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Biomedical subjects

M McCoy

Publications and source records attributed to M McCoy.

At least 19 recordsLinked to original sources

Implementation of serum cardiac troponin I as marker for detection of acute myocardial infarction.

BACKGROUND: The goal of this prospective study was to assess whether cardiac troponin I (cTnI) could replace creatine kinase (CK)-MB mass as the serum biochemical marker for detection of acute myocardial infarction (AMI). METHODS AND RESULTS: Over a 3-month period, 327 nonselected, consecutive patients were evaluated for AMI with the use of modified World Health Organization criteria including serial electrocardiographs and CK-MB mass determinations at admission and 6, 12, and 24 hours after admission. cTnI measurements were also made at all time points. Sixty-two (19%) patients were diagnosed with AMI. Diagnostic sensitivity and specificity for peak concentrations were equivalent or better for cTnI (100%; 96.3%) compared with CK-MB (88. 2%; 93.2%) and total CK (73.5%; 84.6%), respectively. cTnI demonstrated 100% negative predictive accuracy for ruling out AMI. Further, cTnI maintained a high diagnostic sensitivity (>94%) up to 96 hours after onset of chest pain compared with CK-MB and total CK (both 50% sensitive) in patients with AMI. However, patients with documented Q-wave infarctions had a significantly longer clearance compared with non-Q-wave infarctions (dagger(1/2) 24.2 vs 7.3 hours, respectively; P <.01). There was a significant (P <.02) positive correlation (r = 0.89) between increasing CK-MB mass and increasing cTnI for AMI specimens. CONCLUSIONS: These findings have strongly supported our clinical implementation of cTnI, replacing CK-MB mass as the preferred marker for detection of AMI.

Biomarkers

Formation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) by PHA synthase from Ralstonia eutropha.

The acetoacetyl-CoA reductase and the polyhydroxyalkanoate (PHA) synthase from Ralstonia eutropha (formerly Alcaligenes eutrophus) were expressed in Escherichia coli, Klebsiella aerogenes, and PHA-negative mutants of R. eutropha and Pseudomonas putida. While expression in E. coli strains resulted in the accumulation of poly(3-hydroxybutyrate) [PHB], strains of R. eutropha, P. putida and K. aerogenes accumulated poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [poly(3HB-co-3HHx)] when even chain fatty acids were provided as carbon source, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [poly(3HB-co-3HV)] when odd chain fatty acids were provided as carbon source. This suggests that fatty acid degradation can be directly accessed employing only the acetoacetyl-CoA reductase and the PHA synthase. This is also the first proof that the PHA synthase from R. eutropha can incorporate 3-hydroxyhexanoate (3HHx) into PHA and has, therefore, a broader substrate specificity than previously described.

3-Hydroxybutyric Acid

Characterization of large-pore polymeric supports for use in perfusion biochromatography.

Perfusion chromatography is uniquely characterized by the flow of a portion of the column eluent directly through the resin in the packed bed. The benefits of this phenomenon and some of the properties of perfusive resins have been described before, and can be summarized as enhanced mass transport to interior binding sites. Here we extend the understanding of this phenomenon by comparing resins with different pore size distributions. Resins are chosen to give approximately the same specific pore volumes (as shown in the characterization section) but the varying contribution of large pores is used to control the amount of liquid flowing through the beads. POROS R1 has the largest contribution of throughpores, and therefore the greatest intraparticle flow. POROS R2 has a lower contribution of throughpores, and a higher surface area coming from a greater population of diffusive pores, but still shows significant mass transport enhancements relative to a purely diffusive control. Oligo R3 is dominated by a high population of diffusive pores, and is used comparatively as a non-perfusive resin. Although the pore size distribution can be engineered to control mass transport rates, the resulting surface area is not the only means by which binding capacity can be controlled. Surface coatings are employed to increase binding capacity without fundamentally altering the mass transport properties. Models are used to describe the amount of flow transecting the beads, and comparisons of coated resins to uncoated (polystyrene) resins leads to the conclusion that these coatings do not obstruct the throughpore structures. This is an important conclusion since the binding capacity of the coated product, in some cases, is shown to be over 10-fold higher than the precursor polystyrene scaffold (i.e., POROS R1 or POROS R2).

Algorithms

Recidivism in convicted rapists.

