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K Imai

Publications and source records attributed to K Imai.

At least 451 records · Page 25Linked to original sources
PubMed1998

Site-directed mutagenesis in hemoglobin: attempts to control the oxygen affinity with cooperativity preserved.

We synthesized three artificial human hemoglobin mutants in which Lys-66(E10)beta was replaced by Ser, Arg or Thr by site-directed mutagenic protein engineering. These engineered hemoglobins were designated as eHb K66betaS, eHb K66betaR and eHb K66betaT, respectively. By synthesizing these mutants we attempted to control the oxygen affinity of hemoglobin with cooperativity preserved and to clarify the functional role of Lys-66(E10)beta, as well. Such attempts may be useful for creating an oxygen carrier suitable as a blood substitute. The oxygen affinities of eHbs K66betaS, K66betaR and K66betaT were 1.3-, 1.5- and 2.3-fold, respectively, lower than that of reconstituted Hb A. Their allosteric properties such as the Bohr effect and the effect of inositol hexaphosphate were well preserved. Since the oxygen affinity of eHb K66betaT is comparable with that of red cells, it may be a potential candidate for a blood substitute. X-Ray crystallographic data for Hb Chico [Lys-66beta-->Thr], which is identical with eHb K66betaT, together with our computer simulation indicate that an interaction between the introduced Thr and the distal His via a water molecule lowers the oxygen affinity for the T state eHb K66betaT.

Amino Acid Substitution↗
PubMed1998

Influence of drinking green tea on breast cancer malignancy among Japanese patients.

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow-up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.

Adult↗
PubMed1998

Reduced invasive and metastatic potentials of KAI1-transfected melanoma cells.

KAI1 is a metastasis suppressor gene for human prostate cancer. To reveal the effect of KAI1 on the in vivo metastasis of tumors other than prostatic cancer, we transfected a human KAI1 cDNA into highly metastatic B16-BL6 murine melanoma cells and established stable transfectant clones with different expression levels of KAI1 message. The following results were obtained with the use of those transfectants. (1) Cell aggregation assay revealed a significantly enhanced Ca(2+)-independent aggregation of B16-BL6 cells by KAI1 cDNA transfection compared with mock transfectants (P < 0.01). (2) The in vivo phagokinetic activity and invasive ability of KAI1 transfectants were clearly decreased as compared with those of mock transfectants (P < 0.01). There was no significant effect of KAI1 expression on the in vitro or in vivo proliferation of B16-BL6 cells. (3) Lung colony formation of intravenously injected KAI1 transfectants in nude mice was significantly reduced as compared with mock transfectants or parental B16-BL6 cells (P < 0.01). These data suggest that KAI1 expression gives rise to the suppression of invasive and metastatic potentials of B16-BL6 cells.

Animals↗
PubMed1998

Human tumor growth suppression by apoptosis induced with anti-ErbB-2 chimeric monoclonal antibody.

We established an anti-ErbB-2 mouse-human chimeric monoclonal antibody (MoAb), CH401, which was able to kill cancer cells overexpressing the ErbB-2 protein in vitro. The analysis of the killing mechanism indicated that MoAb CH401 might be the first anti-erbB-2 mouse-human chimeric MoAb which can induce the apoptosis of cancer cells, since morphological changes and DNA fragmentation were recognized in MoAb CH401-treated cells. The ErbB-2 receptor appears to have two opposing functions: acting as a receptor both for a growth factor and for an apoptotic factor. Our results indicate that MoAb CH401 treatment may prove to be very useful for cancer therapy.

Animals↗
PubMed1998

Incidence of urogenital cancers in Gunma Prefecture, Japan: a 10-year summary.

