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N Kurihara

Publications and source records attributed to N Kurihara.

At least 37 records · Page 2Linked to original sources

Molecular cytogenetic analysis of 17 renal cancer cell lines: increased copy number at 5q31-33 in cell lines from nonpapillary carcinomas.

Comparative genomic hybridization (CGH) was used to screen for genomic imbalances in cell lines derived from 13 nonpapillary renal-cell carcinomas (RCCs), two papillary RCCs, one renal squamous-cell carcinoma, and one transitional-cell carcinoma of the renal pelvis. Aberrations were found in all 17 lines. The most frequent changes in nonpapillary RCC cell lines were gains of 5q (85%), 7q (69%), 8q (69%) and 1q (54%) and losses of 3p (92%), 8p (77%), 4q (62%) and 14q (54%). High-level gains (HLGs) were detected at 4q12, 5p, 5q23-33, 7q22-qter, 8q23-24, 10q21-qter, 12p and 12q13-22. By means of fluorescence in situ hybridization (FISH) we narrowed the smallest common region involving 5q gains to the genomic segment between D5S642 and D5S673, and found that the HLG at 4q12 possibly involved amplifications of c-kit and PDGFRA. Two papillary RCC cell lines showed gains of entire chromosomes 7, 12 and 17. The CGH data reported here should help to facilitate the choice of individual renal-tumor cell lines for exploring target genes in regions of interest.

Adult↗

Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype.

Osteoclasts (OCLs) in Paget's disease are markedly increased in number and size, have increased numbers of nuclei per multinucleated cell, and demonstrate increased resorption capacity and increased sensitivity to 1,25-(OH)(2)D(3), the active form of vitamin D. These cells also contain nuclear inclusions, reminiscent of those seen in paramyxovirus-infected cells, which cross-react with antibodies to measles virus nucleocapsid (MVNP) antigen. To elucidate the role of MV in the abnormal OCL phenotype of Paget's disease, we transduced normal OCL precursors with retroviral vectors expressing MVNP and the MV matrix (MVM) genes. The transduced cells were then cultured with 1,25-(OH)(2)D(3) for14 or 21 days to induce formation of OCL-like multinucleated cells. The MVNP-transduced cells formed increased numbers of multinucleated cells, which contained many more nuclei and had increased resorption capacity compared with multinucleated cells derived from empty vector-transduced (EV-transduced) and MVM-transduced or normal bone marrow cells. Furthermore, MVNP-transduced cells showed increased sensitivity to 1, 25-(OH)(2)D(3), and formed OCLs at concentrations of 1, 25-(OH)(2)D(3) that were 1 log lower than that required for normal, EV-transduced, or MVM-transduced cells. These results demonstrate that expression of the MVNP gene in normal OCL precursors stimulates OCL formation and induces OCLs that express a phenotype similar to that of pagetic OCLs. These results support a potential pathophysiologic role for MV infection in the abnormal OCL activity and morphology that are characteristic of pagetic OCLs.

Bone Marrow Cells↗

Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone.

Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions is highly osteoclastogenic, or that OCL precursors in these lesions are hyperresponsive to osteoclastogenic factors (or both). To examine these possibilities, we compared RANK ligand (RANKL) mRNA expression in a marrow stromal cell line developed from a pagetic lesion (PSV10) with that in a normal stromal cell line (Saka), and expression in marrow samples from affected bones of Paget's patients with that in normal marrow. RANKL mRNA was increased in PSV10 cells and pagetic marrow compared with Saka cells and normal marrow, and was also increased in marrow from affected bones compared with uninvolved bones from Paget's patients. Furthermore, pagetic marrow cells formed OCLs at much lower RANKL concentrations than did normal marrow. Anti-IL-6 decreased the RANKL responsivity of pagetic marrow to normal levels, whereas addition of IL-6 to normal marrow enhanced RANKL responsivity. Thus, RANKL expression and responsivity is increased in pagetic lesions, in part mediated by IL-6. These data suggest that the combination of enhanced expression of RANKL in affected bones and increased RANKL sensitivity of pagetic OCL precursors may contribute to the elevated numbers of OCLs in Paget's disease.

