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Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 109 records · Page 6Linked to original sources
PubMed1998

Relationship between left ventricular hypertrophy and renal and retinal damage in untreated patients with essential hypertension.

We examined the relationship between left ventricular hypertrophy (LVH) and renal and retinal damage in 174 untreated patients with essential hypertension. As an index of renal and retinal damage, we examined proteinuria and retinal vascular change. LVH was diagnosed according to left ventricular mass obtained from echocardiography. Of the hypertensive patients, 111 patients (64%) had LVH. The incidences of proteinuria and advanced retinal vascular change were higher in patients with LVH than in those without LVH. In a multiple regression model, there was a significant positive correlation between left ventricular mass and proteinuria, as well as diastolic blood pressure, sex, age and body mass index. In conclusion, proteinuria is related to elevated left ventricular mass in patients with essential hypertension.

Blood Pressure↗
PubMed1998

[Acupuncture for urinary incontinence in patients with chronic spinal cord injury. A preliminary report].

PURPOSE: We investigated the possible use of acupuncture for the treatment of urinary incontinence caused by detrusor hyperflexia in patients with chronic spinal cord injury. METHOD: A total of 8 male chronic spinal cord injured patients with urinary incontinence were treated by acupuncture. Their ages ranged from 20 to 33 years (mean 27). The level of lesion was cervical in 4 and thoracic in 4. Detrusor hyperreflexia with uninhibited bladder contraction was confirmed by urodynamic studies in all of them. Acupuncture was performed using a disposable stainless needle (0.3 mm in diameter, 60 mm in length), which was inserted into bilateral BL-33 (Zhongliao) points and was rotated manually for 10 minutes. The treatment was conducted every week for 4 weeks. Urodynamic studies were repeated, immediately after the beginning of and a week after the completion of the treatment. Urinary symptoms were also checked before and after the treatment. RESULTS: No side effects were recognized throughout the treatment period. Among 8 patients, incontinence was controlled completely in 3 (38%) and partially in 3 (38%). The average maximum cystometric bladder capacity increased significantly, from 42.3 +/- 37.9 ml to 148.1 +/- 101.2 ml by the treatment (p < 0.05), while the average maximum bladder pressure was not changed. CONCLUSIONS: These data suggest that acupuncture could be a promising alternative for conventional therapies for urinary incontinence caused by detrusor hyperreflexia in patients with chronic spinal cord injuries.

Acupuncture Therapy↗
PubMed1998

[Predictability of Gleason score and reduction time (tau) of prostatic volume after castration for the prognosis of prostatic cancer].

PURPOSE: The efficacy of the reduction time (tau) after castration as a prognostic factor was examined by comparing to Gleason score. MATERIALS AND METHODS: The change of prostatic volume after castration was observed from the castration to 3 months after in 24 cases of prostatic cancer. Prostatic volume was examined by transrectal ultrasonography of the prostate. Survival curves was calculated by Kaplan-Meier method. Differences among survival curves were analyzed using Cox-Mantel test. RESULTS: tau had a close relationship to the prognosis of each case (Wilcoxon test: p < 0.05, Cox-Mantel test: p < 0.05). Gleason score had a weak relationship to prognosis (Wilcoxon test: N. S., Cox-Mantel test: p < 0.05). CONCLUSIONS: tau was efficient as prognostic factor compared to Gleason score.

Aged↗
PubMed1998

Lymphatics of the rat mammary gland during virgin, pregnant, lactating and post-weaning periods.

The distribution and ultrastructure of the lymphatics of the rat mammary gland in virgin, pregnant, lactating and post-weaning periods were examined by enzyme-histochemistry for 5'-nucleotidase (5'-Nase) and transmission electron microscopy. Enzyme-histochemistry for 5'-Nase stained lymphatics in dark brown. In the lactating period, lymphatics abounded in the interlobular connective tissues, but in other periods they were few. The interlobular lymphatics drained into collecting lymphatics running along the mammary ducts. Gaps between lymphatic endothelial cells were significantly wider in lactating period than in other periods, while both number and area of vesicles in the lymphatic endothelial cells were significantly larger in the virgin period than in other periods. In the pregnant and lactating period, the lymphatics contained many lymphocytes and lipid droplets. The results show that during lactating period, the interlobular lymphatics increase and that gaps between lymphatic endothelial cells serve as a major route through which tissue fluids and particulate matters enter the lymphatics, while vesicles seem to be main trans-endothelial transport route during the virgin period. The results will provide basic information for our next investigation on lymphangiogenesis in association with breast cancer.

