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Biomedical subjects

K Murata

Publications and source records attributed to K Murata.

At least 19 recordsLinked to original sources
PubMed2006

Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene.

No genetically diagnosed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pedigrees with venous insufficiency have been described. In a CADASIL pedigree with varicose veins, the authors have identified a novel heterozygous mutation in the 3' splice acceptor site of intron 15 of the Notch3 gene. This, based on mRNA analysis, resulted in skipping of exon 16 including eight cysteine residues of EGF-like repeats.

Adult↗
PubMed2006

Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study.

Visceral adipose tissue (VAT) is an independent risk factor for metabolic and cardiovascular disorders. There has been no study that demonstrated different abdominal fat distribution between Asian and Caucasian men. As the Japanese are less obese but more susceptible to metabolic disorders than Caucasians, they may have larger VAT than Caucasians at similar levels of obesity. We compared the abdominal fat distribution of the Japanese (n=239) and Caucasian-American (n=177) men aged 40-49 years in groups stratified by waist circumference in a population-based sample. We obtained computed tomography images and determined areas of VAT and subcutaneous adipose tissue (SAT). We calculated VAT to SAT ratio (VSR). The Japanese men had a larger VAT and VSR in each stratum, despite substantially less obesity overall. In multiethnic studies, difference in abdominal fat distribution should be considered in exploring factors related to obesity.

Adult↗
PubMed2006

Inhibition of BRCA1 in breast cell lines causes the centrosome duplication cycle to be disconnected from the cell cycle.

BRCA1-dependent ubiquitination activity regulates centrosome number in several tissue culture cell lines derived from breast cells. In these experiments, we asked how BRCA1 inhibits centrosome amplification. In general, supernumerary centrosomes can accumulate by three mechanisms: (1) failed cytokinesis and the accumulation of centrosomes by duplication in a repeated S-phase of the cell cycle, (2) disruption of the licensing of centrosome doubling such that they duplicate at inappropriate times in the cell cycle, or (3) fragmentation of the centrosomes. In this study, we found that inhibition of BRCA1 caused premature separation of centrioles and reduplication. By blocking cells in early S-phase before centrosome amplification secondary to BRCA1 inhibition could occur and then releasing, we found that inhibition of BRCA1 caused centrosome amplification between late S-phase and G2/M before the cell divided. These results suggest that normal BRCA1 function is critical in these cell lines to prevent centriole separation and centrosome reduplication before mitosis.

Adenocarcinoma↗
PubMed2006

Effect of porcine zonae pellucidae immunisation on ovarian follicular development and endocrine function in domestic ewes (Ovis aries).

Domestic ewes (Ovis aries) were immunised with porcine zonae pellucidae (pZP) or pZP conjugated to keyhole limpet haemocyanin (KLH) in adjuvant(s) to examine the feasibility of the species to serve as a model for further development of pZP-based vaccines in ungulates. Two immunisation groups were employed, with a third group receiving only adjuvant (n = 5 per group). Early in the study, oestrous activity was monitored by the use of a vasectomised ram fitted with a marking harness. Eventually, ewes were exposed to an intact ram for breeding. In addition, weekly serum and every-other-day faecal samples were collected to measure pZP antibodies and progesterone metabolite concentrations respectively. At the conclusion of the study, fecundity was established, and ovarian tissue was examined. Ewes immunised against pZP : KLH with adjuvant produced minimal antibody absorbance levels, displayed normal oestrous cycles, became pregnant upon introduction of the intact ram and exhibited normal ovarian histopathology. Ewes immunised against pZP with adjuvant produced high antibody absorbance levels, were acyclic following primary immunisation and were infertile. Examination of the ovarian tissue revealed atrophic changes that included: (1) the absence of growing follicles; (2) significant reduction in the number of primordial follicles; and (3) the presence of abnormal granulosa cell clusters lacking oocytes. Antisera displayed immunoreactivity to the major components of pZP, and immunohistochemical labelling of ovarian tissue showed specificity to the ZP. These data are the first generated in an ungulate species showing deleterious effects of pZP immunisation on folliculogenesis and oestrous cyclicity.

Adjuvants, Immunologic↗
PubMed2006

C4d deposition and clearance in cardiac transplants correlates with alloantibody levels and rejection in rats.

Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days.

Animals↗
PubMed2005

Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women.

We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.

Adult↗
PubMed2005

Effects of shift schedules on fatigue and physiological functions among firefighters during night duty.

