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Biomedical subjects

I Shimizu

Publications and source records attributed to I Shimizu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis.

We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.

Acetone↗
PubMed2001

Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats.

In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity.

Anesthesia↗
PubMed2001

Uraemia suppresses central dopaminergic metabolism and impairs motor activity in rats.

OBJECTIVE: Uraemia often provokes various neurological disorders, such as mental changes, malperception, confusion, seizures and coma. Since changes in neurotransmissions induce neurological symptoms, we investigated changes in the monoamine metabolism and motor activity in uraemic rats. DESIGN: Prospective, randomised, controlled animal study. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute renal failure was induced by occlusion of bilateral renal arteries for 60 min, and the motor activity and brain monoamine turnover were examined 48 h later. The brain monoamine turnover was evaluated by the depletion of norepinephrine (NE) and dopamine (DA) induced by alpha-methyl-p-tyrosine (alpha-MT), or the accumulation of 5-hydroxyindoleacetic acid (5-HIAA) induced by probenecid. MEASUREMENTS AND RESULTS: Marked damage in renal function was found in animals subjected to renal ischaemia 48 h after the operation. The motor activity of the uraemic rats was impaired. The turnover of DA in the striatum, mesencephalon and hypothalamus was decreased in these rats. The turnover of NE and 5-hydroxytryptamine (5-HT) was unchanged in all regions examined. CONCLUSIONS: Suppression of the central DA turnover appears to be involved in the impairment of motor activity in uraemic rats.

Acute Kidney Injury↗
PubMed2001

Pharmacological effect of amezinium on urethra and bladder of rabbits.

The pharmacological effect of amezinium on the urethra and bladder of rabbits was investigated. Amezinium produced concentration-dependent contractions in isolated urethral strips. The maximum response was approximately 30% of that caused by norepinephrine (NE). The concentration-response curve of NE was shifted to the left by amezinium. Moreover, amezinium enhanced the relaxative effect of NE on carbachol-induced contractions in isolated bladder strips. In anesthetized rabbits, amezinium significantly increased the intraurethral pressure (IUP) but produced only slight increases in mean blood pressure (MBP). Pre-treatment with amezinium ehhanced NE-induced increases in IUP index and MBP. The enhancing effect on the IUP index lasted much longer than that on MBP. In a stress incontinence model amezinium significantly inhibited the incontinence after an i.v. infusion of a low dose of NE. This effect was antagonized by pre-treatment with prazosin. These results suggest that amezinium may produce an excellent effect for stress incontinence, especially mixed, without severe adverse events such as sudden hypertension.

Animals↗
PubMed2001

A technique of cervical aortic graft transplantation in mice.

A new method of mouse aortic graft transplantation into carotid artery was developed with cuff technique. By harvesting the descending aorta of the donor using a small Teflon cuff (external diameter 0.6 mm, internal diameter 0.4 mm) and super fine-tip forceps, and modifying the method of mouse heterotopic heart transplantation with cuff technique, donor descending aortic allografts could be interposed in the common carotid artery of recipient mice. Histological analysis demonstrated neither evidence of tissue damage nor intimal thickening in isograft implanted over 100 days. We strongly recommend that this new model of aortic transplantation in mice is a simple and useful technique for vascular transplantation research.

Animals↗
PubMed2001

Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress.

