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Biomedical subjects

J A Nicholas

Publications and source records attributed to J A Nicholas.

At least 19 recordsLinked to original sources
PubMed2006

Community-associated methicillin-resistant Staphylococcus aureus skin infections in a religious community.

In September 2004, an outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI) was reported among members of a religious community. We conducted a retrospective cohort study on all 175 community members; performed a nasal carriage survey, and environmental swab testing. We identified 24 MRSA cases (attack rate 14%). In multivariate analysis, sauna use [odds ratio (OR) 19.1, 95% confidence interval (CI) 2.7-206.1] and antimicrobial use within 12 months before infection (OR 11.7, 95% CI 2.9-47.6) were risk factors for infection. MRSA nasal carriage rate was 0.6% (1/174). Nine of 10 clinical isolates and an isolate from an administrative office within the community had the pulsed-field gel electrophoresis type USA300. Targeted hygiene improvement, wound care, and environmental cleaning were implemented. We describe the first reported outbreak of MRSA SSTI in a religious community. Adherence to appropriate personal and environmental hygiene might be critical factors in controlling transmission.

Adolescent↗
PubMed1996

Fluid balance and renal response following dehydrating exercise in well-trained men and women.

We examined the recovery of plasma volume, plasma osmolality, renal water and sodium handling and fluid-regulating hormones to dehydrating exercise in well-trained women and compared them to men. Ten male and eight female athletes cycled at anaerobic threshold at an ambient temperature of 32 degrees C until dehydration by 3% of their body mass (mb). After exercise, they drank water equal to 1% mb and rested for 240 min. Plasma renin activity (PRA), serum aldosterone [ALDO]s, plasma arginine vasopressin [AVP]pl, norepinephrine concentrations and plasma osmolality (Osmpl) were determined at baseline, end of exercise, 30, 60, 120 and 240 min postexercise. Urine was collected at baseline, end of exercise, 60, 120 and 240 min postexercise. Renal free water and sodium handling were assessed. The recovery of OSMpl and plasma volume occurred within the first 60 min of recovery and at similar rates between the groups. However, women had lower PRA at the end of exercise (P = 0.05), an earlier recovery of [ALDO]s, and a slower [AVP]pl recovery. Overall fluid balance was similar between the men and women, as were the early recovery of renal free water clearance (CH2O). During the last 120 min of recovery CH2O was more negative (greater water reabsorption) and fractional sodium excretion was increased in the women compared to the men. Despite small differences in sodium and water reabsorption following dehydration, it appears from other study that recovery from dehydrating exercise in well-trained men and women is remarkably similar.

Adult↗
PubMed1994

Systemic effects of ingesting varying amounts of a commercial carbohydrate beverage postexercise.

OBJECTIVE: Although the role of postexercise carbohydrate intake in the replenishment of muscle glycogen is well established, large amounts of carbohydrate may affect other systems which are recovering from exercise as well. METHODS: We varied the timing and amount of a commercial glucose polymer/fructose (CHO) beverage ingested postexercise in 2 groups of 8 normotensive men following 1 hour of cycling exercise. In Study A the subjects ingested 1 L of a 200 g CHO solution or 1 L of water (W) immediately postexercise. The participants in Study B consumed 1 L of a 1.5 g/kg CHO solution, or W, immediately and 2 hours postexercise. RESULTS: Recovery systolic blood pressure was elevated after 200 g CHO as compared to water, but not after 1.5 g/kg CHO. Diastolic blood pressure was decreased, while heart rate, insulin and glucose increased following both doses of CHO. Despite the potassium (K) content of the beverages, serum K decreased in Study A and B, while a trend was noted following CHO for decreased urinary K excretion at 2 hours and for increased sodium excretion at 4 hours in Study B. Post CHO aldosterone declined more rapidly than after W, and urine volumes were decreased compared to W in both studies 2 hours after CHO. CONCLUSIONS: We speculate that hyperinsulinemia contributed to the rapid decline in K and aldosterone by creating a flux of K to the intracellular space. It appears that CHO ingestion postexercise results in systemic effects that are related to the amount and timing of CHO consumed.

