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Biomedical subjects

Y Kita

Publications and source records attributed to Y Kita.

At least 37 records · Page 2Linked to original sources
PubMed2003

What cause of mortality can we predict by cholesterol screening in the Japanese general population?

OBJECTIVE: In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan. DESIGN: A 13.2-year cohort study for cause-specific mortality. SETTING: Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed. SUBJECTS: A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease. RESULTS: There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L-1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval; 1.52-5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L-1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all-cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow-up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person-years, which was threefold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person-years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease. CONCLUSION: Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small.

Adult↗
PubMed2003

A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours.

During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.

Aged↗
PubMed2003

[Intrathoracic chronic expanding hematoma; report of a case].

A case of a patient with a intrathoracic chronic expanding hematoma presenting as a neoplasm is reported. A chronic encapsulated intrathoracic hematoma is rare condition and is clinically included in a category of chronic hemorrhagic empyemas as a type of chronic empyemas in Japan. The clinical picture of our case suggested a slowly growing tumor. Though needle biopsy was performed, only blood was aspirated. Intraoperative findings revealed a intrathoracic hematoma with a tough capsule. It adhered to the chest wall hardly. Histopathological investigations revealed that the capsule consisted of a collagenous outer layer and a newly vascularized inner layer with fibrosis. Hemosiderin deposits suggested recurrent bleeding from fragile vessels. The mechanisms of hematoma formation and its expanding nature are discussed. The hematoma appeared to have been enlarged by repeated exudation or bleeding from capillaries inside the capsule.

Chronic Disease↗
PubMed2002

Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis.

To study the activation states and cytokine profiles of pulmonary T cells in corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. CD25+ CD4+ T cells in BALF were significantly increased in both corticosteroid-resistant and corticosteroid-sensitive IP in DM/PM as compared with those in controls without IP. Furthermore, CD25+ CD4+ T cells in BALF were significantly more increased in corticosteroid-resistant IP than those in cortico teroid- sensitive IP. Moreover, CD25+ CD8+ T cells in BALF were significantly increased only in corticosteroid-resistant IP, but not in corticosteroid-sensitive IP or controls without IP. IFN-gamma mRNA was detected in BALF T cells in corticosteroid-resistant and corticosteroid-sensitive IP but not in controls without IP, whereas IL-4 mRNA was virtually undetected in BALF T cells in both the IP groups. However, there were no significant differences in CD4/CD8 ratio of BALF T cells, HLA-DR+ BALF T cells or CD25+ and HLA-DR+ peripheral blood T cells between the two IP groups. These results indicate that activated Th1-type pulmonary T cells play an important role in the development of corticosteroid- resistant IP in DM/PM and that the increase in CD25+ CD8+ T cells in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM and hence may be an indicator for early use of cyclosporin.

Bronchoalveolar Lavage Fluid↗
PubMed2002

NOR-1: a nitric oxide releasing agent for calibrating low levels of nitric oxide by the chemiluminescence method.

Nitric oxide (NO) is formed in small amounts in vivo and is rapidly oxidized by interacting with oxygen, making measurement of its level difficult. The chemiluminescence assay is the most widely used method for detecting NO and is extremely sensitive to very small amounts of NO. However, it is difficult to prepare small amounts of NO to be used as a standard for NO analysis. NOR-1, a derivative of NOR-3, is a newly discovered NO donor with rapid NO-releasing activity. We assessed the dynamics of NO release and decomposition using NOR-1. Our results demonstrate that NOR-1 is stable in dimethylsulfoxide (DMSO) and is able to dilute at lower concentration (to picomolar levels) by DMSO without decomposition. NOR-1 released persistently 1.4 more excess of NO with 15 min of incubation. There was a linear relationship between the concentration of NOR-1 and that of NO released from NOR-1 (r=0.997) These findings suggest that NOR-1 is a useful reagent for the calibration of lower NO detection.

Benzoates↗
PubMed2002

[Mediastinal signet-ring cell carcinoma of unknown primary site; report of a case].

The question whether the tumor is primary or metastatic sometimes arises in patients with intrathoracic tumor. Especially, adenocarcinoma presents more difficulties in distinguishing primary tumors from secondary or deciding its origin. We reported a case of mediastinal signet-ring cell carcinoma. A 51-year-old female was admitted because of an abnormal shadow during mass screening. Chest X-ray showed a semicircular, well-demarcated shadow on right cardiophrenic angle. Chest computed tomography (CT) revealed a homogeneous mass, approximately 4 cm in diameter. The investigations of whole body failed to reveal any other tumor. At operation, the tumor was adherent to the esophagus but easily resected. Histologically, the tumor was mainly composed of signet-ring cells. Immunohistochemically, surfactant apoprotein (SPA) was strongly demonstrated in tumor cells. SPA is specific to the lung and the tumor was diagnosed as the metastasis in mediastinal lymph nodes. The primary site was considered to exist in lung. But the primary site was not found over 46 months in spite of repeated further examinations.

