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Biomedical subjects

M Nishina

Publications and source records attributed to M Nishina.

At least 19 recordsLinked to original sources

Endogenous GABA in the commissural subnucleus of the NTS inhibits the carotid chemoreceptor reflex via GABA A receptors in rats.

Using urethane-chloralose anesthetized rats, we investigated which GABA receptor is responsible for the action of endogenous GABA on the carotid chemoreceptor reflex in the commissural subnucleus of the nucleus tractus solitarius (commNTS). Microinjection of the selective GABA uptake inhibitor nipecotic acid (40 nmol) into the commNTS attenuated the increases in respiration (respiratory movement and rate) and the elevation in arterial blood pressure elicited by carotid chemoreceptor stimulation. These effects were completely antagonized by premicroinjection of the GABA(A) antagonist bicuculline (20 pmol), but not of the GABA(B) antagonist 2-OH-saclofen (400 pmol), into the same site. These findings suggest that endogenous GABA mainly acts on GABA(A) receptors, and inhibits the chemoreceptor reflex in the commNTS in rats.

Animals↗

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

Adult↗

Preoperative diagnosis of obturator hernia by computed tomography in six patients.

Obturator hernia is a rare condition, and the prognosis of patients with this condition is poor. A retrospective study was performed on six patients with obturator hernia between 1993 and 1998. They had been diagnosed preoperatively by computed tomography (CT). The initial CT scan of the abdomen, including the pelvic area, revealed an incarcerated bowel in the obturator foramen of all six patients. All patients underwent laparotomy on the day of admission. Resection of the small bowel was performed in three patients, and release of the small bowel was performed in the remaining three patients. There were no perioperative deaths. In elderly women who have evidence by abdominal plain X-ray studies of small bowel obstruction, we recommend performing CT scan of the abdomen, including CT scan of the pelvic area, for detection of obturator hernia.

Adolescent↗

Analysis of prognostic predictors in idiopathic membranous nephropathy.

We studied clinical and histologic parameters at the time of renal biopsy of 19 patients with idiopathic membranous nephropathy (IMN) to investigate the predictors for prognosis of IMN. Nineteen patients diagnosed by open renal biopsy between 1988 and 1993 and followed for at least 5 years were divided into two groups according to the latest follow-up renal function. Group I included 16 patients with normal renal function at the last follow-up point. Group II included three patients with end-stage renal failure at the last follow-up point. Antibodies to CD68, CD45RO, alpha-SMA, collagen IV, and collagen VI were used to investigate glomerular and interstitial changes in biopsy specimens by the indirect enzyme-labeled antibody method. Degree of global glomerulosclerosis, segmental glomerulosclerosis, adhesion to Bowman's capsule, and crescent formation were evaluated by light microscopy (periodic acid-Schiff, periodic acid-metheramine [PAM] staining). The difference between the two groups was analyzed by Mann-Whitney U: test. The number of interstitial cells, the number of interstitial CD45RO-positive cells, and increases of interstitial collagen IV and VI were found to be the most important factors for prognosis of IMN. These findings suggest that the extent of tubulointerstitial changes (cellular infiltration and fibrosis) determines the prognosis of renal function in IMN.

Adolescent↗

Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers.

Fos family proteins form stable heterodimers with Jun family proteins, and each heterodimer shows distinctive transactivating potential for regulating cellular growth, differentiation, and development via AP-1 binding sites. However, the molecular mechanism underlying dimer specificity and the molecules that facilitate transactivation remain undefined. Here, we show that BAF60a, a subunit of the SWI.SNF chromatin remodeling complex, is a determinant of the transactivation potential of Fos/Jun dimers. BAF60a binds to a specific subset of Fos/Jun heterodimers using two different interfaces for c-Fos and c-Jun, respectively. Only when the functional SWI.SNF complex is present, can c-Fos/c-Jun (high affinity to BAF60a) but not Fra-2/JunD (no affinity to BAF60a) induce the endogenous AP-1-regulated genes such as collagenase and c-met. These results indicate that a specific subset of Fos/Jun dimers recruits SWI.SNF complex via BAF60a to initiate transcription.

Dimerization↗

Physical aging by soft ultrasonic wave enhances ethanol metabolism: metabolic process of wine as followed by 400 mhz 1H-NMR spectroscopy.

In natural aging of spirits or wine, the dynamic structure of ethanol-water clusters changes to a smaller and more uniform state. Through experience we know that naturally aged ones have higher metabolism than the non-aged ones. Also, the same effect as natural aging can be obtained in various types of spirits or wines by the treatment for a period of time with soft ultrasonic wave (US). In this study, we compared ethanol metabolism in human subjects dosed with non-treated white wine (control = CON) and with US treated wine. Ethanol levels in human sera were followed by 400 MHz 1H-NMR spectroscopy after administration of wine doses. Experimental results indicated that ethanol metabolism was enhanced 18% in subjects when US treated wine was used rather than when non-treated (CON) was used. Other experiments using rabbits showed that a 20% ethanol-aqueous solution was absorbed 18% more rapidly by the group dosed with US wine than by the CON group. From these experimental facts, it was theorized that ethanol metabolism depends on the rapidity of ethanol absorption in the human body. And it can be concluded that US treatment brings about the same effect on spirits or wines as natural aging.