Adult↗
PubMed1994

Shoulder weakness in professional baseball pitchers.

The purposes of this study were to: 1) compare shoulder range of motion and strength in professional baseball pitchers (N = 47) compared with age-matched controls (N = 16), and 2) examine the relationship of injury history to strength and range of motion. Based on injury history pitchers were categorized as: 1) none (N = 26), 2) injury requiring conservative intervention (N = 9), or 3) injury requiring surgical intervention (N = 12). Range of motion was measured for internal rotation (IROM) and external rotation (EROM). Eccentric strength was measured by hand-held dynamometer for internal rotation (IR), external rotation (ER), abduction (ABD), and supraspinatus muscle (SUP) strength. Injury history had no effect on strength and range of motion. Dominant EROM was greater in pitchers, P < 0.0001, and controls, P < 0.05, with pitchers having greater EROM motion bilaterally, P < 0.0001. Pitchers were weaker in SUP on the dominant vs nondominant side, P < 0.0001, and on the dominant side for weight adjusted ER, ABD, P < 0.01, and SUP, P < 0.0001, compared with controls. In conclusion, dominance and pitching resulted in soft tissue adaptation. Pitchers displayed weakness in three of four tests by comparison with controls, suggesting that the demands of pitching are insufficient to produce eccentric strength gains and may in fact lead to weakness. Dominant-side SUP weakness in pitchers may reflect subclinical pathology or chronic fatigue.

Analysis of Variance↗
PubMed1993

The effect of stabilization on isokinetic knee extension and flexion torque production.

The purpose of this study was to examine the effect of four methods of stabilization on maximal reciprocal isokinetic knee extension and flexion. Left knee extension/flexion was tested at 60 degrees /s in 20 subjects. Warm-up consisted of five submaximal and one maximal effort followed by three maximal efforts in each of four randomized stabilization conditions: 1) Hands and back stabilization; the trunk was strapped to the back rest and the hands grasped the seat. 2) Back stabilization; the trunk was strapped to the back rest and the hands were folded across the chest. 3) Hand stabilization; the hands grasped the seat and the back rest was removed. 4) No stabilization; the hands were folded across the chest and the back rest was removed. One-way repeated measures ANOVA showed a significant effect of stabilization for knee extension (F(3,57)=17.44, p=.0001) and knee flexion (F(3,57)= 5.37, p=.002). Paired, two-tailed student's t-tests with Bonferroni correction showed that, in knee extension, no stabilization was significantly less than all others, p<.001. In addition, back stabilization was less than hands and back stabilization, p<.005. In knee flexion, no stabilization was significantly less than all others, p<.01. In conclusion, the method of trunk stabilization significantly affected maximal reciprocal isokinetic knee extension/flexion strength measurements. Maximal knee extension/flexion torque production was achieved when the trunk was strapped to the back support and when the hands grasped the seat.

Journal Article↗
PubMed1992

Predictive accuracy of criteria used to assess maximal oxygen consumption.

To evaluate criteria frequently used to designate an exercise test as maximal, 33 men and 18 women completed progressive incremental cycle ergometry to exhaustion with direct measurement of oxygen consumption (VO2). On a separate day, subjects exercised at 115% of the maximal work rate attained in the first test following a 5-minute warm-up. If VO2 exceeded that of the progressive test by greater than or equal to 150 ml/min, subjects returned on a third day and pedalled at 125% of the first day's work ratepeak. This procedure was repeated until VO2 increased less than 150 ml/min, and defined whether the progressive test was a maximal or nonmaximal test. There were 45 tests that met the criterion for maximum during the progressive test and six nonmaximal tests. Respiratory exchange ratio and 85% age-predicted maximal heart rate were sensitive criteria for a maximal test but were not specific. Attainment of age-predicted maximal heart rate and peak lactate greater than 8 mmol/L were highly specific but insensitive measures of a maximal test. In the absence of a VO2 plateau, age-predicted maximal heart rate and lactate greater than 8 mmol/L can be used as indicators of maximal tests with a high degree of confidence. When age-predicted maximal heart rate or lactate greater than 8 mmol/L are not attained, the test may still be maximal because negative predictive value is low.

