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Biomedical subjects

K Kano

Publications and source records attributed to K Kano.

At least 91 records · Page 5Linked to original sources

Risk Factors for Breast Cancer among Japanese Women: A Case-Control Study in Ibaraki, Japan.

BACKGROUND: The number of epidemiologic studies on breast cancer risk factorsin Japanese women is still quite limited. Our objective was to clarify the relationship between lifestyle, body size and breast cancer risk. METHODS: A matched case-control study was conducted in Ibaraki, Japan. The participants were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January, 1990 and March, 1997. Two controls were individually matched to the cases by age and residence. A self-administered questionnaire was used to obtain information on the family history of breast cancer, reproductive history, education, body size and lifestyle factors. Conditional logistic regression analysis was used to estimate oddsratios (ORs)and 95% confidence intervals (95% CI). RESULTS: After adjustment for potential confounders, heavy weight and higher body mass index were associated with an increased risk of breast cancer among postmenopausal women (OR = 1.76, 95% CI = 0.69, 4.48; OR = 1.57, 95% CI=0.61, 3.99, respectively). Current or ex-smokers were found to be at an increased risk for breast cancer (OR = 3.33; 95% CI = 1.63, 6.80). Women who take hot baths had a decreased risk for breast cancer (OR = 0.67; 95% CI = 0.43, 1.06). Recreational physical activity was associated with a reduced risk of breast cancer (PTrend = 0.005).OR for breast cancer among physically active women was 0.36 (95% CI = 0.19, 0.70), as compared with inactive women. Taller women had an increased risk of breast cancer relative to shorter women (OR = 1.49; 95% CI = 0.83, 2.70). No significant association between alcohol consumption and breast cancer risk was detected. CONCLUSION: Our results suggest that several potentially modifiable lifestyle factors may be useful for the prevention of breast cancer.

Journal Article↗

The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme.

The Ras target AF-6 has been shown to serve as one of the peripheral components of cell-cell adhesions, and is thought to participate in cell-cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of approximately 220 kD (p220) to investigate the function of AF-6 at cell-cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell-cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6.

Animals↗

Dihydroheptaprenyl and dihydrodecaprenyl monophosphates induce apoptosis mediated by activation of caspase-3-like protease.

Dolichyl phosphate, an essential carrier lipid in the biosynthesis of N-linked glycoprotein, has been found to induce apoptosis in rat glioma C6 cells and human monoblastic leukemia U937 cells. In the present study, dolichyl phosphate and structurally related compounds were examined regarding their apoptosis-inducing activities in U937 cells. Dihydroheptaprenyl and dihydrodecaprenyl phosphates, of which isoprene units are shorter than that of dolichyl phosphate, induced apoptosis in U937 cells. This phenomenon occurred in a dose- and time-dependent manner, as seen with dolichyl phosphate-induced apoptosis. Derivatives of the same isoprene units of dolichyl phosphate, such as dolichol, dolichal or dolichoic acid, did not induce DNA fragmentation. Farnesyl phosphate and geranylgeranyl phosphate also failed to induce apoptosis. During apoptosis, the caspase family of cysteine proteases play important roles. We observed that apoptosis induced by dihydroprenyl phosphate was mediated by caspase-3-like (CPP32-like) activation but not by caspase-1-like (ICE-like) activation. This caspase-3-like activation was inhibited by a specific inhibitor of caspase-3, DEVD-CHO, but not by an caspase-1 inhibitor YVAD-CHO. We interpret these results to mean that dihydroprenyl phosphates with more than seven isoprene units have apoptosis-inducing activity and that their signal is mediated by caspase-3-like activation.

Apoptosis↗

DNA cleavage and 8-hydroxydeoxyguanosine formation caused by tamoxifen derivatives in vitro.

