Biomedical subjects

J Yamazaki

Publications and source records attributed to J Yamazaki.

At least 19 recordsLinked to original sources

PubMed1998

Modulatory role of endothelial calcium level in vascular tension of canine depolarized coronary arteries.

The vascular tension in the coronary artery is modulated by factors released by endothelial cells. We investigated the relationship between the Ca2+ level in endothelium and endothelium-mediated changes in smooth muscle tone in high K(+)-depolarized canine coronary arteries by measuring intracellular Ca2+ concentration fluorimetrically with the Ca2+ indicator fura 2. Addition of Ca2+ (1 mM) caused an increase in endothelial Ca2+ and relaxed the 30 mM K(+)-depolarized arteries following inhibition of Ca2+ influx in the smooth muscle with diltiazem. This relaxation was inhibited by NG-monomethyl-L-arginine. As extracellular K+ concentration was decreased, increases of endothelial Ca2+ were augmented, whereas the relaxation was decreased. Basal muscle tone was found to be decreased in low K+ by measuring relaxation by sodium nitroprusside. These results suggest the importance of Ca2+ level in the endothelium in playing a modulatory role in coronary tension through the production of nitric oxide. The correlation of extracellular K+ to Ca2+ level in the endothelium indicates a typical characteristic of the passive Ca2+ entry pathway in the endothelium, whereas the resultant relaxation appears to be restricted by the basal muscle tone.

Acetylcholine↗

PubMed1997

Identification of chiro-inositol and its formation by isomerization of myo-inositol during hydrolysis of glycosylphosphatidylinositol-anchored proteins.

myo-Inositol has been believed to be a sole inositol isomer existing in phosphatidylinositol (PI) and related derivatives. In this experiment, chiro-inositol, an inositol isomer other than myo-inositol, was identified in hydrolytic products from several GPI-anchored proteins. The chiro-inositol contents in several different GPI-anchored proteins including 5'-nucleotidase of bovine liver and alkaline phosphatase of mouse NS-1 varied with hydrolytic conditions of these GPI anchor. Isomerization of 20-60% of myo-inositol occurred on the hydrolysis in 6 N HCl solution. Under the hydrolytic conditions of a HCl gas stream in place of solution, however, isomerization was very low (less than 0.1%). Even in the hydrolysis under HCl gas stream, existence of CNBr accelerated the isomerization of inositol in GPI up to 70-95%. In the hydrolysis of phosphatidylinositol or myo-inositol 1-phosphate, however, a significant amount of chiro-inositol was not detected in 6 N HCl solution or in the existence of CNBr under the HCl stream. These facts indicated that isomerization occurred during the hydrolysis of the GPI anchor, when myo-inositol is substituted by glucosamine at 6-OH and is substituted by phosphate at 1-OH. It also suggested that the former identification of chiro-inositol in GPI structure in the various reports might be due to isomerization.

5'-Nucleotidase↗

PubMed1997

Overexpression of bax enhances the radiation sensitivity in human breast cancer cells.

Bax-alpha, a splice variant of bax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels of bax-alpha. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenous bax-alpha expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗

PubMed1997

Increased apoptosis rate by hyperthermochemoradiotherapy for advanced rectal cancers.

Apoptosis induced in cancer cells by ionizing radiation, hyperthermia, and 5-fluorouracil (5-FU), termed "hyperthermochemoradiotherapy" (HCR), has been well studied in vitro; however, the role of apoptosis in the tumocidal effect of HCR for primary rectal cancers has not yet been clarified. Therefore, we examined the relationship between the therapeutic effect and induction rate of histological apoptosis in 16 patients with rectal cancers after HCR. Numerous Tunel-positive apoptotic cells were found in the tumor tissue after HCR, but few were found in the tumors which had not received HCR. The histological therapeutic effect was closely correlated to the rate of apoptosis. Thus, we suggest that HCR induces a therapeutic effect mainly through apoptosis in human rectal cancers.

Administration, Rectal↗

PubMed1997

Overexpression of bax sensitizes breast cancer MCF-7 cells to cisplatin and etoposide.

Bax, one of the bcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax; and two unique clones, MCF-7/bax-1 and MCF-7/ bax-2, that expressed different levels of bax were generated. Sensitivity to cisplatin (CDDP) and etoposide (VP-16) was examined and each stable transfectant was more sensitive to these agents than the parental MCF-7 cells. The degree of enhancement in sensitivity to these anticancer agents was dependent on the expression level of bax. The enzyme-linked immunosorbent assay (ELISA), which quantifies DNA damage, demonstrated that this sensitization was due to apoptosis. Thus, we suggest that exogenous bax-alpha overexpression may be one of the factors determining cellular chemosensitivity in MCF-7 breast cancer cells and that it could be applied therapeutically to enhance chemosensitivity in breast cancer cells.

