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Biomedical subjects

N Hirose

Publications and source records attributed to N Hirose.

At least 37 records · Page 2Linked to original sources
PubMed1999

A role for the polymorphism at position 247 of the beta2-glycoprotein I gene in the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome.

OBJECTIVE: To determine the frequencies at which either a valine or leucine occurs at position 247 in the beta2-glycoprotein I (beta2GPI) gene of normal individuals of the Caucasian, African American, and Asian ethnic groups and to compare these data with those in patients with the antiphospholipid syndrome (APS), with and without anti-beta2GPI antibodies. METHODS: The DNA segment containing the position-247 polymorphism was amplified by seminested polymerase chain reaction, and the polymorphism was detected by restriction endonuclease digestion. DNA samples from 370 healthy controls of different racial backgrounds were analyzed, and the results were compared with those from 149 APS patients (66 primary; 83 secondary). Allele and genotype frequencies were compared using Fisher's exact test. When significant differences were detected, pairwise comparisons were made using Fisher's exact test with a Bonferroni adjustment. RESULTS: Allele and genotype expression was significantly different (P < 0.0001 for both) among the 3 races, with the V allele and the VV genotype occurring most often among Caucasians, less among African Americans, and least among Asians. Conversely, the V allele and the VV genotype were found more frequently among Asian APS patients than among controls (P = 0.0028 and P = 0.0023, respectively). No significant differences in allele or genotype frequencies were seen in comparisons of the Caucasian or the African American patients with appropriate controls. The differences in allele and genotype frequencies seen in the Asian APS patients were restricted to the anti-beta2GPI-positive patients (P = 0.0018 and P = 0.0005, respectively). CONCLUSION: In Asian patients with APS, expression of a V at position 247, especially in the homozygous state, is significantly associated with the presence of anti-beta2GPI antibodies and, therefore, can be viewed as a major risk factor in this ethnic group (odds ratio 9.19 and 16.33, respectively).

Alleles↗
PubMed1999

Effects of chronic haloperidol and clozapine on vacuous chewing and dopamine-mediated jaw movements in rats: evaluation of a revised animal model of tardive dyskinesia.

Rats received haloperidol (1.0 mg/kg i.p.) or clozapine (10 mg/kg i.p.), twice daily for 4 weeks: vacuous chewing--recorded 26 h after the final injection--similarly increased in both groups. Three h later, the rats were challenged with dopaminomimetics, and automatically recorded jaw movements were analysed. Both apomorphine and a mixture of D1 and D2 receptor agonists (SKF 38393 resp. quinpirole) increased jaw movements in haloperidol-treated, but not clozapine-treated rats; SKF 38393 or quinpirole remained ineffective, when given alone. A fixed dose of quinpirole together with increasing doses of SKF 38393, but not a fixed dose of SKF 38393 together with increasing doses of quinpirole, produced a dose-dependent increase in jaw movements in otherwise non-treated rats, suggesting that the noted haloperidol-induced increase was due to a shift in the D1-D2 receptor balance towards a predominance of D1 receptors. This study presents a new animal model of tardive dyskinesia with predictive validity, good reliability and, especially, great efficiency.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits.

The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.

Analysis of Variance↗
PubMed1999

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors.

The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of D-Phe-Cys-Tyr-D-Trp-Om-Thr-Phe-Thr-NH2 (nmol), a mu-opioid receptor antagonist, and naltrindole (nmol), a non-selective delta-opioid receptor antagonist, in a dose-dependent manner. The delta2-opioid receptor antagonist, naltriben (nmol), also blocked the effects of fentanyl, whereas the delta1-opioid receptor antagonist, (E)-7-benzylidenenaltrexone (nmol), was ineffective. When marginally effective doses of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 and naltriben were given simultaneously, the effect of fentanyl was nearly fully blocked; the pretreatment itself had no effect. Administration of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (nmol), the delta1-opioid receptor agonist [D-Pen2,5]-enkephalin (nmol) or the delta2-opioid receptor agonist [D-Ala2,Glu4]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of delta1- and delta2-opioid receptors, but also activation of mu-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats. We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of mu-opioid receptors and delta2-opioid receptors or due to activation of mu-opioid receptors that interact with delta2-opioid receptors in a complex manner.

