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Biomedical subjects

K Hirose

Publications and source records attributed to K Hirose.

At least 127 records · Page 7Linked to original sources
PubMed1999

Effect of body size on breast-cancer risk among Japanese women.

With the use of data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC), the effect of body size on the risk of breast cancer was evaluated among Japanese women, who are generally leaner than white women. In total, 1,359 breast-cancer cases were included, and 24,207 women, confirmed as free of cancer, were recruited as a reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple-logistic regression analysis. Separate analyses were performed for pre- and post-menopausal women. Furthermore, stratification by decade of age was done to evaluate the effect of body size on the development of breast cancer. The results obtained from the present study were as follows. (1) Current body-mass index (BMI) was positively associated with postmenopausal breast cancer (OR 2.08, 95% CI 1.49-2.92 for highest quintile vs. lowest), although higher BMI did not affect the risk in pre-menopausal women. (2) Estimates of risk were below unity for BMI at around age 20 in post-menopausal women. (3) After stratifying BMI at around age 20, gaining BMI in later life was positively associated with increased risk, regardless of BMI in early life. These findings suggest that avoidance of marked weight gain during adult life, especially after natural menopause and/or after age 60, may reduce the risk of breast cancer.

Adult↗
PubMed1999

Immunogene therapy of murine fibrosarcoma using IL-15 gene with high translation efficiency.

We have recently found that translational efficiency is up-regulated by an alternative exon in IL-15 mRNA in mice. In a malignancy model using BALB/c mice and syngeneic Meth A fibrosarcoma (Meth A), we successfully applied immunological gene therapy with IL-15 protein using alternative IL-15 cDNA with high translational efficiency. Two expression vectors carrying the murine IL-15 gene were constructed for use in tumor immunotherapy, one utilizing IL-15 cDNA with alternative exon 5 and the second utilizing IL-15 cDNA with normal exon 5. The first vector induced the production of a large amount of IL-15 protein in Meth A cells, whereas tumor cells transfected by the second vector produced only a marginal level of IL-15 protein. Although cell growth of both transfectants in vitro remained unchanged, inoculation of clones transfected with normal IL-15 cDNA resulted in progressive tumor growth, while clones transfected with alternative IL-15 cDNA led to the rejection of the tumor. The clone producing high levels of IL-15 grew progressively in nude mice and mice treated with anti-CD4 monoclonal antibodies (mAb), whereas the growth of the transfectants was retarded in anti-CD8 mAb- or anti-asialo GM1 antibody-treated mice. Cured mice were shown to have generated immunity against a subsequent challenge with the wild type of Meth A but not against Meth 1 tumor cells, another type of fibrosarcoma derived from BALB/c mice. Thus, tumor therapy based on IL-15 gene transfection was effective against Meth A tumor cells, suggesting a possible application to human neoplasms.

Animals↗
PubMed1999

Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice.

Interleukin (IL)-15 is a novel cytokine with growth factor activity for T cells, B cells, and natural killer cells (NK cells). We investigated the role of IL-15 in the host defense against infection with avirulent Salmonella choleraesuis strain 31N-1 cured of 50-kb virulent plasmid. IL-15 was abundantly expressed at transcription and protein levels in macrophages infected with S. choleraesuis 31N-1. The number of NK cells in the infected sites was increased during the course of infection coincident with IL-15 production. Anti-IL-15 mAb administration inhibited the emergence of NK cells and interferon-gamma (IFN-gamma) production in serum after infection with S. choleraesuis 31N-1 and concurrently impaired the clearance of the bacteria. These results suggested that IL-15 might be responsible for protection against avirulent S. choleraesuis infection at early stage of infection through activation of NK cells in the infected sites.

Animals↗
PubMed1999

A subclavian artery aneurysm associated with aortitis syndrome.

We performed surgery on a 61-year-old woman who had increasingly severe right shoulder pain and paresthesia in her right upper extremity as a result of a large right subclavian artery aneurysm. She had suffered from aortitis syndrome for 10 years for which she was treated with steroids and had multiple arterial lesions, including bilateral subclavian artery aneurysms, abdominal aortic aneurysm and obstruction of bilateral superficial femoral arteries. The right subclavian artery aneurysm measured 4 cm in diameter and rupture appeared imminent, prompting surgical therapy. Via the supraclavicular incision approach and additional partial sternotomy, the aneurysm was excluded and the brachiocephalic to right axillar arterial bypass was set up using an extended polytetrafluoroethylene graft. The patient recovered without complications and a subclavian artery aneurysm demonstrated by computed tomography was thrombosed 1 month after surgery. In conclusion, we recommend the exclusion technique to treat subclavian artery aneurysms in cases in which aneurysmectomy is likely to injure adjacent veins and nerves.

