Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 307 records · Page 17Linked to original sources

PubMed1998

Regional left ventricular wall motion abnormalities in myocardial infarction and mitral annular descent velocities studied with pulsed tissue Doppler imaging.

We evaluated global left ventricular (LV) systolic function from mitral annular systolic motion velocities measured by pulsed tissue Doppler imaging in patients with previous myocardial infarction (MI) and LV regional wall motion abnormalities. The subject group consisted of 45 patients with wall asynergies, 3 with ischemic cardiomyopathy, 8 with dilated cardiomyopathy, and 15 healthy control subjects. The peak systolic descent velocity (Sw) and the time from the electrocardiographic Q wave to the peak of the systolic wave (Q-Sw) were measured at 6 mitral annular sites obtained from 2-dimensional apical long-axis, 4-chamber, and 2-chamber echocardiograms; these variables were compared with the LV ejection fraction (EF) calculated from the left ventriculogram. The mean Sw at the sites corresponding to the infarct regions was significantly lower and the mean Q-Sw was significantly longer in the MI groups than in the control group. The mean Sw and Q-Sw at all 6 sites in the ischemic and dilated cardiomyopathy groups were significantly lower and longer, respectively, than those of the control group. There were significant correlations between the EF and the means of the Sw and Q-Sw values at the sites corresponding to the infarct regions in the MI groups. In the ischemic and dilated cardiomyopathy groups, significant correlations existed between the EF and the means of the Sw and Q-Sw values at all 6 sites. Thus the parameters obtained from mitral annular systolic motion velocities with pulsed tissue Doppler imaging reflect LV asynergy corresponding to the infarct regions in patients with MI, and global LV systolic function may be evaluated with these parameters.

Cardiac Catheterization↗

PubMed1998

Enhanced efficacy of nilvadipine in hypertensives whose raised ambulatory blood pressure is sustained during sleep.

This study was designed to clarify the relationship between the antihypertensive effects of the calcium antagonist nilvadipine, and circadian changes in blood pressure. Based on measurements using an ambulatory blood pressure monitoring system (ABPM), 17 outpatients with untreated essential hypertension were divided into two groups: a sustained hypertensive group (with a fall in blood pressure during sleep < 10%, n = 7) and a waking time hypertensive group (with a fall in blood pressure during sleep > or = 10%, n = 10). During treatment with nilvadipine (8 mg/day, > or = 2 weeks), patients were reexamined by ABPM. The antihypertensive effect of nilvadipine was significantly and negatively correlated with the night time fall in blood pressure: this effect was significantly greater in the sustained hypertensive group than in the waking time hypertensive group. These data suggest that the long acting calcium antagonist nilvadipine has more potent antihypertensive effects in patients with sustained hypertension ("nondippers") than in those whose hypertension lessens during sleep ("dippers").

Aged↗

PubMed1998

Immunohistochemical measurement of cell proliferation as replicative DNA synthesis in the liver of male Fischer 344 rats following a single exposure to nongenotoxic hepatocarcinogens and noncarcinogens.

We aimed to modify an in vivo/in vitro hepatocyte replicative DNA synthesis (RDS) test using autoradiography of [3H]methylthymidine (3HTdR) into a nonradioactive in vivo version by applying 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. The effects of 12 nongenotoxic hepatocarcinogens and 4 noncarcinogens on RDS induction and histological changes in the liver of male Fischer 344 (F344) rats were investigated 24 or 48 hrs after a single oral administration at diverse dose levels. A statistically significant, dose-related elevation in BrdU labeling indices (LI) was obtained for all of the 12 nongenotoxic hepatocarcinogens with only one exception of D,L-ethionine at relatively lower dose levels. No increase was observed in LI for any of the four noncarcinogens examined. From the results of histopathological evaluation, the increase in hepatocyte proliferation by carbon tetrachloride (CCl4), chloroform (CHCl3), and thioacetamide (TAA) was confirmed to be a regenerative liver response following cytotoxicity. Conversely, safrole, tannic acid, and urethane yet hepatotoxicants did not show inflammatory reaction or necrosis under the condition of the present study, and hence their mode of action by which they induce proliferative response was not obvious. The results of this study showed that the in vivo version of RDS test efficiently discriminated nongenotoxic hepatocarcinogens from noncarcinogens, while it did not well clarify the induction mode of cell proliferation.