DNA damage caused by tamoxifen and its derivatives was examined by estimating the conversion of supercoiled pUC18 plasmid DNA to linear form by means of agarose gel electrophoresis. N-Desmethyltamoxifen induced DNA cleavage and its effect was enhanced by the addition of reducing agents such as dithiothreitol, NADPH and 2-mercaptoethanol. 4-Hydroxytamoxifen itself had little effect, but the cleavage was slightly enhanced by the addition of reducing agents. DNA damage was higher with alpha-hydroxytoremifene than with alpha-hydroxytamoxifen, which had a prominent effect only at high concentration. The cleavage by alpha-hydroxy derivatives were not enhanced by reducing agents. No damage was induced by tamoxifen, toremifene, 3-hydroxytamoxifen or N-desmethyltoremifene. The DNA cleavage by N-desmethyltamoxifen was inhibited by the addition of EDTA, mannitol, sodium azide, methionine, catalase and superoxide dismutase. The formation of 8-hydroxy-2'-deoxyguanosine was also examined with calf thymus DNA in vitro. A slight increase of its level was found with 4-hydroxytamoxifen in the presence of dithiothreitol and also with N-desmethyltamoxifen in the presence of NADPH, but alpha-hydroxytoremifene and alpha-hydroxytamoxifen were ineffective. These experimental data suggest that among metabolites of tamoxifen, N-desmethyltamoxifen and probably also 4-hydroxytamoxifen cause oxidative DNA damage in which redox cycling is involved. The DNA damage by alpha-hydroxytoremifene appears to involve a different mechanism from that by N-desmethyltamoxifen. Tamoxifen and toremifene are possibly metabolized to the forms contributing to DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

Emergent bronchofiberoptic bronchial occlusion for intractable pneumothorax with severe emphysema.

Emergent bronchofiberoptic bronchial occlusion using fibrin glue and woven polyglycolic acid mesh for persistent pneumothorax with severe emphysema is described. A 74-year-old man who had severe pulmonary dysfunction accompanying chronic emphysema was admitted with a complaint of sudden severe dyspnea. The chest X-ray on admission revealed collapse of the right lung. The patient was placed on a mechanical ventilator because of acute respiratory failure. In spite of continuous suction through a chest drainage tube, air leakage persisted. On the seventh hospital day, subcutaneous emphysema was apparent in the face and scrotum in addition to the chest. First, a double-lumen catheter was inserted into the right B5 bronchus, and fibrin glue was infused into the drainage bronchus via the double-lumen catheter. However, the procedure failed. Next, a combination of fibrin glue and woven polyglycolic acid mesh which had been cut into small pieces was introduced and pushed into the B5 bronchus using forceps. The air leakage stopped immediately after the administration. This procedure is simple and a minimally invasive method for the treatment of intractable pneumothorax in a compromised patient on a mechanical ventilator.

Aged↗

Results of a qualitative and field study using the WHOQOL instrument for cancer patients.

The main purpose of the study was to evaluate quality of life (QOL) among cancer patients using the WHOQOL-100 instrument and to see if any significant differences were seen in cancer stages, treatment status and prognosis. This study consisted of two parts; qualitative and quantitative. For the qualitative study, two focus groups were conducted by medical professionals to establish the applicability of the WHOQOL instrument in evaluating the QOL of cancer patients, but most participants were negative about using a generic instrument such as WHOQOL. For the quantitative study, 197 cancer patients (average age 55.86) from eight medical centers using the WHOQOL instrument, in addition to each patient's information sheet filled in by their own physicians, were analyzed. The average overall QOL score was 3.39. There was high reliability (Cronbach's alpha = 0.9685) and a high correlation between the psychological and the environmental domains (r = 0.7021), the physical domain and the level of independence (r = 0.6031) and social relations and the environment (r = 0.6856) and between health conditions perceived by patients and QOL scores. In addition, differences by gender, treatments and cancer sites were also found to be significantly different at the 5% significance level. The results indicated that the WHOQOL core instrument was sensitive enough to evaluate the QOL of cancer patients.

Adult↗

Effects of glycosaminoglycans on the development of in vitro-matured and -fertilized porcine oocytes to the blastocyst stage in vitro.