BACKGROUND/AIMS: Idoxifene is a tissue-specific selective estrogen receptor modulator. Estradiol is a potent endogenous antioxidant, and nuclear factor kappaB (NF-kappaB) is a key transcription factor that induces multiple genes in response to inflammation or oxidative stress. The aim of this study was to explore the inhibitory effects of idoxifene and estradiol on NF-kappaB activation in hepatocytes in a state of oxidative stress. METHODS: Lipid peroxidation was induced in cultured rat hepatocytes by incubation with ferric nitrilotriacetate solution. NF-kappaB activity was evaluated by electrophoretic mobility shift assay. RESULTS: The oxidative stress-induced activation of NF-kappaB and degradation of IkappaB-alpha were maximal at 3-5 h, with an increase in lactate dehydrogenase (LDH) and malondialdehyde (MDA) secretion into the culture medium. Treatment with idoxifene and estradiol inhibited IkappaB-alpha degradation and NF-kappaB activation through the attenuation of hepatocyte oxidative bursts and decreased extracellular levels of LDH and MDA. In addition, idoxifene and estradiol inhibited lipid peroxidation in rat liver mitochondria. A potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate, prevented NF-kappaB activation by inhibition of IkappaB-alpha degradation and decreased LDH and MDA levels, suggesting that NF-kappaB might be a regulator in a genetic response to increase oxidative stress-induced hepatic injury. CONCLUSIONS: These findings suggest that idoxifene and estradiol function as antioxidants and protect hepatocytes from inflammatory cell injury.

Animals↗
PubMed2001

Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection.

AIMS/BACKGROUND: Our preliminary studies showed that estradiol suppresses hepatic carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors (ERs) medicate estradiol action in the liver. This study was performed to assess possible implications of menopause and hepatic ER levels for the development of cirrhosis with hepatocellular carcinoma (HCC). METHODS: One thousand, one hundred and ninety-nine consecutive HCC patients with hepatitis C virus (HCV)-related cirrhosis were divided into two groups, based on a menopausal age of 49 years. Liver tissues were obtained during surgical resection of HCC and metastatic liver tumor. RESULTS: The proportion of females among the HCC subjects < or =49 years of age was significantly lower (15.0%) than was the proportion of females among subjects >49 years of age (29.8%). Univariate analysis showed that HCV-related cirrhotic patients who developed HCC were more likely to have low hepatic levels of ER and copper-zinc superoxide dismutase (CuZn-SOD) protein and a high hepatic level of a lipid peroxidation product, malondialdehyde (MDA). Logistic regression identified age greater than 49 years (odds ratio [OR]: 7.9, 95% confidence interval [CI]: 2.8-21.3), male sex (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER level (OR: 16.8, 95% CI: 7.3-34.6), and an increased MDA (OR: 8.3, 95% CI: 2.8-24.0) as the variables independently associated with the development of HCC in HCV-infected patients with cirrhosis. ER level was significantly correlated with CuZn-SOD level (r=0.583) and was inversely proportional to MDA level (r=-0.553). The study also showed that ER levels in the cirrhotic livers from premenopausal females were significantly higher than in male cirrhotic livers. CONCLUSIONS: These findings suggest that increased lipid peroxidation and impaired SOD function in the liver may be associated with decreased hepatic ER levels in HCV-infected patients with cirrhosis and HCC, and that HCV-related cirrhotic women before menopause might have the ability to protect against developing HCC via hepatic ER.

Age Factors↗
PubMed2001

Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy.

BACKGROUND: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with alpha-interferon (IFN-alpha) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. METHODS AND RESULTS: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. CONCLUSIONS: These findings suggest that IFN-alpha treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C.

Adult↗
PubMed2001

Relationship among gastric motility, autonomic activity, and portal hemodynamics in patients with liver cirrhosis.

