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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 217 records · Page 12Linked to original sources
PubMed1998

Cardioprotective profile of MET-88, an inhibitor of carnitine synthesis, and insulin during hypoxia in isolated perfused rat hearts.

3-(2,2,2-trimethylhydrazinium) propionate (MET-88) is an inhibitor of carnitine synthesis. This study was carried out to investigate whether or not reduction of carnitine content could attenuate hypoxic damage in isolated perfused rat hearts. Rats were divided into four groups: 1) vehicle control; 2) pretreatment with MET-88 (MET-88); 3) application of insulin (500 muU/mL) in the perfusate (insulin); and 4) pretreatment with MET-88 and application of insulin (MET-88 + insulin). MET-88 (100 mg/kg) was orally administered once a day for 10 days until the day before the experiments. Hearts were initially perfused for a 10 min period under normoxia, followed by a 30 min period under hypoxia. Hearts were frozen at the end of hypoxia for the measurement of high-energy phosphates, carnitine derivatives, and glycolysis intermediates. In a separate series of untreated and MET-88 treated hearts, exogenous glucose and palmitate oxidation was measured. MET-88 decreased the extent of the depression of cardiac contractility (+dP/dt), and aortic flow during the hypoxic state. Insulin also improved cardiac function, and co-treatment of MET-88 and insulin additionally improved cardiac function during hypoxia. MET-88 prevented the decrease of high-energy phosphate and the increase of long-chain acylcarnitine after 30 min of hypoxic perfusion. In addition, MET-88 increased the steady state of glucose oxidation in hypoxic perfused rat hearts. These results indicate that MET-88 has cardioprotective effects on contractile function and energy metabolism of isolated perfused rat hearts in a hypoxic condition. Preventing the accumulation of long-chain acylcarnitine may serve to protect hypoxic hearts.

Administration, Oral↗
PubMed1998

Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed neuronal death induced by ischemia in gerbils.

The neuroprotective effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride] were studied and compared with those of nicotine, 9-amino-1,2,3,4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB) using a cerebral ischemia model in Mongolian gerbils. The learning performance and memory retention were elucidated by a step-through passive avoidance task at 2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated gerbils showed impairment of learning performance and memory retention. Neuronal cell death in the hippocampal CA1 area was observed at 7 days after ischemia. When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (-)-nicotine (1.5 mg/kg), THA (5 mg/kg) and PB (50 mg/kg) significantly attenuated the impairment of passive avoidance performance and the neuronal cell death induced by the ischemia. When administered orally twice daily for 2 weeks prior to the ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal cell death, while (-)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the amnesia. These results suggest that GTS-21 exerts a protective activity on not only impairment of learning and memory but also delayed neuronal death and that the underlying mechanism of GTS-21 differs from that of nicotine or THA.

Animals↗
PubMed1998

A comparative study on the effects of nicotine and GTS-21, a new nicotinic agonist, on the locomotor activity and brain monoamine level.

Effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a selective nicotinic agonist, on locomotor activity and dopamine turnover were examined and compared to those of nicotine to test if GTS-21 exhibits side effects similar to those of nicotine. GTS-21 had no effect on locomotor activity in mice or dopamine turnover in rats. In contrast, nicotine produced a biphasic effect on locomotor activity. It also enhanced dopamine turnover rates in the striatum and cerebral cortex, suggesting the involvement of dopaminergic systems in the nicotine-induced changes in locomotor activity. GTS-21 exhibits fewer adverse effects, suggesting that it has therapeutic potential for cognitive disorders related to central cholinergic dysfunction.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

GTS-21, a nicotinic agonist, attenuates multiple infarctions and cognitive deficit caused by permanent occlusion of bilateral common carotid arteries in rats.

