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Biomedical subjects

S Hara

Publications and source records attributed to S Hara.

At least 109 records · Page 6Linked to original sources

Nonlinear dielectric relaxation spectroscopy of ferroelectric liquid crystals

The nonlinear dielectric relaxation spectra of ferroelectric liquid crystals (FLCs) have been studied in the chiral smectic-C phase. The linear and third-order nonlinear dielectric spectra show the relaxation corresponding to the fluctuation in the azimuthal angle of directors called the Goldstone mode. We calculated the nonlinear dielectric spectra of the Goldstone mode theoretically by the torque balance equation which describes the dynamics of FLCs under the electric field. The calculated spectra make good agreement with the measured ones. We also evaluated the material constants of FLCs from the best-fitted values of the linear and nonlinear dielectric increment and relaxation time.

Journal Article↗

An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might modulate volume-dependent hypertension in patients on hemodialysis.

Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 +/- 1.76 micromol/l) was significantly lower than in those without the a allele (35.6 +/- 0.90 micromol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (deltaBP/deltaBW), patients were divided into high responders (High-R: deltaBP/deltaBW >2.0 mm Hg; n = 90) and low responders (Low-R: deltaBP/deltaBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele (b/a + a/a) was 3.64 (95% confidence intervals: 1.60-8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

Alleles↗

Expression of YAV proteins and vaccination against viral ascites among cultured juvenile yellowtail.

Yellowtail ascites virus (YAV) is a member of the family Birnaviridae and causes viral ascites among juvenile yellowtail (Seriola quinqueradiata). We have reported the cloning and expression of two viral cDNAs, the first being segment A encoding a polyprotein of viral capsid proteins (VP2 and VP3) and a protease (NS), and the second being VP2-epitope encoding serotype-specific epitope region on VP2, using a baculovirus expression system. Another viral cDNA encoding a polyprotein of NS and VP3 was cloned and expressed in this study. For the expression of NS/VP3 (YAV nt 1626 to 3066) in insect cells a 31-kDa protein, corresponding to VP3 was detected, indicating an appropriate posttranslational processing of NS/VP3 polypeptide by NS protease itself. The analysis of the N-terminal amino acid sequence of this protein showed that NS protease may cleave an Ala-Ser bond. A study of the potential for vaccination of yellowtail fry by injection of insect cell lysates infected with baculovirus, containing either cDNA of segment A, VP2-epitope, or NS/VP3 was undertaken. Only a vaccination with cell lysates infected with a recombinant virus carrying the full length of YAV segment A gene demonstrated approximately the same effect as that of inactivated YAV. This result suggested that all proteins VP2, VP3, and NS are required for an effective vaccination.

Animals↗

Cloning and expression of the Momordica charantia trypsin inhibitor II gene in silkworm by using a baculovirus vector.

MCTI-II (Momordica charantia trypsin inhibitor II) isolated from bitter gourd (Momordica charantia LINN.) seeds is one of the serine protease inhibitors of the squash family. We cloned cDNA that encodes MCTI-II and constructed an expression system for MCTI-II by using a baculovirus vector. The recombinant baculovirus was inoculated to early fifth-instar larvae of the silkworm (strain: Shunrei x Shougetsu). Four days after infection, the hemolymph of silkworm larvae was collected and the recombinant protein was purified. Two kinds of expressed MCTI-II protein were obtained. An amino acid sequence analysis of the two proteins indicates that both were similar to the authentic inhibitor, except for the addition of a tripeptide derived from the vector at the N-terminus. One of the two inhibitors (MCTI-II A) resulted in a single PTH-amino acid in each Edman degradation cycle, while the other (MCTI-II B) resulted in two PTH-amino acids, suggesting the occurrence of cleavage of the reactive site. The inhibitory activities of MCTI-II expressed toward trypsin are examined in terms of the Ki value, these being 6.4 x 10(-10)M for MCTI-II A and 5.2 x 10(-10) M for MCTI-II B.