We examined the effects of four glycosaminoglycans (GAGs) on the development of in vitro-matured (IVM) and -fertilized (IVF) porcine oocytes to the blastocyst stage. IVM and IVF oocytes were cultured in Whitten's medium supplemented with hyaluronic acid, chondroitin sulfate A, dermatan sulfate, or heparin at 38.5 degrees C in an atmosphere of 5% CO2 in humidified air for up to 6 days. After 2 days in culture, 28-34% of the inseminated oocytes cleaved to the 2- to 8-cell stage, and the GAGs showed no significant effect on development. After 6 days in culture, blastocysts were observed in all groups. The percentage of blastocysts was significantly higher in hyaluronic acid-supplemented medium (14%) than in dermatan sulfate-supplemented (5%), heparin-supplemented (2%), or nonsupplemented (2%) media. In addition, the percentage of blastocysts was significantly higher in chondroitin sulfate A-supplemented medium (11%) than in heparin-supplemented and nonsupplemented media, although the number of blastocysts in chondroitin sulfate A was not significantly different from that in hyaluronic acid- and dermatan sulfate-supplemented media. There were no significant differences in the mean number of nuclei per blastocyst cultured in any group. The effects of hyaluronic acid and chondroitin sulfate A on development to the blastocyst stage was examined at various concentrations. After 6 days in culture, development of IVM and IVF oocytes to the blastocyst stage was best supported in 0.5 mg/ml hyaluronic acid-supplemented (17%) and in 0.1 or 0.5 mg/ml chondroitin sulfate A-supplemented (10% or 9%, respectively) media. It is concluded from these results that hyaluronic acid and chondroitin sulfate A supported the development of porcine oocytes matured and fertilized in vitro to the blastocyst stage.

Animals↗

Uncommon multisystemic involvement in a case of Henoch-Schönlein purpura.

A case of Henoch-Schönlein purpura (HSP) characterized by several unusual complications is reported. A 10-year-old boy was hospitalized with acute abdomen and developed purpura on the lower extremities after 4 days of hospitalization. He had protein-losing enteropathy, diagnosed by an elevated fecal alpha-1-antitrypsin clearance. The colicky abdominal pain and protein-losing enteropathy subsided after methylprednisolone pulse therapy was administered. He had left hydronephrosis and gall-bladder abnormalities detected by ultrasonography, and purpura nephritis. However, after improvement of these abnormalities, he showed steroid-induced epidural lipomatosis, detected by magnetic resonance imaging, which resolved with steroid reduction. Ultrasonography and magnetic resonance imaging were useful for detecting these uncommon multisystemic involvements in HSP.

Child↗

Amperometric determination of high-density lipoprotein cholesterol using polyethylene glycol-modified enzymes and a peroxidase-entrapped electrode.

A peroxidase-entrapped and ferrocene-embedded carbon paste (POD-Fc-CP) electrode allows a highly sensitive detection of H2O2 at levels as low as 10 nmol/L with practically no interference by coexisting substances, turbidity or coloration of samples. The electrode was applied to the amperometric determination of high-density lipoprotein (HDL)-cholesterol in a very small volume (1-2 microL) using polyethylene glycol (PEG)-modified cholesterol esterase and cholesterol oxidase without prior precipitation or separation of HDL. PEG-modified enzymes exhibit a selective activity toward HDL-cholesterol in the presence of dextran sulphate and MgCl2 to generate H2O2. The HDL-cholesterol concentrations of human serum samples determined by this method showed a good correlation with those determined by an ordinary spectrophotometric method using PEG-modified enzymes and peroxidase or by a conventional precipitation method.

Cholesterol, HDL↗

Physical activity and the risk of breast cancer: a case-control study of Japanese women.

A case-control study was conducted in Ibaraki, Japan. Cases were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January 1990 and March 1997. Two controls were individually matched to cases by age (within 1 year) and residence (municipalities). A self-administered questionnaire was used to obtain information on physical activity and the effects of potential confounding factors. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95 percent confidence intervals (95% CIs). After adjustment for potential confounding factors (height, body mass index (BMI), family history of breast cancer, education, age at menarche, age at first birth, parity, menopausal status), recreational physical activity was associated with a reduced risk of breast cancer (p for trend = 0.005). OR for breast cancer among women who played regular sport or exercise more than 15.3 METs per week was 0.35 (95% CI = 0.17, 0.73), as compared to women with no sport or exercise. The risk of breast cancer was also reduced in women with higher occupational physical activity levels, but it was not significant (p for trend = 0.223). The adjusted OR among the highest quartile level was 0.55 (95% CI = 0.27, 1.12) with the lowest quartile level as reference. Our findings support a protective effect of recreational physical activity on breast cancer in Japanese women.

Adult↗

Relationship between exercise and bone mineral density among over 5,000 women aged 40 years and above.

