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Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 199 records · Page 11Linked to original sources

Chronic Japanese schistosomiasis and hepatocellular carcinoma: ten years of follow-up in Yamanashi Prefecture, Japan.

In a preliminary study carried out in the study area we found that 19.1% (173/907) of patients with chronic liver disease and 51% (35/68) of hepatocellular carcinoma cases were infected with Japanese schistosomiasis. Analysis of data from 571 autopsies revealed a similarly high incidence of schistosomiasis among cases of hepatoma and other liver diseases. A prospective case-control study conducted over 10 years showed that hepatoma developed in 5.4% (26/484) of chronic schistosomiasis cases and in 7.5% (23/307) of patients with chronic liver disease (hepatitis, cirrhosis, etc). The difference was not statistically significant (P = 0.228). A high incidence of hepatitis C virus (HCV) antibody (HCVAb) was found in the schistosomiasis group (36.5%; 95% CI = 44.9-28.1%) and in the chronic liver disease group (56.0%), 39% of whom had chronic hepatitis (P = 0.028). Various factors that might have contributed to the development of hepatoma and schistosomiasis were investigated, but no evidence of a significant correlation between schistosomiasis and hepatoma was found. The high incidence of HCVAb was considered to have been responsible for the development of hepatocellular carcinoma in chronic schistosomiasis patients. The role of HBV infection in the development of hepatoma in schistosomiasis patients was not confirmed after an assay for HCVAb was included in the study.

Adult↗

[Surgical repair for ischemic mitral regurgitation: a method of mitral valve plasty with evaluation of morphological changes of mitral valve].

We evaluated a method of mitral valve plasty (MVP) for ischemic mitral regurgitation (IMR) by examining the morphological changes of the mitral valve. From November 1992 to May 1998, 8 patients (M : F = 4/4, age 44-79 years, mean age 65.1 years) with IMR underwent surgical repair. Preoperative mitral regurgitation (MR) was grade III of Sellers classification in 7 patients and grade IV in 1 patient. The cause of MR was mitral valve annular dilatation in 4 patients, mitral valve prolapse due to papillary muscle elongation in 2 patients, and partial papillary muscle rupture (PMR) in 2 patients. Cardiac surgery consisted of CABG + MVP in 7 patients and MVP in 1 patient. Mitral valve repair was separated into three types. Repair for annular dilatation consisted of commissuroplasty in 3 patients (2 patients Kay method, 1 patient Reed method) and ring annuloplasty using a Carpentier-Edwards ring (C-E ring) in 1 patient. Repair for papillary muscle elongation consisted of papillary muscle shortening and ring annuloplasty using a C-E ring. Repair for partial PMR consisted of papillary muscle implantation and ring annuloplasty for anterior leaflet prolapse in 1 patient, and quadrangular resection, posterior leaflet plasty (McGoon method) and ring annuloplasty in 1 patient. There was no hospital death. Postoperative outcome was 6 patients with no MR and 2 patients with grade II MR, but they were well-controlled with medication. Based on the morphological changes of the mitral valve, it is considered that MVP for IMR is an effective and recommended procedure.

Adult↗

[Clinical analysis of thrombocytopenia in chronic dialysis patients].

Thrombopoietic status in dialysis patients is controversial. This study addressed this issue by analyzing factors associated with thrombopoiesis. One hundred and fifty-one dialysis patients(119 HD and 32 CAPD) and 41 age-matched control subjects were studied. Thrombocytopenia was defined as a platelet count less than 150 x 10(9)/l. Reticulated platelets(RET), a marker for marrow megakaryopoiesis, were measured using thiazole orange dye by flowcytometry. Serum thrombopoietin (TPO) level was measured by ELISA. Hepatitis C virus(HCV) antibody, platelet-associated IgG(PAIgG), and other clinical parameters were examined in the patients. The platelet counts in the HD patients were significantly lower than those in the CAPD or controls. The incidence of thrombocytopenia was 30.0% in the HD patients. Thrombocytopenia was more prominent in the HCV-infected HD patients in whom PAIgG was mostly positive(81.8%) and its titer was remarkably high(102.9 +/- 92.7 pg/ml). There were significant differences in the RET counts between patients with and without thrombocytopenia. None of the other parameters, such as iPTH, beta 2 microglobulin, and Kt/V, nor any prescribed drugs were related to thrombocytopenia. Serum TPO was significantly higher in HD patients(135.9 +/- 60.1 pg/ml) than in the controls(97.0 +/- 53.4 pg/ml). In conclusion, thrombocytopenia is frequent in HD patients, especially in HCV-infected HD patients. Reduced marrow magakaryopoiesis is mostly responsible for thrombocytopenia and peripheral destruction of platelets could be, in part, involved. Mild elevation of serum TPO possibly indicates a counter-response to decreased mass of megakaryocyte in bone marrow.