BACKGROUND: Although the incidence of urogenital cancers in Japan is lower than that of other cancers, it is increasing steadily. Thus, an epidemiologic study was necessary to determine the measures that would decrease the mortality rate associated with these cancers. METHODS: The subjects were 4759 patients with urogenital cancer who were living in Gunma Prefecture and who were newly diagnosed between 1985 and 1994. The data were analyzed by year and by patients' ages. The incidence rates of each disease were expressed as the number of cases per 100,000/year, and age-adjusted rates were adjusted to the world population. RESULTS: The number of males and females afflicted by urogenital cancers increased over the 10-year period. The increase in age-adjusted incidence rates was sharpest for prostate, renal cell, and testicular cancers among males, and for renal cell, renal pelvic and ureter cancers among females. When age-specific rates were plotted against age on double logarithmic scales, the cancers were classified as type 1 (linear), type 2 (linear until a certain age, then flattening out or decreasing), or type 3 (irregular) based on the slope of the line. The magnitude of increase in the age-specific incidence rates of type 1 cancers with age was on the order of the 12th power for prostate cancer and the 5th power for bladder cancer. When the 10 years were divided into 2 periods (earlier and later), the age-specific incidence rates of prostate and renal cell cancers increased in all age groups, whereas the age-specific incidence rates of cancers that increased less sharply remained stable or even declined in some age groups. CONCLUSION: These epidemiologic data should be useful in reducing the mortality rates associated with these cancers.

Adult↗
PubMed1998

Chronic ischemic colonic lesion caused by phlebosclerosis with calcification.

We report here two patients in both of whom ileus finally developed and chronic ischemic colonic lesion caused by phlebosclerosis with calcification was diagnosed. We believe that phlebosclerosis is an old-fashioned diagnostic term, but appropriate here because of the remarkable calcification of the sclerotic walls of the colic veins that seems to be one of the most important hallmarks of this previously unrecognized, "new" condition. Phlebosclerosis could be a novel type of ischemic colitis because of its unique clinical presentations, although the pathogenesis of this unusual venopathy remains unknown.

Adult↗
PubMed1998

Use of hyaluronic acid binding protein for detection of hyaluronan in ligature-induced periodontitis tissue.

This study was designed to demonstrate, by use of biotin-labeled hyaluronic acid binding protein (HABP) and an avidin-enzyme system, the localization of hyaluronan (HA) in periodontal tissue of beagle dogs during experimentally induced periodontitis. Experimental periodontitis was induced in the dogs by ligation of the gingival sulcus. Experimental tissue was collected at 0, 3, 7 and 21 days after ligation. HA was revealed by strong staining in the intercellular space around epithelial cells and periodontal ligament, and by light staining in the gingival connective tissue. According to the progression of periodontal tissue breakdown, HA was detected in a small number of leukocytes and monocytes, on the surface of osteoclasts, the surface of alveolar bone, thickened endothelium and in epithelial cells related to rete peg formation. Streptomyces hyaluronidase-treated specimens gave negative staining. This study suggests that HA may be associated with the inflammatory reaction in experimental periodontitis tissue.

Alveolar Process↗
PubMed1998

Zonal differences in effects of HGF/SF and EGF on DNA synthesis in hepatocytes under fed or starved conditions.

Zonal differences of DNA synthesis in hepatocytes induced by hepatocyte growth factor and/or scatter factor (HGF/SF) and epidermal growth factor (EGF) were investigated using male Wistar rats under fed or starved conditions. Overall, DNA synthesis was greater in fed rats than in starved rats. The predominance of EGF in periportal hepatocytes (PPH) on zonal DNA synthesis was reversed by starved conditions, but the predominance of HGF/SF on zonal DNA synthesis in perivenous hepatocytes (PVH) was not influenced by nutritional conditions. 125I-labeled EGF and 125I-labeled HGF/SF-receptor binding studies revealed no significant difference between PPH and PVH in starved or fed rats. To investigate the mechanism of the signal transduction pathway, we used genistein, an inhibitor of tyrosine kinase. Genistein had different effects on zonal difference in EGF and HGF/SF. In EGF, 1 microgram/ml genistein abolished zonal differences, but in HGF/SF 1 microgram/ml genistein did not abolish zonal differences. These data suggest that, in contrast to HGF/SF, zonal difference of DNA synthesis by EGF was dependent on nutritional conditions and DNA synthesis induced by HGF/SF and EGF might be related to tyrosine kinase, but the influence of tyrosine kinase on DNA synthesis was different between HGF/SF and EGF.

Animals↗
PubMed1998

Urinary excretion of D-serine in human: comparison of different ages and species.

