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Biomedical subjects

Kazuhiro Takahashi

Publications and source records attributed to Kazuhiro Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Adrenomedullin in adipocyte differentiation of human mesenchymal stem cells.

Expression of adrenomedullin (AM), a potent vasodilator peptide, was studied during adipocyte differentiation of human mesenchymal stem cells (hMSCs). Immunoreactive AM levels in the medium were increased at day 4 and 8 of the adipocyte differentiation. Northern blot analysis showed increased expression of AM mRNA in hMSCs-derived adipocytes at day 4, 8, 12, and 18. Transient transfection assay showed that the promoter activity was higher in hMSCs-derived adipocytes than in hMSCs, when cells were transfected with plasmids containing a cis-acting region (-70/-29) of the human AM gene. Electrophoretic mobility shift assay showed that specific bands bound to the region (-70/-29) in hMSCs-derived adipocytes but not in hMSCs, and were abolished by the stimulatory protein 1 (Sp1) antibody. The present study has shown that AM expression is up-regulated during adipocyte differentiation of hMSCs probably via the interaction between Sp1 or Sp1-related factor(s) and the AM promoter region (-70/-29).

Adipocytes↗
PubMed2006

Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.

PURPOSE: To evaluate the incidence of Intraoperative Floppy Iris syndrome (IFIS) in relation to the usage of alpha(1)-adrenoceptor antagonists. DESIGN: Prospective, interventional case series. METHODS: In 2,643 consecutive eyes of 1,968 patients undergoing cataract surgery, occurrence of IFIS and use of alpha(1) antagonists were recorded. RESULTS: IFIS was observed in 29 eyes (1.1%) of 25 male patients, all of whom were receiving alpha(1) antagonists. In those receiving systemic tamsulosin, alpha(1A) selective antagonist, IFIS developed in 25 (43.1%) of 58 eyes. In those receiving systemic naftopidil, alpha(1A) and alpha(1D) antagonists, IFIS was found in 4 (19.0%) of 21 eyes. There was no case of IFIS in patients who received other systemic alpha(1) antagonists and in eyes treated with bunazosin eyedrops, a nonselective alpha(1) antagonist. CONCLUSIONS: IFIS occurred in 1.1% of cases treated with systemic alpha(1A)-adrenoceptor antagonists for benign prostatic hypertrophy. Topical nonselective alpha(1) antagonist did not induce IFIS.

Administration, Topical↗
PubMed2006

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.

We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H2KO) mice and histamine H2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system.

Analysis of Variance↗
PubMed2006

Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells.

Vascular endothelial senescence is involved in human atherosclerosis. Telomerase activity is known to be critical in cellular senescence and its level is modulated by regulation of telomerase catalytic subunit (telomerase reverse transcriptase (TERT)) at both the transcriptional and post-transcriptional levels. Since the cardioprotective effect of estrogen itself has not been ruled out, we examined that of raloxifene, which has been classified as a selective estrogen receptor modulator, on the proliferation and telomerase activity of human umbilical vein endothelial cells (HUVECs). Raloxifene, like estrogen, clearly induced the telomerase activity and human TERT (hTERT) expression via estrogen receptor (ER) alpha and ERbeta. Treatment with raloxifene for 5 days significantly induced cell growth, and either cotreatment with a telomerase inhibitor, 3'-azido-3'-deoxythymidine, or transfection with hTERT-specific small interfering RNA significantly attenuated the raloxifene-induced cell growth. Raloxifene also induced the phosphorylation of Akt, and pretreatment with a phosphatidylinositol 3-kinase inhibitor, LY294002, significantly attenuated the raloxifene-induced telomerase activity. In addition, raloxifene induced both the phosphorylation of hTERT and IkappaB. Moreover, cotreatment with an IkappaBalpha phosphorylation inhibitor, BAY-11-7082, or a specific NFkappaB nuclear translocation inhibitor, SN50, significantly attenuated the raloxifene-induced telomerase activity and the association of NFkappaB with hTERT. These results show that raloxifene induced the up-regulation of telomerase activity not only by the transcriptional regulation of hTERT but also by post-translational regulation of the phosphorylation of Akt and hTERT and the association of hTERT with NFkappaB in HUVECs. Thus, the up-regulation of telomerase activity in vascular endothelial cells might be one mechanism contributing to the potential atheroprotective effect of raloxifene.

