Exercise training enhances tumor necrosis factor-alpha-induced expressions of anti-apoptotic genes without alterations in caspase-3 activity in rat epididymal adipocytes

The effect of exercise training on tumor necrosis factor-alpha (TNF-alpha) signaling was investigated in rat epididymal adipocytes. Incubation of isolated adipocytes with TNF-alpha (20 ng/ml) for 5 h enhanced the expression of the inhibitor apoptosis protein 2 (IAP2) gene without any enhancement of caspase-3 activity in both the sedentary control (C) and exercise-trained (TR) groups. However, the ability of TNF-alpha to enhance IAP2 gene expression was significantly greater in TR than in C rats. The basal expression of the IkappaB kinase beta (IKK beta) gene and that of the BCL-x(L) gene were also higher in TR than in C rats. Mn-superoxidedismutase contents in adipocytes were higher in TR than in C rats. Moreover, no apoptotic nucleuses of adipocytes in response to acute exercise were observed in either group at least up to 5 h after exercise. Exercise training also enhanced the inhibitory effect of TNF-alpha on the gene expression of the fatty acid synthase (FAS), a lipogenic enzyme, suggesting that fatty acid synthesis may be reduced. Thus, exercise training enhanced TNF-alpha signaling directed toward the expressions of survival signals and the suppression of FAS gene expression.     

Hypersensitivity pneumonitis due to Bunashimeji mushrooms in the mushroom industry

BACKGROUND: Detection of hypersensitivity pneumonitis (HP) in employees involved in the Bunashimeji mushroom industry is difficult. The level of precipitating antibody is not related with the prediction of progression and resolution of HP. The aims of this study were to examine the actual prevalence of HP in the Bunashimeji industry and the clinical differences among selected employees. METHODS: One hundred and fourteen employees worked in Bunashimeji enterprises. These subjects were divided into the following subgroups: office workers, pickers/packers with mask and pickers/packers without mask. We measured serum Krebs von der Lungen-6 (KL-6), surfactant protein (SP)-A and SP-D, and examined the stimulation index (SI) due to Bunashimeji spores. Chest high-resolution computed tomography (HRCT), pulmonary function tests and bronchoalveolar lavage (BAL) were performed for select employees who showed positive SI values (>200%) to examine the clinical differences. RESULTS: The proportion of respiratory symptoms was significantly higher in the pickers/packers than that in the office workers. The picker/packer group had high serum KL-6 concentrations and SI compared with the office worker group. Thirty select employees were divided into the following three subgroups: HP, select employees without HP, and SI <400% and KL-6 <500 U/ml , using high SI levels (>400%) and positive serum KL-6 concentration (>500 U/ml). Four exhibited ground glass opacities with centrilobular fine nodules on HRCT, and 8 had high numbers of lymphocytes in the BAL fluid. The BAL findings and serum KL-6 concentrations showed significant differences among the three groups. CONCLUSIONS: Four employees were evaluated as having HP. Serum KL-6 and SP-D may be related to the resolution of HP in addition to SI and chest HRCT.     

Premature ovarian failure in a female with proximal symphalangism and Noggin mutation

OBJECTIVE: To report a case of premature ovarian failure (POF) and a mutation of the gene for Noggin (NOG). DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33-year-old Japanese female with POF and proximal symphalangism. INTERVENTION(S): Direct sequence analysis of the NOG gene. MAIN OUTCOME MEASURE(S): Occurrence of POF. RESULT(S): A novel heterozygous G to A transition was identified at the nucleotide position 142 (142 G>A), which is predicted to cause an amino acid substitution of glutamic acid by lysine (E48K). CONCLUSION(S): Because NOG is expressed in the ovary and interacts with bone morphogenetic proteins, which play an important role in the ovarian function, a NOG mutation may constitute one of the multiple susceptibility genes for the development of POF.     

Benefits of oxygen on exercise performance and pulmonary hemodynamics in patients with COPD with mild hypoxemia

