Bone properties and muscle strength of young haemophilia patients.

PURPOSE: To evaluate bone properties, muscle strength and the relationship between the two, in young (7.0-17.7 years) haemophilia patients (h) and healthy boys (c). SUBJECTS: Twenty-seven boys with severe haemophilia and 33 healthy boys, of similar age, body mass, height, (mean +/- sd for h and c, respectively: 11.2 +/- 3.2 vs. 11.4 +/- 2.9 years, 42.6 +/- 16.6 vs. 41.6 +/- 17.3 kg, 145 +/- 18 vs. 146 +/- 17 cm) and pubertal stage according to secondary sex characteristics, volunteered for the study. all subjects were physically inactive (as determined by questionnaire). METHODS: Subjects performed isokinetic elbow and knee extension and flexion tests at two angular velocities (biodex system ii dynamometer). Bone properties were evaluated by qualitative ultrasound (sunlight omnisense), at the distal radius and tibial mid-shaft. H subjects received prophylactic factor viii treatment within the 24 h preceding testing. No test was performed in the presence of haemorrhage. RESULTS: Muscle strength was consistently higher in c compared with h, especially in the lower limbs (e.g. knee extension: 1.80 +/- 0.44 vs 1.48 +/- 0.53 N x m x kg(-1) body mass, respectively, p = 0.01). No differences were observed in tibial or radial speed of sound between groups. Correlations between muscle strength and bone properties were observed only in the lower limbs and only in c (r = 0.37-0.48). CONCLUSION: Muscle strength, especially lower limbs' strength, was lower in haemophilia patients compared with a matched, similarly inactive population of healthy boys. Nevertheless, at this age range, this relative weakness is not associated with inferior bone properties.

Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent.

Taxol is used in chemotherapy regimens against breast and ovarian cancer. Treatment of tumor model cell lines with taxol induces apoptosis, but exact mechanism is not sufficiently understood. Our results demonstrate that in response to taxol, various cell types differentially utilize distinct apoptotic pathways. Using MCF7 breast carcinoma cells transfected with caspase-3 gene, we showed that taxol-induced apoptosis occurred in the absence of caspase-3 and caspase-9 activation. Similar results were obtained with ovarian SKOV3 carcinoma cells, expressing high level of endogenous caspase-3. In contrast, staurosporine-induced apoptosis in these cells was accompanied by proteolytic cleavage of pro-caspase-3 and induction of caspase-3 enzymatic activity. The effect of taxol appears to be cell type-specific, since taxol-induced apoptosis in leukemia U937 cells involved caspase-3 activation step. We conclude that a unique caspase-3 and caspase-9 independent pathway is elicited by taxol to induce apoptosis in human ovarian and breast cancinoma cells.

Implementation of the quantum Fourier transform.

A quantum Fourier transform (QFT) has been implemented on a three qubit nuclear magnetic resonance (NMR) quantum computer to extract the periodicity of an input state. Implementation of a QFT provides a first step towards the realization of Shor's factoring and other quantum algorithms. The experimental implementation of the QFT on a periodic state is presented along with a quantitative measure of its efficiency measured through state tomography. Experimentally realizing the QFT is a clear demonstration of the ability of NMR to control quantum systems.

Experimental demonstration of fully coherent quantum feedback.

In the conventional picture of quantum feedback, control sensors make measurements on a quantum system, a classical controller processes the results of the measurements, and semiclassical actuators act back on the system to alter its behavior. We describe and provide an experimental demonstration of an alternative method for quantum feedback control, in which the sensors, controller, and actuators of conventional feedback control are replaced with quantum systems that interact coherently with the system to be controlled. The resulting control system represents a fully coherent quantum feedback loop.

Effect of creatine feeding on maximal exercise performance in vegetarians.

The effect of creatine supplementation on exercise performance in vegetarians was examined. Creatine was ingested for 1 week by a group of vegetarians (VC) and meat-eaters (MC); a control group of meat-eaters was fed only glucose (MG). Exercise performance during three, 20-s maximal cycling tests (modified Wingate anaerobic test, WAnT) was determined before and after creatine supplementation. Blood samples were also drawn before and after exercise prior to and after supplementation. Basal plasma creatine (after an overnight fast) averaged (SE) 11 (2) microM in VC, and 24 (2) and 23 (7) microM in MG and MC, respectively (P < 0.05 for VC vs meat-eaters). These findings were expected, since most of the body's exogenous creatine source is meat. There was no significant difference in any other parameter between groups prior to supplementation. Creatine feedings significantly increased body mass (approximately 1 kg) and mean power output during the WAnTs (approximately 5%) to a similar extent in the VC and MC groups (P < 0.05-0.001). These parameters were not affected by supplementation in the MG group. Peak power output was also significantly increased by supplementation in MC (approximately 5%, P < 0.05), but not in VC. It is concluded that vegetarians and meat-eaters respond to creatine feedings with similar increases in mean power output during short-term, maximal exercise.