Cell Proliferation↗
PubMed2006

Hypoxia increases endothelin-1 mRNA expression but not immunoreactive endothelin in the medium of T98G glioblastoma cells under cytokine treatment.

Endothelin-1 (ET-1) levels in the culture medium were considered to reflect the transcription of the ET-1 gene and the subsequent secretion of ET-1 from cultured cells. It has not been clarified how different ET-1 mRNA expression levels and immunoreactive (IR)-ET levels in the culture medium are in the cell culture system. We studied ET-1 mRNA expression levels and IR-ET levels in the medium of T98G glioblastoma cells treated with cytokines. T98G glioblastoma cells were cultured with cytokines (interferon-gamma 100 U/ml, tumor necrosis factor-alpha 20 ng/ml and interleukin-1beta 10 ng/ml) under normoxia or hypoxia (1% O(2)). Northern blot analysis showed that ET-1 mRNA expression levels were increased by tumor necrosis factor-alpha alone or a combination of tumor necrosis factor-alpha and interleukin-1beta, or three cytokines, and the increase was further enhanced under hypoxia. Particularly, relative expression levels of ET-1 mRNA were significantly higher under hypoxia than in normoxia in the treatment with a combination of three cytokines. IR-ET levels in the medium were increased by treatment with tumor necrosis factor-alpha, interleukin-1beta or a combination of tumor necrosis factor-alpha and interleukin-1beta, or three cytokines. In contrast to the mRNA expression levels, IR-ET levels in the medium of T98G cells treated with a combination of three cytokines were rather decreased under hypoxia compared with those in normoxia. These findings indicate that hypoxia induces ET-1 mRNA expression in the treatment of three cytokines, but IR-ET levels in the medium do not reflect this induction in T98G glioblastoma cells.

Cell Hypoxia↗
PubMed2006

Cerebral vascular mean transit time in healthy humans: a comparative study with PET and dynamic susceptibility contrast-enhanced MRI.

Cerebral vascular mean transit time (MTT), defined as the ratio of cerebral blood volume to cerebral blood flow (CBV/CBF), is a valuable indicator of the cerebral circulation. Positron emission tomography (PET) and dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) are useful for the quantitative determination of MTT in the clinical setting. The aim of this study was to establish a normal value set of MTT as determined by PET and by DSC-MRI and to identify differences between these methods. Seven healthy volunteers were studied with (15)O-PET (H(2)(15)O and C(15)O) and gradient-echo echo-planar DSC-MRI at 1.5 T. In the DSC-MRI study with bolus injection of contrast agent, deconvolution analysis was performed. Comparison of gray-to-white matter ratios showed fairly good agreement between PET and DSC-MRI for all parameters (relative CBV, relative CBF, and relative MTT), confirming the validity of relative measurements with DSC-MRI. However, quantitative MTT measured by DSC-MRI was significantly shorter than that measured by PET in cerebral cortical regions (2.8 to 3.0 secs for DSC-MRI versus 3.9 to 4.3 secs for PET) and the centrum semiovale (3.5 secs for DSC-MRI versus 4.8 secs for PET). These discrepancies may be because of the differences in the intrinsic sensitivity of each imaging modality to vascular components; whereas PET measurement of CBV is equally sensitive to all vascular components, measurement with DSC-MRI originates from the microvasculature in the vicinity of the brain parenchyma. This underlying difference may influence interpretation of MTT determined by PET or by DSC-MRI for patients with cerebrovascular disease.

Adult↗
PubMed2006

Change in pulse wave velocity throughout normal pregnancy and its value in predicting pregnancy-induced hypertension: a longitudinal study.