Antineoplastic Agents↗

PubMed1997

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional 99mTc-HSAD multigated cardiac pool imaging.

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Adult↗

PubMed1997

Avoidance of oocyte retrieval on the weekend through the use of scheduled ovarian hyperstimulation for in vitro fertilization and embryo transfer.

OBJECTIVE: To avoid oocyte retrieval for IVF-ET during the weekend, the scheduled method of ovarian hyperstimulation, in which oocyte retrieval is planned in advance for Monday through Wednesday, was evaluated. DESIGN: A retrospective study. SETTING: The IVF-ET unit of the Department of Obstetrics and Gynecology at Tokushima University Hospital. PATIENT(S): One hundred seventy-eight cycles in patients undergoing ovarian hyperstimulation for IVF-ET were stimulated according to the scheduled method of ovarian hyperstimulation (scheduled group). One hundred seventy-one cycles in patients of similar age and with comparable causes of infertility were stimulated according to the conventional method of ovarian hyperstimulation for IVF-ET (conventional group). INTERVENTION(S): In the scheduled method, under GnRH-a, the day of oocyte retrieval was determined in advance for IVF-ET. Ovarian stimulation with FSH and hMG was started 12 days before oocyte retrieval. MAIN OUTCOME MEASURE(S): The cancellation and clinical pregnancy rates (PRs), the days of oocyte retrieval, and other clinical parameters were evaluated in the two groups. RESULT(S): The cancellation rates in the scheduled and conventional groups were 9.6% and 4.7%, respectively. In about 75% of cycles in the scheduled group, oocyte retrieval was conducted on the scheduled day. When oocyte retrieval was scheduled for Monday through Wednesday, overtime work on the weekend could be avoided in 91% of the cycles without cancellation. The clinical PR was comparable between the two groups. CONCLUSION(S): The scheduled method of ovarian hyperstimulation for IVF-ET was useful for avoiding oocyte retrieval on the weekend.

Adult↗

PubMed1997

Diltiazem inhibits the late increase in extracellular potassium by maintaining glycolytic ATP synthesis during myocardial ischemia.

During myocardial ischemia, the extracellular potassium concentration increases in a triphasic pattern, an initial early increase, a constant phase, and a late increasing phase. The aim of this study was to determine whether diltiazem inhibits the late increasing phase by maintaining glycolytic adenosine triphosphate (ATP) synthesis in ischemic myocardium. The extracellular potassium concentration and pH were measured simultaneously with ion-sensitive electrodes during 30 min of global ischemia in isolated guinea-pig hearts. In the control hearts, the late increasing phase occurred 13 min after the onset of ischemia when the change in extracellular pH had reached a plateau. There was a sharp increase in the myocardial lactate level in the control hearts, which was maintained for approximately 8 min after the onset of ischemia. Iodoacetate (1 mM) led to a ATP depletion and rapid accumulation in extracellular potassium shortly after the onset of ischemia without a decrease in extracellular pH. The preischemic treatment with diltiazem (3 microM) reduced cardiac function both before ischemia and during the early period of ischemia. Diltiazem almost completely abolished the late increasing phase with a continuous decrease in extracellular pH throughout the ischemic period. The myocardial lactate level in the diltiazem-treated group increased sharply between 2 and 15 min after the onset of ischemia. The myocardial ATP level was preserved throughout the ischemic period. This study shows that diltiazem inhibits the late increasing phase in extracellular potassium by maintaining glycolytic ATP synthesis during ischemia.

Adenosine Triphosphate↗

PubMed1997

Quantitative scintigraphic analysis of 123I-MIBG by polar map in patients with dilated cardiomyopathy.

To evaluate sympathetic dysfunction of the heart, one of the factors responsible for heart failure in patients with dilated cardiomyopathy (DCM), we performed 123I-metaiodobenzylguanidine (123I-MIBG) myocardial single photon emission tomography (SPET) in 22 cases of DCM. There were significant relationships between severity scores and defect scores for the early and delayed images. When the data acquired by 123I-MIBG myocardial SPET were compared with left ventricular function, the extent score (r = -0.754, P < 0.01) and severity score (r = 0.693, P < 0.01) for the early images were both significantly correlated with left ventricular ejection fraction (LVEF). For the delayed images also, a good correlation was obtained between LVEF and extent score (r = -0.704, P < 0.01) and between LVEF and severity score (r = -0.801, P < 0.01). the washout rate for the entire left ventricle, calculated from the early and delayed images, also correlated with LVEF (r = -0.643, P < 0.01). Since the 123I-MIBG defect on the early images was shown to be significantly related to left ventricular function, a decrease in neuronal uptake at sympathetic nerve endings appears in the main to account for the 123I-MIBG defect on the early images. The regional washout rate was increased compared to that in the control group (P < 0.01). It was particularly high in the inferior wall, suggesting that acceleration of turnover and poor retention in the area of the 123I-MIBG defect on the early images and then the entire left ventricle was strongly associated with the 123I-MIBG defect on the delayed images. Our results suggest that 123I-MIBG myocardial SPET may be useful in determining the severity of DCM.