Factors associated with recidivism in 86 men convicted of rape were studied. These men had been out of prison for up to 12 years (mean, 7.6 years). The majority of the men had been assessed in a sexual behaviors clinic of a general psychiatric hospital at the time of their conviction. Almost 50 percent of the group had committed some offense by the fifth year out of prison. The recidivism rates for sexual, violent, and any criminal recidivism were 16 percent, 26 percent, and 53 percent, respectively. The ability to predict sexual and violent recidivism in this population of rapists was rather poor. More sexual recidivists, compared with nonrecidivists, had been removed from their family home prior to age 16. Violent recidivists compared with nonrecidivists were also more frequently removed from their homes prior to 16 years of age, and they showed significantly more problems with alcohol. In terms of any criminal recidivism, recidivists compared with nonrecidivists were younger and scored higher on the Michigan Alcohol Screening Test (MAST). They also had more previous charges and/or convictions for violent offenses and more charges and/or convictions for any criminal acts. The combination of age and MAST scores was able to predict 92.6 percent of the nonrecidivists and 53.3 percent of the recidivists. The outstanding feature of the total group of rapists was their poor sexual adjustment as indicated on the Derogatis Sexual Functioning Inventory, on which they scored at approximately the seventh percentile of the population at large. There was also an indication that rapists have problems with hostility, as measured by the Buss-Durkee Hostility Inventory. Furthermore, the range of scores on the MAST indicated that the total group of rapists has serious problems with alcohol. The inability of phallometric assessments and psychopathy as measured by the Psychopathy Checklist-R to predict recidivism are discussed.

Adult

Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain.

The p53 tumor suppressor oligomerization domain, a dimer of two primary dimers, is an independently folding domain whose subunits consist of a beta-strand, a tight turn and an alpha-helix. To evaluate the effect of hydrophobic side-chains on three-dimensional structure, we substituted residues Phe341 and Leu344 in the alpha-helix with other hydrophobic amino acids. Substitutions that resulted in residue 341 having a smaller side-chain than residue 344 switched the stoichiometry of the domain from tetrameric to dimeric. The three-dimensional structure of one such dimer was determined by multidimensional NMR spectroscopy. When compared with the primary dimer of the wild-type p53 oligomerization domain, the mutant dimer showed a switch in alpha-helical packing from anti-parallel to parallel and rotation of the alpha-helices relative to the beta-strands. Hydrophobic side-chain size is therefore an important determinant of a protein fold.

Amino Acid Sequence

Cocaine self-administration alters brain NADH dehydrogenase mRNA levels.

Using differential display PCR, we identified a cDNA whose expression is altered in several brain regions in rats self-administering cocaine. The cDNA sequence corresponds to bases 13687-13723 of the rat NADH dehydrogenase subunit 6 gene. Northern analysis indicated a 26% decrease in nucleus accumbens, a 305% increase in the ventral midbrain and no changes in the caudate putamen mRNA levels; changes were also noted in the hypothalamus and cerebellum. This is the first demonstration of an effect of cocaine self-administration on mitochondrial gene expression and suggests that regional metabolic changes elicited by cocaine may be relevant to and involved in its reinforcing properties.

Animals

Skeletal muscle GLUT-4 and postexercise muscle glycogen storage in humans.

The purpose of this study was to examine the relationship between skeletal muscle GLUT-4 protein and postexercise glycogen storage in human subjects fed adequate carbohydrate. Eleven men completed 2 h of cycling, and a biopsy of the vastus lateralis was performed immediately after exercise cessation for the determination of muscle GLUT-4 protein and glycogen concentrations, glycogen synthase activity, and citrate synthase activity. The subjects ingested meals providing 2.0 g carbohydrate/kg body weight at 0, 2, and 4 h postexercise, and a second biopsy was performed 6 h postexercise. Muscle glycogen concentration increased significantly during the 6-h recovery period (glycogen immediately postexercise, 27.2 +/- 5.4 mmol/kg wet weight; glycogen storage, 52.4 +/- 2.9 mmol x kg wet weight-1 x 6 h-1; P<0.05). Glycogen storage during recovery was directly related to GLUT-4 protein (2.20 +/- 0.33 arbitrary standard units; r = 0.63; P<0.05) and inversely related to glycogen immediately postexercise (r = -0.70; P < 0.05). A direct correlation existed between glycogen storage during recovery and the activity of the I form of glycogen synthase (r = 0.60; P < 0.05). These results suggest that muscle GLUT-4 protein concentration, as well as factors relating to glucose disposal, may affect postexercise glycogen storage in humans fed adequate carbohydrate.