Analgesics, Opioid↗
PubMed1999

Isolation and genetic determination of a Saccharomyces cerevisiae mutant that produces an endo-polygalacturonase.

A Saccharomyces cerevisiae mutant that produces an endo-polygalacturonase (PGase) was isolated. The PGase gene was revealed to be located on chromosome X in both the mutant and its parental strain. The 5'-upstream region of the PGase gene in the mutant was entirely identical with that of its parent. Crossing of the mutant with a PGase-negative strain showed that the phenotype of PGase production was recessive. These results suggest that the mutant is rendered defective in a transacting factor that normally represses the expression of the PGase gene.

Journal Article↗
PubMed1999

A patient with genetic deletion of glutathione-S-transferase T1 and M1 who developed non-small-cell lung cancer and myelodysplastic syndromes.

Glutathione S-transferase (GST) M1 polymorphism is a marker for susceptibility to smoking-related neoplasms, such as lung and bladder cancer. Recently, a genetic deletion of GSTT1, an isoenzyme of GST, has been reported to be associated with myelodysplastic syndromes (MDS). A 59-year-old man with a long-term smoking habit was treated successfully for non-small-cell lung cancer. Four years after the surgical removal of his lung cancer, he developed MDS and died. Using a polymerase chain reaction-based genotyping method, he was found to have a deletion of both the GSTM1 and GSTT1 genes. Screening for the deletion of the GSTM1 and GSTT1 genes may be useful for assessing individual genetic susceptibility to smoking-related lung cancer and MDS.

Asian People↗
PubMed1999

Okadaic Acid Mimics Nitrogen-Stimulated Transcription of the NADH-Glutamate Synthase Gene in Rice Cell Cultures.

Okadaic acid (OKA), a potent and specific inhibitor of protein serine/threonine phosphatases 1 and 2A, induced the accumulation of NADH-glutamate synthase (GOGAT) mRNA within 4 h in rice (Oryza sativa L.) cell cultures. In contrast to the transient accumulation of NADH-GOGAT mRNA by NH(4)(+), OKA caused a continuous accumulation for at least 24 h. The induction of NADH-GOGAT mRNA by OKA was not inhibited in the presence of methionine sulfoximine, which inhibited the NH(4)(+)-induced accumulation of mRNA. These results suggest that the OKA-sensitive protein phosphatase is involved in the regulation of NADH-GOGAT gene expression and probably plays a role in the signal transduction pathway downstream from NH(4)(+), although a signal transduction pathway other than that of nitrogen sensing could be responsible. Nuclear run-on assays demonstrated that the accumulation of NADH-GOGAT mRNA induced by the supply of either NH(4)(+) or OKA was mainly regulated at the transcription level. OKA effects were synergistic to the NH(4)(+)-induced expression of the NADH-GOGAT gene. In the presence of K-252a, a protein kinase inhibitor, the accumulation of NADH-GOGAT mRNA induced by either NH(4)(+) or OKA was reduced. The possible roles of protein phosphatases in the regulation of NADH-GOGAT gene expression are discussed.

Journal Article↗
PubMed1999

Circadian heart rate rhythms in Japanese centenarians.

