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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 235 records · Page 13Linked to original sources

[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer].

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.

Aged↗

Interaction between CD44 and hyaluronic acid regulates human prostate cancer development.

PURPOSE: This study was designed to investigate the significance of the interaction between CD44 and hyaluronic acid in the development of human prostate cancer. MATERIALS AND METHODS: We transfected the standard CD44 isoform (CD44s) cDNA into PC3, a human prostate cancer cell line that barely expresses CD44s protein. The effects of the reintroduction of CD44s into PC3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and by the cell migration assay. The in vitro growth rate of CD44s transfected PC3 was measured by using the MTT assay. We then evaluated the in vivo tumor development of CD44s transfected PC3 cells by subcutaneous, intravenous, and intraperitoneal injection models in athymic nude mice. RESULTS: The introduction of CD44s in PC3 cells markedly enhanced the binding and migration of these cells to HA, but not to other extracellular matrix molecules. In vitro growth of CD44s-transfected PC3 was found to be significantly decreased. In addition, the CD44s-transfected PC3 cells also demonstrated reduced tumorigenicity and metastatic potential in in vivo experimental models. CONCLUSIONS: These findings suggest that the CD44s downregulation plays an important role in the development of human prostate cancer, in part through reduction of the ability to bind HA.

Down-Regulation↗

Multifocal renal cell carcinoma: evidence for a common clonal origin.

The reported incidence of satellite tumor lesions in kidneys resected by radical nephrectomy for renal cell carcinoma (RCC) is 7-25%; however, genetic analyses of satellite tumors in comparison with those of main tumor lesions have not been performed well. In the present study, we investigated the incidence of loss of heterozygosity (LOH) at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q using 18 microsatellite markers in 10 nonpapillary RCCs of 50 mm or less in diameter and the accompanying satellite tumor lesions to evaluate the genetic alterations in main and satellite tumors. LOH was detected in 10, 3, 5, 3, 2, and 3 cases at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q, respectively. In addition, primary and satellite tumor lesions in 8 of 10 cases exhibited identical patterns of LOH on the 18 loci examined. In the remaining two cases, both main and satellite tumors demonstrated LOH on the common seven and three loci, respectively, whereas for another locus, LOH was observed only in the satellite tumor lesions. The similarity of LOH patterns detected in main and satellite tumor lesions indicates that the presence of satellite tumors might be the result of intrarenal metastasis from the main tumor lesion. These findings strongly suggest that even in case of small nonpapillary RCC, nephron-sparing surgery might carry the risk of failing to prevent postoperative local recurrence due to the incomplete resection of unrecognized satellite tumors with genetic alterations similar to those of the main tumor.

Adult↗

Prognostic significance of Ki-67 and p53 antigen expression in carcinomas of bile duct and gallbladder.

Ki-67 and p53 protein expression was evaluated immunohistochemically in 32 patients with intrahepatic, extrahepatic bile duct and gallbladder carcinomas, who underwent surgery at First Department of Surgery, The University of Tokushima School of Medicine. p53 expression was found more in the well differentiated group than poorly differentiated group (p = 0.007). MIB1 labelling index (MIB1 LI) was higher in EHC than in GBC (p = 0.0061). MIB1 LI (T), (MIB1 LI in tumor) was higher in cases with lymph node metastasis than in those without lymph node metastasis (p = 0.0189). Moreover, MIB1 LI (L) (MIB1 LI in metastasized lymph node) was higher in poorly differentiated than in well differentiated carcinoma (p = 0.0404). Prognostically, patients with high MIB1 LI (T) (> 56.93) had a worse prognosis after surgery than those with low MIB1 LI (T) (p < 0.05). There was no association between p53 positive tumors and MIB1 expression. These results suggest that cancer cell proliferative activity was markedly increased in cases with EHC compared to those with GBC and the poorly differentiated and lymph node metastasis group. MIB1 LI in tumor was found to be a good prognostic indicator whereas there was no association of p53 positive tumor with MIB1 expression and prognosis of the patients.

Adult↗

Sequence of a melibiose transporter gene of Enterobacter cloacae.

We cloned a fragment of the chromosomal DNA of Enterobacter cloacae, which enabled a melibiose-negative Escherichia coli mutant lacking melB to grow on melibiose as the sole source of carbon. Transformed cells harboring the hybrid plasmid carrying the cloned DNA showed melibiose transport activity. The nucleotide sequence of the DNA region was determined. One complete open reading frame (ORF) and a part of another ORF were found in the region, and the amino acid sequences were deduced. The complete ORF was found to encode a melibiose transporter which consisted of 425 amino acid residues. Hydropathy analysis revealed that there are about 12 hydrophobic domains in this transporter. The incomplete ORF which exists in the upstream region of the transporter gene seemed to encode an alpha-galactosidase.