Aging↗
PubMed1992

A novel, spectrophotometric microneutralization assay for respiratory syncytial virus.

We describe a simple and rapid microneutralization assay for respiratory syncytial virus (RSV) based on the colorimetric quantitation of the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to a formazan product by the mitochondria of viable cells. Conditions for RSV infectivity were first optimized for sensitivity and reproducibility based on cell density and on RSV concentration as a function of multiplicity of infection (MOI) and time post-infection and the resulting optical densities were shown to be inversely proportional to MOI. For RSV neutralization, dilutions of heat-inactivated human plasma were preincubated with RSV and complement prior to infection of cells in microtiter plates. Following MTT dye conversion, 50% RSV neutralization titers were determined by linear regression analysis of the optical density values and endpoints were markedly influenced by MOI. The MTT-based assay was shown to be comparably sensitive to the plaque reduction assay for quantitation of neutralizing antibody, but more readily adaptable to the screening of a large number of samples. Finally, we demonstrated that the MTT microneutralization assay for RSV was useful for quantitation assay of neutralization activity in sera of mice and cotton rats.

Adult↗
PubMed1992

Sucrose ingestion following exercise: selected cardiovascular, hormonal, renal, and metabolic effects.

Carbohydrates, frequently consumed following exercise for glycogen resynthesis, have been shown to have other systemic effects in resting men. We examined the effects of postexercise sucrose (a disaccharide carbohydrate) ingestion on the renal, cardiovascular, and sympathetic nervous systems. Eight men consumed 1 l of water (W) or 1 l of a 200 g sucrose solution (S) following 1 hour of bicycle exercise at 70% heart rate reserve. Measurements were made during 2 hours of recovery. Heart rate and systolic blood pressure were elevated following S as compared to W (p < 0.009, p < 0.04, respectively). Diastolic blood pressure was lower after S (p < 0.04) and mean blood pressure did not differ between beverages. Plasma and urinary catecholamines decreased similarly after exercise regardless of treatment. After S insulin (p = 0.0019) and glucose (p = 0.0036) were increased but serum aldosterone (p = 0.0083) and potassium (p = 0.0285) responses were lower. No differences were observed for plasma renin activity. Urine volume and kaliuresis were less after S (p = 0.03, p = 0.03). A 24% increase in metabolic rate (p = 0.002) and increased respiratory exchange ratio (p = 0.02) after S were observed. Systemic effects of sucrose ingestion following exercise include cardiovascular, renal, endocrine, and metabolic changes.

Adult↗
PubMed1992

Monitoring training status in professional ballet dancers.

Methods of non-invasive monitoring of training status for prevention of staleness in athletes and dancers need to be developed and evaluated. In order to monitor physiologic and psychologic changes which may result from overstraining, we measured urinary excretion of free norepinephrine (NE) and epinephrine (E) and mood states over 5 weeks of an intensive ballet season in 12 (6 men, 6 women) professional dancers. First morning urine voids (AM) were collected at the start of the season and following the only off-day each week with final collection on the last day of the season. Additional urine samples were collected before (pre) and after (post) each dancer's subjectively-rated single most difficult performance. Profile of Mood States (POMS) was completed by and collected from each dancer at the same time as the AM urine samples. NE and E excretions (nanograms per mg creatinine) increased significantly with time (r = 0.91, p less than 0.02, and r = 0.94, p less than 0.01, respectively) from beginning to end of season, and pre to post (51.1 +/- 7.3 to 115.6 +/- 19.7, p less than 0.001 and 19.3 +/- 3.2 to 37.7 +/- 4.2, p less than 0.001, respectively). Women had a significantly higher excretion of NE than did men (F = 9.33, p = 0.014) and no gender differences existed in the excretion of E (F = 0.57, p = 0.484).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Viscoelastic stress relaxation in human skeletal muscle.