Animals↗

PubMed1998

Effects of okadaic acid on rat colon.

Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (Gt) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal Gt values were 54+/-6.2 and 36.2+/-4.2 mS/cm2, respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in Gt in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced Gt change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.

Animals↗

PubMed1998

Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells.

1. To approach the mechanisms underlying desensitization of the opioid receptor-mediated Ca2+ channel inhibition, the effects of prolonged application of [D-Ala2, D-Leu5]enkephalin (DADLE) on Ba2+ currents (I(Ba)) through Ca2+ channels were analysed in NG108-15 neuroblastoma x glioma hybrid cells. 2. Inhibition of I(Ba) by 100 nM DADLE desensitized by 57% with a time constant of 4.4 min. 3. Maximal desensitization of the delta-opioid receptor-Ca2+ channel coupling was attained by 1 microM DADLE. The EC50 value for desensitization was estimated to be 78 nM. 4. RNA blot hybridization analysis and immunoblot analysis revealed the expression of beta-adrenoceptor kinase-1 (betaARK1) in NG108-15 cells. 5. Heparin, an inhibitor of betaARK, significantly reduced the magnitude and rate of desensitization, whereas Rp-cyclic AMPS and PKI (14-24)amide, inhibitors of cyclic AMP-dependent protein kinase (PKA), or long-term treatment with phorbol 12-myristate 13-acetate to induce down-regulation of protein kinase C (PKC) had no significant effect. 6. Recovery from desensitization (resensitization) proceeded with a time constant of 6.7 min. Okadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, significantly attenuated the degree of resensitization. 7. In summary, we have characterized the time course and concentration-dependence of the desensitization of DADLE-induced I(Ba) inhibition in NG108-15 cells. This desensitization was reversible after removal of DADLE. It is suggested that betaARK, but neither PKA nor PKC, is involved in desensitization, while serine/threonine phosphatases mediate resensitization.

Animals↗

PubMed1998

Functional sites of human PCNA which interact with p21 (Cip1/Waf1), DNA polymerase delta and replication factor C.

BACKGROUND: PCNA, an eukaryotic DNA sliding clamp interacts with replication factors and the cell cycle protein, p21(Cip1/Waf1) and functions as a molecular switch for DNA elongation. To understand how DNA replication is regulated through PCNA, elucidation of the precise mechanisms of these protein interactions is necessary. RESULTS: Loop-region mutants in which human PCNA sequences were substituted with the corresponding Saccharomyces cerevisiae PCNA regions were prepared. Analysis of their functions, along with previously prepared alanine scanning mutants, demonstrated that some loops interact with DNA polymerase delta (pol delta) and replication factor C (RFC). The p21 binding sites of PCNA, mapped by affinity measurement of the mutant forms, found to be located within a distinct structure of the PCNA monomer, overlap with RFC- and pol delta-interaction sites. Competition between p21 and pol delta or RFC for binding to PCNA results in efficient inhibition of its stimulation of pol delta DNA synthesis and RFC ATPase but not of PCNA loading on DNA by RFC. CONCLUSIONS: Semi-saturated amounts of p21 selectively block formation of the active pol delta complex but not the RFC-PCNA complex at 3'-ends of DNA primers. This differential effect may explain the specific inhibition of DNA replication by p21.

Adenosine Triphosphatases↗

PubMed1998

Activation of phospholipase A2 by the nociceptin receptor expressed in Chinese hamster ovary cells.