We examined the effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a nicotinic agonist, on histopathological changes of the brain and radial maze learning performance in rats with permanent occlusion of the bilateral common carotid arteries (2VO) and elucidated whether this compound has a protective effect against the neuronal degeneration and spatial cognitive deficit caused by chronic ischemia. Rats were administered GTS-21 (1 and 10 mg/kg, p.o.) or vehicle 24 hr and 30 min before the 2VO operation and then once daily for 2 months after the operation. The 2VO rats given vehicle had multiple infarctions in the cerebral cortex, hippocampus and striatum and rarefaction in the white matter at 2 months after the operation, although the number and distribution of infarctions varied among individual animals. In addition, the 2VO rats given vehicle showed a higher rate of errors in the acquisition trials of the 8-arm radial maze task than sham-operated controls. However, 2VO rats treated with GTS-21 (1 and 10 mg/kg, p.o.) showed significantly decreased neuropathological changes and less errors in the acquisition trials compared to the vehicle-treated 2VO rats. These results indicate that GTS-21 attenuates impairment of spatial cognitive deficit and progressive neuronal degeneration induced by 2VO and suggest that this compound is beneficial for the treatment of neurodegenerative diseases following chronic cerebral hypoperfusion.

Animals↗
PubMed1998

Body fat distribution and uterine leiomyomas.

PURPOSE: Investigation of the etiological relationship between body fat and uterine leiomyomas. SETTINGS: This was a case-control study. Percent body fat was measured bioelectrically with a body fat analyzer. SUBJECTS: In Sapporo City, Japan, 100 women with uterine leiomyomas (pathologically diagnosed) and 200 controls who were confirmed to have no uterine leiomyomas by clinical examination. RESULTS: Among the four types classified by BMI (over/under 24.0) and percent body fat (over/under 30%), the occult obesity type (BMI < 24.0 and percent body fat > or = 30%) had the highest risk. There were no patients of muscular type (BMI > or = 24.0 and percent body fat < 30%). Women with more than 0.80 of waist-to-hip ratio were also at significantly higher risk. CONCLUSIONS: Occult obesity and upper body fat distribution may lead to the development of uterine leiomyomas.

Adipose Tissue↗
PubMed1998

Pelvic extension of retroperitoneal fluid: analysis in vivo.

OBJECTIVE: The purposes of this study were to describe the pathway of fluid flow from the retroperitoneal space into the pelvic extraperitoneal space on CT in vivo, to clarify the relation between its occurrence and the site or amount of retroperitoneal fluid, and to delineate the anatomic relation between the retroperitoneal spaces and the pelvic extraperitoneal space. MATERIALS AND METHODS: We reviewed the CT scans of 37 patients with retroperitoneal fluid collections. Patients who had undergone pelvic laparotomy and patients who had either fascial thickening alone or fluid within muscle (such as the psoas muscle or iliac muscle) alone were excluded. RESULTS: Fluid extension into the pelvic extraperitoneal space was seen in six patients (16%). Extension by the infrarenal extraperitoneal space was seen in all six of these patients, but extension by properitoneal fat was seen in only one of the six patients. In patients with large amounts of fluid in the infrarenal extraperitoneal space, we frequently saw extension into the pelvic extraperitoneal space. Extension of pancreatic fluid into the infrarenal extraperitoneal space occurred in only 15% of the 37 patients. However, it occurred in both patients with ruptured abdominal aortic aneurysms. Three pathways from the infrarenal extraperitoneal space into the pelvic extraperitoneal space were seen: extension dorsally medial to the iliac vessels (n = 6), extension dorsally lateral to the iliac vessels (n = 1), and extension medially into the prevesical space (n = 2). Coexistence of two of these three pathways was seen in three patients. CONCLUSION: In vivo, extension of retroperitoneal fluid into the pelvic extraperitoneal space is not rare and occurs more often by the infrarenal extraperitoneal space than by properitoneal fat. Extension of retroperitoneal fluid to the infrarenal extraperitoneal space can be attributed less frequently to sources distant to the pelvic cavity such as pancreatic fluid. Such extension often derives from sources that can produce large amounts of retroperitoneal fluid such as ruptured abdominal aortic aneurysms. Of the three pathways from the infrarenal extraperitoneal space to the pelvic extraperitoneal space, dorsal extension medial to the iliac vessels is the most common, and multiple pathways often coexist.

Body Fluids↗
PubMed1998

Expression of MAGE genes in renal cell carcinoma.