To examine the effects of shift schedules on fatigue and physiological functions among firefighters a 17-day field study at a fire station was carried out. Eleven firefighters, who were engaged in firefighting emergency services, participated in this study. At the fire station, night duty (22:00-07:00) was divided into 5 periods (P1: 22:00-00:00; P2: 23:45-01:45; P3: 01:30-03:30; P4: 03:15-05:15; P5: 05:00-07:00). The participants were assigned to one of these 5 periods and awakened to answer calls from the city's central information centre. They took naps in individual rooms during night duty, except when on night shift or when called out on an emergency. Subjective complaints of fatigue, critical flicker fusion frequencies, 3-choice reaction times, and oral temperature were measured before and after work and following breaks during their 24 working hours. Heart rate variability was also recorded to evaluate autonomic nerve activity. The results show that during P3 and P4, participants who had to wake up at midnight took shorter naps. The rates of subjective complaints regarding P3 and P4 tended to be higher than those for P1, P2, and P5. The ratios of the low frequency component of heart rate variability to the high frequency component during P4 were significantly lower than those during P5. It is assumed that such an irregular sleeping pattern causes many complaints of subjective fatigue, and adversely affects physiological functions. A night-duty shift schedule ensuring undisturbed naps should be considered.

Adult↗
PubMed2005

Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand.

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent.

Antineoplastic Agents↗
PubMed2005

Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells.

Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and leukemic cells always carry the proviral genome monoclonally integrated into their host genomes at the same sequence site, designated as the monoclonal integration. Using Southern blot hybridization (SBH) and sequenced tagged site polymerase chain reaction assays, we examined the proviral status in 558 clinical specimens from 350 patients who are suspected to have ATL. A total of 321 specimens (57.5%) from 241 patients showed positive results for the monoclonal integration according to SBH, using EcoR1 and Pst1. The 241 patients consisted of 136 patients (56.4%) with the complete provirus (C-type), 62 patients (25.7%) with a defective provirus (D-type), and 43 patients (17.8%) with multibands (M-type). The incidence of the D- and M-types were in the order of smoldering, chronic, and acute subtypes of ATL, suggesting that such an aberrant proviral status is generated on the way to multistep carcinogenesis and is subsequently clinically important for the malignant behavior of the disease. Moreover, our data showed that the partial deletion of the proviral genome is initiated first at the site of the gag region and spreads into the sites of the pol and env regions, whereas the long terminal repeats and pX regions are almost always conserved. These results suggest that analysis of the proviral status provides useful diagnostic and virologic-oncological information about ATL and HTLV-1 pathology, especially the important role of pX gene in tumorigenesis.

Adult↗
PubMed2005

Persistence of anti-zonae pellucidae antibodies following a single inoculation of porcine zonae pellucidae in the domestic equine.

In this study of equids, we investigated the antibody response and the effect on the estrous cycle following a single inoculation of porcine zonae pellucidae (pZP) employing controlled-release methodology. We also investigated the use of two different water-soluble adjuvants as an alternative to oil-based adjuvants. Twenty-seven domestic mares were inoculated with various formulations of pZP and adjuvant. We showed that the anti-pZP antibodies generated as a result of the inoculations persisted for at least 43 weeks (length of the study). Of the various formulations used in the study, pZP and QS-21 water-soluble adjuvant, administered in combination with an emulsified preparation of pZP and Freund's Complete Adjuvant generated a significantly (P < 0.05) higher titer of anti-pZP antibodies when compared with other formulations employing the water-soluble adjuvant, Carbopol. Hormone analyses for cyclicity indicated a high incidence and extended duration of persistent corpora lutea among the treated mares. The positive control group of mares receiving two standard inoculations of pZP and Freund's Complete and Incomplete Adjuvants, as well as the placebo group of mares injected with QS-21 only, also exhibited high incidences of persistent corpora lutea. However, all mares eventually returned to normal cyclicity. The basis for the high incidence and extended duration of persistent corpora lutea was unexplained. The results demonstrate for the first time the persistent generation of anti-pZP antibodies following a single inoculation of pZP incorporated into a controlled-released preparation in the horse. This study further suggests that a single inoculation of pZP sequestered in a controlled-release lactide-glycolide polymer may serve as an alternative to traditional two-inoculation protocols for contraception investigations in the equine.

Acrylic Resins↗
PubMed2005

Toxoplasma gondii does not persist in goldfish (Carassius auratus).

Recent reports of toxoplasmosis in marine mammals raise concern that cold-blooded marine animals are a potential source of Toxoplasma gondii infection. To examine the transmissibility of T. gondii to fish, we observed the development of T. gondii tachyzoites inoculated into oviduct epithelial cells of goldfish (Carassius auratus) microscopically in vitro. Further, the survival period of tachyzoites inoculated into goldfish muscle was bioassayed in mice and through PCR analysis. In cell cultures at 37 C, both RH and Beverley strains of T. gondii tachyzoites had penetrated into cells at 6 hr post inoculation, and were multiplying. In cell cultures at 33 C, many tachyzoites of both strains attached to the host cells, but no intracellular tachyzoites were observed at 24 hr post inoculation. In the T. gondii inoculated goldfish kept at 33 C, tachyzoite DNA was detected in the inoculated region on day 3, but not on day 7. When inoculated goldfish were kept at 37 C, live tachyzoites were seen at the inoculation site on day 3, but not on day 7. These results suggest that T. gondii does not persist in fish.

Animals↗
PubMed2004

Collapse of charge order in a quasi-one-dimensional organic conductor with a quarter-filled band.