To gain insight into the molecular mechanism for nociceptin function, functional coupling of the nociceptin receptor expressed in Chinese hamster ovary (CHO) cells with phospholipase A2 (PLA2) was examined. In the presence of A23187, a calcium ionophore, activation of the nociceptin receptor induced time- and dose-dependent release of arachidonate, which was abolished by pretreatment of the cells with pertussis toxin (PTX). Immunoblot analysis using anti-Ca2+-dependent cytosolic PLA2 (cPLA2) monoclonal antibody demonstrates that activation of the nociceptin receptor induces a time- and dose-dependent electrophoretic mobility shift of cPLA2, suggesting that phosphorylation of cPLA2 is induced by the nociceptin receptor. Pretreatment of the cells with PD98059, a specific mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 inhibitor, or staurosporine, a potent inhibitor of serine/threonine protein kinases and tyrosine protein kinases, partially inhibited the nociceptin-induced cPLA2 phosphorylation and arachidonate release. These results indicate that the nociceptin receptor expressed in CHO cells couples with cPLA2 through the action of PTX-sensitive G proteins and suggest that cPLA2 is activated by phosphorylation induced by the nociceptin receptor via mechanisms partially dependent on p44 and p42 mitogen-activated protein kinases.

Animals↗

PubMed1998

The expulsion of Echinostoma trivolvis caused by goblet cell hyperplasia in severe combined immunodeficient (SCID) mice.

Mice with severe combined immunodeficiency (SCID), lacking functional T and B lymphocytes, were each infected with 40 Echinostoma trivolvis metacercarial cysts on day 0. The mice of the test group were given intramuscular injections of dexamethasone (DEX) daily for 2 weeks and necropsied on days 5, 8, 12, 15, 20 and 30 post-infection (p. i.). The control mice, not treated with DEX, were each infected with 40 echinostome cysts on day 0 and necropsied on the same days as the DEX-treated mice. In the control mice, worm rejection began about day 8 p. i. and the worms were completely rejected by day 15 p. i., corresponding to the peak in goblet cell hyperplasia, about day 12 p. i. In the DEX-treated mice, goblet cell hyperplasia was significantly suppressed and the worms were retained until day 15 p. i., and then rejected after the last treatment with DEX. The number of mucosal mast cells, that increased with worm infection and peaked about day 15 p. i., was apparently suppressed by treatment with DEX. The eosinophil number in the controls increased on day 15 p.i. approximately and then decreased. The eosinophil number in the DEX-treated mice increased as in the controls, but was significantly suppressed compared to that of the controls during the period of the experiment. Enzyme-linked immunosorbent assay (ELISA) showed no marked rise in titres of the sera IgM, IgA and IgG throughout the experiment in both groups. These results indicate that DEX-treatment delayed the rejection of E. trivolvis from the small intestine of SCID mice in association with the suppression of goblet cell hyperplasia. It is concluded that the host immune system is not involved in the rejection of E. trivolvis and the effector cells for worm rejection are goblet cells that markedly increase in numbers by infection with E. trivolvis.

Animals↗

PubMed1998

Pandemic versus epidemic influenza mortality: a pattern of changing age distribution.

Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918-1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this century's three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968-1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1) pandemics occurred among persons <65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons <65 years old should be considered in planning for pandemics.

Adolescent↗

PubMed1998

Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice.

The effects of nimesulide, a selective inhibitor of cyclooxygenase-2 (COX-2) on azoxymethane (AOM)-induced colon carcinogenesis were investigated in mice. AOM at a dose of 10 mg/kg body wt was administered to male ICR mice once a week for 6 weeks. The animals were fed on AIN-76A powder diet containing nimesulide at doses of 200 or 400 p.p.m., starting the day before the first carcinogen treatment until the end of the experiment, at week 30. Administration of nimesulide reduced the incidence of colon carcinomas to 32 and 25% for the AOM + 200 and 400 p.p.m. nimesulide groups, respectively, compared with the AOM + basal diet group (50%). Multiplicities of colon carcinomas in the 200 and 400 p.p.m. nimesulide-treated groups were 0.70 +/- 0.28 and 0.35 +/- 0.11, respectively, being significantly smaller than the AOM alone value (1.79 +/- 0.47). The sizes of the colon carcinomas in the nimesulide-treated groups were also decreased. No significant influence on liver and lung tumor development was apparent. Thus, nimesulide exerted a suppressive effect on AOM-induced colon carcinogenesis in mice.