Adult

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Clinical Competence

Effect of detraining on GLUT-4 protein in human skeletal muscle.

The present study was undertaken to examine the effect of 10 days of detraining levels of GLUT-4 protein expression and citrate synthase (CS) activity in the vastus lateralis of trained men. During the course of normal training, seven endurance-trained (T) men and eight age- and weight-matched active but untrained (UT) men underwent an oral glucose tolerance test (OGTT) after an overnight fast. Muscle samples were obtained from the vastus lateralis by needle biopsy for measurement of GLUT-4 protein and CS activity. The tests were repeated on six of the T subjects after 10 days of detraining (DT men). The area under the insulin response curve during OGTT was lower in T men than in DT and UT men (22.4 +/- 2.8, 32.1 +/- 5.9, and 39.9 +/- 4.7 x 10(-3) pmol.l-1.min-1, respectively; P < 0.05). There were no differences between groups in the glucose responses to OGTT. GLUT-4 protein levels and CS activity were higher in T men than in DT and UT men (GLUT-4: 4.37 +/- 0.40, 2.92 +/- 0.53, and 1.71 +/- 0.22 arbitrary standard units and CS: 47.12 +/- 4.75, 33.63 +/- 3.98, and 24.51 +/- 2.97 mumol.min-1.g-1, respectively; both P < 0.05). Muscle GLUT-4 protein content was correlated with CS activity in all three groups (r = 0.64, 0.68, and 0.96 for UT, T, and DT men, respectively). These results suggest that muscle GLUT-4 protein content and oxidative capacity undergo parallel adaptations after detraining in previously well-trained men.

Adult

Skeletal muscle GLUT-4 and glucose uptake during exercise in humans.

The present study examined the relationship between total skeletal muscle GLUT-4 protein level and glucose uptake during exercise. Eight active non-endurance-trained men cycled at 72 +/- 1% peak pulmonary oxygen consumption for 40 min, with rates of glucose appearance and disappearance (Rd) determined by utilizing a primed continuous infusion of [3-3H]glucose commencing 2 h before exercise. Muscle glycogen content and utilization, citrate synthase activity, and total GLUT-4 protein were measured on muscle biopsy samples obtained from the vastus lateralis. A direct relationship existed between preexercise muscle glycogen content and glycogen utilization during exercise (r = 0.76, P < 0.05). Citrate synthase activity and glucose Rd at the end of exercise averaged 21.9 +/- 3.0 mumol.min-1.g-1 and 27.3 +/- 2.5 mumol.kg-1.min-1, respectively. There was a direct correlation between citrate synthase activity and GLUT-4 protein (r = 0.78, P < 0.05); however, at the end of exercise, glucose Rd was inversely related to both GLUT-4 (r = -0.89, P < 0.01) and citrate synthase activity (r = -0.72, P < 0.05). Plasma insulin, which decreased during exercise, was not related to glucose Rd. In conclusion, glucose uptake during 40 min of exercise at 72% peak pulmonary oxygen consumption was inversely related to the total muscle GLUT-4 protein level. This suggests that factors other than the total GLUT-4 protein level are important in the regulation of glucose uptake during exercise.

Adult

Early decrease in GLUT4 protein levels in brown adipose tissue of New Zealand obese mice.

The aim of this study was to determine if the previously described insulin resistance in the New Zealand Obese (NZO) mouse is associated with a decrease in GLUT4 protein and if such changes occur early in the evolution of the syndrome. GLUT4 levels were measured in whole membranes isolated from a variety of tissues in 4 and 20-week-old NZO and control NZC mice by Western blotting using a specific antibody to the C terminal end of the protein. At 20 weeks of age, GLUT4 levels were lower in the NZO mice in brown and white adipose tissue, heart, diaphragm, red and white quadriceps, and red and white gastrocnemius, but not in soleus muscle. At 4 weeks of age, GLUT4 levels were 52% lower in BAT (3309 +/- 1006 vs 6951 +/- 1870 cpm P = 0.039) but were not lower in WAT, heart or red quadriceps. It is concluded that adult NZO mice have a decrease in GLUT4 levels in most insulin-sensitive tissues and that in BAT, this occurs at an early age.

Adipose Tissue

Violent patients and the prehospital provider.