Amino Acid Sequence↗

Sodium butyrate induces apoptosis in human renal cell carcinoma cells and synergistically enhances their sensitivity to anti-Fas-mediated cytotoxicity.

Sodium butyrate (NaBt), one of the short chain fatty acids naturally formed in the gastrointestinal tract, induces differentiation as well as apoptosis in numerous cell types. The objectives of this study were to characterize the effects of NaBt on the growth, cell cycle, and apoptosis of human renal cell carcinoma (RCC) cells, and to determine whether NaBt enhances the Fas-mediated cytotoxicity in these cells. NaBt reduced the in vitro growth rate of human RCC ACHN cells in a time- and dose-dependent manner. Treatment of ACHN cells with 1 mM NaBt resulted in G1 cell cycle arrest, accompanied by up-regulation of p21 (waf1/cip1) and down-regulation of cyclin D1. In contrast, 5 mM NaBt-induced apoptotic cell death in ACHN cells, accompanied by up-regulation of BaK and down-regulation of Bcl-2. Furthermore, NaBt synergistically enhanced the growth-inhibitory effect of anti-Fas monoclonal antibody, CH11 on CH11-sensitive ACHN cells, and apoptotic cell death was induced by the combination of sublethal doses of NaBt and CH11, but not by either agent alone. Similar synergy was also observed in CH11-resistant human RCC KN39 cells. These findings suggest that NaBt could be a novel attractive approach for patients with RCC, and that the efficacy of NaBt may be enhanced by the combined use of Fas-mediated therapy.

Antibodies, Monoclonal↗

[Usefulness of the low protein rice on the diet therapy in patients with chronic renal failure].

Diet therapy for patients with chronic renal failure is based on low protein and high energy. To achieve strict diet therapy, it is necessary to use specially formulated low protein foods. Previously, rice with a low content of protein was not available, but recently, a low protein rice (LGC-1: low glutelin content-1) has been developed. LGC-1 was found to have a low content of glutelin in its seed protein compared to other ordinary rice. Glutelin is the major digestive protein in the rice grain. We studied the usefulness of LGC-1 in the diet therapy of patients with chronic renal failure. Twenty-three patients were placed on the low protein diet (0.6-0.9 g/kg/day) during the pre-study period (a mean of 10 months). Subsequently they were followed with the same diet using LGC-1 for the staple foods during the study period (mean of 7 months). Protein intake and the slope of the reciprocal of serum creatinine did not differ between each study period in all patients. Among the 23 patients, 9 consumed rice mainly as the staple food (120-180 g/day as polished rice: rice group), according to the results of a questionnaire. In the rice group, protein intake decreased (from 47 +/- 9 to 42 +/- 9 g/day, p < 0.05), and the slope of the reciprocal of serum creatinine reduced (from -4.59 +/- 4.33 to -1.47 +/- 3.51 x 10(-4) dl/mg/day, p < 0.05) during the study period, compared with the pre-study period. We conclude that LGC-1 is a useful and effective food for a low protein diet in patients with chronic renal failure, especially, for those who consume rice mainly as their staple food.

Aged↗

[Choriocarcinoma of the renal pelvis: a case report].

A 68-year-old male presented to our hospital complaining of gross hematuria. Intravenous pyelography subsequently demonstrated a left non-visualized kidney, and he was admitted for further evaluation. Cystoscopy revealed a bladder tumor around the left ureteral orifice and retrograde pyelography showed a filling defect in the left renal pelvis. The urinary cytology from the left renal pelvis indicated class IV, and the microscopic findings of a bladder biopsy demonstrated grade 1 transitional cell carcinoma. We performed transurethral resection of bladder tumor (TUR-BT) followed by left nephroureterectomy with bladder cuff. The pathological diagnosis was high grade transitional cell carcinoma with choriocarcinomatous component. After the operation, the serum human chorionic gonadotropin-beta (hCG-beta) level was slightly elevated, and the combination chemotherapy with methotrexate, vinblastine and cisplatin (MVC) was administered. Although the serum hCG-beta level fell to 0.1 ng/ml, after two courses of MVC chemotherapy, bilateral pulmonary metastases appeared in the chest X-ray with increasing hCG-beta levels. Salvage chemotherapy with cisplatin, etoposide and bleomycin (PEB) was performed. After two courses of PEB chemotherapy, the serum hCG-beta level fell to within the normal range and all pulmonary metastases disappeared.