Antibodies↗

[Chlorinated hydrocarbon insecticides(DDT, methoxychlor, HCH etc.)].

Endocrine disrupting properties of organochlorine(chlorinated hydrocarbon) insecticides are reviewed. Physicochemical properties such as water solubility and partition coefficient of the organochlorine insecticides greatly influence their environmental fates. Insolubility in water and high partition coefficient usually enhance the environmental persistence of the compounds. On the endocrine disrupting properties, an important metabolite of p,p'-DDT, p,p'-DDE, is known to exhibit weak anti-androgenic properties. An isomer o,p'-DDT is estrogenic. Metabolites of methoxychlor, mono-demethylated and di-demethylated methoxychlor derivatives, are weakly estrogenic. Their dehydochlorinated product also exhibits estrogenicity. HCH isomers are environmentally persistent compounds, but there is few reports on their endocrine disrupting properties. Some other organochlorine pesticides such as cyclodienes and chlordecone is reported to be estrogenic.

Androgen Antagonists↗

Hydrogen bonding interaction of the amide group of Asn and Gln at distal E7 of bovine myoglobin with bound-ligand and its functional consequences.

Asn and Gln with an amide group at gamma- and delta-positions, respectively, were substituted for distal His-E7 of bovine myoglobin to establish a system where hydrogen bonding interaction between the distal residue and bound-ligand can be altered by changing donor-acceptor distance. Two mutant myoglobins showed nearly identical (1)H-NMR spectral pattern for resolved heme peripheral side-chain and amino acid proton signals and similar two-dimensional NMR connectivities irrespective of cyanide-bound and -unbound states, indicating that the heme electronic structure and the molecular structure of the active site are not affected by a difference in one methylene group at the E7 position. Chemical exchange rate of Asn-E7 N(delta)H proton in met-cyano myoglobin is larger than that of Gln-E7 N(epsilon)H proton by at least two orders of magnitude, suggesting a considerable difference in the strength of hydrogen bond between the E7 side-chain and bound-ligand, due to the differential donor-acceptor distance between the two mutants. Thus a comparative study between the two proteins provides an ideal system to delineate a relationship between the stabilization of bound-ligand by the hydrogen bond and myoglobin's ligand affinity. The Asn-mutant showed a faster dissociation of cyano ion from met-myoglobin than the Gln-mutant by over 30-fold. Similarly, oxygen dissociation is faster in the Asn-mutant than in the Gln-mutant by approximately 100-fold. Association of cyanide anion to the mutant met-myoglobin was accelerated by changing Gln to Asn by a 4-fold. Likewise, oxygen binding was accelerated by approximately 2-fold by the above substitution. The present findings confirm that hydrogen bonding with the distal residue is a dominant factor for determining the ligand dissociation rate, whereas steric hindrance exerted by the distal residue is a primary determinant for the ligand association.

Amides↗

Echocardiographic assessment of cardiac function in conscious and anesthetized mice.

Using a high-frequency linear transducer (15L8), we studied 1) the feasibility of performing echocardiography in nonanesthetized mice compared with mice given pentobarbital sodium (Pento) or a mixture of ketamine and xylazine and 2) the feasibility of echocardiographic evaluation of left ventricular (LV) hypertrophy, dilatation, and function in mice with two-kidney, one-clip hypertension or myocardial infarction (MI). Heart rate (HR) in awake mice was 658 +/- 9 beats/min; Pento and ketamine plus xylazine reduced HR to 377 +/- 11 and 293 +/- 19 beats/min, respectively, associated with a significant decrease in shortening fraction (SF), ejection fraction (EF), and cardiac output (CO) and an increase in LV end-diastolic (LVEDD) and end-systolic dimensions (LVESD). Mice with 4 wk of two-kidney, one-clip hypertension had increased LV mass (15.62 +/- 0. 62 vs. 22.17 +/- 1.79 mg) without altered LV dimensions, SF, EF, or CO. Mice studied 4 wk post-MI exhibited obvious LV dilatation and systolic dysfunction, as evidenced by increased LVEDD and LVESD and decreased SF, EF, and CO. Our findings clearly show the adverse impact of anesthesia on basal cardiac function and the difficulty in interpreting data obtained from anesthetized mice. We believe this is the first study to demonstrate the feasibility of using echocardiography to assess cardiovascular function in the nonanesthetized mouse.