OBJECTIVE: To investigate age-associated changes in the circadian rhythm of the heart rate. DESIGN: The circadian rhythm was extracted from diurnal heart rate (HR) variations, and patterns of HR rhythm were compared in centenarians and controls. SETTING: Centenarians living in the metropolitan area of Tokyo and in Aichi prefecture in 1992. PARTICIPANTS: Fifty centenarians underwent 24-hour ambulatory electrocardiogram (Holter) monitoring. The control group, comprised of 100 clinically healthy subjects who underwent similar Holter monitoring, was subdivided, by age, into two groups: the younger controls (age range 23 to 54 years, mean age 41) and the older controls (age range 55 to 82 years, mean age 69). MEASUREMENTS: Harmonic analysis was used to approximate the 24-hour RR interval (the interval between two neighboring R waves on the electrocardiogram) data obtained by Holter monitoring to a summation of three cosine waves with 24-hour, 12-hour, and 8-hour periods. The power of the period was adjusted for the goodness of curve-fit. The power of each period and the circadian acrophase (the timing of the peak in a 24-hour rhythm) were compared among the centenarians, older controls, and younger controls. HR rhythms were classified by k-means cluster analysis based on the power of the period. The prevalence of each pattern was compared among the three age groups. In the centenarians, the relationship between clinical parameters (activities of daily living, cognitive function, nutritional status, and present illness) and patterns of HR rhythm was investigated. RESULTS: The power of the 24-hour period in the centenarians was significantly smaller than that in the older (P < .05) and younger (P < .001) controls. The power of the 8-hour period in the centenarians was significantly larger than that in the younger controls (P < .05). Advances or delays in the circadian acrophase were frequently observed in the centenarians compared with the younger controls. The power of each period did not differ between centenarians with (n = 11) and without (n = 39) overt diseases capable of altering HR rhythms. Five patterns of HR rhythm were identified: 24-hour period dominant (n = 84), 24-hour+12-hour period (n = 18), 12-hour period dominant (n = 11), 8-hour period dominant (n = 7), and low goodness of curve-fit (n = 30). The 8-hour period dominant pattern and the low goodness of curve-fit pattern were observed commonly in the centenarians, whereas the 24-hour period dominant pattern and the 24-hour+12-hour period pattern were observed frequently in the younger controls. Patterns of HR rhythm were not related to clinical parameters in the centenarians. CONCLUSIONS: The circadian rhythm of HR changed with aging: there was reduction in the power of the 24-hour period, augmentation in the power of the 8-hour period, and a shift in the circadian acrophase.

Activities of Daily Living↗
PubMed1999

Granular-lattice (Avellino) corneal dystrophy.

Granular-lattice (Avellino) corneal dystrophy has rarely been reported in the literature. It consists of a combination of granular and lattice dystrophy. We describe the histopathologic examination of the corneal button of one Japanese patient who had undergone unilateral keratoplasty because of severely decreased vision caused by what had been diagnosed clinically as granular dystrophy. However, on pathologic examination, lesions characteristic of both granular dystrophy and lattice dystrophy were found. We also describe 2 Japanese patients who had a clinical appearance characteristic of both granular and lattice dystrophy. Granular-lattice corneal dystrophy was found in a wider geographic distribution than previously proposed and should not be named after the geographic area.

Adult↗
PubMed1999

Purification and characterization of an endo-polygalacturonase from a mutant of Saccharomyces cerevisiae.

An extracellular endo-polygalacturonase (PGase) produced by a mutant of Saccharomyces cerevisiae was isolated. The enzyme was regarded, immunologically, as a PGase belonging to the Kluyveromyces marxianus group. The enzyme had properties similar to the PGase from K. marxianus in heat and pH stability, and N-terminal amino acid sequence. However, the enzyme showed different properties in optimum pH and temperature, molecular weight, and reactivity in antiserum against PGase from K. marxianus, indicating that the enzyme has a different molecular structure from the PGase from K. marxianus.

Antibodies, Monoclonal↗
PubMed1998

Involvement of DNA methylation in binding of a highly repetitive DNA component to nuclear scaffold proteins from rat liver.