Animals↗

PubMed1998

Inhibition by 1'-acetoxychavicol acetate of lipopolysaccharide- and interferon-gamma-induced nitric oxide production through suppression of inducible nitric oxide synthase gene expression in RAW264 cells.

Although nitric oxide (NO) is an important biological mediator, excessive production in inflammation is thought to be a causative factor of cellular injury and cancer in the long term. In the present study the effects of 1'-acetoxychavicol acetate (ACA), which has anticarcinogenic properties, on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide or interferon-gamma were examined. ACA suppressed NO production dose dependently with an IC50 of 160 ng/ml (680 nM). The decrease in NO production was shown to parallel reduced expression of iNOS mRNA and protein. The influence of ACA on transcription factors, such as NF-kappaB, AP-1 and Stat1, which are involved in expression of the iNOS gene was assessed. ACA was found to suppress degradation of IkappaB, an NF-kappaB inhibitory factor, and consequently inhibit NF-kappaB activation. Activation of AP-1 and Stat1 was also blocked by ACA treatment. Thus we demonstrate that ACA exerts potent inhibitory effects on NO production, apparently mediated by modulation of activation of several transcription factors. This could contribute to the anticarcinogenic properties of ACA.

Animals↗

PubMed1998

Contralateral ovulation shortens follicular phase length and favours pre-embryo development during ovarian stimulation with clomiphene citrate.

The present study was undertaken to evaluate whether the site of ovulation affects the following follicular phase length and pre-embryo development during infertility treatment with ovarian stimulation using clomiphene citrate. A total of 363 cycles in 97 patients undergoing infertility treatment (182 intrauterine insemination (IUI) cycles in 60 patients and 181 in-vitro fertilization (IVF) cycles in 52 patients) were studied. The cycles were divided into two main groups: preceding unilateral ovulation (PUO) and preceding bilateral ovulation (PBO). In the PUO group, the cycles were subdivided into contralateral ovulation, bilateral ovulation and ipsilateral ovulation. In IVF cycles alone, bilateral ovulations were further divided into bilateral ovulation-contralateral side and bilateral ovulation, ipsilateral side. Contralateral ovulations were seen in 134 of 240 cycles (56%), excluding bilateral ovulation and PBO. The follicular phase length in contralateral ovulation (16.2 +/- 2.6 days, mean +/- SD) was significantly (P < 0.05) shorter than that of ipsilateral ovulation (16.9 +/- 2.8). There were no significant differences of follicular phase length among contralateral ovulation, bilateral ovulation and PBO. Of IVF cycles including contralateral ovulation-ipsilateral ovulation and bilateral ovulation a total of 107 preovulatory follicles was assessed in the contralateral side (contralateral ovulation + bilateral ovulation-contralateral side) and 97 in the ipsilateral side (ipsilateral ovulation + bilateral ovulation, ipsilateral side). The oocyte retrieval rate (88%), fertilization rate (84%), cleavage rate (95%), embryo transfer rate (70%) of contralateral follicles were higher than those of ipsilateral follicles (71, 62, 86, 38% respectively) and those of PBO (76, 62, 87, 41% respectively). The total pregnancy rate of both IUI and IVF did not differ among contralateral ovulation (15%), ipsilateral ovulation (8%), bilateral ovulation (11%) and PBO (10%). The results confirm and extend our previous findings in natural cycles, suggesting that local ovarian factors, e.g. from corpus luteum, affect the health of preovulatory follicle and the enclosed oocyte in the same ovary (ipsilateral) negatively. Contralateral selection of preovulatory follicles in the succeeding cycle shortens the follicular phase length and favours pre-embryo development. The chance of conceiving during ovarian stimulation with clomiphene citrate may thus be affected by the site of ovulation in the previous cycle.