Adjuvants, Anesthesia↗

Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide.

BACKGROUND AND OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). METHOD: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). RESULTS: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = -0. 503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0. 533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). CONCLUSION: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Aged↗

The relationship between cerebral infarction and angiographic characteristics in childhood moyamoya disease.

BACKGROUND AND PURPOSE: In childhood-onset moyamoya disease, the angiographic disease process of stenoocclusive lesions is progressive, and cerebral infarctions often develop as a result of ischemia. Our purpose was to determine how the severity of stenoocclusive lesions in the anterior and posterior circulations affects the distribution of cerebral infarction in patients with childhood-onset moyamoya disease. METHODS: In 69 patients with childhood-onset moyamoya disease, angiograms were reviewed for stenoocclusive lesions, and CT scans, MR images, or both were reviewed for the sites and extent of cerebral infarction. The relationship between the angiographic and CT/MR findings was examined. RESULTS: The prevalence and degree of stenoocclusive lesions of the posterior cerebral artery (PCA) significantly correlated with the extent of lesions around the terminal portion of the internal carotid artery (ICA). The prevalence of infarction significantly correlated with the degree of stenoocclusive changes of both the ICA and PCA. Infarctions tended to be distributed in the anterior borderzone in less-advanced cases, while in more advanced cases lesions were additionally found posteriorly in the territory of the middle cerebral artery, the posterior borderzone, and the PCA territory. CONCLUSION: Our results indicate that progressive changes of the anterior and posterior circulations are associated with the distribution of cerebral infarction, culminating in a patchily disseminated or honeycomb pattern of infarction on CT and MR studies in late stages of the disease.

Adolescent↗

[Zinc (Zn)].

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Child↗

Reactivity of monoclonal antibody to HSP60 homologue of Helicobacter pylori with human gastric epithelial cells and induction of IL-8 from these cells by purified H. pylori HSP60.

The monoclonal antibody (mAb) designated H20, which recognizes heat shock protein 60 (HSP60) of Helicobacter pylori, was previously established; and the epitope recognized by the mAb was shown to be species-specific. Using immunohistochemical staining of six gastric biopsy specimens with the H20 mAb, gastric epithelial cells of four biopsy samples stained positively. Flow cytometric analysis showed that H20 mAb reacted with primary human gastric epithelial (PHGE) cells, though the reactivities of the mAbs were different among the PHGE cells prepared. These results indicate that the species-specific epitope recognized by H20 mAb exists on human gastric cells. In addition, affinity-purified HSP60 from H. pylori by H20 mAb induced interleukin-8 (IL-8) secretion from PHGE cells (in one of four cases). These results indicate that H. pylori HSP60 induces IL-8 secretion from human gastric cells, and the levels of IL-8 differ among the various prepared PHGE cells.

Antibodies, Monoclonal↗

Altered expression of endothelin-1 and endothelial nitric oxide synthase in the juxtaglomerular apparatus of rats with HgCl2-induced acute renal failure.