STUDY OBJECTIVES: To estimate the frequency of violence directed toward prehospital providers; to identify the methods used to manage violent patients in the prehospital setting; and to identify the educational, medical, and legal issues in the prehospital management of violent patients. DESIGN: A convenient sample survey and a descriptive review of ambulance call reports from June to December 1991. SETTING: The survey was distributed to registrants at the National Association of EMS Physicians in Pittsburgh, Pennsylvania, in June 1992. Ambulance call reports were reviewed for a metropolitan county with a service population of 60,000. INTERVENTIONS: None. RESULTS: Only about 50% of survey respondents reported having protocols for the management of violent patients. Law enforcement officers provided assistant in managing violent patients for 97% of respondents, and 81% reported that a violent patient who refused transport could be arrested. Injury to prehospital providers in the past year was reported by 67% of respondents. Although 67% reported some training in the management of violent patients, only 9% had training by law enforcement officers and only 25% thought that they were trained in assessing the scene for potential violence. Ambulance call report review identified an 0.8% incidence of violent episodes. Weapons were evident in 12% of violent encounters. Transport was refused by 18% of violent patients. In 9% of violent encounters, patients were hypoglycemic. No emergency medical technician injuries were reported for the study period. CONCLUSION: The potential for injury to prehospital providers from violent patients is probably widespread, and no mechanism for identifying injuries or exposure to violent patients currently exists. All systems should have protocols for managing violent patients and for restraint application. Educational sessions for self-defense and assessment of the scene for violence may be indicated.

Adult

Potassium and ventilation during incremental exercise in trained and untrained men.

The present investigation was undertaken to examine the relationship between plasma potassium (K+) and ventilation (VE) during incremental exercise. Blood lactate (La-) was also measured, and its relationship with VE was similarly examined. Eight endurance-trained triathletes (ET) and eight active but untrained men (UT) performed an incremental cycling test to volitional fatigue. Maximal oxygen uptake (VO2max) and oxygen uptake (VO2) at lactate threshold (LT) were higher (P < 0.05) in ET (VO2max 4.60 +/- 0.10 l/min, LT 2.77 +/- 0.85 l/min) than in UT (VO2max 3.79 +/- 0.11 l/min, LT 1.94 +/- 0.60 l/min). There were significant (P < 0.05) correlations between VE and K+ (UT 0.87, ET 0.77) and between VE and La- (UT 0.88, ET 0.85). In ET compared with UT, VE was lower (P < 0.05) at 330 W, K+ was lower at 300 and 330 W, and La- was lower at all work loads > 90 W. These results suggest that K+ may make an important contribution to the regulation of ventilation during incremental exercise and that endurance training attenuates the K+ response to that exercise.

Adult

Regulation of interleukin 2 and interleukin 2 receptor gene expression in human T cells: I. Effect of Ca2+-ionophore on phorbol myristate acetate co-stimulated cells.

Human peripheral blood T lymphocytes were treated with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) activity, and with the calcium ionophore A23187. The resulting accumulation of specific mRNA for interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R), as well as IL-2 secretion and membrane IL-2R expression were examined. At low concentrations (0.1 microM), A23187 synergized maximally with PMA to induce proliferation, to increase IL-2R mRNA levels and the expression of membrane IL-2R, and to produce a low but sufficient accumulation of IL-2 mRNA and IL-2 secretion. A high concentration of A23187 (1.0 microM) did not show any synergism for the accumulation of IL-2R mRNA, membrane IL-2R expression and inhibited the proliferation of PMA co-stimulated T cells. It did, however, induce maximum accumulation of IL-2 mRNA and IL-2 secretion.

Calcimycin

[Rectal shielding for a Selectron-ring applicator system (HDR- and LDR-afterloading)].

In order to decrease the morbidity rate after combined radiotherapy of the cervix carcinoma, a tungsten shield 3 and 5 mm thick for the rectum has been developed by the authors which is applied with the ring and pin applicator of the Selectron unit (LDR- and HDR-afterloading). The isodose curves were measured in a plexiglas phantom, and the radiation dose at the reference points was determined by means of a ionization dosimeter. The phantom measurements were performed with the same arrangement of sources as applied in radiotherapy. The measurements showed a dose reduction at point Rmax of 33% (HDR) and 44% (LDR) with the tungsten shield 5 mm thick.

Brachytherapy