Adult↗

PubMed1998

Decline in sex ratio at birth after Kobe earthquake.

We investigated the possible association between the Kobe earthquake (January 1995) and the sex ratio among live-born infants after the catastrophe. A significant decline in the sex ratio (0.501) of Hyogo Prefecture in October 1995 was observed 9 months after the Kobe earthquake as compared with an expected value of 0.516 in the period from January 1993 to January 1996 (P = 0.04; one-tailed). Simultaneously, a reduction in fertility of approximately 6% was also observed, compared with the month of October 2 years previously. Thus, the acute stress resulting from a great natural catastrophe can be a cause of a low sex ratio at birth 9 months later.

Disasters↗

PubMed1998

Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP.

BACKGROUND: Epidemiological studies have suggested that soybean isoflavones are associated with a lower risk of prostate cancer. However, the mechanisms of prostate cancer prevention by soybean isoflavones have yet to be fully clarified. METHODS: Two soybean isoflavones (genistein and daidzein) and their glucosides (genistin and daidzin) were tested for their effects on cell growth and apoptosis of the LNCaP human prostatic cancer cell line. RESULTS: Among these isoflavones, genistein was found to inhibit the growth of LNCaP most effectively, with an IC50 value of 40 microM. The inhibition of cell growth by genistein was accompanied by the suppression of DNA synthesis and the induction of apoptosis. Expression of prostate-specific antigen (PSA) in LNCaP was also significantly reduced by the treatment with genistein. CONCLUSIONS: The results suggest that genistein might primarily influence human prostate cancer development by reducing tumor growth.

Apoptosis↗

PubMed1998

Partial agonistic activity of naloxone on the opioid receptors expressed from complementary deoxyribonucleic acids in Chinese hamster ovary cells.

UNLABELLED: Naloxone is a widely used opioid antagonist. To analyze the cellular responses induced by naloxone in the absence of opioid agonists, Chinese hamster ovary (CHO) cells, which do not endogenously express the opioid receptors, have been permanently transfected with the cloned complementary DNAs to produce the mu-, delta-, and kappa-opioid receptors. Naloxone dose-dependently reduced forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation in the cells expressing the mu- and kappa-opioid receptors, although the effect was less than that of opioid agonists [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin and U50,488, respectively. The naloxone-induced cAMP reduction was abolished by pretreatment of the cells with pertussis toxin, which suggests that pertussis toxin-sensitive G proteins (Gi and/or Go) are involved in the response. Cellular guanosine triphosphatase activity was significantly increased by naloxone in the cells expressing the mu- and kappa-opioid receptors, which suggests that the application of naloxone to these receptors induces activation of the G proteins. We conclude that naloxone possesses partial agonistic activity on the mu- and kappa-opioid receptors expressed from complementary DNAs in CHO cells. IMPLICATIONS: In this study, we examined whether naloxone has agonistic activity on the opioid receptors by using cultured cells transfected with delta-, mu-, and kappa-opioid receptor complementary DNAs. Our data indicate that naloxone is a partial agonist on the mu- and kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1998

Anthropometric and other risk factors for ovarian cancer in a case-control study.

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.

Adult↗

PubMed1998

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats.

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.

Animals↗

PubMed1998

Core temperature pattern and self-rated lifestyle.

We investigated the relationship between a subject's self-rated lifestyle and their pattern of nocturnal rectal temperature. Fifty-five students participated in the study. Among several significant findings, irregularity and eveningness component of lifestyle (irregular and delayed sleep phase) showed a significant negative correlation with temperature at the morning rising time. Examination of the nocturnal temperature pattern revealed that rectal temperature stayed at its lowest level in the early morning hours in the subjects with irregular and eveningness-like lifestyles.

Adult↗