3-Iodobenzylguanidine↗

PubMed1997

Inhibitory effects of glibenclamide on cystic fibrosis transmembrane regulator, swelling-activated, and Ca(2+)-activated Cl- channels in mammalian cardiac myocytes.

Recent studies have provided evidence that sulfonylureas, in addition to blocking ATP-sensitive K+ (KATP) channels, also inhibit cystic fibrosis transmembrane regulator (CFTR) Cl- channels in epithelial and cardiac cells. The purpose of this study was to test whether the sulfonylurea glibenclamide might also inhibit other types of cardiac Cl- channels. Whole-cell patch-clamp techniques were used to compare the effects of glibenclamide on CFTR Cl- currents in guinea pig ventricular myocytes, swelling-activated Cl- currents in guinea pig atrial myocytes, and Ca(2+)-activated Cl- currents in canine ventricular myocytes. Glibenclamide markedly inhibited CFTR Cl- currents in a voltage-independent manner at 22 degrees C, with estimated IC50 values of 12.5 and 11.0 mumol/L at +50 and -100 mV, respectively. The outwardly rectifying swelling-activated Cl- current in atrial cells was less sensitive to glibenclamide, and the block exhibited voltage dependence. At 22 degrees C, the estimated IC50 values were 193 and 470 mumol/L at +50 and -100 mV, respectively, and block was enhanced at 35 degrees C. Macroscopic Cl- currents activated by a rise in intracellular Ca2+, induced by either Ca(2+)-induced Ca2+ release or by external application of the Ca2+ ionophore A23187, were also markedly inhibited at 22 degrees C by glibenclamide in a voltage-independent manner. The estimated IC50 values were 61.5 and 69.9 mumol/L at +50 and -100 mV, respectively. These results suggest that glibenclamide, an inhibitor of cardiac CFTR Cl- channels, also inhibits swelling-activated and Ca(2+)-activated Cl- channels at higher concentrations. The results also suggest that studies attributing the beneficial or deleterious effects of sulfonylurea compounds in the heart solely to blockade of KATP channels should use submicromolar concentrations of these agents to minimize possible secondary interactions with cardiac Cl- channels.

Animals↗

PubMed1996

Flow dependence of nitric oxide-mediated pressure change in rat mesenteric beds with different tonus.

To investigate the flow-dependent contribution of basally released nitric oxide (NO) to vascular perfusion pressure, we compared the effects of a NO synthesis inhibitor on the pressure changes in some models of rate mesenteric vascular beds. Spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats (13-14-weeks-old) were used. The perfusion pressure at each flow rate was slightly higher in the SHR bed than in the WKY bed when no contractile compounds were applied. NG-Monomethyl-L-arginine (L-NMMA) significantly increased the pressure in WKY at flow rates more than 5 ml/min (8.9 mm Hg at 7 ml/min). L-NMMA increased the pressure in SHR at flow rates of 2-7 ml/min (40.2 mm Hg at 7 ml/min). L-NMMA markedly increased the pressure at each flow rate in both beds which methoxamine (30 microM) had constricted. The effects of L-NMMA were concentration-dependent, and were blocked by L-arginine. Therefore, basal NO release appears to contribute to the vasolidating tone although flow dependence of the effect is different in the absence or presence of an exogeneous tone in both hypertensive and normotensive rats.

Acetylcholine↗

PubMed1996

Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis.

Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21WAF1 about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗

PubMed1996

Role of milky spots as selective implantation sites for malignant cells in peritoneal dissemination in mice.

We investigated the significance of milky spots for malignant cells in peritoneal dissemination using three mouse carcinomatous peritonitis models. P388 leukemia and Colon 26 cancer cells were labeled with bromodeoxyuridine (BrdU) and mice were inoculated intraperitoneally. After 24 h the greater omentum and the mesenterium were removed and stained immunohistochemically with anti-BrdU antibody. The labeled cells were found to have preferentially infiltrated into the milky spots in these specimens. Next, using B16 PC melanoma cells, which can be easily distinguished from the other cells by the intrinsic black melanin, the distribution of the melanoma cells was observed macro- and microscopically following intraperitoneal inoculation. The melanoma cells were similarly found to have selectively infiltrated into the milky spots in the omentum and mesenterium after 1 day. Moreover, the melanoma cells were growing and forming distinct metastic lesions within the milky spots 1 week later.