We investigated the expression of MAGE genes in 10 renal cell carcinoma (RCC) cell lines, 50 RCC tumor samples and 5 normal kidney samples using reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1, -2, -3 and -4 genes were expressed in 4, 1, 10 and 3 of 10 RCC cell lines, respectively, and 11, 8, 38 and 15 of 50 RCC samples. In contrast, there was no expression of MAGE genes detected in any of the normal kidneys. The incidence of the expression of plural MAGE genes in high stage RCC was significantly higher than that in low stage RCC. An analysis based on clinicopathological factors revealed that MAGE-4 gene was more frequently expressed in clear cell subtype than in granular cell subtype RCCs. Our results suggest that owing to the high incidence of MAGE gene expression in RCC, a large proportion of patients could be suitable candidates for novel immune therapies involving tumor-specific antigens encoded by MAGE genes.

Antigens, Neoplasm↗
PubMed1998

p53 modulation of Fas/Apo-1 mediated apoptosis in a human renal cell carcinoma cell line.

The mutant p53 gene was transfected into ACHN, a wild-type p53-containing human renal cell carcinoma (RCC) cell line. The colony forming efficiency in soft agar in the mutant-type p53-transfected cell line (ACHN/MP) was significantly higher than that in the vector-only transfected control cell line (ACHN/C). The anti-Fas monoclonal antibody (CH11) induced apoptosis in the ACHN/C cells in a dose-dependent manner, whereas the effect of CH11 on the ACHN/ MP cells was markedly suppressed. In addition, the cytotoxic effect of CH11 on the ACHN/MP cells was augmented by the pretreatment with interferon- , but the corresponding effect on ACHN/C cells was not. These findings suggest that Fas-mediated therapy could be a novel approach to RCC, if interferon- treatment is added according to the p53 gene status.

Antibodies, Monoclonal↗
PubMed1998

Chronic cerebral hypoperfusion-induced neuropathological changes in rats.

We investigated the time courses of histopathological changes in various brain regions following permanent occlusion of the bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus CA1-3 and dentate gyrus areas 1-3 days after the operation. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2), a marker protein of neuronal dendrites. Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after the 2VO operation. A marked increase in GFAP staining of the astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. Eight-arm radial maze performance was tested from 14 days to 60 days after the operation. The 2VO rats showed fewer initial correct responses than sham-operated control rats during a repeated training period. These findings suggested that the loss in dendritic MAP2 immunoreactivity and an increase in astroglial staining and/or rarefaction of the white matter may cause neuronal death, infarction and learning impairment under conditions of chronic hypoperfusion.

Animals↗
PubMed1998

Multifocal renal cell carcinoma in Japanese patients with tumors with maximal diameters of 50 mm. or less.

PURPOSE: We determined the risk of local recurrence in 64 Japanese patients a median of 69 years old with renal cell carcinoma who were possible candidates for nephron sparing surgery and who underwent radical nephrectomy. MATERIALS AND METHODS: A total of 64 kidneys in which tumors 50 mm. or less were resected were prospectively examined pathologically in 3 mm. sections. The incidence of satellite tumors and the relationship between the pathological findings of the primary and satellite tumors were evaluated. RESULTS: Satellite tumors were identified in 10 of the 64 kidneys (15.6%), a rate similar to that reported in the United States. The correlation of histological findings between primary and satellite tumors was 70% for tumor grade. Satellite tumor grade was less than that of the primary lesion in 3 cases. In 60% of the specimens with multifocal renal cancer satellite tumors were within 10 mm. of the margin of the primary tumor. At this distance, if partial nephrectomy had been performed, the satellite lesions would have been missed in 4 of these 10 patients (40%). Of the 10 kidneys with satellite renal tumors 8 (80%) had vascular invasion of the primary tumor. Multiple logistic regression analysis demonstrated that vascular invasion was a significant predictor of multifocality of renal cell carcinoma. CONCLUSIONS: Our results suggest that vascular invasion is a risk factor for multifocality in Japanese patients with renal cell carcinoma. Therefore, careful and long-term followup is necessary in patients with renal cell carcinoma who have undergone nephron sparing surgery, especially those with vascular invasion of the primary tumor.