Experimental reduction of the amount of CpG methylation in a highly repetitive DNA component was achieved by growth of Ac2F cells in the presence of 5-aza-2'-deoxycytidine or procainamide, as judged by the results of methyl-sensitive restriction endonuclease digestion and colony hybridization. Modification of genomic DNA with these DNA methylation inhibitors increased the release of 370-bp highly repetitive DNA from rat chromosomal DNA by HindIII digestion. This result indicated that highly repetitive DNA components in the nuclear scaffold fraction are hypermethylated. On the other hand, methylated DNA was used for southwestern analysis to investigate the protein(s) which bind specifically to the DNA in the nuclear scaffold fraction. The introduction of additional methylated cytosines within a highly repetitive DNA component affected the binding of DNA to the nuclear scaffold proteins. Thus, cytosine methylation may be involved in the regulation of gene expression and construction of the higher-order structure of chromatin.

Animals↗
PubMed1998

Involvement of phosphorylation in binding of nuclear scaffold proteins from rat liver to a highly repetitive DNA component.

The results of our previous work [Hibino et al., Biochim. Biophys. Acta 1174 (1993) 162-170] suggested that a highly repetitive DNA component facilitates bending of the helix axis to be recognized by the nuclear scaffold proteins from rat liver, P123 and P130. In the present experiment, it was shown that binding of these proteins to such a repetitive DNA component from rat liver nuclei (370-bp XmnI fragment) is based on a cooperative mode of interaction, although the binding activity of P130 is much higher than that of P123. The immunoblot analysis with anti-phosphoamino acid antibodies suggested that phosphorylation of serine and threonine residues occurs on P123 and P130, but also of tyrosine residue(s) on P130. The phosphatase assay showed that phosphoryl groups on these proteins may be involved in altering the DNA binding activities of the proteins. Thus, the results in the present study imply that phosphorylation of a nuclear scaffold protein in addition to the degree of bending of the DNA helix axis plays an important role in anchoring chromatin to the nuclear scaffold and in construction of a higher-order chromatin structure.

Animals↗
PubMed1998

Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer. Fukuoka Lung Cancer Study Group.

PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. METHODS: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.

Aged↗
PubMed1998

Effects of propofol and fentanyl on extracellular levels of gamma-aminobutyric acid in the rat nucleus accumbens: an in vivo microdialysis study.

The effects of propofol, a hydrophobic intravenous anaesthetic, and fentanyl, an opiate analgesic, on extracellular concentrations of gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied using in vivo brain microdialysis. The concentrations of GABA in the microdialysate of the nucleus accumbens reached a stable baseline value approximately 24 h after probe insertion and were not affected over the ensuing 250 min by intravenous injection of vehicle (1.0 ml/kg) or perfusion of tetrodotoxin (2 microM) into the nucleus accumbens via the dialysis membrane. Propofol (2.5 mg/kg and 10.0 mg/kg i.v.) did not significantly affect the accumbens microdialysate concentration of GABA over the 250 min of quantification. Fentanyl (100 microM) infused for 25 min into the nucleus accumbens via the dialysis membrane produced a marked and transient increase in accumbens GABA concentration to a maximum of approximately 1200% at its peak effect that occurred at 25 min after cessation of the fentanyl infusion.

Analgesics, Opioid↗
PubMed1998

[Nutritional intake by the oldest elderly Japanese. Tokyo Centenarian Study 6].

Rapid demographic aging has made caring for the elderly an increasingly important social issue in Japan. To study current conditions of the oldest elderly citizens, we investigated the dietary practices of centenarians in the Tokyo metropolitan area. First, we compared the food intake of centenarians with that of octogenarians. Next, to identify dietary trends, we investigated whether food intake by centenarians had changed significantly between 1981 and 1995. Nutritional intake by the centenarians and octogenarians in 1995 was about 60% and 75% that of the control, respectively. However, the nutritional intake of well nourished centenarians was similar to that of the octogenarians. Cognitive function and daily activity have an influence on nutritional intake. The centenarians were similar to the control subjects in their consumption of dairy products, sweets, and fruit. However, their intake of cereals, meat, fish, and fatty oils was loss than 60% that of the control, which indicates their preference for soft and sugary foods. The pattern of dietary practices of centenarians in 1981 was similar. Although the total food intake of centenarians amounted to 60% of the control in 1995 energy intake per kilogram of body weight averaged over 30 kcal. As to dietary trends, centenarians in 1981 are more cereals, eggs, algae products, and legumes than did their 1995 counterparts. This finding seems to reflect a generational difference in dietary habits.