Aged↗

[Accidental pyriform sinus perforation with Savary-Gilliard esophageal bougie during general anesthesia].

A 71-year-old female with esophagohiatal hernia underwent a laparoscopic Nissen's fundoplication under general anesthesia. During the operation a Savary-Gilliard bougie was temporarily inserted to the esophagus to prevent esophagostenosis. After the emergence from anesthesia, the patient complained of severe back pain and developed tachypnea and a low SpO2 associated with an enlargement of mediastinal shadow on the chest X-ray, suggesting mediastinal perforation. Examination by endoscopy and thoracotomy revealed a pyriform sinus perforation reaching down to the mediastinum. This case demonstrates the possibility of accidental perforation by various devices inserted blindly to esophagus, especially during general anesthesia, and the importance of close observation of patients after the emergence from anesthesia.

Aged↗

A case of mixed connective tissue disease (MCTD) complicated with MPO-ANCA-related necrotizing glomerulonephritis.

Renal diseases of mixed connective tissue disease (MCTD) are not unusual. Although most of them are SLE-like renal impairment with immune complex deposits, systemic sclerosis- (SSc) like renal impairments with intimal thickening of interlobular arteries or arterioles are also encountered. Several cases of SSc complicated with MPO-ANCA-related necrotizing glomerulonephritis (nGN) are reported. Here we report a case which developed MPO-ANCA-related nGN 16 years after the diagnosis of MCTD. She exhibited pauci-immune focal nGN and significantly high titer of MPO-ANCA. She was successfully treated with prednisolone and cyclophosphamide. We believe this is the first case in which MPO-ANCA-related nGN was demonstrated in a patient with MCTD.

Antibodies, Antineutrophil Cytoplasmic↗

Cardiac troponin I level correlates with chronic-phase left ventricular function after successful direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: The relationships between cardiac troponin I, various biochemical markers, and chronic-phase left ventricular ejection fraction (LVEF) after successful direct percutaneous transluminal coronary angioplasty (PTCA) were examined in 36 patients with acute myocardial infarction. METHODS: Biochemical markers were measured on admission, immediately after, and from 6 hours to 9 days after PTCA. RESULTS: The time to peak values were: creatine kinase-MB 9.7 hours, cardiac troponin I 9.8 hours, myoglobin 10.7 hours, creatine kinase 10.6 hours, cardiac troponin T 18.6 hours, and myosin light chain 68.9 hours. Cardiac troponin T, cardiac troponin I and myosin light chain levels were elevated over 9 days after successful direct PTCA. Chronic-phase LVEF inversely correlated with peak values of creatine kinase-MB (r = -0.519, p < 0.01), cardiac troponin T (r = -0.500, p < 0.01), cardiac troponin I (r = -0.441, p < 0.05) and creatine kinase (r = -0.411, p < 0.05). The values of cardiac troponin I, cardiac troponin T, creatine kinase and creatine kinase-MB at each sampling point were significantly inversely related to chronic-phase LVEF. The value of cardiac troponin I at each time point for 7 days correlated well with chronic-phase LVEF. CONCLUSIONS: Cardiac troponin I has high specificity for predicting long-term cardiac function after successful direct PTCA when early values are unavailable.

Adult↗

Effects of NKH477 on renal nerve stimulation-induced responses in anesthetized dogs.

