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Biomedical subjects

T M Kelly

Publications and source records attributed to T M Kelly.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

Classical conditioning of the eyeblink reflex in the decerebrate-decerebellate rabbit.

The purpose of these experiments was to test the hypothesis that a conditioned nictitating membrane reflex can be acquired in decerebrate rabbits in the absence of the cerebellum. Experiments examining the effects of large cerebellar lesions on the acquisition and performance of the conditioned reflex were performed in acutely prepared decerebrate rabbits. Most lesions encompassed all of the cerebellar nuclear regions ipsilateral to the eye receiving the unconditioned stimulus. In all rabbits included in this study the continuity between the cerebellar nuclei and the brainstem was interrupted, even in those preparations in which small regions of the nuclei were present in the lateral hemisphere. The findings demonstrate that these animals could acquire the conditioned reflex independent of whether conditioning had occurred prior to the cerebellectomy. Strong associativity was found between the latency of the conditioned response and the interstimulus interval between the conditioned and unconditioned stimuli. The behavior of the conditioned reflex observed in the decerebrate-decerebellate animals differed from that reported for awake intact rabbits in two ways. Once the conditioned behavior had been acquired, the percent of trials showing conditioned responses was somewhat less in decerebrate-decerebellate rabbits and was also more variable in these animals. The data demonstrate that the nictitating membrane reflex can be classically conditioned in the absence of the cerebellum, indicating that this structure is neither necessary nor sufficient for the acquisition of this type of conditioned behavior. In addition, an hypothesis is presented which addresses the difference between the data reported here and those previously reported by other laboratories based on observations in awake intact animals.

Animals

Predicting microbial growth: graphical methods for comparing models.

Some simple computer-based graphics were used to compare different models predicting microbial growth responses of salmonellae to three factors (pH, sodium chloride concentration and incubation temperature). Simple linear regression, contour and three-dimensional surface plots all revealed gross differences between the predicted growth parameters from different growth models. Regression and contour plots were found to be more sensitive to small differences in surface topography, but three-dimensional surface plots provided a good overview.

Computer Graphics

Kinematic analysis of the defense response in crayfish.

1. A threatening visual stimulus frequently elicits the defense response (DR) in crayfish, a behavior that comprises orienting the body to face the stimulus, raising the thorax, and extending and opening the claws. Although this behavior has been reported previously, its kinematics have not been characterized. This work employs kinematic analysis to provide a quantitative description of the claw (cheliped) as it is moved during the DR. 2. The cheliped was modeled as an open kinematic chain with three segments and 4 df. Simulations employing the model were compared with actual cheliped trajectories during the DR to ascertain the applicability of the model. The model was then employed to demonstrate the effects of individual joint rotations on the overall trajectory of the claw. 3. The individual segments of the cheliped were monitored during the DR, and spatial trajectories, tangential velocities, and intersegmental joint angles were calculated. 4. The joint angles assumed at the final position of the DR were highly stereotyped. This constancy in joint angle at the endpoint of the movement stands in contrast to the variability in both the angular and spatial trajectories of the cheliped as it was moved towards the final position. 5. Movement time was relatively constant. Larger amplitude movements were performed with a proportional increase in velocity similar to arm movements in primates. 6. The DR positions the cheliped in a fixed location in the workspace. Unlike the primate arm during reaching, the cheliped does not proceed towards the endpoint with a smooth controlled trajectory characteristic of a system with fine interjoint coordination. Instead, it appears that individual joint rotations are performed independently, thus precluding trajectory control although permitting an accurate specification of the endpoint.

Animals

Predicting microbial growth: the consequences of quantity of data.

Having developed a mathematical model of the growth responses in a laboratory medium of salmonellae (mixed inoculum of Salmonella thompson, S stanley and S. infantis) as affected by pH level, NaCl concentration and storage temperature, the consequences of systematic removal of data has been examined. Three-dimensional plots of fitted response surfaces for the whole data set and the data reduced by three strategies highlighted differences between models and illustrated the consequences of using insufficient data. The risk of an erroneous model was demonstrated.

Culture Media

Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal.

Activated charcoal usually provides effective and safe treatment for drug overdose. We describe a patient who developed bronchiolitis obliterans and respiratory failure following aspiration of activated charcoal. This patient had a markedly reduced vital capacity with roentgenographic evidence of airtrapping. Chest roentgenograms did not demonstrate the large amount of charcoal identified at postmortem examination.

Adolescent

Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum.

A corticosteroid induced increase in a circulating inhibitor of serum phospholipase A2 activity is described. Inhibitor activity was found to be normally present in serum in agreement with the findings of other workers, and this activity was significantly increased by either acute or chronic administration of corticosteroids. The possible relation of this inhibitor to the known inhibitory effects of lipocortin and sphingomyelin on phospholipase A2 activity is briefly discussed.

Enzyme Inhibitors

An inexpensive, microcomputer-based system for recording movements in real time.

An inexpensive, microcomputer-based system was developed for recording movements in real time. The positions of 5 serially illuminated, infrared emitting diodes fixed on the object of interest were tracked by a remote, position-sensing photodiode. Positional information from the photodetector was digitized by an LSI 11/23+ microcomputer (sampling rate = 50/s/channel) and stored for subsequent analysis. Any microcomputer equipped to perform analog-digital conversion is compatible for use with this system. The small size of the components that are mounted on the animal allows movement to occur virtually unimpeded and makes this recording system especially suited for small animal observation.

Animals