Amino Acid Sequence↗

Mass screening for neuroblastoma and mortality in birth cohorts.

Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and the whole of Japan was investigated to evaluate the effects of a high-performance liquid chromatography (HPLC) mass screening program, targeting on 6 month-old infants. In Sapporo City, the non-HPLC screened cohort showed no reduction in mortality at 4 years of age compared with the pre-screening cohort. However, the HPLC screened cohort showed a reduction of 69% in mortality compared with the pre-screening cohort. On a nation-wide scale, there was a significant decline in mortality for the non-HPLC screened cohort compared with the pre-screening cohort; for the HPLC screened cohort for 1989-1991, there was also a reduction in mortality for children younger than 2 years of age. The incidence of neuroblastoma at 1-4 years of age in the HPLC cohort in Sapporo City was about half that in the pre-screening cohort, along with and probably because of an increasing incidence among infants in the same cohort. Our findings suggest that HPLC screening may detect some poor-prognosis neuroblastoma cases at early stages, thus providing for more favorable therapy.

Adolescent↗

Association between cigarette smoking and prostatism in a Japanese community.

BACKGROUND: The purpose of this study was to examine the association between cigarette smoking and prostatism among Japanese men. METHODS: Male residents of Shimamaki-mura, Japan, aged 40-79 years old (n = 286), completed a self-administered questionnaire that included the international prostate symptom score (IPSS). A detailed cigarette smoking history was also obtained. All men had a transrectal ultrasonographic estimate of prostatic volume and a peak urinary flow rate measurement. RESULTS: Current cigarette smoking was inversely associated with an impaired peak urinary flow rate (< 15 mL/sec) (odd ratio [OR] = 0.39, 95% confidence interval [CI] = 0.18, 0.84), and with moderate to severe symptoms (IPSS > 7) (OR = 0.84, 95% CI = 0.48, 1.49), but was not significantly associated with prostatic volume. Smokers of 1 to 1.4 packs a day were less likely and smokers of less than a pack a day or 1.5 or more packs a day were more likely to have moderate to severe symptoms and a greater prostatic volume. CONCLUSION: These findings suggest that cigarette smoking may have a protective effect on prostatism at certain smoking intensities, but no effect or a deleterious effect at other intensities.

Adult↗

Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine.

Aranidipine, a novel dihydropyridine derivative, gives rise to two active metabolites, M-1(alpha) and M-1(beta), which exhibit hypotensive activity comparable to that of nifedipine. The aim of this study was to examine the recovery phase of the vasodilating effect of M-1(alpha) and of M-1(beta), to determine their binding characteristics and to compare the results with those for aranidipine and other dihydropyridine derivatives. During intra-arterial infusion into the femoral vascular beds of anesthetized dogs, M-1(alpha), M-1(beta), and nifedipine, produced increases in femoral blood flow at doses three times higher than the dose of aranidipine required to produce a comparable effect. The onset and recovery of the effects of the metabolites on femoral blood flow were significantly slower than the onset and recovery of the effect of nifedipine. The inhibitory activities of M-1(alpha) and M-1(beta) towards stimulated 45Ca uptake in isolated guinea pig aorta were less than that of aranidipine. In binding studies, using porcine heart membrane preparations, [3H]M-1(alpha) and [3H]M-1(beta) had larger Kd values than [3H]aranidipine and [3H]nitrendipine, but the maximal binding number for each of them was almost the same. The association and dissociation rate constants for [3H]M-1(alpha) and [3H]M-1(beta) binding, as well as those for [3H]aranidipine binding, were significantly smaller than those for [3H]nitrendipine, corresponding to the recovery of the in vivo vasodilating effects of the metabolites. The dissociation rate constants of these radiolabeled ligands were highly positively correlated with the elimination rate constants of their in vivo vasodilating effects. From these results, we conclude that M-1(alpha) and M-1(beta), although their binding affinities and Ca2+ antagonistic actions are less potent, possess slower kinetic binding properties than many other dihydropyridines and that the slow kinetic interaction of these metabolites with the dihydropyridine receptor may contribute to the long-lasting in vivo vasodilating effect of aranidipine.

Animals↗

Superficial temporal artery to anterior cerebral artery direct anastomosis in patients with moyamoya disease.