BACKGROUND AND AIMS: We examined the effects of the autonomic nervous function and the volume of portal blood flow to clarify the mechanism of the abnormal gastric motility in patients with liver cirrhosis. METHODS: Heart rate variability, electrogastrogram (EGG), and volume of portal blood flow were measured before and after a meal in 27 patients with liver cirrhosis (LC group) and in 20 normal subjects (N group). Autonomic nervous function was evaluated by using spectral analysis of heart rate variability. We used the cine phase-contrast (PC) method, using magnetic resonance imaging (MRI) to measure the portal flow, while the peak frequency and spectral power of the EGG were measured at pre- and postprandial change. RESULTS: The ratio of low frequency power to high frequency power (LF/HF) was significantly higher, and the HF power was significantly lower in the LC group than in the N group both before and after a meal. In both groups, the electrogastrographic peak power ratio before and after a meal showed a positive correlation with the HF ratio, and an inverse correlation with the LF/HF ratio. In addition, portal blood flow volume was significantly decreased in the LC group than in the N group. However, the increased rate of portal blood flow after a meal correlated positively with the increased rate of electrogastrographic peak power. Moreover, gastric motility was positively correlated with esophageal varices and coma scale with the use of multivariate analysis. CONCLUSIONS: Parasympathetic hypofunction, sympathetic hyperfunction and portal hemodynamics were closely related with gastric motility in cirrhotic patients. In addition, gastric motility was decreased, at least in part, by the ingestion of food in cirrhotic patients because of abnormalities in autonomic functions and portal blood flow following a meal.

Aged↗
PubMed2001

Quantitative analysis of red color sign in the endoscopic evaluation of esophageal varices.

BACKGROUND AND STUDY AIMS: Bleeding due to esophageal variceal rupture is associated with an extremely high mortality rate. Variceal bleeding is frequent in patients who have a red color sign on endoscopy. However, the red color sign is subjectively evaluated on the basis of color tone and the shape of the varices. To allow standardization and facilitate consensus, an objective method of assessing the red color sign is needed. In this study, a system was established for quantifying the red color sign during endoscopic evaluation. PATIENTS AND METHODS: Between July 1995 and February 1997, 55 untreated patients with portal hypertension and esophageal varices identified on upper gastrointestinal endoscopy were enrolled in the study. Images obtained about 5 cm oral to the esophagogastric junction during endoscopy were stored on magnetic optical disks using an endoscopic image processor. The still images were transmitted to a computer and analyzed using computer software. The RGB components (R, red; G, green; B, blue) were measured at points showing flare consistent with the red color sign. The endoscopic assessment was based on the Japanese Research Society for Portal Hypertension's general rules for recording endoscopic findings in esophagogastric varices. RESULTS: The ratio of the red color area to the variceal area increased with increasing red color grade. There were significant positive correlations between the R and G, and G and B components. This suggests that comparing the R components alone would allow assessment of the color differences in the red color area and in the varices. The R value was significantly higher in the red color area (115 +/- 20) than in the varices (57 +/- 19). An R value of 90 was found at the boundary between the two parts (P < 0.001). CONCLUSIONS: The red color area can be automatically calculated and quantified using the analysis program. Improvements in data storage methods may allow real-time evaluation during endoscopy in the future.

Aged↗
PubMed2001

Detection of human gastric cancer in resected specimens using a novel infrared fluorescent anti-human carcinoembryonic antigen antibody with an infrared fluorescence endoscope in vitro.

BACKGROUND AND STUDY AIMS: An indocyanine green derivative (ICG-sulfo-OSu) that can be used as an infrared fluorescent labeling substance suitable for detecting microlesions with an infrared fluorescence endoscope has been developed. The aims of the present study were to develop an infrared fluorescence endoscope and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-sulfo-OSu. MATERIALS AND METHODS: ICG-sulfo-OSu-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and an infrared fluorescence endoscope were used in this study. Biopsy specimens of gastric cancer were stained with anti-CEA antibody using the avidin-biotinylated peroxidase complex method. The positive specimens used for the infrared imaging analysis were freshly resected stomachs from three patients. RESULTS: Treatment of freshly resected stomach specimens with ICG-sulfo-OSu-labeled-anti-CEA antibody complex resulted in positive staining of the tumor sites on infrared fluorescence endoscopy, and the infrared fluorescent images correlated well with the tumor sites. CONCLUSIONS: An anti-CEA antibody with affinity for cancerous lesions and labeled with ICG-sulfo-OSu can therefore be imaged using this infrared fluorescence endoscope. Specific antibodies tagged with ICG-sulfo-OSu can label cancer cells and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope.