OBJECTIVE: We longitudinally examined the changes of brachial to ankle distensibility using pulse wave velocity (PWV) throughout pregnancy and its difference between normal pregnancy and pregnancy-induced hypertension (PIH) groups. STUDY DESIGN: One hundred and eighty-three pregnant women were included in this study. The PWV examinations were performed in a longitudinal way during the first, second, and third trimesters of pregnancy, and immediately and 1 month after delivery. RESULTS: In normal pregnancies, the PWV significantly decreased at the second trimester, increased from the third trimester through immediately after delivery, and decreased again at 1 month after delivery. In PIH patients, it increased in proportion to the progression of gestation. CONCLUSION: We monitored the longitudinal changes in PWV and constructed a PWV normogram during pregnancy. The predictive value of PWV and blood pressure for PIH was higher than that of blood pressure alone, suggesting the usefulness of measuring PWV to predict PIH.

Adolescent↗
PubMed2006

18F-FDG accumulation in atherosclerosis: use of CT and MR co-registration of thoracic and carotid arteries.

PURPOSE: The purpose of this study was to depict( 18)F-fluoro-2-deoxy-D: -glucose (FDG) accumulation in atherosclerotic lesions of the thoracic and carotid arteries on CT and MR images by means of automatic co-registration software. METHODS: Fifteen hospitalised men suffering cerebral infarction or severe carotid stenosis requiring surgical treatment participated in this study. Automatic co-registration of neck MR images and FDG-PET images and of contrast-enhanced CT images and FDG-PET images was achieved with co-registration software. We calculated the count ratio, which was standardised to the blood pool count of the superior vena cava, for three arteries that branch from the aorta, i.e. the brachial artery, the left common carotid artery and the subclavian artery (n=15), for atherosclerotic plaques in the thoracic aorta (n=10) and for internal carotid arteries with and without plaque (n=13). RESULTS: FDG accumulated to a significantly higher level in the brachial artery, left common carotid artery and left subclavian artery at their sites of origin than in the superior vena cava (p=0.000, p=0.000 and p=0.002, respectively). Chest CT showed no atherosclerotic plaque at these sites. Furthermore, the average count ratio of thoracic aortic atherosclerotic plaques was not higher than that of the superior vena cava. The maximum count ratio of carotid atherosclerotic plaques was significantly higher than that of the superior vena cava but was not significantly different from that of the carotid artery without plaque. CONCLUSION: The results of our study suggest that not all atherosclerotic plaques show high FDG accumulation. FDG-PET studies of plaques with the use of fused images can potentially provide detailed information about atherosclerosis.

Aged↗
PubMed2006

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: a project of the Kyushu University Liver Disease Study Group.

AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.

Adult↗
PubMed2006

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients: a project of Kyushu University Liver Disease Study.

AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

Adult↗
PubMed2006

Identification of adipocyte differentiation-related regulatory element for adrenomedullin gene repression (ADRE-AR) in 3T3-L1 cells.

Adrenomedullin (AM), a potent vasodilator peptide, has been suggested to act against cardiovascular complications and insulin resistance in the metabolic syndrome. We have already reported the AM gene repression in the early phase of adipocyte differentiation of NIH 3T3-L1 cells. Here we show adipocyte differentiation-related regulatory element for AM gene repression (ADRE-AR) in 36-bp region (-2135/-2100) of the AM gene. 3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. On the third day of differentiation, the promoter function was analyzed using the reporter plasmids, which contain the promoter region of AM gene (-4616/+108) in pGL3-basic luciferase reporter vector. The promoter activity decreased to about 20% in 3T3-L1 adipocytes when compared with 3T3-L1 preadipocytes, and a 36-bp region (-2135 to -2100) upstream from the transcription initiation site of the AM gene was necessary for higher AM gene expression in preadipocytes. This 36-bp ADRE-AR contains three copies of G/AAAA sequence (5'-GAAATGAAAGTAAAA-3') (-2124/-2110), which are conserved between mouse and human, and the introduction of mutations in each copy of G/AAAA sequence decreased the promoter activity in preadipocytes and adipocytes. Electrophoretic mobility shift assay showed that the full-length ADRE-AR was specifically bound by a certain nuclear protein(s). The present study has raised the possibility that ADRE-AR may play important roles in the AM gene expression in preadipocytes, and that the AM gene may be repressed through the ADRE-AR in adipocytes.