We evaluated the effects of an adenylate cyclase activator, N, N-dimetyl-beta-alanine[3R-(3alpha,4alphabeta,5beta+ ++,6beta,6aalpha, 10alpha,10abeta,10balpha)]-5(acetyloxy)-3-eth enyldodecahydro-10, 10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho[2, 1-b]pyran-6-yl ester hydrochloride (NKH477), on neural control of renal functions in anesthetized dogs. Renal nerve stimulation (2 Hz) increased renal norepinephrine efflux and reduced renal blood flow, glomerular filtration rate, urine flow rate, urinary Na(+) excretion and fractional Na(+) excretion. Intrarenal arterial infusion of NKH477 (300 ng/kg/min) suppressed the stimulation-induced reductions in renal blood flow and glomerular filtration rate and attenuated the reductions in urine flow rate and urinary Na(+) excretion but not the changes in renal norepinephrine efflux and fractional Na(+) excretion. Infusion of NKH477 did not affect the urinary responses induced by renal nerve stimulation at a lower frequency (0.5-1 Hz) which had little influence on renal blood flow and glomerular filtration rate. The present results demonstrate that NKH477 inhibits renal vasoconstriction and hypofiltration but not the enhanced tubular Na(+) reabsorption during activation of the renal sympathetic nervous system.

Adenylyl Cyclases↗

Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement delivers an inhibitory signal through the membrane-proximal region in the absence of the tyrosine motif in the cytoplasmic tail.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif ((165)YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain-containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4-mediated suppression of T cell activation.

Abatacept↗

Regulatory role of metallothionein in NF-kappaB activation.

Metallothionein (MT), a low molecular weight, cysteine-rich metal binding protein, has been associated with cytoprotection from heavy metals and cellular oxidants. As MT has the ability to scavenge hydroxyl radicals, MT may control intracellular redox status. In the present study, we examined whether MT regulates the activity of nuclear factor-kappaB (NF-kappaB), which is one of the redox-regulated transcription factors, using the MT null embryonic cell lines established from MT null mice. We first found that tumor necrosis factor (TNF)-induced activation of the binding of NF-kappaB protein to DNA in wild type MT+/+ cells was lower than that in MT-/- cells. The NF-kappaB activation in MT-expressing cells established from MT-/- cells by the transfection of mouse MT-1 gene was also significantly lower than that in MT-/- cells. In addition, transfection of the MT gene inhibited TNF-induced IkappaB degradation and suppressed NF-kappaB-dependent gene expression induced by TNF. These results demonstrate that MT may function as a negative regulator of NF-kappaB activity.

Animals↗

Effects of NKH477 on renal functions and cyclic AMP production in anesthetized dogs.

The present study was undertaken to evaluate the effects of an adenylate cyclase activator N,N-dimethyl-beta-alanine[3R-(3alpha, 4alphabeta, 5beta, 6beta, 6aalpha, 10alpha, 10abeta, 10balpha)]-5(acetyloxy)-3-ethenyldodecahydro-10, 10b-dihydroxy-3, 4a, 7, 7, 10a-pentamethyl-1-oxo-1H-naphtho [2,1-b] pyran-6-yl ester hydrochloride (NKH477) on renal functions and cyclic AMP production in the dog kidney. The intrarenal arterial infusion of NKH477 (30, 100 and 300 ng kg(-1) min(-1)) increased renal blood flow, glomerular filtration rate, urine flow rate, urinary Na+ and cyclic AMP excretion, fractional Na+ excretion and arterial and renal venous plasma cyclic AMP concentrations in a dose-dependent manner. The intrarenal arterial infusion of rolipram (0.3 microg kg(-1) min(-1)), a cyclic AMP-specific phosphodiesterase inhibitor, also caused the same renal responses as NKH477. The increasing effects of NKH477 on renal blood flow, fractional Na+ excretion and renal venous plasma cyclic AMP concentration were facilitated in the presence of rolipram. NKH477 reduced glomerular filtration rate and filtration fraction in the presence of rolipram. The increasing effects of NKH477 on urine flow rate and urinary Na+ excretion were not affected by rolipram. The present results suggest that NKH477 increases glomerular filtration and suppresses tubular sodium reabsorption through activation of cyclic AMP production, and thereby induces natriuresis. The results also demonstrate that renal cyclic AMP level during the activation of adenylate cyclase is regulated by phosphodiesterase IV in both the vascular and tubular sites.

Anesthesia↗