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Biomedical subjects

A Nakano

Publications and source records attributed to A Nakano.

At least 127 records · Page 7Linked to original sources
PubMed1997

Role of the angiotensin II type 1 receptor in preconditioning against infarction.

OBJECTIVE: To assess the role of angiotensin II type 1 (AT1) receptor in the mechanism of limitation of infarct size by preconditioning. METHODS: Myocardial infarction was induced by 30 min coronary artery occlusion and 3 h reperfusion in the rabbit. The infarct size was determined by tetrazolium staining and expressed as a percentage of the area at risk (%ISAR). Rabbits were subjected to one of the following four treatments: no drug (i.e. control); administration of 1 mg/kg CV-11,974, a specific AT1 receptor antagonist, 20 min before ischemia; preconditioning with 5 min ischemia and then 5 min reperfusion; and administration of CV-11,974 plus preconditioning. RESULTS: It was confirmed that the same dose of CV-11,974 (i.e. 1 mg/kg) could block the pressor response to injection of 0.5 microgram/kg angiotensin II completely for 60 min. The %ISAR for the untreated control group was 45.1 +/- 3.9%, and administration of CV-11,974 alone did not modify the %ISAR (47.5 +/- 5.9%). The %ISAR for the group administered both CV-11,974 and subjected to preconditioning (30.4 +/- 3.5%) was modestly smaller than that for the controls, but was significantly larger than for the preconditioned group (12.0 +/- 1.8%). The angiotensin II level in arterial plasma did not differ before and after the 5 min preconditioning. It was shown with separate groups of rabbits that a modest protection conferred by preconditioning with 3 min ischemia was also attenuated by administration of CV-11,974 (%ISAR 28.4 +/- 4.3 with CV-11,974 versus 19.3 +/- 1.7% without CV-11,974, P < 0.05). CONCLUSION: These results suggest that activation of AT1 receptors by angiotensin II produced locally in the heart contributes to the limitation of infarct size by preconditioning.

Angiotensin II↗
PubMed1997

Chronic effects of methylmercury in rats. I. Biochemical aspects.

To examine chronic effects of methylmercury (MeHg), male Wistar rats were fed on MeHg-contaminated diet, 0, 1 and 5 ppm Hg, under a restricted feeding schedule of 16 g/rat/day for 6 days a week. Rats were killed at 6-month intervals for examination of Hg accumulation, tissue levels of glutathione, metallothionein and lipid peroxide, as well as anti-oxidative enzyme activities. The survival of the 5 ppm Hg group, 50% of which died by the end of 32nd month of the exposure, was somewhat shorter than control and 1 ppm Hg groups, 50% of which survived for 34 months. Although the rats showed no neurological signs or decreased body weight gain even in 5 ppm Hg-exposed group until the end of the 2nd year, crossing of hind limb was evident after 2.5 years in all three groups. Accordingly, the neurological sign observed here possibly due to aging rather than MeHg toxicity. Tissue Hg levels showed a dose-dependent accumulation except for the kidney, where the highest Hg accumulation was observed among tissues examined. Renal Hg levels in the 1 ppm group showed about 40% of those in the 5 ppm group. Significant effects by MeHg were evident only in the kidney, where glutathione and metallothionein levels increased in both MeHg-exposed groups. However, lipid peroxide levels elevated only in 1 ppm group. Among the antioxidative enzymes examined, the renal glutathione peroxidase was found to be the most labile enzyme against MeHg exposure. Renal dysfunction suggested by increased plasma creatinine levels was also significant in 5 ppm Hg rats at 2 years. Furthermore, anemia which would be caused by reduced erythropoietin production in the kidney was also evident in this group. The present study suggested that the kidney was the most susceptible organ against MeHg toxicity under the present exposure schedule and that the renal dysfunction might at least partly account for the shortened survival in 5 ppm Hg rats.

Administration, Oral↗
PubMed1997

Problems in the initial diagnosis of renal infarction.