Animals↗

Enhancer and silencer binding proteins involved in the rat cdc2 promoter activation at the G1/S boundary.

BACKGROUND: Expression of the rat cdc2 gene during G1-S phase progression is negatively and positively regulated by the silencer and enhancer elements located upstream of the basal promoter. The silencer and enhancer sequences resemble each other, but the silencer contains extra internal AG residues. RESULTS: The cDNA clones encoding the enhancer binding proteins cdc2E1 and cdc2E2 were isolated by South-Western blotting. cdc2E1 and cdc2E2 comprise 436 and 256 amino acids and have two RNA binding domains which contain an RNP1 octamer and an RNP 2 hexamer. Both cdc2E1 and cdc2E2 bind to the double-stranded and single-stranded silencer and enhancer sequences, but their binding affinity to the enhancer was stronger than that to the silencer. Transfection of quiescent 3Y1 cells with the cdc2 promoter-luciferase constructs, followed by serum stimulation, showed that the promoter activation at the G1-S phase boundary was reduced greatly by base substitutions within the enhancer, but not within the silencer. Gel shift assays with oligonucleotides containing both the silencer and enhancer showed that formation of the large complex was greatly reduced if base-substitutions were introduced into the enhancer, but not within the silencer. The complex was supershifted completely by anti-cdc2E1 antibody and partially by anti-cdc2E2 antibody. CONCLUSION: These results suggest that cdc2E1 and cdc2E2 preferentially form the multimeric complex at the enhancer site after the late G1 phase for activation of the cdc2 promoter.

Amino Acid Sequence↗

In vitro high resolution proton magnetic resonance study of human cerebellar development during the period from the fetus to childhood.

In the development of the human cerebellum, the intracellular metabolites were monitored during the period from the fetus to childhood by in vitro high resolution proton (1H) magnetic resonance (MR) spectroscopy. The spectra from fetus (15-30 post-menstrual weeks; n = 3), infant (1-24 months of age; n = 6) and child (7-14 years of age; n = 5) groups showed resonances from seventeen different metabolites. The level of N-acetylaspartate (NAA), one of the metabolites, was observed in age-dependent increases, two- and three-fold increases for infant and child groups from the NAA of the fetus group, respectively. The rapid increases in the creatine (Cre) level (approximately three-fold) in the fetus and infant groups were observed in the child group (approximately four-fold). Taurine (Tau) was noted at the highest concentration in the fetus group. Slight increases in concentrations of alanine, glutamate, glutamine, and glycine and a significant increase in the concentration of N-acetylaspartylglutamate were also noted in the fetus and infant groups. Other metabolite concentrations did not change significantly throughout the studied age groups. These findings indicate that synthesis of metabolites, especially of NAA and Cre, during the development of the cerebellum are closely correlated with mitochondrial energy metabolism, and as such, may reflect mitochondrial integrity in the cerebellum.

Aging↗

Effects of hypertonic saline and dextran 70 on cardiac contractility after hemorrhagic shock.

OBJECTIVE: The effects of a bolus of 7.5% NaCl-6% dextran 70 (HSD) on cardiac contractility were evaluated in anesthetized sheep with hemorrhagic shock. BACKGROUND: HSD has been shown to be effective at resuscitation in cases of hypovolemia caused by hemorrhage. Common hemodynamic findings after the injection of HSD in hemorrhagic shock are the restoration of cardiac output, increased blood pressure, and improvement of peripheral circulation. Some mechanisms by which HSD maintains circulation in hemorrhagic shock have been proposed: rapid shift of fluid from intracellular to extracellular space, improved peripheral perfusion, and increased cardiac contractility. Conflicting data exist, however, regarding the positive effect of HSD on cardiac contractility after hemorrhagic shock. METHODS: Hemorrhagic shock was induced by shedding mean blood volume of 31.4 mL/kg, and mean blood pressure was maintained at 50 mm Hg for 30 minutes. The HSD group (n = 6) received HSD (4 mL/kg), and the saline group (n = 6) received normal saline (40 mL/kg) after shock. Cardiac functions were measured in both groups using the left ventricular end-systolic pressure-volume relationship and preload recruitable stroke work during the experimental period: before shock, immediately after the resuscitation, and 2 hours after resuscitation. RESULTS: Hemodynamic parameters in both groups demonstrated similar changes throughout the experimental period without significant difference between the two groups. Not only the slopes of end-systolic pressure-volume relationship and preload recruitable stroke work but also their placements did not result in any significant differences between the groups. CONCLUSION: HSD seems to be an effective resuscitation fluid after hemorrhagic shock because the volume required to maintain circulation is smaller than that of normal saline. Our data, however, show that HSD does not enhance cardiac contractility after hemorrhagic shock.

Animals↗

Relationships of disability, health management and psychosocial conditions to cause-specific mortality among a community-residing elderly people.