Aneurysm↗
PubMed1999

Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats.

The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 degrees C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H2O2) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H2O2, and consequently hydroxyl radical are generated during Cu-catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H2O2 in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non-hepatitic LEC rats and Wistar rats. Moreover, in addition to the reported decrease in glutathione peroxidase (GPX) activity, we found that CAT activity was markedly decreased in LEC rats with hepatitis. The increased generation of H2O2 with reduced activities of GPX and CAT may result in cellular accumulation of H2O2 in the liver of hepatitic LEC rats. Taken altogether, it is suggested that the accumulated H2O2 undergoes the Fenton-type reaction with also accumulated free Cu, thus generating hydroxyl radical in the livers of hepatitic LEC rats and increasing LPO levels in these animals.

Alanine Transaminase↗
PubMed1999

Cartilage degeneration in talocrural and talocalcaneal joints from Japanese cadaveric donors.

In a study human cadavers, degenerative change (DC) was observed more frequently on articular surfaces of the talocrural joint (55. 8%) than on the articular surfaces of the talocalcaneal joint (29. 5%). In the talocrural joint, the anteromedial segments of the tibial plafond, talar dome, and the medial malleolar facet exhibited a high frequency of DC. Moreover, most DCs were found to coexist in multiple segments that often included both the tibial and talar sides. In the talocalcaneal joint, by contrast, DC tended to be distributed diffusely over the articular surfaces. If the DC occurred initially and progressed to a cartilage defect, it tended to be restricted to a certain portion of the talocalcaneal joint. Mirror-image lesions were observed much less frequently than expected in both the talocrural (28.3%) and talocalcaneal joint (25. 0%). Notably, these lesions were not usually observed even if the DC had progressed to a cartilage defect. We considered that the DC tended to advance to the adjacent segment on the same side rather than to the complementary segment on the opposite side. We demonstrated that the more multiple DC lesions were present in the talocrural joint, the more often DC occurred in the talocalcaneal joint. Consequently, we believe than multiplicity of DCs is more critical for the downward joint-to-joint progression of DC than is increased severity.

Adult↗
PubMed1999

Intraoperative detection of embedded coronary arteries in MIDCAB using a color Doppler microprobe.

Intraoperative detection of deeply embedded coronary arteries is difficult, especially in minimally invasive coronary artery bypass grafts. This report describes an effective method to identify embedded coronary arteries by using a color Doppler microprobe. Five embedded left anterior descending coronary arteries were successfully identified by intraoperative ultrasonography. We believe that the color Doppler microprobe is helpful for surgeons in this difficult situation.

Coronary Artery Bypass↗
PubMed1999

Production of calves by transfer of nuclei from cultured somatic cells obtained from Japanese black bulls.

We investigated the possibility of producing calves from transferable bovine embryos obtained by nuclear transfer using somatic cell-derived cell lines. Muscle cells obtained from 2 Japanese Black bulls were dispersed in Hank's solution supplemented with collagenase Type-I. The separated muscle cells were cultured in Dulbecco's Modified Eagle's medium (D-MEM) supplemented with 10% fetal bovine serum (FBS) at 39 degrees C in an atmosphere of 5% CO2 in air. Cells were passaged at least 4 times, and for 5 d prior to nuclear transfer they (donor cells: karyoplasts) were cultured in D-MEM supplemented with 0.5% FBS (to induce quiescence) or 10% FBS. Recipient oocytes were produced by in vitro culture of bovine oocytes that were obtained at a slaughterhouse and then enucleated in modified phosphate buffered saline supplemented with cytochalasin B. Embryos were reconstructed by 3 protocols using karyoplasts cultured in the medium with 0.5% FBS. 1) Group A: recipient oocytes (cytoplasts; n = 157) were treated with Ca ionophore A 23187, ethanol and cycloheximide, and then a karyoplast was fused to an activated cytoplast. 2) Group B: karyoplasts were transferred to cytoplasts (n = 117), and the couplets were treated with electric stimulation and then Ca ionophore A 23187 and cycloheximide. 3) Group C: cytoplasts (n = 104) were cultured for a further 12 h before fusion, and then the couplets were treated with electric stimulation and cycloheximide. 4) Group D: in addition to the above 3 groups, karyoplasts cultured in the medium with 10% FBS were transferred to recipient cytoplasts (n = 137) and treated as in Protocol 2. Reconstructed embryos were cultured in modified CR1aa for 8 d, and the development of embryos was assessed. In total 73 blastocysts were obtained, and the frequency of development to the blastocyst stage in Group A (2.5%) was lower than that of Groups B, C and D (20.5, 18.3 and 19.0%, respectively; P < 0.01). Of these the sex of 21 blastocysts was determined by rapid Y-chromosome detection assay, and all were male, suggesting that nuclear replacement had been achieved successfully. When 26 blastocysts were transferred to 20 recipient cows, 8 of them became pregnant; 4 cows subsequently aborted about 60 d after embryo transfer while the remaining 4 cows calved. These results indicate that reconstructed embryos obtained by nuclear transfer of muscle cell-derived cell lines can develop to the blastocyst stage, and some are sufficiently competent to develop to term. Particularly important was the finding that special culture protocols for somatic cells prior to nuclear transfer were not necessary in our system.