3T3-L1 Cells↗
PubMed2006

Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models.

The phosphatidylinositol 3-kinase (PI3K)/Akt cascade has an important role in the resistance of ovarian cancer cells to cisplatin in vitro; however, there have been no reports about whether blocking the PI3K/Akt cascade enhances the sensitivity to cisplatin in vivo. We investigated whether inhibition of PI3K increased the efficacy of cisplatin in an in vivo ovarian cancer model. Blocking the PI3K/Akt cascade with a PI3K inhibitor (wortmannin) increased the efficacy of cisplatin-induced inhibition of intraabdominal dissemination and production of ascites in athymic nude mice inoculated ip with the Caov-3 human ovarian cancer cell line. In addition, wortmannin increased the efficacy of cisplatin-induced apoptosis in tumors cells. There were no detectable side effects in mice treated with wortmannin. Moreover, the antitumor effect of cisplatin detected in mice inoculated with Caov-3 cells stably transfected with empty vector was significantly attenuated, compared with mice inoculated with Caov-3 cells stably transfected with a dominant-negative Akt, K179M-Akt. We confirmed that wortmannin blocked Akt phosphorylation and the downstream targets of the PI3K/Akt cascade, such as BAD (Bcl-2-associated death protein) and nuclear factor-kappaB in vivo by immunohistochemical staining and Western blotting. In accordance with the previously reported in vitro results, these in vivo results support the idea that combination therapy with cisplatin and a PI3K inhibitor would increase the therapeutic efficacy of cisplatin.

Androstadienes↗
PubMed2006

Usefulness of intraovarian artery pulsatility and resistance indices measurement on the day of follicle aspiration for the assessment of oocyte quality.

OBJECTIVE: To examine the correlation between the pulsatility and resistance indices (PI and RI) of the intraovarian artery on the day of follicle aspiration and the oocyte quality, intrafollicular oxidative stress, and luteinization. Pulsatility index and RI on the day of hCG administration also were measured. DESIGN: Prospective study. SETTING: Obstetrics and gynecology department of a university medical school in Japan. PATIENT(S): Thirty-five patients in an IVF-ET program. INTERVENTION(S): The PI and RI of the intraovarian artery were measured by transvaginal color ultrasonographic pulsed wave Doppler on the day of hCG administration and the day of follicle aspiration. Follicular fluids and the granulosa cells were collected at follicle aspiration. MAIN OUTCOME MEASURE(S): The PI and RI of the intraovarian artery blood flow on the day of hCG administration and of follicle aspiration, as well as the rate of development of mature oocytes, follicular fluid steroid levels, and the incidence of apoptosis in the granulosa cells. RESULT(S): The PI and RI on the day of follicle aspiration were correlated positively with the rate of mature oocytes retrieved (PI: r = 0.429; RI: r = 0.348), were correlated negatively with the incidence of apoptotic mural (PI: r = -0.383; RI: r = -0.459) and cumulus (PI: r = -0.378; RI: r = -0.469) granulosa cells, and were negatively correlated with the concentration of P in the follicular fluid (PI: r = -0.429; RI: r = -0.359). The PI and RI on the day of hCG administration were negatively correlated only with the total number of retrieved oocytes (PI: r = -0.393; RI: r = -0.374). CONCLUSION(S): The PI and RI of the intraovarian artery blood flow measured on the day of follicle aspiration may be good indicators of the follicle luteinization and oxidation as well as of oocyte quality.

Adult↗
PubMed2006

Expression of endothelin-1 and adrenomedullin was not altered by leptin or resistin in bovine brain microvascular endothelial cells.