Viscoelastic stress relaxation refers to the decrease in tensile stress over time that occurs when a body under tensile stress is held at a fixed length. The purpose of this study was to demonstrate viscoelastic stress relaxation in human skeletal muscle. Resistance to stretch (tensile force), hip flexion range of motion (ROM), and reflex contractile activity (IEMG) of the hamstring muscle group were measured during a passive straight leg raise. The testing protocol involved a first stretch to the maximum tolerated ROM with the lower extremity held at that point for 45 s (test 1). All 15 subjects tested (9 men, 6 women) had a stretch induced EMG response. The onset of a sustained EMG response occurred at a specific hip flexion angle in 10 subjects. These 10 subjects (6 men, 4 women) underwent a second straight leg raise stretch (test 2) to a ROM 5 degrees below the ROM at which the onset of EMG activity occurred in test 1. The stretch was held at this hip flexion angle for 45 s. There was a significant decrease in force at final ROM during the 45 s in test 1 (11.35 +/- 1.75 N, P < 0.0001) and in test 2 (4.2 +/- 1.55 N, P < 0.05). The percent decrease from the force at the respective final ROM was not significantly different between the tests (14.4 +/- 2.2% in test 1 and 13 +/- 2.3% in test 2). In test 1 there was a significant decrease over time in IEMG of 59.71 +/- 16.01 microV.s (P < 0.01) which was not significantly correlated to the decrease in force.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Gender differences in the systolic blood pressure response to exercise.

Previous work has shown a gender difference in the normal cardiac response to exercise. Men had significantly higher absolute systolic blood pressure responses at 50%, 75%, and 100% peak heart rate on all modalities (p less than 0.05). This difference is absent when systolic blood pressure is adjusted for body surface area, is reduced when adjusted for body weights, and is reversed when systolic blood pressure is adjusted for lean body mass. The influence of gender on the systolic blood pressure response to dynamic exercise was independent of exercise modality. Men had a higher systolic blood pressure in spite of the fact that they had similar sympathetic nervous system response as indicated by urinary norepinephrine excretion. Gender differences in systolic blood pressure responses were altered when adjusted for body weight, body surface area, and lean body mass.

Blood Pressure↗
PubMed1991

Cytotoxic T cell activity against the 22-kDa protein of human respiratory syncytial virus (RSV) is associated with a significant reduction in pulmonary RSV replication.

Recombinant vaccinia viruses expressing the RSV F glycoprotein (Vac-F), or a previously described chimeric protein consisting of the extracellular domains of the F and G glycoproteins (Vac-FG), or the 22-kDa membrane protein (Vac-22 kDa) were evaluated for their ability to protect BALB/c mice against infection by RSV subgroup A or subgroup B viruses and for their ability to induce a humoral immune response or a cytolytic T lymphocyte (CTL) response. Immunization with Vac-F or Vac-FG fully protected mice against challenge with RSV of subgroup A or B and induced high levels of both humoral and CTL-mediated immunity. Immunization with Vac-22 kDa partially to fully protected mice against challenge with RSV of subgroup A or B, depending on the immunization and challenge conditions, and induced a potent CTL response in the apparent absence of a significant humoral response. These vectors fortuitously allowed us to evaluate the contribution of a protein-specific memory CTL response to subgroup-specific and subgroup-cross-reactive reductions in pulmonary RSV replication independently from a humoral response. Our data suggest that 22-kDa-specific CTL contribute significantly to the reduction of RSV within the lung, but that complete protection also requires a humoral component.

Animals↗
PubMed1991

Effects of a soluble CD4 and CD4-Pseudomonas exotoxin A chimeric protein on human peripheral blood lymphocytes: lymphocyte activation and anti-HIV activity in vitro.

