in delaying visible growth except at higher concentrations and also at lower incubation temperatures.

Colony Count, Microbial↗