High REE in Sumo wrestlers attributed to large organ-tissue mass

PURPOSE: It is unknown whether high resting energy expenditure (REE) in athletes is attributable to changes in organ-tissue mass and/or metabolic rate. The purpose of this study was to examine the contribution of organ-tissue mass of fat-free mass (FFM) components to REE for Sumo wrestlers who have large FFM and REE. We investigated the relationship between the REE measured by indirect calorimetry and the REE calculated from organ-tissue mass using a previously published approach. METHODS: Ten Sumo wrestlers and 11 male untrained college students (controls) were recruited to participate in this study. FFM was estimated by two-component densitometry. Contiguous magnetic resonance imaging (MRI) images with a 1-cm slice thickness were obtained from the top of head to the ankle joints, and the cross-sectional area and volume were determined for skeletal muscle (SM), liver, kidney, and brain. The volume of adipose tissue, heart, and residual was calculated from each equation. The volume units were converted into mass by an assumed constant density. The measured REE was determined by indirect calorimetry. The calculated REE was estimated as the sum of individual organ-tissue masses (seven body compartments) multiplied by their metabolic rate constants. RESULTS: The measured REE for Sumo wrestlers (2286 kcal x d(-1)) was higher (P<0.01) than for controls (1545 kcal x d(-1)). Sumo wrestlers had a greater amount of FFM and FFM components (e.g., SM, liver, and kidney), except for brain. The ratio of measured REE to FFM and the measured REE adjusted by FFM were similar between the two groups. The measured REE values for Sumo wrestlers were not significantly different from the calculated REE values. CONCLUSIONS: The high REE for Sumo wrestlers can be attributed not to an elevation of the organ-tissue metabolic rate, but to a larger absolute amount of low and high metabolically active tissue including SM, liver, and kidney.     

Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.     

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan

BackgroundAnticardiolipin antibodies (aCL) and anti‐β₂‐glycoprotein I antibodies (aβ₂GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ₂GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays.MethodsWe evaluated two manual and three automated assays for aCL and aβ₂GPI of IgG‐ and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well‐defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve.ResultsA variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between‐year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aβ₂GPI‐IgG and aCL‐IgG were generally high (AUC: 0.84−0.93); whereas those for IgM‐class assays were low (AUC: 0.57−0.67), implicating its utility is limited to rare IgG negative APS cases.ConclusionTo ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.     

Evaluation of extensive lymph node dissection for carcinoma of the stomach

We compared the results of curative resection for carcinoma of the stomach in 254 patients who underwent simple resection (SR) and 454 patients who underwent extensive regional lymph node dissection (ELD). The 5-year survival rates of the 2 procedures were significantly different in carcinoma involving the serosa of the stomach; it was 45% in the ELD group and 18% in the SR group (p<0.001). In patients with regional lymph node metastasis we obtained a 5-year survival rates of 39% and 18% by ELD and SR, respectively (p<0.001). The incidence of metastasis to the secondary lymph nodes, removable only by ELD, was higher in cases with carcinomatous invasion of the deeper layers of the gastric wall, and this may have been the reason why ELD proved to be more effective than SR. ELD is discussed in relation to the site of the primary carcinoma and the extent of lymph node metastasis.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine

Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature. IMPLICATIONS: The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.     

Median sternotomy and extended left anterior thoracotomy for repair of traumatic aortic transection with ruptured right atrium

A 22-year-old man presented with traumatic aortic transtion associated with rupture of the right atrium and underwent urgent median sternotomy to repair the right atrium. A T-shaped extended left anterior thoracotomy was performed, and ruptured descending thoracic aorta was repaired under total bypass. A Y-shaped connector was inserted in the arterial catheter to allow cannulation of both ascending aorta and femoral arteries. A 4-cm long Hemoshield graft was used to repair the aortic transection. The patient made a full recovery and was discharged 13 days after the accident.     

Unit approach for vermilion repair in unilateral cleft surgery

In conventional unilateral cleft lip surgery the suture line proceeds from the philtral ridge to the vermilion in succession. However, when observed carefully, in a noncleft upper lip the existence of a whitish vertical line in the midline of the vermilion can be seen. Therefore we consider that the vermilion can be separated by the midline into two subunits. On the basis of this unit principle we placed the suture line in the vermilion at the midline in the repair of the unilateral cleft lip. This method has been performed in 14 cases of unilateral cleft lip since February 1994. The postoperative follow-up period ranges from 4 months to 7 years and 2 months. The suture line appears to almost correspond to the vertical line at the midline of the noncleft vermilion, thus resulting in a natural contour. Although the number of cases is still small, and the follow-up period is not long enough to draw positive conclusions, unilateral cleft lip surgery according to the unit principle is considered useful in making the scarring less conspicuous.