Hypertension frequently occurs in obese subjects. It has been reported that leptin and resistin induce endothelin-1 expression in vascular endothelial cells. Altered function of brain microvascular endothelial cells may be related to increased occurrences of stroke in hypertensive patients. In the present study, we therefore studied the effects of leptin and resistin on the expression of endothelin-1 and adrenomedullin in bovine brain microvascular endothelial cells. Northern blot analysis showed that leptin (10(-10)-10(-8) mol/l), resistin (10(-10)-10(-8) mol/l) or a combination of leptin and resistin (10(-8) mol/l for each) had no significant effects on the expression of endothelin-1 mRNA or adrenomedullin mRNA in cultured bovine brain microvascular endothelial cells. On the other hand, hypoxia induced, and tumor necrosis factor-alpha (10 ng/ml) decreased, the expression levels of endothelin-1 and adrenomedullin mRNAs, indicating that the bovine brain microvascular endothelial cells were able to respond to hypoxia and tumor necrosis factor-alpha. Consistent with the results of Northern blot analysis, immunoreactive endothelin and immunoreactive adrenomedullin concentrations in the medium were not significantly changed by the treatment with leptin, resistin, or a combination of leptin and resistin. The present study thus showed that neither leptin nor resistin affects the expression of endothelin-1 or adrenomedullin in bovine brain microvascular endothelial cells.

Adrenomedullin↗
PubMed2006

Role of a surfactant in caustic alkali cleaning of polyethylene terephthalate surfaces fouled with organic substances.

The role of polyoxyethylene lauryl ether (POELE), a nonionic surfactant, in removing bovine serum albumin (BSA) and catechin from polyethylene terephthalate (PET) particles was quantitatively studied. Relatively large fractions of adsorbed BSA and catechin were removed from PET particles under weak alkaline conditions below pH 9, whereas cleaning with high concentrations of NaOH was not so effective, especially on the removal of BSA. This was attributed to the lower susceptibility of PET particles to water-based alkali (OH-) cleaning because of the lower degree of the polarity of PET surfaces. The combined use of NaOH solutions of moderate pHs and POELE could successfully improve the efficiency of cleaning of PET particles without a significant dissolution of PET materials. There was a good correlation between the lowered surface tension (7) of the NaOH solution with POELE and the removal efficiency of BSA or catechin. No effect of POELE was observed on the NaOH cleaning of hydrophilic alumina (A12O3) particles fouled with BSA. It could be concluded that the role of POELE in NaOH cleaning of PET particles was to lower the gamma of the NaOH solution and hence to facilitate penetration of OH- ions into the PET-BSA and PET-catechin interfaces.

Adsorption↗
PubMed2006

Cleanability of stainless steel surfaces as influenced by heat treatment.

The cleanability of heat-treated 316L stainless steel particles treated at various temperatures of 100 to 500 degrees C was studied in a plug-flow column fed by a 0.1M NaOH solution. Bovine Serum albumin (BSA) was used as the model fouling agent. Heat treatment resulted in the enrichment of iron in passive films on stainless steel particles depending on temperature. The degree of surface hydroxylation and the apparent surface charge density (sigma(app)) of stainless steel particles decreased markedly with increasing heating temperatures. The saturation amounts of BSA adsorbed (gamma(sat)) were larger on the particles heated at higher temperatures. No correlation was observed between the gamma(sat) and sigma(app) values. With increasing heating temperatures, the rate of BSA desorption from stainless steel particles decreased gradually in the initial and later stages of cleaning, resulting in larger amounts of BSA remaining on the particles at the end of 120-min of cleaning. The susceptibility to BSA adsorption and the cleanability were found to be correlated with the iron content of the passive films on stainless steel particles. It could be suggested that the decrease in the cleanability was probably due to the formation of iron-enriched passive films with lower degrees of surface hydroxylation of stainless steel particles due to heat treatment.

Adsorption↗