The urinary excretion of D-serine (D-Ser) in human, rat and dog of various ages was studied. Great amounts of D-Ser were consistently excreted in human urine throughout life. No age-dependent changes were observed in urinary D-Ser/total-Ser ratios from the newborn to the aged. D-Ser/creatinine ratios in adult human urine were found to be relatively constant in individuals. The constant excretion of D-Ser in human urine was confirmed by analyzing the consecutive 24 h urine of three volunteers. High concentrations of D-Ser and D-alanine (D-Ala) were found in adult dog urine. The urinary D-Ser concentration was high in young rats at unweaned and weaned periods, and then declined with increasing age. In contrast, the urinary D-Ala concentration was very low in suckling rats, and increased rapidly after the weaned state and then declined with increasing age. The species- and age-related excretion of D-Ser in mammalian urine is considered to be due to the differences in the renal handing of D-Ser, because plasma D-Ser concentrations among the groups were not so different. Although free D-Ser has been detected in animal foods and human colostrum, the amount is insufficient to explain the concentration of D-Ser found in urine. These results indicate that urinary D-Ser in mammals may be mainly of endogenous origin.

Adult↗
PubMed1998

Left coronary artery-left ventricle fistula with right coronary artery spasm.

A 72-year-old woman was admitted to our hospital for evaluation of chest pain. Coronary angiography showed a left coronary artery-left ventricle fistula. An acetylcholine provocation test induced vasoconstriction of the right but not the left coronary artery. Her chest pain was not relieved by combined therapy with isosorbide dinitrate, diltiazem and nicorandil. Because of the coronary spasm, beta-blockers could not be used. However, her chest pain was relieved after the administration of a minor tranquilizer. Thus, the patient's chest pain was unlikely to be associated with either the fistula or the coronary spasm.

Acetylcholine↗
PubMed1998

Minimum structure of diapause hormone required for biological activity.

Diapause hormone is a 24-amino acid peptide amide, and its C-terminal penta-peptide amide structure of FGPRL-NH2 is believed to be essential for biological activity. The penta-peptide amide, the shorter peptide amides, and their derivatives and analogs were prepared to determine the minimal structure for biological activity. The C-terminal amide group of penta-peptide amide was not replaced with the other functional groups, but Gly, the 4th amino acid from the C terminal, could be substituted with an other amino acid while maintaining the biological activity. The shorter peptide amide, PRL-NH2, possessed low but significant activity, indicating the minimum structure of diapause hormone. By modifying its N-terminal, the aromatic ring of Phe is shown to enhance the activity of PRL-NH2.

Animals↗
PubMed1998

Age-related weakening of baroreflex-mediated sympathetic activity in spontaneously hypertensive rats in response to blood pressure reduction.

Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate, and the concentration of plasma catecholamines (CAs), norepinephrine (NE), and epinephrine (E) were concomitantly determined, and the correlations between these three variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic activity countering the blood pressure reduction caused by calcium antagonists.

Aging↗
PubMed1998

Isolation of serotype 2 Marek's disease virus from a cell line of avian lymphoid leukosis.

To determine a serotype of Marek's disease virus (MDV) persistently infected in a lymphoid leukosis (LL)-cell line, LSCC-BK3, clone A (BK3A), and to examine the pathogenicity of the virus, an attempt was made to isolate MDV from culture fluid of the LL-cell line, using chick embryo fibroblast cultures resistant to infection with subgroup A avian leukosis virus (ALV) to eliminate subgroup A ALV. The MDV isolate, serologically identified as serotype 2 MDV and designated as the 2H strain, was free from ALV and reticuloendotheliosis virus. A serotype 2-specific antigen of MDV was detected in 44% of BK3A, but antigens of serotypes 1 and 3 were not detected in this cell line, by the indirect immunofluorescent antibody test using serotype-specific monoclonal antibodies. MDV antigens were undetectable in LSCC-BK3, clone 2C; both cell lines were established from the same chicken. Neither clinical signs nor macroscopic lesions were observed in any of 19 chicks inoculated with the 2H strain. Three out of 19 chicks histopathologically examined had no lesions. These results suggest that serotype 2 MDV can persist in B cells transformed by ALV without cytopathic effect at a high rate, and the isolate may become a candidate for MD vaccine strains.

Animals↗
PubMed1998

Age-related changes in blood coagulation and fibrinolysis in mice fed on a high-cholesterol diet.

