QT interval and QT dispersion before and after diet therapy in patients with simple obesity

To evaluate whether a disordered QT interval and its dispersion in obese patients, if any, may be improved by therapeutic weight reduction, 36 obese patients admitted to our university hospital were examined over a 5-year period from April 1, 1992 to March 31, 1997. Participants included 18 males and 18 females whose mean age +/- SD was 28 +/- 9 and 33 +/- 14 years, respectively, and whose mean body mass index +/- SD was 35 +/- 5 and 38 +/- 6 kg/m2, respectively. Thirty-six control patients were matched in age and gender with the obese patients. All the obese patients were treated with behavioral therapy together with very-low-calorie conventional Japanese diet (VLCD: 370 kcal/day). A standard 12-lead electrocardiogram (ECG) revealed longer maximum (445 +/- 32 msec, mean +/- SD) and minimum (388 +/- 29 msec) heart rate corrected QT intervals (QTc intervals) in the obese group than in the control group (P < 0.0001 for each). QTc dispersion, defined as the difference between maximum and minimum QTc intervals derived from 12-lead ECG, was greater in the obese group (57 +/- 19 msec) than in the control group (32 +/- 13 msec) (P < 0.0001). Both the maximum and minimum QTc intervals in the obese patients were shortened, respectively, to 434 +/- 28 msec and 377 +/- 29 msec (P < 0.05 for each) with no significant change in either QTc dispersion, QRS voltage, or QRS duration following weight reduction. The coefficient value from the linear regression line between QT interval and RR interval in the obese group was less than in the control group. Together, the results show that obesity per se causes both a prolongation of QTc interval and an increase in QTc dispersion, and that weight reduction improves the prolonged QTc interval observed in obese patients.     

Human immunodeficiency virus type 1 Vpr induces G2 checkpoint activation by interacting with the splicing factor SAP145

Vpr, the viral protein R of human immunodeficiency virus type 1, induces G(2) cell cycle arrest and apoptosis in mammalian cells via ATR (for "ataxia-telangiectasia-mediated and Rad3-related") checkpoint activation. The expression of Vpr induces the formation of the gamma-histone 2A variant X (H2AX) and breast cancer susceptibility protein 1 (BRCA1) nuclear foci, and a C-terminal domain is required for Vpr-induced ATR activation and its nuclear localization. However, the cellular target of Vpr, as well as the mechanism of G(2) checkpoint activation, was unknown. Here we report that Vpr induces checkpoint activation and G(2) arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b). Vpr interacts with and colocalizes with SAP145 through its C-terminal domain in a speckled distribution. The depletion of either SAP145 or SAP49 leads to checkpoint-mediated G(2) cell cycle arrest through the induction of nuclear foci containing gamma-H2AX and BRCA1. In addition, the expression of Vpr excludes SAP49 from the nuclear speckles and inhibits the formation of the SAP145-SAP49 complex. To conclude, these results point out the unexpected roles of the SAP145-SAP49 splicing factors in cell cycle progression and suggest that cellular expression of Vpr induces checkpoint activation and G(2) arrest by interfering with the function of SAP145-SAP49 complex in host cells.     

Vinculin Is Indispensable for Repopulation by Hematopoietic Stem Cells,Independent of Integrin Function

Vinculin is a highly conserved actin-binding protein that is localized in integrin-mediated focal adhesion complexes. Although critical roles have been proposed for integrins in hematopoietic stem cell (HSC) function, little is known about the involvement of intracellular focal adhesion proteins in HSC functions. This study showed that the ability of c-Kit⁺Sca1⁺Lin⁻ HSCs to support reconstitution of hematopoiesis after competitive transplantation was severely impaired by lentiviral transduction with short hairpin RNA sequences for vinculin. The potential of these HSCs to differentiate into granulocytic and monocytic lineages, to migrate toward stromal cell-derived factor 1α, and to home to the bone marrow in vivo were not inhibited by the loss of vinculin. However, the capacities to form long term culture-initiating cells and cobblestone-like areas were abolished in vinculin-silenced c-Kit⁺Sca1⁺Lin⁻ HSCs. In contrast, adhesion to the extracellular matrix was inhibited by silencing of talin-1, but not of vinculin. Whole body in vivo luminescence analyses to detect transduced HSCs confirmed the role of vinculin in long term HSC reconstitution. Our results suggest that vinculin is an indispensable factor determining HSC repopulation capacity, independent of integrin functions.     

An ocular cysticercosis in Bali, Indonesia caused by Taenia solium Asian genotype

An ocular cysticercosis case of a nine-year-old Balinese girl in Indonesia is reported. She presented with redness and pain in the left eye and showed a cysticercus in the anterior chamber in December 2010. Morphological feature of the cysticercus removed from the anterior chamber indicated that it was an immature cysticercus of Taenia species with no hooklets. However, mitochondrial DNA analysis using a piece of histopathological specimen revealed it a cysticercus of Taenia solium Asian genotype. Serology by immunoblot and ELISA highly specific to cysticercosis was negative.     