We retrospectively analyzed 20 cases of renal infarction to identify the problems in tentatively diagnosing renal infarction. The subjects consisted of 12 outpatients and 8 inpatients whose diagnosis was confirmed by renal scintigram and/or contrast computed tomography. Renal infarction was tentatively diagnosed in only 4 of the 12 outpatients. Causes of hospitalization were cerebral emboli in 5 cases, peripheral emboli in the extremities in 2 cases and one case involved percutaneous transmitral commissurotomy. On initial urinalysis, 11 cases (55%) showed less than 2+ hematuria using dipsticks to test for occult blood. The mean lactic dehydrogenase value was as high as 2,096 IU while the mean aspartate aminotransferase and mean alanine aminotransferase were 83.1 IU and 78.6 IU. Abdominal ultrasonography revealed abnormalities in only one of 18 cases. In conclusion, since only a moderate degree of hematuria was seen in about half the cases and it was difficult to detect renal abnormalities by ultrasonography, a tentative diagnosis of renal infarction may be difficult in some cases.

Aged↗
PubMed1997

Synergistic antitumor effects of human interferon-beta and interferon-gamma on human gastric adenocarcinoma cells.

The combined effects of different classes of interferon (IFN) on human gastric adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro. Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to the cytocidal effect of IFN-gamma. The modulatory effect was independent of the cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta did not influence the growth kinetics of the cells and was effective in modulate the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN-alpha or-beta resulted in a variable level of modulation, whereas coculture of the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect indicating a different level of activity induced by IFN-alpha and -beta with the common type I receptor. These results suggest that IFN-beta-induced modulation was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic cell death induced by one or more IFN agents. The morphological changes included chromatin condensation and nuclear fragmentation which were apparent at as early as 6 hr of culture with a high concentration of IFN(s). Our results indicate that IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma against GAC-2 tumor cells.

Adenocarcinoma↗
PubMed1997

Recovery of perfusion, glucose utilization and fatty acid utilization in stunned myocardium.

We describe the clinical features and results of cardiac catheterization, PET ([13N]ammonia, 18F-fluorodeoxyglucose (FDG)) and SPECT [123I-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP)], in a patient with acute myocardial infarction successfully treated with intracoronary thrombolytic therapy. We compared the clinical and electrocardiographic changes with the myocardial glucose and fatty acid metabolism in stunned myocardium over a period of several months. The patient we studied illustrates the features of stunned myocardium. In the subacute phase, there was a concordant depression of myocardial [13N]ammonia and FDG uptake, and the metabolic abnormalities persisted even after regional wall motion at rest had returned to normal. The electrocardiographic recovery of deep negative T waves appeared to be related to the metabolic recovery in regions of stunned myocardium in this patient.

Ammonia↗
PubMed1996

Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

Climate↗
PubMed1996

Benign schwannoma of the breast: report of a case.

We report herein the case of a 62-year-old woman who presented to our hospital for investigation of occasional pain in her left breast. Although there was no mass palpable in her left breast, mammography and ultrasonography revealed a round tumor in the upper outer quadrant of the right breast. Although the mammography findings indicated that the tumor was benign, the possibility of a malignant neoplasm could not be ruled out by the ultrasonographic images. A final diagnosis of schwannoma was established by histopathological examination of the excised mass.

Breast Neoplasms↗
PubMed1996

Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain.

Yeast Sec12p is a type II transmembrane protein in the ER, which is essential for the formation of transport vesicles. From biochemical and morphological lines of evidence, we have proposed that Sec12p is localized to the ER by two mechanisms: static retention in the ER and dynamic retrieval from the early Golgi compartment. We have also shown that Rer1p, a membrane protein in the Golgi, is required for correct localization of Sec12p. In the present study, we have performed a systematic analysis to determine the ER localization signals in Sec12p corresponding to these two mechanisms. Both the transmembrane domain (TMD) and the NH2-terminal cytoplasmic domain of Sec12p show the ability to localize the protein to the ER. The effect of the TMD is potent and sufficient by itself for the ER localization and is strongly dependent on Rer1p. On the other hand, the cytoplasmic domain shows a moderate ER-localization capability which is independent of Rer1p. The rate of mannosyl modification has been measured to distinguish between retention and retrieval. The cytoplasmic domain significantly delays the transport from the ER to the cis-Golgi. In contrast, the TMD shows only a subtle retardation in the transport from the ER to the cis-Golgi but strictly prevents the transport beyond there. From these observations, we conclude that the TMD mainly acts as the retrieval signal and the cytoplasmic domain contains the retention signal. This study not only supports the two-mechanisms hypothesis but also provides powerful tools to dissect the two.

Amino Acid Sequence↗
PubMed1996

Characterization of yeast sar1 temperature-sensitive mutants, which are defective in protein transport from the endoplasmic reticulum.

