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Biomedical subjects

M Nishina

Publications and source records attributed to M Nishina.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

[Effectiveness of LH-RH agonist for bone metastases of breast cancer--report of a case].

A 44-year-old premenopausal woman with bone metastases of breast cancer was initially treated with systemic chemotherapy (CEF) and radiation therapy after standard mastectomy. However, progressive change of bone metastases with elevation of tumor markers (CEA, NCC-ST 439) was detected, so continuous administration of LH-RH agonist and combination chemotherapy (CEF) were conducted. Subsequently, complete objective regression was attained after 40 weeks.

Adult↗
PubMed1996

The effect of mefloquine and quinine on the relaxation times of water protons in human erythrocytes, as revealed by NMR.

Effects of mefloquine and quinine on human erythrocyte membranes were investigated by 1H-NMR spectroscopy. The observed spin-spin relaxation time (T2) of intracellular water protons was found to reflect water permeability of the membrane. The effects of these drug treatments on the erythrocytes were determined by the ratio of the T2 of control and experimental samples. Comparing the results of quinine and mefloquine treatments, quinine decreased the T2 ratio to 0.79 at 5 mM and mefloquine increased the ratio to 1.14 at 0.5 mM. These results demonstrated that quinine increases water permeability through the membranes whereas mefloquine decreases it.

Adult↗
PubMed1996

[Cardiac contractile dysfunction in response to surgical stress including trauma, hemorrhage, and infection].

Shock and multiple organ failure are complications of primary conditions such as trauma, hemorrhage and infection. Ample evidence of cardiac contractile dysfunction has been obtained in both septic patients and experimental animal models of endotoxin shock. Recent advance in molecular biology and immunology has improved our understanding of the pathogenesis of septic shock, and thus, it is now believed that the host's inflammatory response to infection contributes to the development of septic shock. In addition, effects of toxic host mediators including cytokines, kinins, eicosanoids, platelet-activating factor, and nitric oxide, which are produced by activated cells, on cardiovascular system have been examined. The possible involvement of the nitric oxide pathway, not only as a marker for cytokine-induced effects on myocyte gene expression, but also as a mediator for cytokine-induced contractile dysfunction, was explored. According to this hypothesis, trauma and hemorrhage, both of which lead to host's inflammatory response, is also considered to induce contractile dysfunction. In this paper we reviewed the influences of various shock states on cardiac contractility. Hemorrhagic and burn shocks possibly depress cardiac contractility as well as septic and endotoxin shocks. Therefore, it is necessary to improve contractile depression in the diseased states to meet oxygen demand of each patient under monitoring patient's circulatory and metabolic conditions.

Animals↗
PubMed1996

[Dapsone (4,4'-diaminodiphenyl sulfone) resolved severe leukocytopenia and thrombocytopenia in a patient with systemic lupus erythematosus].

A 47 year old woman was presented in June, 1994 with a ten years history of systemic lupus erythematosus. Since six months before first visit to our hospital, she had experienced general malaise, myalgia and persistent low grade fever. Among this period, titers of anti DNA antibody in her blood were gradually increased. She had been treated with the prednisolone which was step-wisely increased up to 15 mg/day, but her symptoms had been worsened. On admission, physical examination showed low grade fever and erythema on her both hands. Investigations showed her white blood cell count 1400/microliter, platelet 90000/microliter, positive test result for ANA, anti DNA antibody and anti Sm antibody, low serum concentrations of complements, and persistent proteinuria. She was treated with 60 mg/day of oral prednisolone. Though her symptoms and immunological abnormalities were gradually improved, her platelet count and white blood cell count were gradually decreased to 50000/microliter and 1400/microliter in August, respectively. Platelet associated IgG was increased (102.9 ng/10(7) cells). In spite of the various trials of treatment, such as plasmapheresis, high-dose intravenous gammaglobulin, and cyclophosphamide, the white blood cell and platelet number could not be raised. Finally, the administration of 75 mg/day of dapsone brought a significant rise in both blood cell counts. Thus being certainly effective against leukocytopenia and thrombocytopenia, dapsone should be considered an one of the beneficial therapeutic procedures for refractory autoimmune leukocytopenia and thrombocytopenia in SLE patients.

