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Biomedical subjects

Kengo Usui

Publications and source records attributed to Kengo Usui.

12 recordsLinked to original sources

Left ventricular structural adaptations to obstructive sleep apnea in dilated cardiomyopathy.

RATIONALE AND OBJECTIVES: Obstructive sleep apnea is common among patients with heart failure and exposes the left ventricle to trophic mechanical and adrenergic stimuli. We hypothesized that in heart failure patients with nonischemic dilated cardiomyopathy (a condition characterized by eccentric hypertrophy), those with obstructive sleep apnea would have a higher prevalence of left ventricular hypertrophy by wall thickness criteria (> or = 12 mm), and greater septal thickness than those without obstructive sleep apnea. METHODS AND RESULTS: We performed echocardiography and polysomnography in 47 patients with nonischemic dilated cardiomyopathy. Obstructive sleep apnea was present in 45% of these patients. The prevalence of left ventricular hypertrophy was greater in those with than in those without obstructive sleep apnea (47.6 vs. 15.4%, p = 0.016). Interventricular septal thickness (p < 0.001) and relative wall thickness (p = 0.011) were significantly greater in those with than in those without obstructive sleep apnea. However, there was no significant difference in posterior wall thickness between the groups. The frequency of obstructive apneas and hypopneas during sleep was the only significant independent correlate of septal thickness (p = 0.001). CONCLUSIONS: In patients with nonischemic dilated cardiomyopathy, the presence of obstructive sleep apnea is associated with an increased prevalence of left ventricular hypertrophy. The higher relative wall thickness and interventricular septal thickness in patients with obstructive sleep apnea indicate that the left ventricle is relatively less eccentric than in patients without obstructive sleep apnea, and that such remodeling affects mainly the septum. These structural adaptations may reflect unique nocturnal mechanical and adrenergic stimuli associated with obstructive sleep apnea.

Adaptation, Physiological↗

Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome.

We investigated the prevalence of metabolic syndrome in patients with obstructive sleep apnea syndrome (OSAS) referred to a tertiary university-based medical center. A cross-sectional study of patients with a definite diagnosis of OSAS was performed using new diagnostic criteria for metabolic syndrome that were designed for the Japanese population. Clinical features and comorbidities related to metabolic syndrome were compared between 819 patients with OSAS (719 men and 100 women) and 89 control subjects without OSAS. Metabolic syndrome was significantly more common in the patients with OSAS than in the controls (49.5% vs. 22.0% for men, p < 0.01; 32.0% vs. 6.7% for women, p < 0.01). Men with OSAS (apnea-hypopnea index [AHI] > or =5/h) had a higher risk of metabolic syndrome compared with controls (odds ratio [OR]: 3.47; 95% confidence interval [CI]: 1.84-6.53). There was a significantly increased risk of metabolic syndrome in men with moderate OSAS (AHI: 15-29.9/h) (OR: 2.83; 95% CI: 1.42-5.66) and men with severe OSAS (AHI > or =30/h) (OR: 5.09; 95% CI: 2.67-9.71). Women with OSAS (AHI> or =5/h) also had an increased risk of metabolic syndrome (OR: 6.59; 95% CI: 1.47-29.38), and the risk was significantly higher in women with severe OSAS (AHI > or =30/h) (OR 14.00; 95% CI: 2.93-66.82). Risk factors for metabolic syndrome differed by gender: in men, age, body mass index (BMI), and OSAS (AHI > or =15/h) were significantly associated with metabolic syndrome, whereas, in women, BMI was the only risk factor for metabolic syndrome. The increase of metabolic syndrome in Japanese OSAS patients suggests that this patient population is burdened with multiple risk factors for cardiovascular disease.

Adult↗

Protein-protein interactions of the hyperthermophilic archaeon Pyrococcus horikoshii OT3.

BACKGROUND: Although 2,061 proteins of Pyrococcus horikoshii OT3, a hyperthermophilic archaeon, have been predicted from the recently completed genome sequence, the majority of proteins show no similarity to those from other organisms and are thus hypothetical proteins of unknown function. Because most proteins operate as parts of complexes to regulate biological processes, we systematically analyzed protein-protein interactions in Pyrococcus using the mammalian two-hybrid system to determine the function of the hypothetical proteins. RESULTS: We examined 960 soluble proteins from Pyrococcus and selected 107 interactions based on luciferase reporter activity, which was then evaluated using a computational approach to assess the reliability of the interactions. We also analyzed the expression of the assay samples by western blot, and a few interactions by in vitro pull-down assays. We identified 11 hetero-interactions that we considered to be located at the same operon, as observed in Helicobacter pylori. We annotated and classified proteins in the selected interactions according to their orthologous proteins. Many enzyme proteins showed self-interactions, similar to those seen in other organisms. CONCLUSION: We found 13 unannotated proteins that interacted with annotated proteins; this information is useful for predicting the functions of the hypothetical Pyrococcus proteins from the annotations of their interacting partners. Among the heterogeneous interactions, proteins were more likely to interact with proteins within the same ortholog class than with proteins of different classes. The analysis described here can provide global insights into the biological features of the protein-protein interactions in P. horikoshii.

Genes, Archaeal↗

Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea.

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.

Cardiac Output, Low↗

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure.

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.

Blood Pressure↗

Crystallization and preliminary X-ray crystallographic studies of XynX, a family 10 xylanase from Aeromonas punctata ME-1.