SAR1 encodes a low molecular weight GTPase that is essential in the early process of vesicular transport in the secretory pathway. By random and site-directed mutagenesis of the SAR1 gene, we have obtained three temperature-sensitive mutants, N132I, E112K, and D32G. They all show a defect in transport from the endoplasmic reticulum to the Golgi apparatus, and accumulate endoplasmic reticulum membranes at the restrictive temperature. This is consistent with our previous observations in vivo on a galactose-shutoff mutant as well as the in vitro results, and provides powerful tools for further genetic analyses.

Alleles↗
PubMed1996

Identification and characterization of extragenic suppressors of the yeast sec12 ts mutation.

The product of the yeast SEC12 gene is the most upstream player as far as we know in the events of vesicle budding from the endoplasmic reticulum membrane. To understand how the Sec12p function could be regulated, I identified three extragenic suppressor mutations of the sec12 ts mutation. RST1DS is a dominant mutation and causes elevated expression of Sec12p. rst2 and rst3 are recessive and give pleiotropic phenotypes including slow growth at low temperatures and heterogeneous modification of Sec12p. Their possible roles are discussed.

Endoplasmic Reticulum↗
PubMed1996

An Arabidopsis gene isolated by a novel method for detecting genetic interaction in yeast encodes the GDP dissociation inhibitor of Ara4 GTPase.

The Arabidopsis Ara proteins belong to the Rab/Ypt family of small GTPases, which are implicated in intracellular vesicular traffic. To understand their specific roles in the cell, it is imperative to identify molecules that regulate the GTPase cycle. Such molecules have been found and characterized in animals and yeasts but not in plants. Using a yeast system, we developed a novel method of functional screening to detect interactions between foreign genes and identified this Rab regulator in plants. We found that the expression of the ARA4 gene in yeast ypt mutants causes exaggeration of the mutant phenotype. By introducing an Arabidopsis cDNA library into the ypt1 mutant, we isolated a clone whose coexpression overcame the deleterious effect of ARA4. This gene encodes an Arabidopsis homolog of the Rab GDP dissociation inhibitor (GDI) and was named AtGDI1. The expression of AtGDI1 complemented the yeast sec19-1 (gdi1) mutation. AtGDI1 is expressed almost ubiquitously in Arabidopsis tissues. The method described here indicates the physiological interaction of two plant molecules, Ara4 and GDI, in yeast and should be applicable to other foreign genes.

Amino Acid Sequence↗
PubMed1996

Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis.

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.

Animals↗
PubMed1996

Protective effects of Ca2+ channel blockers against methyl mercury toxicity.

The protective effects of Ca2+ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca2+ channel blockers (20 mg/kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca2+ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1, 25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 microM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 microM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca2+ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca2+ plays an important role in the mechanisms of methyl mercury toxicity.

Animals↗
PubMed1996

Salazosulfapyridine-induced angioimmunoblastic lymphadenopathy.

A 20-year-old man with ulcerative colitis was admitted because of fever, eruption and lymphadenopathy. He had started taking salazosulfapyridine one month previously. Lymph node biopsy revealed angioimmunoblastic lymphadenopathy. Autoantibody titers were all negative, and viral antibody titers were not increased retrospectively. Rearrangement of T-cell receptor beta and chromosomal aberration were not seen on the lymph node. This case is considered not to be a peripheral T-cell lymphoma but rather salazosulfapyridine-induced angioimmunoblastic lymphadenopathy (AIL), which is the second case in English language literature.

Adult↗
PubMed1995

STT3, a novel essential gene related to the PKC1/STT1 protein kinase pathway, is involved in protein glycosylation in yeast.

Mutations of genes involved in the STT1/PKC1 pathway in yeast show staurosporine and temperature sensitivities (stt) which are suppressed by the addition of 1 M sorbitol [Yoshida et al., Mol. Gen. Genet. 242 (1994) 631-640]. Among the stt mutants, stt3-2 shares this phenotype. The STT3 gene encodes a novel 718-amino-acid protein with significant homology to potential transmembrane proteins of Caenorhabditis elegans and mouse mandibular condyle (about 80% homologous and 60% identical). Unlike the STT1/PKC1 gene, STT3 is essential for cell growth irrespective of osmotic support. Pulse-chase experiments show that the sst3 mutants are defective in protein glycosylation. The stt3 mutants are sensitive to hygromycin B and resistant to sodium orthovanadate, whose phenotypes are common to those defective in protein glycosylation.

Alkaloids↗