A progressive fall in glomerular capillary plasma flow (QA) is observed in mercury chloride (HgCl2)-induced acute renal failure (ARF) although the site of the main lesion of this ARF is the proximal tubule. To elucidate this mechanism, we examined the expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS) protein at the glomerulus level in the kidneys of control rats and rats with HgCl2-induced ARF. Both ET-1 and eNOS protein were detected in the juxtaglomerular cells of afferent arterioles. The expression of ET-1 was significantly increased in ARF rats when compared to control rats. Inversely, the expression of eNOS protein was markedly reduced in ARF rats as opposed to control rats. These observations suggest the participation of the vasoconstrictor, ET-1 and the vasodilator, NO in a reduction in QA observed in HgCl2-induced ARF.

Acute Kidney Injury↗

Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice.

Cellular and molecular characterization of osteoclasts (OCL) has been extremely difficult since OCL are rare cells, and are difficult to isolate in large numbers. We used the tartrate-resistant acid phosphatase promoter to target the bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL lineage in transgenic mice as a means of immortalizing OCL precursors. Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL, Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly transgenic bcl-XL or Tag mice, have survived in continuous culture for more than a year. These cells form high numbers of bone-resorbing OCL when cultured using standard conditions for inducing OCL formation, with approximately 50% of the mononuclear cells incorporated into OCL. The OCL that form express calcitonin receptors and contract in response to calcitonin. Studies examining the proliferative capacity and the resistance of OCL precursors from these transgenic mice to apoptosis demonstrated that the increased numbers of OCL precursors in marrow from bcl-XL/Tag mice was due to their increased survival rather than an increased proliferative capacity compared with Tag, bcl-XL, or normal mice. Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there were increased numbers of OCL precursors (TRAP + mononuclear cells) present in vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL with an efficiency that is 300-500 times greater than that of normal marrow.

Acid Phosphatase↗

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

We used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

Adult↗

Hemorrhage in pituitary adenoma: correlation of MR imaging with operative findings.

The aim of this study was to correlate MR imaging and operative findings of hemorrhage in pituitary macroadenomas. We retrospectively reviewed MR images of 113 surgically proven pituitary adenomas. All patients were examined on a 1.5-T MR system. The intensity of intratumoral cystic cavities was correlated with operative findings. In 15 patients with pituitary apoplexy, we determined relationship between interval of MR examination after apoplectic event and MR signal intensity. In 8 patients with repeated preoperative MR examination, we evaluated sequential changes of intratumoral hemorrhage. There were 54 cavities at surgery: 52 were hemorrhagic and 2 were nonhemorrhagic. Twenty-nine of 52 hemorrhagic cysts demonstrated high/low signal (H/L) fluid-fluid levels on T2-weighted image (T2WI). In 19 of them, two components could be separately seen at operation: the supernatant high-intensity area represented xanthochromic fluid, and the dependent low-intensity area represented liquefied hematoma. The H/L fluid-fluid level was observed predominantly in hematomas on MR images obtained after longer intervals. In patients with repeated MR examination, follow-up MR imaging revealed additional hemorrhage or new formation of fluid-fluid levels. It was surprising that 12 of 14 cysts preoperatively judged as nonhemorrhagic in fact contained hemorrhagic components. The preoperative MR images are well correlated to the operative findings in hemorrhagic pituitary macroadenomas. It proved that 52 of 54 cystic cavities had hemorrhagic component.

Adenoma↗

Lymph node metastasis of early gastric cancer with submucosal invasion.

BACKGROUND: A clinicopathological study of early gastric cancer with submucosal invasion was carried out in relation to lymph node metastasis. METHODS: A retrospective study was conducted of 245 patients with submucosal gastric cancer treated by gastrectomy combined with D2 lymph node resection between 1985 and 1994 in a university hospital. RESULTS: Lymph node metastasis was observed in 34 patients (14 per cent). The mortality rate due to recurrence in patients with lymph node metastasis (three of 34) was significantly higher than in those without lymph node metastasis (five (2 per cent) of 211) (chi2 = 3.95, 1 d.f., P < 0.05). Tumour size, depth of invasion, lymphatic involvement of cancer cells and preoperative diagnosis of advanced cancer correlated significantly with the presence of lymph node metastasis. When the submucosal carcinomas were classified into three categories according to depth of invasion by dividing the submucosal (sm) layer into three equal parts, sm1, sm2 and sm3, the incidence of lymph node metastasis increased from 2 per cent to 12 and 20 per cent respectively. CONCLUSION: When the pathological report reveals sm1 invasion after laparoscopic or endoscopic surgery, reoperation should not be necessary because sm1-carcinomas with diameters of less than 2 cm do not usually metastasize to the lymph nodes.