Adenocarcinoma↗
PubMed2001

Different expressions of Ly-49 receptors on mouse NK and NK T cells.

NK T cells are a unique T cell lineage and are reported to express Ly-49 molecules which are inhibitory receptors specific for class I molecules. In this study, we examined the expression of activation and inhibitory receptors on NK T cells in different organs of beta2-microgloblin knock out (beta2mKO), C57BL/6 (B6; H-2b), C57BL/10 (B10; H-2b) and B10.D2 (H-2d) mice. The low level expression of inhibitory receptors Ly-49A and G2 on NKT cells as well as NK cells, which are specific for Dd antigen, were observed in B10.D2 mice, but not in beta2mKO, B6, or B10 mice. The small percentage of inhibitory receptor Ly-49C positive NK and NKT cells, which is specific for Kb and Dd antigens, was observed in BMC, LMC and SC of B6, B10 and B10.D2 mice compared to beta2mKO mice. On the contrary, the large percentage of Ly-49C positive NK T cells was observed in thymocytes of B6, B10 and B10.D2 mice compared to beta2mKO mice. Interestingly, Ly-49D activation receptor was hardly detectable on NK T cells in any organs of the 4 strains of mice whereas it was clearly detectable on NK cells. These findings suggest that the unique characteristics of NK T cells may mediate regulatory function in MHC class I antigen-restricted immunity.

Animals↗
PubMed2001

Estrogen therapy in a male patient with chronic hepatitis C and irradiation-induced testicular dysfunction.

We report an 18-year-old male patient who developed chronic hepatitis C after blood transfusion and had testicular dysfunction after irradiation for a testicular relapse of childhood acute lymphocytic leukemia after cessation of maintenance therapy, and the initiation of testosterone replacement therapy at puberty. Concomitant administration of estradiol resulted in a reduction in serum alanine aminotransferase and ferritin levels and hepatic iron concentration and staining after 2 years of estrogen therapy, although interferon therapy was withdrawn because of adverse effects. This observation suggests that endogenous estradiol may play a beneficial role in male patients with chronic hepatitis C.

Adolescent↗
PubMed2001

Antifibrogenic therapies in chronic HCV infection.

The most common cause of hepatic fibrosis is currently chronic HCV infection, the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also regarded as the primary target cells for inflammatory stimuli, and produce extracellular matrix components. It should be noted that transforming growth factor beta (TGF-beta) is a potent fibrogenic cytokine produced by Kupffer cells and HSCs. There are several approaches to inhibit TGF-beta; use of decorin, soluble receptors, and gene therapy approaches. Hepatocyte growth factor (HGF) is a hepatotrophic factor for liver regeneration and seems to suppress hepatic fibrogenesis in animals. HOE 77, Safironil, and S 4682 are inhibitors of prolyl 4-hydroxylase, which is essential for thecollagen formation. Although HOE 77, Safironil, and S 4682 seem to work by inhibiting HSC activation, further studies will be required before their clinical application. alpha-Tocopherol, retinyl palmitate, and silybinin reduce lipid peroxidation and attenuate HSC activation in experimental models. Retinyl palmitate is the main storage type for retinoids in HSCs. Silymarin is extracted from milk thistle, the principle component of which is the silybinin. Unfortunately, they have had mixed effects in human liver diseases. A Japanese herbal medicine Sho-saiko-to functions as a potent antifibrosuppressant via the inhibition of oxidative stress in hepatocytes and HSCs. Its active components are baicalin and baicalein of flavonoids with chemical structures very similar to silybinin. Understanding the basic mechanisms underlying the HCV-mediated fibrogenesis provides valuable information on the search for effective antifibrogenic therapies.

Antioxidants↗
PubMed2001

[Evaluation of the mental state of elderly diabetic patients in education].