To examine the factors associated with cause-specific mortality, a cohort of 1,405 randomly selected elderly people aged 65 years and over living in Settsu, Osaka Prefecture, was followed up for 54 months. Multivariate analysis using Cox proportional hazards model identified male sex, age, disability, medical treatment, and no participation in social activities as independent factors for overall mortality. Use of health checks and daily health enhancing practices showed an independent negative association with overall mortality. As for cause-specific mortality, male sex was a constant factor for the three major causes of death: cancer, heart disease and stroke. Advanced age and no participation in social activities showed a close association with heart disease mortality, while disability and medical treatment were independent factors for death caused by stroke and cancer, respectively. Use of health checks and daily health enhancing practices exhibited a strong negative association with all three major causes of death. The same tendencies were seen after those who reported undergoing medical treatment for the index diseases of heart disease and stroke at entry were excluded. These results suggest that predictive factors for mortality vary for specific causes of death, but that health promoting measures contribute to a reduction in mortality related to three major causes of death, thus resulting in a decrease in overall mortality among the elderly.

Activities of Daily Living↗

Increased cerebral choline-compounds in Duchenne muscular dystrophy.

We investigated the hypothesis that cell membrane function is abnormal in brains of subjects with Duchenne muscular dystrophy (DMD) using proton-nuclear magnetic resonance (NMR) spectroscopy of human brain extracts. The total amount of choline-containing compounds was significantly higher (about three times) than in normal controls and patients with other myopathies, while N-acetyl-L-aspartic acid and creatine were within the normal range. These findings indicate that abnormal cell membrane function may be correlated with the abnormal dystrophin or lack of dystrophin in the brain of patients with DMD.

Adolescent↗

Decrease in cerebral free magnesium concentration following closed head injury and effects of VA-045 in rats.

1. We examined the alterations in cerebral free Mg2+ concentration in closed head injury (CHI) in rats and the effects of VA-045, a novel apovincaminic acid derivative, on them with in vivo 31P-NMR. 2. Free Mg2+ decreased by about 30% within 20 min after head impact and, afterward, it gradually decreased further to reach about 60% of the control level after 3 hr. VA-045 inhibited the decrease. 3. In nonimpacted rats, VA-045 did not alter the free Mg2+ level. 4. The decrease in cerebral free Mg2+ following CHI may be a critical factor in the development of irreversible tissue injury, and VA-045 may prevent it.

Animals↗

Neuronal maturation and N-acetyl-L-aspartic acid development in human fetal and child brains.

The developmental changes in N-acetyl-L-aspartic acid (NAA) were assessed in human fetal and child brains by means of high resolution proton magnetic resonance spectroscopy (MRS). NAA was detected in the cerebral cortex and white matter of fetuses of 16 weeks' gestation. NAA increased gradually from 24 weeks' gestation and remarkably from 40 weeks' gestation to 1 year of age. The developmental changes in tissue NAA in postnatal brains were found to be similar to those of NAA/Cr on clinical proton MRS. As the neuronal cell density in the cerebral cortex decreases with dendritic maturation, an increase in NAA with age may reflect the normal and abnormal development of axons, dendrites and synapses as well as neuronal soma.

Adolescent↗

Measurement of lactate levels in serum and bile using proton nuclear magnetic resonance in patients with hepatobiliary diseases: its utility in detection of malignancies.

Proton nuclear magnetic resonance (1H-NMR) has been utilized for qualitative and quantitative measurement of the components of nonhomogeneous biological specimens, as it can analyze sensitively the chemical structure of organic compounds without pretreatment of the materials. Levels of lactate in serum and bile were measured by 1H-NMR in healthy volunteers and patients with non-malignant or malignant diseases of the liver and biliary tract, and the usefulness of such measurements for the diagnosis of hepatobiliary malignancies was determined. The mean (+/- SD) serum lactate levels were 0.52 +/- 0.33 mmol/l in five healthy volunteers, 1.38 +/- 1.59 mmol/l in 30 patients with non-malignant diseases and 2.95 +/- 2.00 mmol/l in 21 patients with malignant diseases, the differences among the three groups being significant. Biochemical enzymatic measurement of serum lactate levels revealed no such difference. In bile, the spectrum of lactate was observed in all of 16 patients with malignant diseases, but in none of two healthy volunteers and 12 patients with non-malignant diseases. The mean time required for the measurement was 36.77 min for serum and 6.40 min for bile. The measurement of lactate levels in serum and bile using 1H-NMR may be useful for the detection of hepatobiliary malignancies.

Adult↗

Proton nuclear magnetic resonance detects leucine, 2,3-butanediol, and a prominent increase in the level of choline in the sera from patients chronically infected with schistosomiasis japonica.

1H-NMR spectroscopy with 'Hahn' spin-echo pulse sequence has been employed to investigate the metabolic profiles of sera of chronic patients with schistosomiasis japonica, and compared with those of healthy volunteers and former patients who had been treated successfully. 1H-NMR clearly detected 2,3-butanediol and leucine, and markedly elevated levels of choline in sera from the chronic patients. Profiles of the sera from former patients were essentially similar to those from healthy volunteers, except that ketone bodies (3-hydroxybutyrate and acetone) were detectable in sera from 58% of the former patients but not in those of the normal controls patients.

Adolescent↗