Adult↗

[Relationship between renal function and morphometric assessment in chronic glomerulonephritis].

In an attempt to reveal a correlation between the degree of glomerular hypertrophy, interstitial damage, and hemodynamic parameters in chronic nephritis, the glomerular area (GA) and proportion of interstitial area (IA%) were determined quantitatively with an image analyzer, and the effective renal plasma flow (ERPF) and filtration fraction (FF) were determined simultaneously. The subjects were 12 patients with focal glomerulosclerosis (FGS) and 12 patients with IgA nephropathy (IgAN), all of whom had a similar glomerular filtration rate (GFR). The GFR was 58.6 +/- 11.4 ml/min/1.48 m2 in the FGS group and 53.9 +/- 13.1 ml/min/1.48 m2 in the IgAN group, and the difference between the two groups was not significant. On the other hand, ERPF was significantly lower and FF was significantly higher in the FGS group than in the IgAN group. GA was significantly higher in the FGS group than in the control group (10 kidney donors), and GA in the IgAN group was equivalent to that in the control group. IA% was almost equal in the FGS and IgAN groups, and significantly higher in both groups than in the control group. Although GA was not correlated with GFR in the two groups, it tended to be positively correlated with FF in the FGS group, and the correlation between GA and FF reached statistical significance when the IgAN group was combined with the FGS group. The above findings suggest that the pattern of progression of the glomeruli and interstitial lesions and of the intrarenal hemodynamics involved in them may differ in the FGS and IgAN groups. However, since ERPF significantly decreased in the FGS group, even though IA% was the same in both groups, the possibility that ERPF was functionally decreased in the FGS group cannot be ruled out.

Adult↗

Alz-50/Gallyas-positive lysosome-like intraneuronal granules in Alzheimer's disease and control brains.

The Gallyas-Braak silver impregnation method revealed neurons containing well-defined intraneuronal granules in both Alzheimer's disease and normal control brains. The granules were immunostained prominently with the Alz-50 antibody and, to a lesser degree, with the tau-2 antibody, but not with other anti-tau antibodies examined. The areas of distribution of granule-containing neurons detected by the Gallyas-Braak method appeared to overlap with the reported main sites of subcortical distribution of neurofibrillary tangles. They, however, were not observed in the cerebral cortex, including the hippocampal region. The Alz-50 immunoreactive granules showed ultrastructural features similar to those of lysosomes or lipofuscin. These findings suggest that denatured tau might be degraded in lysosomes.

Aged↗

The attenuated effect of ATP-sensitive K+ channel opener pinacidil on renal haemodynamics in spontaneously hypertensive rats.

In hypertension, impairment of hyperpolarization by K+ efflux through ATP-sensitive K+ (K(ATP)) channels may contribute to the elevated renal vascular resistance. To elucidate such a role for K(ATP) channels in the renal vasculature, we used micropuncture techniques to examine the effect of K(ATP) channel opener, pinacidil (0.15 mg/h per kg body wt i.v.), on renal and glomerular haemodynamics in spontaneously hypertensive rats (SHR) and in normotensive controls (Wistar Kyoto, WKY). Since pinacidil reduced blood pressure significantly in both groups, the abdominal aorta was clamped before pinacidil administration to yield a renal perfusion pressure equivalent to that during pinacidil infusion. Pinacidil significantly decreased renal vascular resistance in both groups, but the relative change from baseline value was greater in WKY than in SHR. These effects of pinacidil were abolished by pretreatment with glibenclamide (3 mg/kg body wt i.v.). Proximal tubular stop-flow pressure (Psf), an index of glomerular capillary pressure, was significantly elevated by pinacidil infusion in WKY, a response abolished by pretreatment with glibenclamide, but not in SHR. The tubuloglomerular feedback response of Psf was not affected by pinacidil in either group. These data suggest that the activity of K(ATP) channels in SHR may be attenuated in the renal microvasculature. This may contribute to the elevated vascular tone in the renal preglomerular vasculature in SHR.

Animals↗

A clinical, genetic, neuropathological study in a Japanese family with SCA 6 and a review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy.

This report concerns a Japanese family with genetically confirmed SCA 6, including an autopsy case, and a review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy (ADCCA). The proband (Case 1) was a Japanese woman. She developed gait disturbance at age 62. The father and younger sister (Case 2) had the same disorder. She died at age 67 due to subarachnoid hemorrhage. Neuropathological examination revealed severe loss of Purkinje cells in the cerebellum, prominently in the dorsal vermis, and absence of neuronal loss in the inferior olives. Molecular genetic study showed the CAG-repeat expansion of SCA 6 gene. The younger sister (Case 2) developed gait disturbance at age 62. Neurological examination at age 66 revealed cerebellar signs without sensory disturbance. Neuroimaging at this time showed cerebellar atrophy, prominently in the vermis. She died of multiple myeloma at age 66. A neuropathological review of Japanese autopsy cases of ADCCA showed that there are two patterns in the distribution of cerebellar cortical lesions of Japanese patients with ADCCA. The distribution of cerebellar cortical lesions in genetically confirmed Japanese patients with SCA 6 is more prominent in the vermis than in the hemisphere.