Adult↗
PubMed1998

Expression patterns of CD44 adhesion molecule in testicular germ cell tumors and normal testes.

Despite recent extensive immunohistochemical studies, the expression patterns of CD44 in testicular germ cell tumors are still controversial. In the present study, we investigated the CD44 gene expression in 40 specimens including 18 seminomas, 16 nonseminomatous germ cell tumors (NSGCT), and 6 normal testes by reverse transcriptase-polymerase chain reaction and Western blotting. Reverse transcriptase-polymerase chain reaction analysis revealed that the standard CD44 isoform (CD44s) was expressed in all of the specimens, whereas the variant CD44 isoforms were highly expressed in NSGCTs but barely detectable in seminomas and normal testes. In addition, we confirmed by direct DNA sequence analysis that the predominantly expressed variant isoform in NSGCTs was CD44v8-10. In germ cell tumors, these results were paralleled in Western blot analysis; that is, CD44s protein was expressed in all of the tumor specimens, whereas high molecular weight variant isoforms were expressed only in NSGCTs. However, at the protein level, no detectable CD44 was expressed in normal testes. These findings show that the combined assessment of CD44 expression patterns at both the RNA and protein levels enables us to distinguish among seminoma, NSGCT, and normal testis specimens; hence, it could serve as a useful practical adjunct to conventional diagnostic methods for testicular germ cell tumors.

Adolescent↗
PubMed1998

Inhibitory effect of a marine microalgal polysaccharide on the telomerase activity in K562 cells.

An extracellular polysaccharide from marine microalga, dinoflagellate Gymnodinium sp. A3 (GA3), showed cytotoxicity to human myeloid leukemia K562 cells. We measured telomerase activity in K562 cells cultured with GA3 polysaccharide. 10.0 micrograms/ml of GA3 polysaccharide inhibited the telomerase activity in the cells completely. Also, we found a decrease in expression of the catalytic subunit of protein phosphatase (PP) type 1, PP1 gamma 1, in K562 cells cultured with GA3 polysaccharide.

Animals↗
PubMed1998

Decrease of nuclear protein phosphatase 1 activity and induction of mitotic arrest and apoptosis by a marine microalgal polysaccharide in human myeloid leukemia U937 cells.

An extracellular polysaccharide, which we designate GA3P, produced from a marine microalga dinoflagellate Gymnodinium sp. A3, has been previously reported to induce apoptosis in lymphoid and myeloid cell lines. We found that the GA3P accumulates cells into the mitotic phase of the cell cycle and decreases nuclear protein phosphatase 1 (PP1) activity in a dose-dependent manner in myeloid leukemia U937 cells. Dose-dependent patterns in the decrease of nuclear PP1 activity and in the accumulation of cells into mitotic phase or apoptotic status by the GA3P were concordant with each other, indicating that the decrease of nuclear PP1 activity at least mediates some of the etiological steps in development of mitotic arrest and apoptosis induced by the GA3P. In addition, the GA3P repressed the expression of protein levels of the PP1 catalytic subunit isoform PP1 gamma 1 gamma 1. We thus suggest that the decrease of nuclear PP1 activity is due to down-regulation of the protein levels of the PP1 gamma 1.

Animals↗
PubMed1998

Can the liver with Gilbert's syndrome be used as graft of living-related liver transplantation?

Gilbert's syndrome is the common cause of non hemolytic unconjugated hyperbilirubinemia with a prevalance of 3-7%. Gilbert's syndrome may introduce a selection of potential liver donors from brain death patients. We present a case of living-related liver transplantation (LRLT) from a donor with Gilbert's syndrome. A 22-year-old woman had been diagnosed as having liver cirrhosis at the age of 5. She underwent liver transplantation with the donor's left lobe as the graft. The donor, who was the father of the patient, had been diagnosed with Gilbert's syndrome. Although the recipient was well until 11 months after surgery, she died of subacute fulminant hepatitis 16 months after surgery. However, it was clear that the liver with Gilbert's syndrome could be used as a graft of living-related liver transplantation for adult recipients.