Animals↗
PubMed1999

Air concentration of radiocaesium in Tsukuba, Japan following the release from the Tokai waste treatment plant: comparisons of observations with predictions.

On March 11, 1997 a fire and explosion accident occurred at the bituminization facility of the Power Reactor and Nuclear Fuel Development, Tokai, Japan. As a result of this accident, 134,137Cs was detected in an air filter sample collected at the Meteorological Research Institute, Tsukuba during March 10 to 12. The 134,137Cs air concentration was about 100 and 10 muBq m-3, respectively. This result suggests that there was little radiation exposure of the residents in the area. The average 137Cs air concentration during this period was about two orders of magnitude higher than "baseline" air (sub-muBq m-3) during February to April, 1997, measured by ultra-low background gamma-spectrometry. By a simple calculation using a Gaussian plume model with the measured data, we estimated the minimum emission of the radioactivity by the PNC accident to be in the range 60 MBq to around 600 MBq. The meteorological condition during the week of the accident are also described.

Air Pollutants, Radioactive↗
PubMed1999

Reproductive factors related to the risk of colorectal cancer by subsite: a case-control analysis.

The authors hypothesized that reproductive factors of colorectal cancer, which are probably mediated by endogenous hormones, would differ according to colonic subsite. Information on reproductive factors was obtained from 372 female colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and 31,061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between 1988 and 1995. Multiple logistic analysis showed that late age at interview, family history of colorectal cancer among first-degree relatives, menstrual regularity, late age at menopause, late age at first pregnancy and late age at first full-term pregnancy were significantly associated with the risk of colorectal cancer. None of the risk factors were significantly dissociated between colon and rectal cancer. In polytomous logistic regression analysis, particularly noteworthy was the fact that the odds ratios for age at menarche (P-value for heterogeneity of odds ratios = 0.010), age at first pregnancy (P = 0.016) and age at first full-term pregnancy (P = 0.028) were significantly higher for distal than for proximal colon cancer. This study supports the hypotheses that there might be an association between reproductive factors and risk of colon cancer, and that the carcinogenesis of colon cancer, by subsite, might show aetiologic distinctions.

Case-Control Studies↗
PubMed1999

Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo.

We examined the effect of interleukin-15 (IL-15) gene transfer into tumour cells on the host's anti-tumour response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T-cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8* T-cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells. These results demonstrate that IL-15-secreting tumour cells can stimulate local and systemic T-cell-dependent immunity and therefore may have a potential role in cancer therapy.

Animals↗
PubMed1999

The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma.

Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisense-transfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy.

Aged↗
PubMed1999

Interleukin-15 production at the early stage after oral infection with Listeria monocytogenes in mice.

We previously reported that exogenous interleukin-15 (IL-15) induces proliferation and activation of intestinal intraepithelial lymphocytes (i-IEL) in naive mice. To investigate the ability of endogenous IL-15 to stimulate i-IEL in vivo, we monitored i-IEL and intestinal epithelial cells (i-EC) in mice after an oral infection with Listeria monocytogenes. Although the populations of alphabeta and gammadelta i-IEL were not significantly changed after the oral infection, the expression level of interferon-gamma (IFN-gamma) was increased both at transcriptional and protein levels, and a conversely marked decrease in interleukin-4 (IL-4) was detected in the i-IEL on day 1 after infection as compared with before infection. The T helper 1 (Th1)-biased response of i-IEL coincided with a peak response of IL-15 production in the i-EC after oral infection. These results suggested that IL-15 produced from i-EC may be at least partly involved in the stimulation of i-IEL to produce IFN-gamma after oral infection with L. monocytogenes.