An epidemiological survey was conducted to clarify the relationship between bone mineral density(BMD) and exercise at 14 health centers in Ibaraki Prefecture, Japan from September 1994 through March 1995. More than 5,000 women participated in this survey. Second metacarpal BMD was measured by CXD(Computed X-ray Densitometry) method. Information about past history of exercise was obtained by questionnaire. sigma GS/D < 2.3(sigma GS/D: a parameter of BMD) was used to estimate the suspicion of osteoporosis. Data on 5,124 women aged 40 years and above were analyzed. Subjects were categorized into two groups according to the presence(n = 1,687) or absence(n = 3,437) of past history of regular exercise. sigma GS/D values were significantly (p < or = 0.05) higher in women who have had regular exercise in the past than those of the non-exercise group except those aged over 70 years. Ball game, foot sports and gymnastics were the main exercises. When osteoporosis was suspected based on the measurements of bone mineral density, the odds ratio (exercise present/absent) was 0.27 (95% confidence limits: 0.08-0.94), 0.82 (0.65-1.04), 0.78 (0.61-0.99), and 1.25 (0.67-2.35) at 40-49, 50-59, 60-69, and over 70 years, respectively. The results of the present study suggest the beneficial influence of exercise on bone mineral density and its utility for preventing osteoporosis.

Adult↗

Lifestyle evaluation system to support health education.

A computer-based system for evaluation of one's lifestyle was designed so that public health nurses could use it for health education to improve a patient's lifestyle and to prevent lifestyle-related diseases. The Lifestyle Evaluation System (LES) is a computer program that works on a personal computer. The LES is consist of four parts; inputting personal data, answering the questionnaire, showing the result and getting health check up data. The questionnaire includes 40 questions regarding diet, smoking, drinking, physical activity, rest, social activity and health care activities, based on Breslow's seven lifestyles. The result offers participants' lifestyle evaluation in forms of values, graphs, tables and messages. Evaluation values are deviation value, rank, BMI and standard weight. The LES also offers participant's periodic health check data, average data derived from all residents' data, and past results of LES so that public health nurses are able to use these for health education. The health check data is obtained from another database stored on floppy disks. The participants input data by themselves and get result immediately. The interactive style is effective in raising interest in health education.

Computer Systems↗

The Ras target AF-6 interacts with ZO-1 and serves as a peripheral component of tight junctions in epithelial cells.

The dynamic rearrangement of cell-cell junctions such as tight junctions and adherens junctions is a critical step in various cellular processes, including establishment of epithelial cell polarity and developmental patterning. Tight junctions are mediated by molecules such as occludin and its associated ZO-1 and ZO-2, and adherens junctions are mediated by adhesion molecules such as cadherin and its associated catenins. The transformation of epithelial cells by activated Ras results in the perturbation of cell-cell contacts. We previously identified the ALL-1 fusion partner from chromosome 6 (AF-6) as a Ras target. AF-6 has the PDZ domain, which is thought to localize AF-6 at the specialized sites of plasma membranes such as cell-cell contact sites. We investigated roles of Ras and AF-6 in the regulation of cell-cell contacts and found that AF-6 accumulated at the cell-cell contact sites of polarized MDCKII epithelial cells and had a distribution similar to that of ZO-1 but somewhat different from those of catenins. Immunoelectron microscopy revealed a close association between AF-6 and ZO-1 at the tight junctions of MDCKII cells. Native and recombinant AF-6 interacted with ZO-1 in vitro. ZO-1 interacted with the Ras-binding domain of AF-6, and this interaction was inhibited by activated Ras. AF-6 accumulated with ZO-1 at the cell-cell contact sites in cells lacking tight junctions such as Rat1 fibroblasts and PC12 rat pheochromocytoma cells. The overexpression of activated Ras in Rat1 cells resulted in the perturbation of cell-cell contacts, followed by a decrease of the accumulation of AF-6 and ZO-1 at the cell surface. These results indicate that AF-6 serves as one of the peripheral components of tight junctions in epithelial cells and cell-cell adhesions in nonepithelial cells, and that AF-6 may participate in the regulation of cell-cell contacts, including tight junctions, via direct interaction with ZO-1 downstream of Ras.

Animals↗

Influence of fasting and neuropeptide Y on the suppressive food intake induced by intracerebroventricular injection of glucagon-like peptide-1 in the neonatal chick.

