Hyperthermia and maximal oxygen uptake in men and women

To compare the effect of hyperthermia on maximal oxygen uptake (O_2max) in men and women, O_2max was measured in 11 male and 11 female runners under seven conditions involving various ambient temperatures (T_a at 50% RH) and preheating designed to manipulate the esophageal (T_es) and mean skin temperatures at O_2max. The conditions were: 25°C, no preheating (control); 25, 35, 40, and 45°C, with exercise-induced preheating by a 20-min walk at ~33% of control O_2max; 45°C, no preheating; and 45°C, with passive preheating during which T_es and were increased to the same degree as at the end of the 20-min walk at 45°C. Compared to O_2max (l·min^–1) in the control condition (4.52±0.46 in men, 3.01±0.45 in women), O_2max in men and women was reduced with exercise-induced or passive preheating and increased T_a, ~4% at 35°C, ~9% at 40°C and ~18% at 45°C. Percentage reductions (7–36%) in physical performance (treadmill test time to exhaustion) were strongly related to reductions in O_2max (r=0.82–0.84). The effects of hyperthermia on O_2max and physical performance in men and women were almost identical. We conclude that men and women do not differ in their thermal responses to maximal exercise, or in the relationship of hyperthermia to reductions in O_2max and physical performance at high temperature. Data are reported as mean (SD) unless otherwise stated.     

HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex

Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs), the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs) give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs). Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A) showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb), TRL345, reactive with glycoprotein B (gB), but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.     

The effects of anagrelide on human megakaryocytopoiesis

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro . In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.     

High energy flux mediates the tonically augmented beta-adrenergic support of resting metabolic rate in habitually exercising older adults

The sympathetic nervous system contributes to resting metabolic rate (RMR) via beta-adrenergic receptor (beta-AR) stimulation of energy metabolism. RMR and beta-AR support of RMR are greater in habitually exercising compared with sedentary older adults possibly due to greater energy flux (magnitude of energy intake and energy expenditure during energy balance). In 10 older adults regularly performing aerobic endurance exercise (mean +/- se, 66 +/- 1 yr) compared with baseline, a reduction in energy flux (via abstention of exercise and proportional reduction in dietary intake) decreased (P < 0.05) energy expenditure (7746 +/- 440 vs. 9630 +/- 662 kJ.d(-1)), caloric intake (7808 +/- 431 vs. 9433 +/- 528 kJ.d(-1)), RMR (5192 +/- 167 vs. 5401 +/- 209 kJ.d(-1)), and skeletal muscle sympathetic nervous system activity (36 +/- 2 vs. 42 +/- 2 bursts.min(-1)). Significant beta-AR support of RMR was observed at baseline (167 +/- 42 kJ.d(-1)) but not during reduced energy flux. The change in RMR from baseline to reduced energy flux was related to the corresponding change in beta-AR support of RMR (r = 0.77, P = 0.009). No changes were observed in seven time controls (69 +/- 3 yr) who maintained energy flux. High energy flux is a key mechanism contributing to the elevated RMR and beta-AR support of RMR in habitually exercising older adults. Maintenance of high energy flux via regular exercise may be an effective strategy for maintaining energy expenditure and preventing age-associated obesity.     

Effects of prior exercise on postprandial lipemia: a quantitative review

The purpose of this report is to synthesize the results from studies examining the effect of exercise on postprandial lipemia to summarize the existing data and provide direction for future research. A quantitative review of the literature was performed using meta-analytic methods to quantify the effect sizes. Moderator analyses were performed to examine features of the studies that could potentially influence the effect of exercise on postprandial lipemia. Thirty-eight effects from 555 people were retrieved from 29 studies. The mean weighted effect was moderate as indicated by Cohen's d (d = -0.57; 95% confidence interval [CI], -0.71 to -0.43), indicating that people who perform exercise before meal ingestion exhibit a 0.5 standard deviation reduction in the postprandial triglyceride (TG) response relative to persons in comparison groups. There was no significant effect of study design, gender, age, type of meal ingested, exercise intensity, exercise duration, or timing of exercise on the postprandial response (P >.05). There was, however, significant variation in the effect sizes, for women for exercise performed within 24 hours of meal ingestion, and for exercise performed more than 24 hours before meal ingestion (P <.01). For studies that reported the energy expenditure of exercise, there was a significant relationship between effect size and energy expenditure (r = -.62, P =.02). Results from this quantitative review of the literature suggest that exercise has a moderate effect on the postprandial lipemic response and that the energy expenditure of prior exercise may play a role in the magnitude of this effect. Other factors that may affect the response remain to be clarified.     