Specific inspiratory muscle training in well-trained endurance athletes.

PURPOSE: It has been reported that arterial O2 desaturation occurs during maximal aerobic exercise in elite endurance athletes and that it might be associated with respiratory muscle fatigue and relative hypoventilation. We hypothesized that specific inspiratory muscle training (SIMT) will result in improvement in respiratory muscle function and thereupon in aerobic capacity in well-trained endurance athletes. METHODS: Twenty well-trained endurance athletes volunteered to the study and were randomized into two groups: 10 athletes comprised the training group and received SIMT, and 10 athletes were assigned to a control group and received sham training. Inspiratory training was performed using a threshold inspiratory muscle trainer, for 0.5 h x d(-1) six times a week for 10 wk. Subjects in the control group received sham training with the same device, but with no resistance. RESULTS: Inspiratory muscle strength (PImax) increased significantly from 142.2 +/- 24.8 to 177.2 +/- 32.9 cm H2O (P < 0.005) in the training but remained unchanged in the control group. Inspiratory muscle endurance (PmPeak) also increased significantly, from 121.6 +/- 13.7 to 154.4 +/- 22.1 cm H2O (P < 0.005), in the training group, but not in the control group. The improvement in the inspiratory muscle performance in the training group was not associated with improvement in peak VEmax, VO2max breathing reserve (BR). or arterial O2 saturation (%SaO2), measured during or at the peak of the exercise test. CONCLUSIONS: It may be concluded that 10 wk of SIMT can increase the inspiratory muscle performance in well-trained athletes. However, this increase was not associated with improvement in aerobic capacity, as determined by VO2max, or in arterial O2 desaturation during maximal graded exercise challenge. The significance of such results is uncertain and further studies are needed to elucidate the role of respiratory muscle training in the improvement of aerobic-type exercise capacity.

Impairment in quality of life among patients seeking surgery for hyperhidrosis (excessive sweating): preliminary results.

BACKGROUND: The present paper describes the initial stages of the development and administration of a short, disease-specific, health related questionnaire to assess the impact of suffering from hyperhidrosis (excessive sweating) on the Quality of Life (QoL) of patients who are anticipating surgery for this disorder. METHOD: The study was performed in two stages: 1. The life domains in which the condition impairs QoL were assessed by in-depth interviews with 10 patients suffering from hyperhidrosis. 2. A questionnaire covering five life domains was built based on these interviews. 3. This questionnaire was administered to 48 patients, 30 females and 18 males between the ages 15 and 48. RESULTS: Results showed that subjective QoL was significantly lower among females in four of the five life areas and that duration of the condition correlates with a lower quality of life. A regression analysis showed that the subjective suffering of the patients was explained mainly by social aspects. CONCLUSIONS: The questionnaire is a novel attempt to assess QoL in a disorder with strong esthetic and social consequences and could improve communication between patients and their physicians.

Anaerobic power and muscle strength in young hemophilia patients.

PURPOSE: The purpose of this study was to evaluate muscle strength and anaerobic power in young boys with hemophilia compared with healthy boys. METHODS: Thirteen boys with severe hemophilia (H) (mean (+/- SD) age = 12.0 +/- 3.17 yr) and 16 control (C) boys (age = 11.9 +/- 2.8 yr) performed elbow and knee flexion and extension on the Biodex System II dynamometer at two angular velocities. They also performed a Wingate Anaerobic Test (WAnT) for the legs and for the arms. All H subjects received prophylactic factor VIII treatment in the 24 h pretesting, and no test was performed in the presence of hemorrhage. RESULTS: C were consistently stronger than H in all dynamic strength measures (e.g., elbow flexors: 0.47 +/- 0.15 vs 0.36 +/- 0.08 N x m x kg(-1) for C and H, respectively, P < 0.05). Anaerobic mean power was also higher in C compared with H in both upper and lower extremities (arms: 3.08 +/- 0.99 vs 2.22 +/- 0.46 W x kg(-1) for C and H, respectively; legs: 6.94 +/- 1.62 vs 5.54 +/- 1.03 W x kg(-1) for C and H, respectively, P < 0.05). Upper and lower extremity strength, as well as anaerobic power, increased with age in C but not in H. By using the Godin Leisure-Time Exercise Questionnaire, H were found to be much less active, especially in intense activities, compared with C. CONCLUSION: Children and adolescents with hemophilia are characterized by lower muscle strength and anaerobic power compared with age-matched controls. This may be related to their lower leisure-time activity.

Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells that display short-term interleukin 1alpha expression.

Expression of cytokines in malignant cells represents a novel approach for therapeutic treatment of tumors. Previously, we demonstrated the immunostimulatory effectiveness of interleukin 1alpha (IL-1alpha) gene transfer in experimental fibrosarcoma tumors. Here, we report the antitumor and immunotherapeutic effects of short-term expression of IL-1alpha by malignant T lymphoma cells. Activation in culture of T lymphoma cells with lipopolysaccharide-stimulated macrophages induces the expression of IL-1alpha. The short-term expression of IL-1alpha persists in the malignant T cells for a few days (approximately 3-6 days) after termination of the in vitro activation procedure and, thus, has the potential to stimulate antitumor immune responses in vivo. As an experimental tumor model, we used the RO1 invasive T lymphoma cell line. Upon i.v. inoculation, these cells invade the vertebral column and compress the spinal cord, resulting in hind leg paralysis and death of the mice. Activated RO1 cells, induced to express IL-1alpha in a short-term manner, manifested reduced tumorigenicity: approximately 75% of the mice injected with activated RO1 cells remained tumor free. IL-1 was shown to be essential for the eradication of activated T lymphoma cells because injection of activated RO1 cells together with IL-1-specific inhibitors, i.e., the IL-1 receptor antagonist or the M 20 IL-1 inhibitor, reversed reduced tumorigenicity patterns and led to progressive tumor growth and death of the mice. Furthermore, activated RO1 cells could serve as a treatment by intervening in the growth of violent RO1 cells after tumor take. Thus, when activated RO1 cells were injected 6 or 9 days after the inoculation of violent cells, mortality was significantly reduced. IL-1alpha, in its unique membrane-associated form, in addition to its cytosolic and secreted forms, may represent a focused adjuvant for potentiating antitumor immune responses at low levels of expression, below those that are toxic to the host. Further assessment of the immunotherapeutic potential of short-term expression of IL-1alpha in activated tumor cells may allow its improved application in the treatment of malignancies.

Reliability of peak-lactate, heart rate, and plasma volume following the Wingate test.

PURPOSE: The 30-s Wingate Anaerobic Test (WAnT) has been used to assess anaerobic performance capacity and to evaluate physiological responses to supramaximal exercise. Blood lactate concentration ([La]) following supramaximal exercise is often used in the field and in the laboratory to assess the glycolytic contribution to exercise. Although the reliability of the performance in the WAnT has been established, this has not been the case with the WAnT's [La] response. Thus, the main purpose of this research was to study the test-retest reliability of peak [La] following the WAnT. Additionally, the test-retest reliability of the heart rate (HR) and plasma volume changes (deltaPV) response was also evaluated. METHODS: Twenty-nine subjects (15 male, 14 female) of diverse training levels as well as physical characteristics (mean +/- SD: 23.3+/-7.0 yr, 62.5+/-12.0 kg, 170.8+/-9.7 cm, and 16.3+/-6.2% fat) performed two WAnTs within 1 wk. Capillary blood was sampled from a prewarmed fingertip at rest, just before the WAnT and at 3, 5, 7, and 9 min following it. HR was also measured during these times. RESULTS: Mean-power (MP) (+/-SE) in test 1 and test 2 was 8.4+/-0.2 and 8.3+/-0.2 W X kg(-1) body mass, respectively. Peak [La] was attained 5-7 min following the WAnTs and was not significantly different between test 1 and test 2 (9.7+/-0.3 vs 9.8+/-0.3 mM, respectively). Peak HR occurred within 5 s post-WAnT and was not different between tests (170.8+/-2.2 and 171.3+/-2.2 beats X min(-1), in test 1 and test 2, respectively). Peak deltaPV was not different between tests (-12.0+/-3.4 and -11.1+/-3.2%, in test 1 and test 2, respectively). The intraclass reliability coefficients for peak [La]. peak HR and deltaPV were 0.926, 0.941, and 0.878, respectively, whereas the corresponding value for MP was 0.982. CONCLUSIONS: We conclude that peak [La], peak HR, and deltaPV following the WAnT are reliable measures.