Anti-Infective Agents↗
PubMed1996

[A study on angiotensin-I converting enzyme polymorphism in CAPD patients].

To clarify the role of genes related to angiotensin-I converting enzyme (ACE), the author investigated polymorphism of the ACE gene in 60 patients undergoing chronic ambulatory peritoneal dialysis (CAPD) and 50 patients undergoing hemodialysis (HD). One hundred healthy subjects were used as controls. The polymorphism was classified into three genotypes, II, ID and DD, according to insertion (I) and deletion (D) using the polymerase chain reaction method. In dialysis patients (CAPD or HD, n = 110), 21.8% had the II genotype, 48.2% the ID genotype, and 30.0% the DD genotype. There was a significant difference in allele frequency between normal subjects (n = 100) (J = 0.63, D = 0.37) and dialysis patients (I = 0.46, D = 0.54) (chi 2 = 12.321, p < 0.001). The mean plasma ACE activity was 9.9 +/- 1.6 IU/l in CAPD patients with the II genotype, 11.6 +/- 4.7 IU/l in CAPD patients with the ID genotype, and 14.5 +/- 3.5 IU/l in CAPD patients with the DD genotype. The mean rate of decrease in residual urinary volume was 0.8 +/- 0.7% per month in CAPD patients with the II genotype 1.4 +/- 1.3% per month in CAPD patients with the ID genotype, and 2.5 +/- 2.0% per month in CAPD patients with the DD genotype. These data showed a significant decrease in urinary volume in CAPD patients with the DD genotype (p < 0.05). The mean rate of decrease in residual urinary volume was positively correlated with the plasma ACE activity (r = 0.13389, p < 0.02). In CAPD patients, the mean cardiothoracic ratio was 46.6 +/- 3.5% in cases with the II genotype, 47.6 +/- 5.5% in cases with the ID genotype, and 52.9 +/- 8.4% in cases with the DD genotype. These data indicated significant cardiac enlargement in DD genotype cases. It can be concluded that CAPD patients with the DD genotype lost their residual renal function more rapidly and had a larger heart, than patients with the other genotypes.

Adult↗
PubMed1995

Effects of hypertonic saline and dextran 70 on cardiac functions after burns.

The effects of hypertonic saline-dextran (HSD) on cardiac contractility and hemodynamics after burns were studied in anesthetized animals with full-thickness 50% total body surface area burns that were resuscitated with HSD or lactated Ringer solution (LR) alone. No significant difference in cardiac contractility during 6 h postburn was observed between the two groups, as assessed by the end-systolic pressure-volume relationship and the stroke work-end-diastolic volume relationship. An additional bolus of HSD at 6 h postburn caused no significant changes in the end-systolic pressure-volume relationship and stroke work-end-diastolic volume relationship in the burned and sham-burned animals, both of which were resuscitated with HSD. Ten minutes of hemodynamic changes following HSD infusion at 30 min postburn revealed a sudden increase in stroke volume with biphasic responses in left ventricular systolic pressure, which first decreased, then increased, and finally returned to the pre-HSD value. End-diastolic volume was maintained at approximately 110% of the pre-HSD value during this period. We concluded that HSD does not enhance cardiac contractility after severe burns but does produce direct effects on postburn circulation to reduce afterload and augment preload, resulting in a short-lived increase in cardiac output.

Animals↗
PubMed1994

Nuclear magnetic resonance (NMR) analysis on the serum lipids of rabbits infected with Schistosoma japonicum: oxidative modifications of diene system in fatty chains.

Proton nuclear magnetic resonance (1H NMR) spectroscopy was used to characterize the oxidized products in the serum lipoprotein lipids (LPL) of rabbits infected with Schistosoma japonicum. The loss of bis-allylic and allylic methylenes proton peaks (2.7 and 2.0 p.p.m.) of unsaturated systems of the LPL and the appearance of the signals of the conjugated diene systems of hydroperoxide (5.43-6.45 p.p.m.) and epidioxide (2.45 p.p.m.) of the fatty chains of the serum demonstrated the lipids degradation associated with the Schistosoma infection.

Animals↗