Some patients with Moyamoya disease require revascularization not only to the territory of the middle cerebral artery (MCA) but also to that of the anterior cerebral artery (ACA). To revascularize the ACA territory, we performed superficial temporal artery (STA)-ACA direct anastomosis in five patients with Moyamoya disease. After paramedian frontal craniotomy (approximately 5 cm diameter), STA-ACA anastomosis was carried out at the convexity using a cortical branch of the ACA as a recipient. An interposed STA graft was used in four patients: all of the grafts were shorter than 4 cm. Bypass flow was satisfactory in four patients. One patient who underwent simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow probably due to spontaneous leptomeningeal collateral channels between the ACA and MCA. Our method using a cortical branch of the ACA as a recipient and a branch of the STA for the interposed graft can be performed at the convexity and much easier than in a deep operative field. A short arterial graft does not easily occlude. The diameter of a branch of the STA is small and therefore, a size discrepancy does not present a problem. Our STA-ACA anastomosis method is useful and effective for revascularization of the ACA territory in any patients with Moyamoya disease.

Adolescent↗

Effects of interleukin-11 on carboplatin-induced thrombocytopenia in rats and in combination with stem cell factor.

The effects of interleukin-11 (IL-11) which stimulates megakaryopoiesis and thrombopoiesis and/or stem cell factor (SCF) which stimulates multiple lineage cells in the peripheral blood by an increase in marrow cellularity on hematopoietic suppression in carboplatin (CBDCA)-treated rats were determined. CBDCA was administered to rats at a dose of 35 mg/kg as a single intraperitoneal bolus on day 0. IL-11 (20 micrograms/day) was given subcutaneously for 10 days from day 5 after CBDCA treatment. IL-11 ameliorated the suppression of hematopoiesis in rats treated with CBDCA. Especially, the production of the platelets was stimulated by IL-11 more markedly than that of cells of other lineages. However, the combination of SCF and IL-11 intensified the CBDCA-induced suppression of hematopoiesis. These findings may be helpful in the design of future therapies to prevent or treat thrombocytopenia induced by chemotherapy.

Animals↗

A new ventriculoperitoneal shunt with a telemetric intracranial pressure sensor: clinical experience in 94 patients with hydrocephalus.

OBJECTIVE: We have developed a telemetric intracranial pressure sensor (OSAKA telesensor; Nagano Keiki Seisakusyo Co. Ltd., Tokyo, Japan) and investigated the clinical usefulness of new ventriculoperitoneal shunting with an OSAKA telesensor, an on-off valve, and a programmable valve. METHODS: The OSAKA telesensor was applied in 94 patients at Osaka Medical College between March 1986 and December 1995. Postoperative management, postoperative course, postural change of intracranial pressure (ICP), and zero drift of the OSAKA telesensor were investigated. RESULTS: ICP was measured easily in all patients with no inconvenience. The setting of the programmable valve was adjusted postoperatively 38 times in 25 patients. Postoperative ICP in the upright position was -14.9 +/- 4.5 mm Hg, and the difference in ICP between the supine and the upright position was about 20 mm Hg. The slope of the decrease in ICP with continuous postural changes from the supine to the upright position was steep until about 30 to 45 degrees but became incrementally less or even rose slightly about this angle. The initial slope was steeper when the shunt was open than when the shunt was closed; it was also steeper postoperatively than preoperatively. This initial slope, therefore, may indicate the intracranial compliance. Seven cases of shunt malfunction were diagnosed correctly by ICP measurements. Zero drift of the OSAKA telesensor was easily corrected by comparing the ICP reading from the telesensor with the puncture pressure in the on-off valve. CONCLUSION: The OSAKA telesensor is very useful in the postoperative care and pathophysiological evaluation of patients with hydrocephalus.

Equipment Design↗

A quantitative assessment of serum chylomicron by light scattering intensity: application to the intestinal fat absorption test.

A novel fat absorption test to clarify the malabsorption syndrome was developed using a micronephelometric technique and compared with the classic conventional technique using 131I-triolein. An integrity of time-sequential light scattered from chylomicron-related turbidity in serum was determined between 0 and 300 min after butter fat load, being expressed in terms of the light scattering intensity (LSI). A good correlation was obtained between LSI and the serum level of chylomicron-triglyceride determined by an ultracentrifugation technique (r = 0.819, P < 0.001). The maximal LSI was consistently observed at 180 min after administration of a test meal in the normal group (n = 39), whereas the malabsorption syndrome group (n = 35) was distinctly different and could be further classified according to four patterns of LSI changes. In addition, an inverse correlation was found between this fat absorption test and the 131I-triolein absorption test. It was concluded that the micronephelometric technique which does not use a radionuclide is advantageous in its simple and safe evaluation of fat malabsorption syndrome.

Adult↗

Pharmacological profile of TH-142177, a novel orally active AT1-receptor antagonist.