The ftsZ gene as a tool for detection of Mycoplasma fermentans.

Mycoplasma fermentans was reported as a common contaminant of cell cultures, and was shown to either induce or suppress several immunological functions. A strain of M. fermentans was recently isolated from a mouse T-lymphoma cell line, which differs from other M. fermentans strains by its growth characteristics and was designated (in the authors' records) as strain 609. Using the differential display technique (DD), a differentially expressed gene that was identified as the M. fermentans 609 ftsZ gene was isolated. Comparison of the nucleotide sequence of the M. fermentans 609 ftsZ gene to other ftsZ genes showed a 98% homology with Mycoplasma fermentans strain K7 and approximately 50% homology with Mycoplasma pulmonis and Mycoplasma genitalium. Comparison of the putative amino acid sequences of the FtsZ proteins showed similar homology. A polymerase chain reaction (PCR) assay to detect the presence of this ftsZ gene was established; it is a fast and convenient assay to detect infection of cells by the M. fermentans species. This work demonstrates that: (i) DD can be used as a useful technique to identify and isolate mycoplasmal genes from infected cells; and (ii) the ftsZ gene can be a useful marker to distinguish between different species of mycoplasma.

The effect of heat exposure on performance of and recovery from high-intensity, intermittent exercise.

Environmental heat is known to hamper aerobic performance. The purpose of this study was to examine the effect of heat on the performance of anaerobic exercise and the recovery from such exercise. Eleven trained men underwent two identical exercise-recovery protocols in neutral (22 degrees C, N) and hot (35 degrees C, H) conditions, in a cross-balanced order. Exercise consisted of a series of five 15 s bouts separated by 30 s of active recovery between bouts. The 60 min resting recovery was evaluated with a subsequent exercise series. Subjects were kept euhydrated with water. Peak power developed in the initial exercise series was higher in H compared with N (720 +/- 80 vs 664 +/- 74 W, respectively, p < 0.05). In the second series of exercise, peak power slightly improved in N but decreased in H (6.1 vs -4.1 %, respectively). Mean power was higher in the initial exercise series in H compared with N (636 +/- 83 vs 584 +/- 60 W, respectively, p < 0.05). No significant change occurred in the subsequent series of exercise. There was no difference in peak lactate following the initial series, nor in the decrease of lactate during recovery between the two conditions. Likewise, there were no differences in the changes in electrolyte concentrations and serum osmolality during recovery. VO2 and heart rate decreased following exercise in a similar manner in the two conditions. Rectal temperature increased similarly but remained elevated during H compared with N (p<0.05). In conclusion, the results of this study suggest that heat exposure may improve anaerobic performance but does not appear to affect the physiological responses during 60 min of recovery. Future research should examine the effect of more extreme heat stress, as well as shorter recovery periods.

Identification of genes induced by interleukin-3 and erythropoietin via the Jak-Stat5 pathway using enhanced differential display-reverse southern.

Cytokines mediate their effects on growth and maturation of hematopoietic cells by binding to their cognate receptors and activating target genes. Interleukin-3 (IL-3) and erythropoietin (Epo) induce signal transduction via the Jak-Stat pathway. We report here on the identification of several known and novel genes induced by IL-3 and Epo, using a modified version of the PCR-based technique, enhanced differential display (EDD). We modified the technique to facilitate the screening and verification of the differential expression of the genes by using reverse Southern blotting (RS) and PCR-Southern blotting, and we called it EDD-RS. From the initial 110 genetags that were identified as differential expressed genes, 14 contained more than one gene. Among the differentially expressed genes, 24 are known genes and 39 are novel genes. Several of the known genes, such as IRF-1 and P21waf, were previously observed by others to be induced by IL-3 and Epo, but their dependence on Stat5 activation in cytokine-dependent cells was unknown. Other known genes, such as crp and Mssp2/1, were not described previously as target genes for cytokine induction. The results demonstrate that EDD-RS is an efficient method to identify cytokine-induced genes and can be productive in delineating the signal required for their induction.