To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we examined age-dependent changes in platelet activity, blood coagulation and fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'-diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated aggregation compared with the same in control mice. Yohimbine as alpha 2-adrenergic blocker antagonized these aggregations in a dose-dependent manner. A significant increase in plasma total cholesterol and VLDL (very low-density lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the early phase of this experiment, a significant increase in fibrinogen was observed. In the middle phase, increases in the activity of antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content gradually decreased in both normal diet and HCD mice throughout the experiment. The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD mice. Morphological observation of the aortic arch from 3-month HCD mice revealed apparent atheromatous plaques not seen in control mice. These results suggest that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic model and the changes in platelet activity, coagulation and fibrinolysis in the early phase may be a cause of pathologic changes in this model.

Aging↗
PubMed1998

Significance of measurement of prostate specific antigen (PSA) in familial prostate cancer lines.

The concentration of prostate specific antigen (PSA) in serum was measured in 20 brothers or sons in 10 families in which the father and son or brothers had prostate cancer using the E test TOSOH IIPA. The patients were between 32 and 70 years old with a mean age of 48.2 years. The PSA value was between 0.4 and 19.5 ng/ml with a mean value of 3.4 ng/ml. Five patients (25%) had PSA values exceeding the cut-off value of 4.0 ng/ml. After obtaining their consent, systematic prostate needle biopsy by transrectal ultrasonography was performed on 3 patients (15%). Prostate cancer was detected in all of them. Among them 2 patients were brothers, and since the other two brothers already had prostate cancer, all four brothers were confirmed to have prostate cancer. This is the first report of a familial prostate cancer in four brothers in Japan. In the western countries where the incidence of prostate cancer is higher than that in Japan, studies have been performed on the risk factors. Family history is one of the most important risk factors. In Japan, the incidence of prostate cancer is increasing rapidly. Moreover, patients with a prostate cancer family history are expected to increase. In such cases, prostate cancer screening should be performed aggressively from a young age.

Adult↗
PubMed1998

Association of fatty liver with increased ratio of visceral to subcutaneous adipose tissue in obese men.

We studied the association of fatty liver with subcutaneous and visceral obesity in 46 male and 36 female patients with body mass index (BMI) over 22 kg/m2. The correlation coefficient between the ratio of the visceral adipose tissue to the subcutaneous adipose tissue (V/S) and the computed tomography (CT) number of the liver was -0.299 (P < 0.05) and that between the V/S ratio and the ratio of the CT number of the liver to that of the spleen (CT-L/CT-S) was -0.335 (P < 0.05) in the males. Partial correlation analysis after making correction for BMI showed an increased correlation coefficient of -0.485 (P < 0.05) between the V/S ratio and the CT-L/CT-S ratio in the males. The odds ratio in the males for CT-L/CT-S below 1.0 and V/S above 1.0 was 3.25 with a 95% confidence interval of 1.02 to 9.39. No such association between the V/S ratio and the CT-L/CT-S ratio was present in the female patients. Multiple regression analysis with serum level of alanine aminotransferase, a marker of fatty liver, as an independent variable revealed a partial regression coefficient of -17.7 for CT-L/CT-S (P < 0.05) in the males and -21.7 (P < 0.05) in the females, validating the CT-L/CT-S ratio as an index of fatty liver. The results indicate the association of fatty liver as determined by the CT-L/CT-S ratio with visceral obesity in males.

Adipose Tissue↗
PubMed1998

Comparison of diets among elderly female residents in two suburban districts in Chiang Mai Province, Thailand, in dry season--survey on high- and low-risk districts of lung cancer incidence.

By means of duplicate meals, we collected food samples of general female residents, aged 50 to 74 years at two suburban districts in Chiang Mai Province, which are distinguished by very high and low incidence rates of lung cancer. Then, on the basis of analyses of their consumption of foods by food groups, we compared their dietary habits in the dry season of northern Thailand with special reference to the difference in lung cancer incidence. In brief, the following features and difference in their dietary habits were found; 1) Rice, vegetables, and pork were most frequently eaten in both the districts. 2) Consumption of fruits, in both quantity and variety, at a high-risk district was much less than that at a low-risk district. 3) Female residents at a low-risk district consumed more variety of green and yellow vegetables than those at a high-risk district. 4). Potato was not found in food samples of a high-risk district. 5) confectionery was more prevalent in a low-risk district than at a high-risk district.

Aged↗