Maintaining to good glycemic control is necessary to treat diabetes effectively and it is also necessary to understand the mental characteristics of elderly patients with diabetes. We investigated evaluation of the mental state, using self-depressive scale (SDS) and the Tokyo university egogram form (TEG), of 356 asymptomatic diabetic patients (254 non-elderly, 102 elderly) admitted for educational about diabetes. On TEG, we studied evaluation of five ego states for the following showing: critical parent (CP), nurturing parent (NP), adult (A), free child (FC) and adapted child (AC). First of all, we studied evaluation of mental characteristics of the elderly, NP and A of TEG were higher in the elderly than in the non-elderly (p < 0.01). Furthermore, the SDS was lower on discharge than on admission in both groups (p < 0.01). The group showing improvement had a significantly higher SDS score on admission than the group showing aggravation (p < 0.01). We classified the group with an SDS score 50 or more SDS as the depressed group; those with a 40 to 49 score as the slight distress group; and a score of 39 or less score was considered normal. The depressed group had significantly lower A and FC, and a higher AC on TEG, than other groups (p < 0.01). Therefore, elderly diabetic patients seem to be rational and obliging. This study revealed the mental effects of diabetic education to be similar in elderly and non-elderly diabetic patients.

Adult↗
PubMed2001

Recurrent giant longitudinal duodenal ulcer with massive hemorrhage in a Helicobacter pylori-negative patient.

A 67-year-old man, in whom a linear ulcer running from the duodenal bulb to the descending part had been noted 3 years previously, was admitted to our hospital because of abdominal pain and melena. Duodenoscopy revealed a bleeding giant longitudinal ulcer, which was more extensive than before. Tests for Helicobacter pylori (Hp) were negative. The ulcer was cured by endoscopic hemostasis and repeated blood transfusions. Attention must be paid to Hp-negative post-bulbar duodenal ulcers because of the frequent complications including hemorrhage.

Aged↗
PubMed2000

Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.

We elucidated the possible role of chimerism in skin and heart allograft tolerance using cyclophosphamide (CP)-induced tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were i.v. primed with 1x10(8) spleen cells (SC) from H-2 matched AKR (H-2k; Thy1.1, Mls-1a) mice and then treated i.p. with 200 mg/kg of CP, the survivals of both AKR skin grafts and heart grafts (HG) were permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism, the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery, and the clonal deletion of Vbeta6+ thymocytes were all observed. When AKR SC and 100 mg/kg CP were used for conditioning, the AKR HG were permanently accepted, but the survival of the AKR skin grafts was only mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery and the intrathymic clonal deletion of Vbeta6+ thymocytes were induced in both the SC and the 100 mg/kg CP-treated C3H mice. A minimal degree of mixed chimerism was detectable at 4 and 12 weeks after AKR SC and 100 mg/kg CP treatment, and still did not disappear at 40 weeks. The degree of mixed chimerism induced with SC and 100 mg/kg CP was significantly lower than that with SC and 200 mg/kg CP during the observation. No posttransplant cardiac allograft vasculopathy (CAV) was observed to develop, while both the Th1 type (interferon-gamma) and Th2 type (interleukin-4 and -10) cytokine expressions decreased in the AKR HG of the tolerant C3H mice treated with both AKR SC plus 200 mg/kg CP, and AKR SC plus 100 mg/kg CP. A second set of skin grafts from donor AKR mice survived for more than 100 days in a tolerogen-specific fashion in all C3H mice treated with AKR SC and 200 mg/kg CP and also accepted the AKR HG for over 200 days, while 80% of the C3H mice treated with AKR SC and 100 mg/kg CP and accepted the AKR HG for more than 200 days. These results strongly suggested the following conclusions: 1) the degree of chimerism can strongly influence the induction of skin and heart allograft tolerance, 2) posttransplant CAV does not develop in the donor HG maintained by chimerism-based CP-induced tolerance, 3) the mRNA expression of both Th1 and Th2 type cytokine decreased in the donor HG maintained by chimerism-based CP-induced tolerance, and 4) the induction of skin allograft tolerance is more difficult than the prevention of posttransplant CAV.

Animals↗