The effect of environmental temperature on testosterone and cortisol responses to high intensity, intermittent exercise in humans.

The purpose of this study was to examine the testosterone, cortisol, and the molar ratio of testosterone to cortisol (T:C) blood concentration responses to intermittent, high intensity exercise in the heat. Eight active men [mean age 25 (SD 3) years, mass 71.1 (SD 5.5) kg, height 175.9 (SD 4.4) cm] performed two series of five 15-s Wingate anaerobic power tests in both hot (H, 35 degrees C) and thermoneutral (TN, 22 degrees C) environments. Each period of exercise was separated by 30-s of active recovery. Each series was separated by 60 min of passive recovery. Blood samples were obtained before (PRE), immediately post (IP), and 5(5R), 10(10R), 15(15R), 30(30R), 45(45R), and 60(60R) min following exercise. Peak power was significantly higher, during the first series of exercise, in the H compared to TN. No significant differences were seen in any of the variables between the first and second series of exercise in either environmental condition. Furthermore, no significant differences between these conditions were observed in heart rate, blood lactic acid concentration, or rectal temperature. A significant decrease in cortisol concentration was observed between PRE and IP, during both conditions. However, no significant interactions between TN or H were seen. No change from PRE was observed in testosterone or T:C during either TN or H. It would appear that testosterone and cortisol respond similarly to repeated periods of short duration high intensity exercise, in either thermoneutral or moderately hot environments.

Physiological and cognitive responses to cold exposure in 11-12-year-old boys.

This study investigated the effects of cold and exercise in the cold on the physiological and cognitive responses of 11-12-year-old boys. Children were dressed in sweat suits and exposed to cold (CD, 7°C), cool (CL, 13°C), and neutral (N, 22°C) environments for 110 minutes, with 10 minutes of light exercise (1 watt · kg body wt-1 ) midway through the exposure. A 30-minute "recovery" in neutral conditions followed each session. Session order was randomized. Rectal temperature (Tre) decreased significantly more in CD compared to CL and N, and continued to decrease during the recovery period. Chest skin temperature (Tch) was significantly different between conditions and remained stable even in CD, despite the decrease in Tre. Tch returned to prechamber values during the recovery period. Hand temperature (Th) decreased during CL and CL, and remained significantly lower than prechamber values following the recovery. Exercise heart rate was lower in the CD and CL(115 ± 13 and 119 ± 20 beats · min-1 ) compared to N (130 ± 17 beats · min-1 ). No differences were observed in oxygen consumption between sessions. No differences were also observed between sessions in cognitive performance on language and math tests. It was concluded that while the study conditions did not appear to affect cognitive capacity in boys, they proved sufficient to disturb core temperature. This disturbance was not corrected 30 minutes following cold exposure. Am. J. Hum. Biol. 9:39-49 © 1997 Wiley-Liss, Inc.

A treadmill test of sprint running.

Anaerobic power is characterized by a high degree of specificity regarding both the recruited muscles as well as the recruitment pattern. The popular Wingate Anaerobic Test (WAnT) is a cycling test that does not satisfy the need for a running-specific anaerobic test. We describe such a test, using a novel type of a commercially available treadmill (BRL 1800, Gymrol, France). The ergometer is equipped with a torque motor to neutralize the frictional resistance of the treadmill belt, and a hip-belt harness connected to a horizontal rod. Force applied to the harness is monitored by a strain gauge mounted on the rod, while vertical movement is monitored by a potentiometer at the posterior fixed end of the rod. These, in conjunction with the treadmill belt speed, enable the computation of horizontal and vertical power as well as the combined total output. Power is calculated both as 'peak' power (highest 2.5 s segment) and 'mean' power (20 s duration). Preliminary results of young athletes were generally consistent with the expected age-related changes in anaerobic power. Values obtained on the anaerobic treadmill were always higher than the corresponding WAnT values previously obtained in comparable age groups. The higher values were probably due to the larger muscle mass involved and the shorter peak and mean power durations (2.5 and 20 s versus 5 and 30 s in the WAnT, respectively). This test should enable not only running-specific anaerobic power monitoring but also the characterization of the relationship between the horizontal and vertical components of that power.

Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response.

The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor gamma locus (TCR-gamma), and c-pim-1. The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts for cis, TCR-gamma, or c-fos, suggesting a role for Stat5 in their regulation.