The sixth transmembrane region of a pheromone G-protein coupled receptor,Map3, is implicated in discrimination of closely related pheromones in Schizosaccharomyces pombe

Most sexually reproducing organisms have the ability to recognize individuals of the same species. In ascomycete fungi including yeasts, mating between cells of opposite mating type depends on the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors (GPCRs). Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation, very few studies have focused on the stringency of pheromone receptors. The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M). Here, we investigated the stringency of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor, in fission yeast. First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus, which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable. Next, we swapped individual domains of Mam2 and Map3 with the respective domains in SoMam2 and SoMap3, which revealed differences between the receptors both in the intracellular regions that regulate the downstream signaling of pheromones and in the activation by the pheromone. In particular, we demonstrated that two amino acid residues of Map3, F214 and F215, are key residues important for discrimination of closely related M-factors. Thus, the differences in these two GPCRs might reflect the significantly distinct stringency/flexibility of their respective pheromone/receptor systems; nevertheless, species-specific pheromone recognition remains incomplete.     

A new gobiid fish,Acanthogobius insularis,from the Ryukyu Islands,Japan

A new gobiid species,Acanthogobius insularis, is described from 88 specimens collected from Amami-oshima Island and Okinawa Island, Ryukyu Islands, southern Japan. The species is distinguished from its congeners by the combination of dorsal and anal fin ray counts, vertebral counts, cephalic sensory system patterns and coloration.     

Decoding ABA and osmostress signalling in plants from an evolutionary point of view

The plant hormone abscisic acid (ABA) is fundamental for land plant adaptation to water-limited conditions. Osmostress, such as drought, induces ABA accumulation in angiosperms, triggering physiological responses such as stomata closure. The core components of angiosperm ABA signalling are soluble ABA receptors, group A protein phosphatase type 2C and SNF1-related protein kinase2 (SnRK2). ABA also has various functions in non-angiosperms, however, suggesting that its role in adaptation to land may not have been angiosperm-specific. Indeed, among land plants, the core ABA signalling components are evolutionarily conserved, implying their presence in a common ancestor. Results of ongoing functional genomics studies of ABA signalling components in bryophytes and algae have expanded our understanding of the evolutionary role of ABA signalling, with genome sequencing uncovering the ABA core module even in algae. In this review, we describe recent discoveries involving the ABA core module in non-angiosperms, tracing the footprints of how ABA evolved as a phytohormone. We also cover the latest findings on Raf-like kinases as upstream regulators of the core ABA module component SnRK2. Finally, we discuss the origin of ABA signalling from an evolutionary perspective.     

Studies on the Polymorphism of L-Glutamic Acid

The velocity of the α-β transition was measured in two cases, i.e., when α-crystals stayed in the saturated aqueous solution, and when they were left to stand in an air-bath at various temperatures ranging from 20° to 100°C. And it was deduced from the results of the measurement that this transition is due to the recrystallization of α-crystals into the β-form on the inner surfaces of the crystal and in the bulk of the solution, and the transition on the inner surfaces will be dominant, especially at the initial stage of the transition.     

Thyrotropin-secreting pituitary adenoma: a case report.

We report a 44-year-old male with a thyrotropin (TSH)-secreting pituitary adenoma. Based serum free triiodothyronine (FT3, 12.1 pmol/l) and free thyroxine (FT4, 28 pmol/l) were increased with normal basal TSH (3.1 mU/l). There was impaired TSH response to thyrotropin releasing hormone (TRH) test. Serum TSH was suppressed to 59% of the basal level after oral administration of 1.4 mg 3,3'-5-triiodothyroacetic acid (triac), whereas no suppression was observed after 75 micrograms daily administration of triiodothyronine (T3). Serum concentrations of alpha-subunit of TSH (TSH-alpha) and TSH-alpha/TSH molar ratio were high, being 1.95 micrograms/l, and 4.4, respectively. Pituitary CT and MRI scan showed the presence of a macroadenoma in the anterior lobe of the pituitary gland. Histopathology of the excised pituitary confirmed the diagnosis of a TSH-producing adenoma. A positive correlation between TSH and FT3 (r = 0.66, P less than 0.01) or FT4 (r = 0.54, P less than 0.01) was observed in serial sera obtained before and after operation.     

A Multicenter,Randomized, Double-Blind,Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

Background

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.

Aim

We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.

Methods

We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.

Results

The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.

Conclusions

High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.

Trial Registration

UMIN Clinical Trials Registry UMIN000003463