Animals↗

PubMed1996

Clinical application of three-dimensional myocardial imaging: evaluation of efficacy of medical treatment on myocardial perfusion.

To investigate the clinical applicability of the three-dimensional (3D) myocardial imaging using a newly developed system (the Application Visualization System-Medical Viewer), thallium-201 myocardial single photon emission computed tomography was performed in 19 patients with previous myocardial infarction before and after treatment with nisoldipine. We have developed a new method for automatically reconstructing 3D imaging for the stereoscopic evaluation of myocardial perfusion. The left ventricular myocardial volume with a radioisotope count > or = 50% of maximum was calculated by using the conventional surface rendering method. With these images, the effect of nisoldipine on myocardial perfusion was assessed and the myocardial volume with a radioisotope count > or = 50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine significantly increased the myocardial volume with a radioisotope count > or = 50% of maximum from 141 +/- 17 to 153 +/- 18 ml on the stress 3D imagings. These findings indicate that nisoldipine improved myocardial perfusion during exercise. 3D imaging provided stereoscopic assessment of the changes in myocardial perfusion following treatment with nisoldipine and also detected transient enlargement of the left ventricular lumen induced by exercise.

Aged↗

PubMed1996

Pharmacological effects of 5-fluorouracil microspheres on peritoneal carcinomatosis in animals.

A new delivery formulation (5FU-MS) of 5-fluorouracil (5FU), 5FU incorporated in microspheres composed of poly(glycolide-co-lactide) matrix, has been developed for the treatment of peritoneal carcinomatosis, and is designed to slowly release the incorporated 5FU for 3 weeks. Intraperitoneal 5FU-MS distributed higher concentrations of 5FU to the intraperitoneal tissues, such as the omentum and the mesentery, for a longer period with lower blood plasma concentrations than did the aqueous 5FU solution in rats. In experiments using mice, the lethal toxicity, determined by the probit method, in 5FU-MS was reduced to less than half that in aqueous 5FU solution. We evaluated the therapeutic effects on peritoneal carcinomatosis induced by the intraperitoneal inoculation of B-16 PC melanoma cells. The therapeutic effects of 5FU-MS were enhanced when compared with both the equivalent doses and same toxicity doses of the aqueous 5FU solution.

Animals↗

PubMed1996

Interleukin (IL)-12 deficiency in susceptible mice infected with Mycobacterium avium and amelioration of established infection by IL-12 replacement therapy.

Mycobacterium avium is an intracellular microorganism that infects and multiplies within macrophages. Cell-mediated immunity plays an important role in host defense, and interleukin (IL)-12, which is produced mainly by macrophages, is critical for its development. In a mouse model of disseminated M. avium infection, genetically susceptible BALB/c mice had increased mycobacterial growth and decreased IL-12 expression and developed large and numerous granulomas. In contrast, resistant DBA/2 mice exhibited reduced mycobacterial burden with increased IL-12 expression and developed fewer and smaller granulomas. In susceptible mice with established M. avium infection, IL-12 replacement therapy resulted in persistent reduction of mycobacterial burdens. IL-12 itself, however, could not inhibit mycobacterial growth in vitro. By enhancing host defenses, IL-12 exerts a potent mycobactericidal activity in vivo with low toxicity. This suggests that IL-12 replacement therapy is rational for M. avium infection in susceptible hosts.

Animals↗

PubMed1996

Cisplatin microcrystals suspended in oil: pathological study of acute toxicity in mice.

The pathological changes brought about by the i.p. administration of a new dosage format, cisplatin microcrystals suspended in oil (CDDP-Oil), was examined in mice. CDDP-Oil decreased the absolute weight and the relative weight (organ weight/body weight) of the kidney, liver and spleen in the mice receiving the dosage form. However, the severity of the reduction of the organ weight in the CDDP-Oil administration groups was not different from that in the cisplatin aqueous solution (CDDP-Sol) administration groups. Histologically, severe degeneration and atrophy were recognized in the kidney, large intestine, small intestine, thymus, spleen, bone marrow and lymph nodes in the CDDP-Oil administration groups as well as CDDP-Sol administration groups. However, there were no additional changes in the macroscopic and microscopic findings in the CDDP-Oil groups. From these results, we concluded that this dosage form did not change the toxicity of cisplatin in terms of pathological effects.

Animals↗

PubMed1996

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Animals↗