The pharmacological properties of TH-142177 (N-n-butyl-N-[2'-(1-H-tetrazole-5-yl) biphenyl-4-yl]-methyl-(N-carboxymethyl-benzylamino)-acetamide), a novel antagonist of the angiotensin II (AII) AT1 receptor, were studied in vitro and in vivo, and compared to those of losartan. In the rat isolated aorta, TH-142177 produced parallel shifts to the right of the concentration-response curves for AII-induced contractions without affecting the maximal response (pA2 = 9.07). The inhibitory potency of TH-142177 in the aorta was about three times greater than that of losartan. TH-142177 completely inhibited the specific binding of [125I]AII to AT1 receptor in rat aortic membranes (Ki = 1.6 x 10(-8) M), whereas specific [125I]AII binding to AT2 receptor in bovine cerebellum and human myocardium was not affected by concentrations of TH-142177 up to 10(-5) M. Losartan also inhibited the [125I]AII binding to rat aortic membranes (Ki = 2.2 x 10(-8) M). Following the intravenous administration to anesthetized normotensive rats, TH-142177 dose-dependently inhibited the increase in systolic blood pressure induced by an intravenous bolus injection of AII that was 1.5 times less potent than losartan. Furthermore, the oral administration of TH-142177 to conscious renal hypertensive rats exerted a dose-dependent reduction of systolic blood pressure without significantly effecting the heart rate. TH-142177 was at least three times more potent than losartan. These results demonstrate that TH-142177 is a potent and selective antagonist of AT1 receptors and by oral administration has a long-lasting antihypertensive activity.

Angiotensin II↗

A melibiose transporter and an operon containing its gene in Enterobacter cloacae.

We detected inducible melibiose transport activity in cells of Enterobacter cloacae IID977. H+, but not Na+, was found to be the coupling cation for this transporter. We cloned and sequenced the gene encoding the melibiose transporter. A homology search of a protein sequence database revealed that this melibiose transporter has high sequence similarity with the lactose transporter (LacY) and the raffinose transporter (RafB) and has some similarity with the melibiose transporter (MelB) of Escherichia coli.

Amino Acid Sequence↗

GTS-21, a nicotinic agonist, protects against neocortical neuronal cell loss induced by the nucleus basalis magnocellularis lesion in rats.

Effect of subchronically administered GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a selective nicotinic agonist, on neuronal cell loss caused by nucleus basalis magnocellularis (nBM) lesion was studied in rats. After 2 weeks of bilateral nBM excitotoxic lesion, GTS-21 was orally administered once daily for 20 weeks. Neuronal cell loss was observed in layers II-III of the parietal cortex in the lesioned control rats. GTS-21 significantly attenuated the neuron loss in these layers. These results suggest that GTS-21 exhibits a protective action against the neuronal cell death in the parietal cortex and may have a beneficial effect on neurodegenerative disorders such as an Alzheimer-type disease.

Animals↗

Mental depression and death in elderly persons.

To investigate the relationship between mental depression and death among elderly persons, a prospective study was conducted. 2,166 inhabitants aged from 60 to 74 years in the Hidaka district of Hokkaido Prefecture, Japan were employed. From December 1990 to January 1991 we estimated the degree of depression of the subjects, using the self-rating depression scale (SDS) developed by Zung. The subjects were classified into 3 groups according to the average SDS score (Group A, < 2.00; Group B, 2.00-2.39 and Group C, > or = 2.40), and were followed up periodically until February 1995 to confirm whether they were still alive. The highest mortality was noted in Group C which consisted of those who had severe depression. Their mortalities for cancer, pneumonia and suicide were significantly high. After the adjustment of age, number of current diseases, smoking state and sex, a similar tendency was noted. Mental depression increased mortality of the aged. Part of this mechanism might be explained by the suppression of immunological resistance.

Aged↗

Age-related differences in internal prostatic architecture on transrectal ultrasonography: results of a community based survey in Japan.

PURPOSE: We determined age-related differences in prostate internal architecture and prostate volume by transrectal ultrasonography in Japanese men 40 to 79 years old. MATERIALS AND METHODS: The 287 study participants were categorized by transition zone disease: group 1-not visible (normal prostate), group 2-visible, borders unclear (diffusely enlarged hyperplasia) and group 3-visible, border clear (nodularly enlarged hyperplasia). RESULTS: Group 1 comprised 40% of men 50 to 79 years old and showed slightly decreased median prostate volume with age. Prostate volume and its variance increased with age in group 3 but differed little across age in group 2. CONCLUSIONS: In a community sample the prostatic internal architecture relationship with age and prostate volume suggested differing growth patterns.

Adult↗