Animals↗
PubMed1999

Congruent docking of dimeric kinesin and ncd into three-dimensional electron cryomicroscopy maps of microtubule-motor ADP complexes.

We present a new map showing dimeric kinesin bound to microtubules in the presence of ADP that was obtained by electron cryomicroscopy and image reconstruction. The directly bound monomer (first head) shows a different conformation from one in the more tightly bound empty state. This change in the first head is amplified as a movement of the second (tethered) head, which tilts upward. The atomic coordinates of kinesin.ADP dock into our map so that the tethered head associates with the bound head as in the kinesin dimer structure seen by x-ray crystallography. The new docking orientation avoids problems associated with previous predictions; it puts residues implicated by proteolysis-protection and mutagenesis studies near the microtubule but does not lead to steric interference between the coiled-coil tail and the microtubule surface. The observed conformational changes in the tightly bound states would probably bring some important residues closer to tubulin. As expected from the homology with kinesin, the atomic coordinates of nonclaret disjunctional protein (ncd).ADP dock in the same orientation into the attached head in a map of microtubules decorated with dimeric ncd.ADP. Our results support the idea that the observed direct interaction between the two heads is important at some stages of the mechanism by which kinesin moves processively along microtubules.

Adenosine Diphosphate↗
PubMed1999

Utility of laboratory testing in autoimmune inner ear disease.

OBJECTIVES: To assess the utility of various laboratory tests used to diagnose autoimmune inner ear disease. STUDY DESIGN: Retrospective study of 82 patients evaluated at the University of Washington Otology Clinic from 1996 through 1998 with review of clinical history, laboratory tests, audiograms, response to therapy, and final diagnoses. METHODS: Charts were reviewed for presenting history and initial workup including test results for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Clq binding assay, anticardiolipin antibody (aCL), antineutrophil cytoplasmic antibody (ANCA), microhemagglutinin assay for Treponema pallidum (microhemagglutination assay), Lyme disease titers, and the Western blot for heat shock protein 70 (hsp 70). RESULTS: The Western blot for hsp 70 is the best test for predicting corticosteroid responsiveness. The sensitivity was low at 42%, although the specificity was 90%, and the positive predictive value of this test was excellent at 91%. The ESR was as good as the CRP in detecting acute-phase reactants. The other, more specific tests in the laboratory panel (aCL, ANCA, MHA, and Lyme disease titers) did not detect any new cases of autoimmune disease in addition to those which were already identified by an abnormal ESR. CONCLUSIONS: A diagnostic test panel for autoimmune inner ear disease should include an ESR and the Western blot for hsp70. More specific laboratory testing for systemic disease is warranted when the ESR is elevated. In patients with a positive Western blot, a trial of corticosteroid therapy can be given with good conviction because the test is quite specific. However, many people who are Western blot negative may also respond to corticosteroid therapy because the test lacks sensitivity.

Autoimmune Diseases↗
PubMed1999

Comparative case-referent study of risk factors among hormone-related female cancers in Japan.

To assess the impact of reproductive and anthropometric factors as a risk indicator for female cancers in hormone-related organs, i.e., the breast, endometrium and ovary, we conducted a comparative case-referent study using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The case group consisted of 1,465, 133 and 99 women who had first been diagnosed as having breast, endometrial and ovarian cancer, respectively. The referents were 25,488 female first-visit outpatients who had not previously been diagnosed with any type of cancer. The odds ratios (ORs) and their 95% confidence intervals (95%CI) were estimated using an unconditional logistic regression model. An inverse association with experience of delivery and a positive association with body mass index (BMI) and with change of BMI after 20 years of age, were observed consistently for all three cancer sites. We observed similar risk and protective factors for breast and endometrial cancer, but the effect of reproduction and overweight condition (BMI> or =25) were more prominent in endometrial cancer. Although the present study failed to find site-specific risk factors for ovarian cancer, the results provided evidence that being overweight and/or weight gain in adult life is a common risk factor for all three cancer sites. The results obtained from this study suggested that avoidance of weight gain may reduce the risk of female hormone-related cancers.

Adult↗
PubMed1999

Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.

Adult↗