Influence of adiposity on tonic sympathetic support of resting metabolism in healthy adults

BACKGROUND: beta-Adrenergic receptor sympathetic nervous system (beta-AR SNS) support of resting metabolic rate (RMR) is attenuated with older age, female sex, and a sedentary lifestyle. Total and abdominal adiposity and/or body fat pattern modulate some SNS-mediated physiological functions. OBJECTIVE: To determine if total and abdominal adiposity and/or body fat distribution are independently related to SNS support of RMR. DESIGN: Cross-sectional comparison of beta-AR SNS support of RMR. SUBJECTS: A total of 54 healthy male and female subjects aged 18-75 y. MEASUREMENTS: RMR (ventilated hood, indirect calorimetry) before (baseline) and during complete beta-AR blockade; body composition by dual energy X-ray absorptiometry. RESULTS: Forward stepwise multiple regression analysis using sex, exercise status, age group, %body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity as variables revealed sex to be the strongest predictor, explaining 21% of the variability in beta-AR SNS support of RMR (P=0.0006). Age group explained an additional 4% and exercise status a further 4% (both P=0.10). %Body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity did not enter the equation. CONCLUSION: Total and abdominal adiposity and body fat pattern are not independent physiological determinants of beta-AR SNS support of RMR among healthy men and women. Moreover, further support is provided for our previous finding of attenuated beta-AR SNS support of RMR with age, female sex, and sedentary lifestyle.     

Paroxysmal nocturnal hemoglobinuria: erythrocyte acetylcholinesterase deficit analyzed by immunoassay and fluorescence-activated sorting

An immunodisplacement assay based on a specific, solid-phase monoclonal antibody was designed to measure acetylcholinesterase in tissue extracts. Sample enzyme content was determined from the competitive reduction of binding of a purified acetylcholinesterase standard, with a detection limit of 5 ng or less. Washed erythrocyte membranes from six normal subjects averaged 1.8 units of acetylcholinesterase activity and 0.45 microgram of acetylcholinesterase content per milligram of total protein. Enzyme activity and content in samples from three patients with paroxysmal nocturnal hemoglobinuria (PNH) were reduced approximately in parallel, by as much as 70%. The residual cholinesterase had almost the same homospecific activity as the normal enzyme and was bound with equivalent affinity by six different antibodies. Therefore, the cholinesterase defect was dominated by enzyme loss rather than by structural abnormalities affecting enzyme function. Fluorescence-activated sorting of antibody-labeled erythrocytes revealed a bimodal population distribution. Up to 66% of the PNH cells lacked cholinesterase, and the rest had a near-normal enzyme content. Inasmuch as enzyme-deficient cells represent the complement-sensitive population, cell sorting may help in assessing clinical status and, perhaps, in developing new therapeutic modalities for PNH.     

Autosomal dominant familial Mediterranean fever-like syndrome with amyloidosis

We report a pedigree in which a syndrome that resembled familial Mediterranean fever occurred in four family members over three successive generations. All four patients had systemic amyloidosis. Typically, patients with familial Mediterranean fever show an autosomal recessive inheritance pattern. The disorder commonly afflicts Sephardic Jews, Arabs, and persons of Turkish descent. Colchicine therapy dramatically reduces the attack rate of serositis. The family described herein is unique because of their European ethnicity and the autosomal dominant inheritance pattern. Unlike typical familial Mediterranean fever, colchicine had no influence on the attacks and did not prevent amyloidosis in the three patients who received this treatment.     

Prognostic significance of computed tomography of the brain in thrombotic thrombocytopenic purpura

We studied the prognostic value of computed tomography (CT) of the brain for neurologic morbidity in patients with thrombotic thrombocytopenic purpura. On review of Mayo Clinic records for 1975 through 1985, we found 32 patients with thrombotic thrombocytopenic purpura, 20 of whom had undergone CT of the brain during their hospitalization. Despite major neurologic symptoms and signs, normal CT findings were associated with complete neurologic recovery. Seventy percent of patients with normal results of CT of the brain recovered and had no neurologic deficits, whereas 80% of patients with CT abnormalities died or had permanent neurologic sequelae. A review of the literature supports these conclusions. Thus, we suggest that CT of the brain be done in any patient with thrombotic thrombocytopenic purpura and neurologic deficits. Regardless of the severity of neurologic involvement, normal CT findings should encourage continued vigorous treatment of the patient because a normal scan supports the possibility of full clinical recovery.