Aged↗

Cloning of inv, a gene that controls left/right asymmetry and kidney development.

Most vertebrate internal organs show a distinctive left/right asymmetry. The inv (inversion of embryonic turning) mutation in mice was created previously by random insertional mutagenesis; it produces both a constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys. Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant, indicating that inv may act early in left/right determination. Here we identify a new gene located at the inv locus. The encoded protein contains 15 consecutive repeats of an Ank/Swi6 motif at its amino terminus. Expression of the gene is the highest in the kidneys and liver among adult tissues, and is seen in presomite-stage embryos. Analysis of the transgenic genome and the structure of the candidate gene indicate that the candidate gene is the only gene that is disrupted in inv mutants. Transgenic introduction of a minigene encoding the candidate protein restores normal left/right asymmetry and kidney development in the inv mutant, confirming the identity of the candidate gene.

Amino Acid Sequence↗

Endothelin-1-(1-31), a novel vasoactive peptide, increases [Ca2+]i in human coronary artery smooth muscle cells.

We have previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any further degradation products. In this study, we investigated the effect of synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration ([Ca2+]i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1-31) increased [Ca2+]i in a concentration-dependent manner (10(-14) to 10(-10) M). This endothelin-1-(1-31)-induced [Ca2+]i increase was not affected by phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by 10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A) receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B) receptor antagonist. These results suggest that endothelin-1-(1-31) by itself exhibits vasoactive properties probably through endothelin ET(A) receptors. Since human chymase has been reported to play a role in atherosclerosis, endothelin-1-(1-31) may be one of the candidate substances for its cause.

Calcium↗

Reconstruction for the brilliance-upgrading project of the Photon Factory storage ring.

Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in progress to provide very brilliant synchrotron radiation to users, i.e. the emittance is being reduced by a factor of five. Components, such as the quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position monitors, are being replaced by new ones in 16 normal-cell sections of the PF ring. The accelerating cavities, injection systems and control systems are also being replaced. Operation will commence when the improvements are completed on 1 October 1997.

Journal Article↗

A practically zero horizontal magnetic field in a planar undulator used in the Tristan Super Light Facility.

The Tristan Main Ring (MR) at KEK (High Energy Accelerator Research Organization) has been used as a third-generation synchrotron radiation ring with an undulator installed in the MR as a third-generation light source. The magnetic field irregularities of the undulator were examined precisely. Measurement of the magnetic field after synchrotron radiation experiments showed that the magnetic irregularities in both the horizontal and vertical directions are negligibly small. This result suggests that our previous estimates of emittance, made using the measured undulator spectrum, should correctly represent the properties of the electron beam in the MR.

Journal Article↗

Cell cycle arrest and antitumor activity of pironetin and its derivatives.

The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.

Animals↗

Distribution of cerebellar cortical lesions in multiple system atrophy: a topographic neuropathological study of three autopsy cases in Japan.

We investigated neuropathologically the distribution of the cerebellar cortical lesions in three Japanese autopsy cases of multiple system atrophy (MSA) using hemisphere specimens. The lesions were classified as mild, moderate or severe. The distribution of cerebellar cortical lesions in all three cases were uniform: the cerebellar cortical lesions were more conspicuous in the vermis than in the hemisphere. These neuropathological findings differ from the established theory that cerebellar lesions of MSA are more pronounced in the hemisphere than in the vermis. The degree of cerebellar cortical lesions in our cases increased in relation to the duration of the disease. Our pathological data may contribute to the morphological differential diagnosis in various neurodegenerative disorders including late cortical cerebellar atrophy. Our neuropathological findings may also make a contribution to the neuroradiological progress in the differential diagnosis of spinocerebellar disease.

Brain Mapping↗

Positive and negative controls by protein kinases of sodium-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells stimulated by lysophosphatidic acid.