Activities of Daily Living↗
PubMed1998

[Circadian rhythmicity of heart rates in centenarians].

Holter electrocardiography was used to study the circadian rhythm of heart rate in 50 centenarians living in Tokyo and in Aichi prefecture. As a control group, 50 healthy subjects aged under 65 years old underwent medical check-ups including Holter electrocardiography at Keio Health Consulting Center. Harmonic analysis was used to approximate the 24-h time-series data on the RR intervals to a summation of three cosine waves with 24-h, 12-h and 8-h periods. The power of each period was adjusted for the goodness of the curve-fit, and the powers of the centenarians were compared with those of the controls. Then all the subjects were classified by k-means cluster analysis into k groups based on the power of the period, and patterns of heart rate rhythms were then identified. The power of the 24-h period in centenarians (32.7 +/- 16.0%) was significantly lower than that in controls (45.8 +/- 17.8%). Although there were no significant differences in the powers of the 12-h and 8-h periods, the power of the 8-h period in centenarians (7.0 +/- 8.4%) was slightly higher than that in controls (4.2 +/- 3.3%). Advances or delays in acrophase (acrophasal shift) were more common in centenarians than in controls. Five patterns of heart rate rhythms were identified: 24-h period dominant (n = 58). 24-h + 12-h period (n = 15), 12-h period dominant (n = 7), 8-h period augmented (n = 7), and low curve-fitting (n = 13). Both the 8-h period augmented pattern and the low curve-fitting pattern were more common in centenarians than in controls. Both the 24-h period dominant pattern and the 24-h + 12-h period pattern were less common in centenarians than in controls. These data indicate that the circadian rhythm of heart rate changes with aging.

Activities of Daily Living↗
PubMed1997

Roles of C-terminal Src kinase in the initiation and the termination of the high affinity IgE receptor-mediated signaling.

As an attempt to analyze the roles of C-terminal Src kinase (Csk) in the high affinity IgE receptor (FcepsilonRI)-mediated signaling, we overexpressed Csk, a membrane-targeted form of Csk (mCsk), and a kinase-defective, membrane-targeted form of Csk (mCsk(-)) in rat basophil leukemia (RBL) 2H3 cells. Specific activity of Lyn at the basal state was decreased in Csk-expressing cells, and further decreased in mCsk-expressing cells. In mCsk(-)-expressing cells, basal specific activity of Lyn was increased, thereby indicating that mCsk(-) functioned as a dominant negative molecule. The onset of FcepsilonRI-mediated Lyn activation was delayed in Csk-expressing cells, and further delayed in mCsk-expressing cells. In mCsk(-)-expressing cells, Lyn activation was rapid and quite long lasting. These findings indicate (i) Csk negatively regulates rapid FcepsilonRI/Lyn coupling, and (ii) Csk activity is potentially required for its termination. The onsets of the series of events including tyrosyl phosphorylation of Syk, mitogen-activated protein (MAP) kinase activation, elevation of intracellular calcium concentration ([Ca2+]i), and histamine release were all stepwisely delayed in Csk-expressing cells and in mCsk-expressing cells. The durations of Syk phosphorylation and MAP kinase activation also closely correlated with those of Lyn activation, but [Ca2+]i elevation and histamine release followed different temporal patterns: the delayed responses in Csk-expressing cells and in mCsk-expressing cells led to sustained [Ca2+]i oscillation and histamine release, while the prompt responses in parent cells and mCsk(-)-expressing cells rapidly subsided. These findings provide further evidence that the initiations of the FcepsilonRI-mediated signals are upstreamly regulated by Src family protein tyrosine kinases and revealed that their terminations are regulated by Lyn-dependent (Syk and MAP kinase) and -independent ([Ca2+]i elevation and histamine release) mechanisms.

Amino Acid Sequence↗