Recombinant sCD4-based proteins were evaluated for their effects on antigen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC) and for antiviral activity against PBMC infected with human immunodeficiency virus (HIVD34). Two sCD4-based proteins were solubilized, refolded, and purified to homogeneity from recombinant E. coli and consisted of the 178 amino-terminal residues of CD4 fused with the translocating and catalytic domains of Pseudomonas exotoxin A (sCD4-PE40) or 183 amino-terminal residues of CD4 (sCD4-183); a third sCD4 consisting of 369 amino acids of CD4 was purified from recombinant mammalian cells for comparative purposes (sCD4-369). Increasing molar concentrations of these sCD4s were evaluated for inhibition of PBMC proliferation induced by alloantigen (MLR), by tetanus toxoid (TTOX), or in response to crosslinking with antibody to CD3 (OKT3). In addition, the concentrations of each protein required to inhibit replication of the HIVD34 isolate in primary PBMC was determined by quantitation of HIV p24 antigen released into supernatant fluids by infected cells. By comparing antiviral activity with anti-proliferative activity a relative estimate of the selectivity index for each recombinant sCD4 was determined. Proliferation of PBMC in response to alloantigen or OKT3 was less sensitive to inhibition than proliferation induced by TTOX, and the selectivity indices estimated for sCD4-PE40 were 170, 170 and 17, respectively. The selectivity index for sCD4-183 was greater than 350 under all assay conditions. Comparative evaluation of alloantigen-stimulated proliferation with antiviral activity of sCD4-183 versus sCD4-369 suggested that the E. coli-derived sCD4-183 may have a higher selectivity index under these conditions than its mammalian cell-derived counterpart.

ADP Ribose Transferases↗
PubMed1991

Soluble CD4-PE40 is cytotoxic for a transfected mammalian cell line stably expressing the envelope protein of human immunodeficiency virus (HIV-1), and cytotoxicity is variably inhibited by the sera of HIV-1-infected patients.

Sera were obtained from 50 individuals infected with human immunodeficiency virus type 1 or from HIV-1-uninfected individuals before or after vaccination with recombinant gp160. These sera were evaluated for activity antagonistic to the cell-killing activity of the chimeric Pseudomonas exotoxin hybrid protein, sCD4-PE40. For these studies, Chinese hamster ovary (CHO) cells were transfected with a chimeric plasmid encoding the tat, rev, and envelope genes of HIV-1 and a cell line was selected for stable expression of the envelope glycoproteins at the cell surface (CHO-env). Cytotoxicity of sCD4-PE40 for CHO-env in the presence or absence of added human serum was quantitated spectrophometrically following enzymatic reduction of a tetrazolium bromide within the mitochondria of viable cells (MTT assay). Several HIV+ sera inhibited the cytotoxic activity of sCD4-PE40; the antagonist had properties consistent with those of immunoglobulins in that it was heat stable, absorbed by protein A, and reversible by increasing the concentration of sCD4-PE40. Of 15 HIV+ sera which strongly reacted with gp120, 11 (73%) also potently inhibited sCD4-PE40 cytotoxicity, and cytotoxicity was inhibited by sera from some HIV- individuals after, but not before, immunization with gp160. These data suggested a role for antibody to gp120 in the antagonistic activity. However, not all sera with antibody to gp120 antagonized sCD4-PE40 cytotoxicity and high levels of antagonist activity were frequently (40%) found in HIV+ sera lacking immunoblot-detectable antibody to gp120, or antibody to either CD4 or PE40. Grouping of the HIV+ sera according to the patients' absolute number of CD4+ cells revealed that the degree of inhibition of sCD4-PE40 cytotoxicity approached a Gaussian distribution, suggesting that persons with CD4+ cell counts between 200 and 700/mm3 may be more likely to possess significant levels of serum antagonist. This data have implications for the clinical development of sCD4-PE40 or other sCD4-based therapeutics in the management of HIV-1 infection.

ADP Ribose Transferases↗
PubMed1991

Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes.