Carcinoma, Signet Ring Cell↗
PubMed2001

Remarkable effect of aluminum reagents on rearrangements of epoxy acylates via stable cation intermediates and its application to the synthesis of (S)-(+)-sporochnol A.

A remarkable effect of (C(6)F(5)O)(3)Al for promoting the rearrangement of epoxy acylates via stable cation intermediates was found, and new methods for constructing chiral benzylic, vinylic, and acetylenic quaternary carbon centers were developed. During the study, the importance of the ionic nature of the O-metal bond in the intermediates of such epoxides was addressed. This method was applied to the asymmetric total synthesis of (S)-(+)-sporochnol A.

Alkenes↗
PubMed2001

Enantiodivergent synthesis of either enantiomer of ABCDE-ring analogue of antitumor antibiotic fredericamycin A via intramolecular [4 + 2] cycloaddition approach.

[reaction: see text] An intramolecular enantiodivergent synthesis of both enantiomers of the ABCDE-ring analogue 22 of fredericamycin A is reported. Key steps involve an intramolecular [4 + 2] cycloaddition of 17 and an aromatic Pummerer-type reaction of 19. A lipase-catalyzed enantioselective desymmetrization of prochiral diol 2 using 1-ethoxyvinyl 2-furoate 3 led to the pivotal intermediate (R)-4.

Antibiotics, Antineoplastic↗
PubMed2001

Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults.

A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants of amyloid precursor protein (APP), M146L-presenilin (PS) 1, and N141I-PS2] and by Abeta1-43 with clear action specificity ineffective on neurotoxicity by polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit neurotoxicity by other AD-relevant insults: other familial AD genes (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, and H163R-PS1), APP stimulation by anti-APP antibody, and other Abeta peptides (Abeta1-42 and Abeta25-35). The action specificity was further indicated by the finding that HN could not suppress neurotoxicity by glutamate or prion fragment. Against the AD-relevant insults, essential roles of Cys(8) and Ser(14) were commonly indicated, and the domain from Pro(3) to Pro(19) was responsible for the rescue action of HN, in which seven residues turned out to be essential. We also compared the neuroprotective action of S14G HN (HNG) with that of activity-dependent neurotrophic factor, IGF-I, or basic FGF for the antagonism against various AD-relevant insults (V642I-APP, NL-APP, M146L-PS1, N141I-PS2, and Abeta1-43). Although all of these factors could abolish neurotoxicity by Abeta1-43, only HNG could abolish cytotoxicities by all of them. HN and HN derivative peptides may provide a new insight into the study of AD pathophysiology and allow new avenues for the development of therapeutic interventions for various forms of AD.

Alzheimer Disease↗
PubMed2001

Proton relay in a one-dimensional hydrogen-bonded chain composed of water molecules and a squaric acid derivative.

The crystal structure of a hydrated crystal of bis(squaryl)biphenyl (BSQB*4H2O), in which two squaric acid moieties are connected with a 4,4'-biphenyl unit, was characterized by the presence of a one-dimensional hydrogen-bonded chain composed of BSQB and water molecules. X-ray crystallographic analysis showed that BSQB exists in a dianion form and that, on average, two of the four water molecules are protonated. The enhanced temperature dependence of the thermal parameters of the oxygen atoms of the water molecules suggested dynamic disorder of the water molecules. The solid-state magic angle spinning deuterium NMR spectrum of BSQB*4D2O revealed that deuterons are exchanged between heavy water molecules and oxonium ions with an exchange rate of ca. 700 Hz around 250 K and that deuterons start to migrate in a hydrogen-bonded cluster of water molecules. Ac dielectric measurements were also used to examine the dynamic process in the hydrated crystal. The dielectric permittivity of the crystal dramatically increased above 250 K with a distinct frequency dependence (epsilon' = 4.7 x 10(4) at 340 K and 1 kHz). The frequency dependence of tan delta at 290 K exhibited a maximum at 3.0 kHz, and this maximum shifted to lower frequencies when the temperature of the crystal decreased. These experimental results suggested that in the one-dimensional hydrogen-bonded chain of BSQB*4H2O a proton relay between oxonium ions and water molecules occurred within a cluster of four water molecules and that the relay was transmitted to the adjacent cluster mediated by the modulation of the negative charge distribution of the BSQB dianion. These phenomena were interpreted as the solitonic migration of the charged domain boundaries along the one-dimensional hydrogen-bonded chain.

Crystallography, X-Ray↗
PubMed2001

c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK.

Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries. In addition to known interacting proteins containing a phosphotyrosine-interaction-domain (PID)-Fe65, Fe65L, Fe65L2, X11, and mDab1, we identified, as a novel APP-interacting molecule, a PID-containing isoform of mouse JNK-interacting protein-1 (JIP-1b) and its human homolog IB1, the established scaffold proteins for JNK. The APP amino acids Tyr(682), Asn(684), and Tyr(687) in the G(681)YENPTY(687) region were all essential for APP/JIP-1b interaction, but neither Tyr(653) nor Thr(668) was necessary. APP-interacting ability was specific for this additional isoform containing PID and was shared by both human and mouse homologs. JIP-1b expressed by mammalian cells was efficiently precipitated by the cytoplasmic domain of APP in the extreme Gly(681)-Asn(695) domain-dependent manner. Reciprocally, both full-length wild-type and familial Alzheimer's disease mutant APPs were precipitated by PID-containing JIP constructs. Antibodies raised against the N and C termini of JIP-1b coprecipitated JIP-1b and wild-type or mutant APP in non-neuronal and neuronal cells. Moreover, human JNK1beta1 formed a complex with APP in a JIP-1b-dependent manner. Confocal microscopic examination demonstrated that APP and JIP-1b share similar subcellular localization in transfected cells. These data indicate that JIP-1b/IB1 scaffolds APP with JNK, providing a novel insight into the role of the JNK scaffold protein as an interface of APP with intracellular functional molecules.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Alterations of repeated sequences in 5' upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome.

One of the characteristics of tumors from patients with germline mutations of DNA mismatch repair genes is instability at microsatellite regions (MSI). We analysed alterations at repeated sequences of coding regions, as well as those of 5' upstream regions, in 29 MSI-High colorectal tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot syndrome. We found that repeated sequences in 5' upstream regions were altered in these tumors, at considerable frequencies. The (A)10 repeat in the promoter region (position -178 to approximately -169) of the GAPDH gene was altered in 17% of the tumors. The (A)10(TA)9 in the 5' upstream region (position -318 to approximately -291) of the mitochondrial isoleucyl tRNA synthetase gene (IleRS-A), coded in nuclear DNA, was altered in 59% of the tumors, whereas (A)9 in the 5' upstream region (position -859 to approximately -851) of cytoplasmic isoleucyl tRNA synthetase gene (IleRS-B) was not altered. Alteration at repeated sequences in the coding regions were 72% at TGFbetaRII(A)10, 24% at IGFIIR(G)8, 45% at BAX(G)8, 55% at E2F4(CAG)13, 66% at caspase-5 (A)10, 31% at MBD4(A)10, 55% at hMSH3(A)8 and 34% at hMSH6(C)8. The number of altered genes increased with the advancement of carcinoma according to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6 for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mean number for adenomas was 2.0. These results suggest that the MSI phenotype also causes alteration of 5' upstream regions which may affect apoptosis and some mitochondrial functions in HNPCC and Turcot tumors, and that accumulation of altered genes with repeated sequences is associated with the progression of HNPCC and Turcot colorectal tumors.

Adenoma↗
PubMed2001

Two types of movement-related cortical potentials preceding wrist extension in humans.

We compared the occurrence patterns of movement-related cortical potentials (MRCPs) preceding wrist extension in athletes (kendoists and gymnasts) and non-athletes. The MRCPs of the non-athletes started approximately 1.5 s before the EMG onset of wrist extension. In the athletes, the duration of the MRCPs was shorter and the amplitudes of early component (Bereitschaftspotential) were smaller than in the non-athletes. The MRCPs in the athletes started approximately 400 ms before the onset of wrist extension and increased rapidly. In topographical maps, MRCPs of the athletes were localized markedly on the contralateral motor area (C3) compared with the non-athletes. In the present study, the duration of MRCPs was classified into two types.

Adolescent↗
PubMed2001

Generational and regional differences in trends of mortality from ischemic heart disease in Japan from 1969 to 1992.

The authors compared generational and regional trends of premature mortality from ischemic heart disease (IHD) from 1969 to 1992 for persons aged 30-69 years. They selected Tokyo and Osaka prefectures as the most urbanized and compared them with the rest of Japan. The data were divided into two periods: period I (1969-1978, International Classification of Diseases, Eight Revision) and period II (1979-1992, International Classification of Diseases, Ninth Revision). In both populations, IHD mortality decreased for both sexes, but mortality from nonspecific heart disease remained constant in men and decreased in women. In Tokyo and Osaka prefectures, the percentage decline per year in IHD mortality for both sexes was significantly smaller in period II than in period I. However, in the rest of Japan, it did not decrease for either sex. Age-specific analysis showed that the percentage decline per year in period II was smallest for the group aged 30-49 years (men, 0.05%; women, 0.76%) in Tokyo and Osaka prefectures, while it was similar for all age groups in the rest of Japan. For men, the IHD mortality rate in 1991-1992 for those aged 30-49 years was higher in Tokyo and Osaka prefectures (9.4/100,000) than in the rest of Japan (5.4/100,000).

Adult↗