Adult↗
PubMed1998

TAS-301, an inhibitor of smooth muscle cell migration and proliferation, inhibits intimal thickening after balloon injury to rat carotid arteries.

The purpose of this study was to determine the efficacy and the possible mechanism of action of a recently synthesized drug, TAS-301 [3-bis (4-methoxyphenyl)methylene-2-indolinone], on intimal formation in comparison with those of tranilast, the clinical efficacy of which was reported earlier. Rat carotid arteries were injured using a balloon catheter. Neointimal thickening, measured 14 days after injury, was reduced by the oral administration of TAS-301 in a dose-dependent fashion (3-100 mg/kg), and the effect of TAS-301 at a dose of 100 mg/kg was significantly greater than that of tranilast (300 mg/kg). Fewer cells were found on the intima of balloon-injured arteries of TAS-301-treated rats than on arteries of tranilast-treated rats. In an in vitro assay, TAS-301 inhibited the migration of smooth muscle cells (SMCs) stimulated by platelet-derived growth factor-BB, insulin-like growth factor-1 or heparin-binding epidermal growth factor-like growth factor. In addition, TAS-301 and tranilast reduced the proliferation of medial and intimal SMCs at 4 and 8 days, respectively, after the injury. In vitro, TAS-301 inhibited basic fibroblast growth factor-induced proliferation of SMCs dose dependently. These findings indicate that TAS-301 shows a higher inhibitory potency on intimal formation than tranilast due to inhibition of both migration of medial SMCs and proliferation of medial and intimal SMCs. Our results suggest that further evaluation of TAS-301 as an inhibitor of postangioplasty intimal thickening is warranted.

Animals↗
PubMed1998

Assessment of the biological malignancy of hepatocellular carcinoma: relationship to clinicopathological factors and prognosis.

It is difficult to determine the prognosis of patients with hepatocellular carcinoma (HCC). Assessment of the clinicopathological and biological malignancy of HCC may help in determining treatment strategies and predicting outcome. The tumor DNA content, p53 protein expression, proliferating cell nuclear antigen labeling index, and argyrophilic proteins of nuclear organizer regions were used as markers of biological malignancy. A correlation between these biological parameters and clinicopathological factors was sought. DNA aneuploidy was observed in 31 of 80 tumors (38.8%). Aneuploidy increased as differentiation decreased. The overall survival rate of patients with aneuploid tumors was significantly poorer than that of patients with diploid tumors. p53 overexpression was observed in 18 of 80 tumors (22.5%). The incidence of p53 positivity increased significantly with increasing tumor size and poorer differentiation. The overall survival rate of p53-positive patients was significantly worse than that of p53-negative patients. The proliferating cell nuclear antigen labeling index and the mean number of argyrophilic proteins of nuclear organizer regions were higher in more poorly differentiated lesions. We conclude that DNA ploidy and p53 expression are useful prognostic indicators in HCC. Cell proliferation increases as HCC progresses. With progression, tumors tend to become more poorly differentiated.

Adult↗
PubMed1998

[Evaluation of 99mTc-DTPA-HSA abdominal imaging of protein-losing gastroenteropathy].

Abdominal images were obtained after the intravenous injection of 99mTc-HSA-D in 8 patients with protein-losing gastroenteropathy (PLG). Six neck images and 7 abdominal images were obtained in 11 patients with ischemic heart disease as a control study. We evaluated all the images with respect to visualization, initial appearance time, and movement of abnormal radioactivity. In 7 of 8 patients with PLG, abnormal radioactivity in the intestine appeared from 10 min to 4 hours after injection, and moved 6 hours after injection. In 6 of 7 abdominal images of control cases, slight activity was observed in the alimentary tract 6 hours or 24 hours after injection. The thyroid was not visualized in any of the 6 cases. In conclusion, if radioactivity in the alimentary tract was first observed 6 hours or later after injection, the diagnosis of PLG may be difficult by this method alone. It still may be necessary to perform the alpha 1-antitrypsin test for the correct diagnosis of PLG.

Abdomen↗