Adult↗

[The role of heat shock protein 60 (HSP60) of Helicobacter pylori in adhesion of H. pylori to human gastric epithelial cell].

Adhesion of Helicobacter pylori to both human gastric carcinoma cell lines (MKN45, MKN28 and KATO III) and prepared primary human gastric epithelial cells were analyzed with flow-cytometry. All strains adhered to human gastric carcinoma cells. Especially, these strains strongly adhered to MKN45 cells. Adhesion of H. pylori strains to prepared primary human gastric epithelial cells was also observed. However, the adherence rates of H. pylori to these cells were different among the cells used. These results suggested that the host factor might be important for adhesion of the bacteria to human gasgric cells. In addition, H20 monoclonal antibody directed to H. pylori HSP60 inhibited the adhesion of H. pylori to both cells. These results indicate that H. pylori HSP60 might be associated with the adhesion of the bacteria to human gastric epithelial cells.

Bacterial Adhesion↗

Role of nNOS in blood pressure regulation in eNOS null mutant mice.

The role of neural nitric oxide synthase (nNOS) in regulating blood pressure (BP) remains uncertain. Recently it was reported that in mice lacking functional endothelial NOS (eNOS) genes (-/-), acute administration of a nonselective NOS inhibitor, Nw-nitro-L-arginine, decreased mean BP, suggesting that NO released by non-eNOS isoforms increases BP. Because the inducible NOS isoform is not constitutively expressed and when induced causes hypotension, we hypothesize that it is NO produced by nNOS that increases BP in the absence of eNOS activity. To test this hypothesis, we studied the acute effect of selective and nonselective nNOS inhibitors on BP and cerebellar NOS activity in eNOS (-/-), wild-type (+/+), and heterozygous (+/-) mice as well as in +/+ mice with renovascular hypertension. Because it is not known whether the decrease in BP caused by acute NOS inhibition in -/- mice can occur chronically, we also studied the effect of chronic NOS inhibition on both BP and cerebellar NOS activity. eNOS (-/-) mice had higher BP than +/+ or +/-mice, and acute administration of the selective nNOS inhibitor 7-nitroindazole (7-NI) decreased their mean BP from 137+/-13 to 124+/-12 mm Hg (P<0.01). In +/+, +/-, or renovascular hypertensive +/+ mice, 7-NI caused a small but insignificant rise from 105+/-5 to 110+/-6 mm Hg, from 115+/-9 to 119+/-13 mm Hg, and from 146+/-6 to 150+/-6 mm Hg, respectively. Fifteen minutes after administration of 7-NI, cerebellar NOS activity decreased by 70%; however, this inhibitory effect was brief, since 2 hours after 7-NI administration NOS returned toward control values. Chronic oral or intraperitoneal administration of 7-NI did not inhibit cerebellar NOS activity, whereas the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) decreased this activity by 50%. Therefore, we studied the effect of chronic L-NAME administration (4 weeks) on BP. In -/- mice, chronic L-NAME administration decreased BP from 135+/-4 to 120+/-3 mm Hg (P<0.05), whereas in +/+ and +/-mice, as expected, it increased BP from 109+/-2 to 125+/-3 mm Hg (P<0.001) and from 107+/-6 to 119+/-5 mm Hg (P<0.02), respectively. After L-NAME administration was stopped, BP returned to baseline. These results suggest that in eNOS -/- mice, NO derived from nNOS increases BP both acutely and chronically.

Animals↗