Xylanases catalyze the hydrolysis of beta-1,4-glycosidic linkages within the xylan backbone. XynX is a xylanase from Aeromonas punctata ME-1 and belongs to glycoside hydrolase family 10. While most xylanases show endo-type catalytic activities, XynX shows exo-like catalytic activities, selectively producing xylobiose from birchwood xylan. In this study, XynX was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 79.0, b = 88.6, c = 93.2 A, and diffracted to beyond 1.8 A resolution.

Aeromonas↗

Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea subjects the failing heart to adverse hemodynamic and adrenergic loads and may thereby contribute to the progression of heart failure. We hypothesized that treatment of obstructive sleep apnea by continuous positive airway pressure in patients with heart failure would improve left ventricular systolic function. METHODS: Twenty-four patients with a depressed left ventricular ejection fraction (45 percent or less) and obstructive sleep apnea who were receiving optimal medical treatment for heart failure underwent polysomnography. On the following morning, their blood pressure and heart rate were measured by digital photoplethysmography, and left ventricular dimensions and left ventricular ejection fraction were assessed by echocardiography. The subjects were then randomly assigned to receive medical therapy either alone (12 patients) or with the addition of continuous positive airway pressure (12 patients) for one month. The assessment protocol was then repeated. RESULTS: In the control group of patients who received only medical therapy, there were no significant changes in the severity of obstructive sleep apnea, daytime blood pressure, heart rate, left ventricular end-systolic dimension, or left ventricular ejection fraction during the study. In contrast, continuous positive airway pressure markedly reduced obstructive sleep apnea, reduced the daytime systolic blood pressure from a mean (+/-SE) of 126+/-6 mm Hg to 116+/-5 mm Hg (P=0.02), reduced the heart rate from 68+/-3 to 64+/-3 beats per minute (P=0.007), reduced the left ventricular end-systolic dimension from 54.5+/-1.8 to 51.7+/-1.2 mm (P=0.009), and improved the left ventricular ejection fraction from 25.0+/-2.8 to 33.8+/-2.4 percent (P<0.001). CONCLUSION: In medically treated patients with heart failure, treatment of coexisting obstructive sleep apnea by continuous positive airway pressure reduces systolic blood pressure and improves left ventricular systolic function. Obstructive sleep apnea may thus have an adverse effect in heart failure that can be addressed by targeted therapy.

Blood Pressure↗

A cytoplasmic xylanase (XynX) of Aeromonas caviae ME-1 is released from the cytoplasm to the periplasm by osmotic downshock.

Aeromonas caviae ME-1 is a multiple xylanase-producing gram-negative bacterium which was isolated from the gut contents of a wild silkworm, Samia cynthia pryeri. One of the xylanases produced by A. caviae ME-1, XynX (38 kDa, family 10 xylanase), hydrolyzes xylan to xylobiose and xylotetraose as final degradation products. Generally, xylanases are extracellular or cell surface enzymes. However, XynX is not exported to the extracellular fluid by A. caviae ME-1 and an Escherichia coli transformant harboring the xynX gene. In this study, we investigated the intracellular localization of XynX in A. caviae ME-1 and an E. coli transformant. XynX was found in the cytoplasm when the cells were grown under normal culture conditions. However, XynX was released from the cytoplasm to the periplasm during osmotic downshock. This release of XynX in the E. coli transformant was blocked in the presence of gadolinium chloride, which has been reported to be an inhibitor of bacterial mechanosensitive channels.

Journal Article↗

Force measurement for antigen-antibody interaction by atomic force microscopy using a photograft-polymer spacer.

To determine the intermolecular force on protein-protein interaction (PPI) by atomic force microscopy (AFM), a photograft-polymer spacer for protein molecules on both surfaces of the substrate and AFM probe tip was developed, and its effectiveness was assessed in a PPI model of a pair of human serum albumin (HSA) and its monoclonal antibody (anti-HSA). A carboxylated photoiniferter, N-(dithiocarboxy)sarcosine, was derivatized on both surfaces of the glass substrate and AFM probe tip, and subsequently water-soluble nonionic vinyl monomers, N,N-dimethylacrylamide (DMAAm), were graft-polymerized on them upon ultraviolet light irradiation. DMAAm-photograft-polymerized spacers with carboxyl groups at the growing chain end but with different chain lengths on both surfaces were prepared. The proteins were covalently bound to the carboxyl terminus of the photograft-polymer chain using a water-soluble condensation agent. The effects of the graft-spacer length on the profile of the force-distance curves and on the unbinding characteristics (unbinding force and unbinding distance) were examined in comparison with those in the case of the commercially available poly(ethylene glycol) (PEG) spacer. The frequency of the nonspecific adhesion force profile was markedly decreased with the use of the photograft spacers. Among the force curves detected, a high frequency of single-peak curves indicating the unbinding process of a single pair of proteins and a very low frequency of multiple-peak profiles were observed for the photograft spacers, regardless of the graft chain length, whereas a high frequency of no-force peaks was noted. These observations were in marked contrast with those for the PEG spacer. The force peak values determined ranged from 88 to 94 pN, irrespective of the type of spacer, while the standard deviation of force distribution observed for the photograft spacer was lower than that for the PEG spacer, indicating that the photograft spacers provide a higher accuracy of force determination.

Adhesiveness↗