Recently, we have reported that central administration of glucagon-like peptide-1 (GLP-1) strongly decreased food intake of chicks. The aim of the present study was to elucidate whether suppressed food intake by central injection of GLP-1 would be modified by an appetite stimulant such as fasting and neuropeptide Y (NPY). Birds (2 days old) were starved for 3 or 6 h and then GLP-1 (0.03 microg/10 microl) or saline was injected by the intracerebroventricular (i.c.v.) route. Birds starved for 6 h ate significantly more food than those starved for 3 h, while irrespective of the time for fasting GLP-1 strongly inhibited food intake as rapidly as 10 min after i.c.v injection. The suppressive effect on food intake continued until 4 h after injection. Central administration of NPY (2.5 microg/10 microl) greatly enhanced food intake, but co-injection of GLP-1 (0.01, 0.02 or 0.03 microg/10 microl) decreased food intake in a dose-dependent fashion. Under GLP-1 (0.03 microg/10 microl) treatment, whether NPY modifies food intake of chicks in a dose-dependent manner was investigated by co-injection of graded levels of NPY (0.4, 1.0 and 2.5 microg/10 microl). GLP-1 completely inhibited the effect of NPY on food intake without a dose response. These results suggest that central GLP-1 may interact with NPY and may be the most potent inhibitor of food intake in the chicken.

Animals↗

CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells.

Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32 to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration. The results suggest that modulation of cAMP synthesis due to the stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in CPP32 activation and apoptosis.

Adenine↗

Sodium dodecyl sulfate-Tween 20 mixed micellar electrokinetic chromatography for separation of hydrophobic cations: application to adrenaline and its precursors.

Separation of hydrophobic cations in capillary electrophoresis under the mixed micellar system composed of SDS and Tween 20 was investigated from the viewpoints of thermodynamics and practical application. Hydrophobic cations interact strongly with the anionic SDS micelle, and this often lead to predominant dissolution of the analytes into the micellar phase, resulting in poor resolution. The ionic interaction was evaluated to be close in strength to the hydrophobic interaction between benzenes and the SDS micelle. Tween 20 as a component to the mixed micelle was found to weaken the attractive ionic interactions between the cationic solutes and SDS. In addition, the polyether chain of Tween 20 serves also as a hydrogen acceptor to cause the attractive hydrogen-bonding interactions with hydrogen-donating analytes. The two different functions of Tween 20 improve the separation of hydrophobic cations remarkably. Separation patterns are well controlled by varying the mixing ratio of the two surfactants. Adrenaline and its six precursors were successfully separated with this mixed micellar system. The improved separation efficiency was not affected by the presence of bovine serum matrix, realizing the direct MEKC analysis of serum sample without deproteination, in which proteins were comigrated with the micelle.

Animals↗

Novel regulation of delta-aminolevulinate synthase in the rat harderian gland.

The mode of expression of delta-aminolevulinate synthase (ALAS), as well as that of mRNAs for other heme pathway enzymes, was examined in the rat Harderian gland. Northern blot and in situ hybridization analyses demonstrated that the non-specific ALAS (ALAS-N) mRNA is highly expressed in this tissue, whereas the erythroid-specific ALAS (ALAS-E) mRNA is not. Immunoblot analysis of ALAS also confirmed this finding at the protein level. ALAS-N mRNA was maximally induced in the Harderian gland and was not increased further by treatment of animals with 2-allyl-2-isopropylacetamide (AIA). The levels of mRNAs for other heme pathway enzymes, i.e., delta-aminolevulinate dehydratase, porphobilinogen deaminase, uroporphyrinogen decarboxylase, and coproporphyrinogen oxidase, also were increased markedly in the Harderian gland and not influenced by AIA treatment. The level of ferrochelatase (FeC) mRNA in the gland was, however, lower than that in the liver. The gland contained an extremely high level of protoporphyrin, while heme was undetectable. Microsomal heme oxygenase-1 (HO-1) mRNA levels were significantly higher in the Harderian gland than in the liver. When isolated glands were incubated with hemin in vitro in organ cultures, the level of HO-1 mRNA was increased, whereas the ALAS-N mRNA level was not. These findings indicate that markedly elevated levels of protoporphyrin and extremely low levels of heme in the Harderian gland are the results of both decreased expression of FeC and markedly increased expression of ALAS-N and HO-1. The constitutive expression of the ALAS-N gene in the Harderian gland suggests a novel transcriptional control mechanism of this gene.

5-Aminolevulinate Synthetase↗