STUDY OBJECTIVES: To clarify the effects of oxygen on exercise performance and pulmonary hemodynamics during exercise in patients with COPD with mild hypoxemia at rest. DESIGN: Seventy-five male patients with stable COPD ("pink puffer" type), accompanied by mild hypoxemia (> 60 mm Hg) at rest and with mild (percentage of predicted FEV1 [%FEV1] > 50%, n = 16), moderate (%FEV1 > 35% to < or = 50%, n = 25), and severe (%FEV1 < or =35%, n = 34) airflow obstruction were recruited from an outpatient clinic. A 6-min walking distance (6MD) test was administered to 75 patients, and the pulmonary hemodynamics of 43 subjects were determined during exercise on a supine bicycle ergometer at 25 W and breathing compressed air and oxygen at 2 L/min. RESULTS: Supplemental oxygen resulted in a significant increase in 6MD, except for patients with mild airflow obstruction and mild desaturation. This increase in 6MD produced by oxygen was greater as the restriction of the airflow was more severe, and correlated negatively with %FEV1, but not with PaO2 at rest or exercise hypoxemia. Pulmonary artery pressure (Ppa) and pulmonary artery occlusion pressure (Pop) increased with exercise, while the rates of increase in both types of pressure were significantly higher for severe COPD than for mild COPD and moderate COPD. Oxygen inhalation significantly reduced the increases in Ppa and Pop during exercise in patients with moderate-to-severe COPD, and the effect of oxygen on the increase in Pop correlated positively with airtrapping (vital capacity - FVC). CONCLUSION: These findings suggest that supplemental oxygen benefits patients with COPD with moderate-to-severe airflow obstruction and mild hypoxemia at rest, as reflected in improvement in exercise performance and pulmonary hypertension during exercise.     

Effects of a selective nitric oxide synthase inhibitor on endotoxin-induced alteration in hypoxic pulmonary vasoconstriction in sheep

It has been suggested that overproduction of nitric oxide (NO) by nitric oxide synthase (NOS) contributes to blunted hypoxic pulmonary vasoconstriction (HPV) during endotoxemia. We investigated the effect of a selective inducible NOS (iNOS) inhibitor, ONO-1714, on the loss of HPV during endotoxemia in awake sheep to clarify the role of iNOS. We prepared 11 intubated, awake sheep with hemodynamic monitoring. Hypoxic challenges (FiO2; 12%) were performed before, and 5, 24, 48, 72 hours after endotoxin (1 microg/kg) infusion for 15 minutes. Pulmonary artery (Ppa) and left atrial pressure (Pla) were continuously measured and cardiac output (CO) was measured by the thermodilution method. Pulmonary vascular resistance (PVR) was calculated by (Ppa - Pla)/CO. The percent change in PVR (%PVR) before (pre-PVR) and after (post-PVR) hypoxia was calculated as (post-PVR - pre-PVR)/pre-HPV x 100. ONO-1714 (0.1 mg/kg, n=5, Exp 1) or normal saline (n=6, Exp 2) was administered 5 hours before hypoxic challenge every day. ONO-1714 did not affect the baseline pulmonary hemodynamics before endotoxin administration. % PVR before and after hypoxic exposure was significantly decreased 5 hours after endotoxin administration and gradually improved to baseline at 72 hours. Treatment with iNOS inhibition significantly restored % HPV (24.7+/-5.5% in Exp1 versus -3.1+/-3.6% in Exp 2, 5 hours, 25.3+/-2.5% in Exp 1 versus 7.7+/-2.2% in Exp 2, 24 hours). It is suggested that inducible nitric oxide is related to pulmonary vascular hyporesponsiveness to hypoxia during endotoxemia in sheep.     

Influence of 320-detector-row volume scanning and AAPM report 111 CT dosimetry metrics on size-specific dose estimate: a Monte Carlo study

The American Association of Physicists in Medicine (AAPM) task group 204 has recommended the use of size-dependent conversion factors to calculate size-specific dose estimate (SSDE) values from volume computed tomography dose index (CTDI_vol) values. However, these conversion factors do not consider the effects of 320-detector-row volume computed tomography (CT) examinations or the new CT dosimetry metrics proposed by AAPM task group 111. This study aims to investigate the influence of these examinations and metrics on the conversion factors reported by AAPM task group 204, using Monte Carlo simulations. Simulations were performed modelling a Toshiba Aquilion ONE CT scanner, in order to compute dose values in water for cylindrical phantoms with 8–40-cm diameters at 2-cm intervals for each scanning parameter (tube voltage, bow-tie filter, longitudinal beam width). Then, the conversion factors were obtained by applying exponential regression analysis between the dose values for a given phantom diameter and the phantom diameter combined with various scanning parameters. The conversion factors for each scanning method (helical, axial, or volume scanning) and CT dosimetry method (i.e., the CTDI₁₀₀ method or the AAPM task group 111 method) were in agreement with those reported by AAPM task group 204, within a percentage error of 14.2 % for phantom diameters ≥11.2 cm. The results obtained in this study indicate that the conversion factors previously presented by AAPM task group 204 can be used to provide appropriate SSDE values for 320-detector-row volume CT examinations and the CT dosimetry metrics proposed by the AAPM task group 111.