The lymphocyte proliferative responses to respiratory syncytial virus (RSV) were evaluated for 10 healthy adult donors and compared with proliferative responses to a chimeric glycoprotein (FG glycoprotein) which consists of the extracellular domains of both the F and G proteins of RSV and which is produced from a recombinant baculovirus. The lymphocytes of all 10 donors responded to RSV, and the proliferative responses to the whole virus were highly correlated with the responses to the FG glycoprotein. These data suggested that one or both of these glycoproteins of RSV were major target structures for stimulation of the human lymphocyte proliferative response among virus-specific memory T cells. The lymphocytes of four donors were evaluated further for their proliferative responses to a nested set of overlapping peptides modeled on the extracellular and cytoplasmic domains of the F protein of RSV. Strikingly, the lymphocytes of all 4 donors responded primarily to a region defined by a single peptide spanning residues 338 to 355, and the lymphocytes of 2 donors responded to an overlapping peptide spanning residues 328 to 342 also, thus defining a region of the F1 subunit within residues 328 to 355 that may circumscribe an immunodominant site for stimulation of human T cells from a variety of individuals. This region of the F protein is highly conserved among A and B subgroup viruses. As revealed by monoclonal antibody blocking studies, the lymphocytes responding to this antigenic site had characteristics consistent with T helper cells. Similar epitope mapping studies were performed with BALB/c mice immunized with the FG protein in which a relatively hydrophobic peptide spanning residues 51 to 65 within the F2 subunit appeared to be the major T cell recognition determinant. The data are discussed with respect to an antigenic map of the F protein and the potential construction of a synthetic vaccine for RSV.

Animals↗
PubMed1990

The influence of flexibility on the economy of walking and jogging.

The relationship of 11 measures of trunk and lower limb flexibility to the economy of treadmill walking and jogging as measured by steady-state oxygen consumption (VO2) was studied. Subjects (38 women, 62 men, aged 20-62 years) were tested at six speeds between 53.6 and 187.7 m/min. By combining scores from all flexibility tests, and beginning at speeds of 107.3 m/min, the "tightest" third used significantly less O2/m/kg (9%, p less than 0.05) than the "loosest" third, with "normals" in between. Two tests, trunk rotation and lower limb turnout, gave the best separation for walking/jogging economy, with the "tightest" third differing significantly from the "loosest" (8-12%) at all speeds tested (ANOVA with Scheffe). We conclude that nonpathological musculoskeletal tightness was associated with a decreased steady-state VO2 for treadmill walking and jogging.

Adult↗
PubMed1990

Synthetic immunogens constructed from T-cell and B-cell stimulating peptides (T:B chimeras): preferential stimulation of unique T- and B-cell specificities is influenced by immunogen configuration.

In our effort to develop synthetic immunogens as vaccines, we have focused on the combination of a known T-cell stimulating peptide with putative B-cell stimulating peptide epitopes derived from the sequences of respiratory syncytial (RS) virus proteins. The T-cell stimulating peptide consists of residues 45 through 60 of the 1A protein of RS virus, and it also contains an overlapping antibody binding (B-cell) site. Herein, we have combined the 1A T-cell stimulating peptide with a putative B-cell peptide epitope derived from the viral G glycoprotein using linear synthesis or using chemical crosslinking. The chimeric immunogens were compared to each other and to free peptides for their T- and B-cell stimulating properties. Both chimeras had potent T-cell stimulating and antibody-inducing activity. However, T-cells primed to free peptide differentially recognized the two chimeras and immunization with the chimeras primed T-cells with different specificity. Most strikingly, the two chimeras had opposite antibody-inducing properties: The chimera constructed by linear synthesis overwhelmingly elicited antibody directed against the G peptide, whereas the chimera constructed by chemical crosslinking overwhelmingly elicited antibody directed against the 1A peptide. Competition blocking studies revealed that the chimeras adopted different configurations in solution. The resulting antibody response, and hence the B-cell clone elicited, was consistent with the antibody accessibility of the individual peptide epitope.

Amino Acid Sequence↗