We previously found that lysophosphatidic acid (LPA), a bioactive phospholipid, induced Na+-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells, possibly by activating a Na+/Ca2+ exchanger. The present study on the structure-activity relationship of its action revealed that 1-acyl type LPAs were stronger stimulants than the corresponding 1-O-alkyl type LPAs having a long alkyl moiety with the same chain length. Lysophosphatidylglycerol, suramin and N-palmitoyl-tyrosine phosphoric acid have all been reported to inhibit the action of LPA in some animal cells and platelets, but only lysophosphatidylglycerol was found to inhibit selectively LPA-induced Ca2+ efflux from chromaffin cells. LPA-induced Ca2+ extrusion was suggested to be involved in both acceleration of return of intracellular Ca2+ in Fura 2-loaded bovine chromaffin cells after addition of carbachol, and inhibition of carbachol-induced catecholamine release when the cells were co-incubated with LPA. The Ca2+ efflux from chromaffin cells stimulated by LPA was augmented by their pretreatment with staurosporine or calphostin C, inhibitors of protein kinase C, but reduced by their preincubation with phorbol 12-myristate 13-acetate. Furthermore, the response to LPA was potentiated by sodium vanadate, a protein tyrosine phosphatase inhibitor, but inhibited by genistein, an inhibitor of protein tyrosine kinase. These results suggest that protein kinase C and protein tyrosine kinase are involved negatively and positively, respectively, in the signal transduction triggered by LPA, leading to activation of the Na+/Ca2+ exchanger.

Adrenal Glands↗

A new inbred strain JF1 established from Japanese fancy mouse carrying the classic piebald allele.

A new inbred strain JF1 (Japanese Fancy Mouse 1) was established from a strain of fancy mouse. Morphological and genetical analysis indicated that the mouse originated from the Japanese wild mouse, Mus musculus molossinus. JF1 has characteristic coat color, black spots on the white coat, with black eyes. The mutation appeared to be linked to an old mutation piebald (s). Characterization of the causative gene for piebald, endothelin receptor type B (ednrb), demonstrated that the allele in JF1 is same as that of classic piebald allele, suggesting an identical origin of these two mutants. Possibly, classic piebald mutation was introduced from the Japanese tame mouse, which was already reported at the end of the 1700s. We showed that JF1 is a useful strain for mapping of mutant genes on laboratory strains owing to a high level of polymorphisms in microsatellite markers between JF1 and laboratory strains. The clarified genotypes of JF1 for coat color are "aa BB CC DD ss".

Alleles↗

Cloning and mapping of bovine ZFX gene to the long arm of the X-chromosome (Xq34) and homologous mapping of ZFY gene to the distal region of the short arm of the bovine (Yp13), ovine (Yp12-p13), and caprine (Yp12-p13) Y chromosome.

A part of mouse Zfy-2 sequence was synthesized and used to screen a genomic library of the spinous country-rat (Tokudaia osimensis spp., 2n = 45). An isolated clone had the C-terminal region of Zfy, which consisted of 1190 bp, encoded 336 amino acid residues, and harbored 11 out of 13 zinc finger motifs. With this as a probe, a bovine testis cDNA library was screened. Two ZFX clones were isolated and their sequences combined. The short sequence, lacking part of the 5' upstream region, was amplified by PCR or RT-PCR, cloned, and sequenced. A full-length ZFX was constructed by combining these three sequences. The bovine ZFX consisted of 5328 bp and encoded 800 amino acid residues, which contained 13 zinc finger motifs. ZFX was used as a probe for fluorescence in situ hybridization and was mapped to Xq34, different from its previously reported site at Xq21-q231. A SINE (short interspersed nuclear element) sequence consisting of 188 bp was found close to the end of the 3'-untranslated region of ZFX. The SINE sequence hybridized to all bovine chromosomes. ZFY is highly homologous with ZFX and, as a result, ZFY could be mapped simultaneously. ZFY was mapped to the distal region of the short arm of the Y Chromosome (Chr) (Yp13), contradicting the previously reported position Yq1. Ovine and caprine ZFY were also mapped with bovine ZFX. Both were mapped to the distal region of the short arm of the Y Chr (Yp12-p13). Ovine ZFX was mapped to a region close to the centromere of the X Chr (Xq13).

Amino Acid Sequence↗

Dentatorubropallidoluysian atrophy: clinicopathological study of dementia and involvement of the nucleus basalis of Meynert in seven autopsy cases.

This report concerns a clinicopathological study including a quantitative pathological study on the nucleus basalis of Meynert (nbM) of seven Japanese autopsy cases (four male, three female) of dentatorubropallidoluysian atrophy (DRPLA) with special reference to the clinicopathological correlation of dementia in DRPLA. In each case the pattern of the inheritance was consistent with that of an autosomal dominant trait. The neurological examination revealed that all seven individuals had cerebellar signs. Six patients had epilepsy and choreoathetoid involuntary movement; myoclonus was evident in five patients. Dementia was noted in all seven patients. Degeneration of the globus pallidus (particularly the lateral segment) and of the dentate nucleus was the principal pathological feature. Brain weights at autopsy ranged from 1020 to 1400 g (average 1241 g: male 1320 g, female 1135 g). The quantitative evaluation revealed no significant loss of neurons in the nbM as compared with a control group. There was no clinicopathological correlation between dementia and involvement of the nbM. We suggest that the dementia of DRPLA is due not to the involvement of the nbM, but to - as yet - unidentified pathology elsewhere.

Adolescent↗