A charge-ordered insulator, (DI-DCNQI)2Ag, with a quasi-one-dimensional quarter-filled band is metallized by pressure. It was found that the charge order melts into a curious metallic state with cubic-temperature dependence of the resistivity, which implies the unprecedented mechanism of the electron-electron scattering. We constructed the pressure-temperature phase diagram, where the melting line has a tricritical point dividing the second-order line at low pressures and the first-order line at high pressures just before it vanishes.

Journal Article↗
PubMed2004

Pituitary-gonadal axis and secondary sex characters in the spontaneously masculinized pintail, Anas acuta (Anatidae, Aves), with special regard to the gonadotrophs.

This paper describes some aspects of the pituitary gland, gonads, and secondary sex characters of unusual pintails, Anas acuta, found in the wild. They were demonstrated to be females with partially masculinized plumage; i.e., their plumage showed various degrees of intersex, but the genital organs, syrinx, and electrophoretic pattern of sex-specific DNA were of the female type. Their left ovary underwent a marked involution and was associated with the mesonephros (the Wolffian body), as was the degenerated right ovary. Neither testicular tissue nor ovotestis was found in the gonad of either side. The oviduct was anatomically normal and comparable to that of the control adult. The plasma concentration of estradiol-17beta (E2) was shown to be 5.7+/-0.5 (mean+/-SE)pg/ml in the masculinized birds, 7.0+/-0.7 pg/ml in control males, and 22.5+/-6.1 pg/ml in control females, whereas plasma testosterone (T) was below the detection level in all of the samples. As to the pituitary gland, hypertrophy and/or deformity of the pars distalis was evident in the majority of the masculinized birds. Among others, hyperactive gonadotrophs, mainly luteinizing hormone (LH)- and LH/follicle-stimulating hormone (FSH)-immunoreactive cells, were prominent in the entire gland; and typical signet ring cells (castration cells) or giant gonadotrophs were frequently observed. These changes in the gonadotrophs may have been caused by a feedback response to the physiologically ovariectomized condition in the masculinized birds. Causal factor(s) of the ovarian degeneration remain to be further investigated.

Animals↗
PubMed2004

An insertional mutation in the rice PAIR2 gene, the ortholog of Arabidopsis ASY1, results in a defect in homologous chromosome pairing during meiosis.

To elucidate the genetic system that establishes homologous chromosome pairing in monocot plants, we have isolated an asynaptic mutant of rice, designated pair2 (homologous pairing aberration in rice meiosis 2), in which 24 completely unpaired univalents are observed at pachytene and diakinesis. The mutation was caused by an insertion of the retrotransposon Tos17, as demonstrated by complementation of the mutation by transformation with the corresponding wild-type gene. The gene in which the element was inserted is orthologous to the ASY1 gene of Arabidopsis thaliana and the HOP1 gene of Saccharomyces cerevisiae. Mature PAIR2 mRNA and several splicing variants were found to be highly expressed in wild-type reproductive tissues, and lower expression was also detected in vegetative tissues. In situ hybridization and BrdU incorporation experiments revealed that PAIR2 expression is specifically enhanced in male and female meiocytes, but not in those at pre-meiotic S phase or in the pollen maturation stages. The results obtained in this study suggest that the PAIR2 gene is essential for homologous chromosome pairing in meiosis, as in the case of the genes ASY1 and HOP1. The study also suggested the possibility that a highly homologous copy of the PAIR2 gene located on a different chromosome is in fact a pseudogene.

Amino Acid Sequence↗
PubMed2004

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis.

BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.

Adenocarcinoma↗
PubMed2004

Ectoparasites of the Pallas squirrel, Callosciurus erythraeus, introduced to Japan.

The squirrel Callosciurus erythraeus (Pallas) (Rodentia: Sciuridae) was intentionally introduced to Japan in 1935 and has become established throughout much of the country. Although they live mainly in forests, Pallas squirrels come into gardens and are frequently fed by people or kept as pets, so their ectoparasites could be of potential medical as well as veterinary importance. During 2001-2003 we conducted the first ectoparasite survey of Pallas squirrels in Japan. From 105 C. erythraeus captured in Kamakura District of Kanagawa Prefecture on Honshu Island, three types of ectoparasite were found: 52 specimens of the sucking louse Neohaematopinus callosciuri Johnson (Anoplura: Haematopinidae), 26 fleas Ceratophyllus (Monopsyllus) anisus Rothschild (Siphonaptera: Ceratophyllidae) and four nymphs of the tick Haemaphysalis flava Neumann (Acari: Ixodidae) on 22, 13 and one squirrels, respectively. Evidently in Japan C. erythraeus carries relatively few ectoparasite species; this may be a contributory factor to their invasive success. Further investigations are needed to assess risks of zoonotic transmission of plague or murine typhus by C. anisus, of louse-borne typhus by N. callosciuri and of tularaemia and especially Japanese spotted fever (Rickettsia japonica) by H. flava.

Animals↗