5'-Nucleotidase↗
PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with acute heart failure.

Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine), a calcium channel blocker, were investigated in anesthetized normal dogs and dogs with acute heart failure (AHF), and compared with those of nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10 micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no effect on heart rate (HR) or maximum rate of rise of left ventricular pressure (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did not change the other cardiovascular parameters. NIC and NTG did not prolong PQ, QRS or QTc intervals. In addition, NIC was effective in the presence of dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min i.v.) increased CO and stroke volume, and reduced total peripheral resistance without decreasing HR or cardiac contractility. Furthermore, in the ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end-diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.) decreased LVEDP in both AHF models; but did not increase CO. These results suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing afterload without adversely affecting the cardiac contractility or conduction system, while NTG exerts its effect on AHF by reducing preload. NIC injection would thus appear to be beneficial in the treatment of AHF.

Acute Disease↗
PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 2: Effect on myocardial metabolism.

The effect of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine) on myocardial metabolism was investigated in an experimental model of ischemic acute heart failure (AHF) induced by coronary ligation in anesthetized dogs. The left anterior descending and/or circumflex coronary ligation decreased coronary sinus blood flow (CBF), maximum rate of rise of left ventricular pressure (max. dp/dt), cardiac output (CO) and stroke volume (SV), and increased left ventricular end-diastolic pressure, indicating the development of AHF. In this ischemic AHF model, NIC (3 micrograms/kg/min i.v. infusion for 15 min) increased CBF, CO and SV, and reduced systemic and coronary artery resistances, resulting in the improvement of AHF. During the effective period, NIC decreased myocardial oxygen consumption and the coronary arterio-venous difference of oxygen content, carbon dioxide pressure and pH. At the same time, NIC did not decrease the lactate extraction. These results suggest that NIC improves hemodynamics and the balance of myocardium oxygen supply and demand in dogs with AHF by means of reducing afterload and dilating coronary artery.

Acute Disease↗
PubMed1998

Evidence for apoptosis signal-regulating kinase 1 in the regenerating palatal epithelium upon acute injury.

Apoptosis signal-regulating kinase 1 (ASK1), a recently identified mitogen-activated protein (MAP) kinase kinase kinase, is a key element in the mechanism of stress- and cytokine-induced apoptosis. However, pathophysiologic roles of ASK1 in vivo are poorly understood. In the present study, we analyzed the ASK1 expression in injured rat palate using an immunohistochemical approach to investigate the roles of ASK1 during the process of wound healing. In the normal rat palatal epithelium, a weak cytoplasmic staining of ASK1 was observed in keratinocytes of the prickle cell layer. After mucoperiosteal injury of the palate, ASK1 was clearly observed in the suprabasal keratinocytes surrounding the wound. ASK1 expression was most evident at Day 2 after injury in the edge of the migrating epithelium. Thereafter, the intensity of ASK1 staining decreased gradually until the re-epithelialization was completed at Day 10 to 14. A staining with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labeling method identified a number of apoptotic keratinocytes in the suprabasal layers at the healing edge. Active induction of epithelial apoptosis was readily detectable from Day 5 after injury. In double-staining analysis, the temporal and spatial pattern of ASK1 expression correlated well with the appearance of apoptotic keratinocytes. p38 MAP kinase, a downstream component of ASK1, was found to be activated at the sites of ASK1 expression, suggesting that increased expression of ASK1 leads to activation of downstream MAP kinase signaling pathway in vivo. These results suggest a significant contribution of ASK1 to the epithelial apoptosis in the process of mucoepithelial wound repair.

Animals↗
PubMed1997

Single-step isolation method for six glycoforms of human alpha1-acid glycoprotein by hydroxylapatite chromatography and study of their binding capacities for disopyramide.

A single-step isolation method for the glycoforms of human serum alpha1-acid glycoprotein (AAG) using a hydroxylapatite column under a gradient elution program was developed. The concentrations of N-acetylneuraminic acid and monosaccharides (fucose, N-acetylglucosamine, galactose and mannose) of six AAG glycoforms were determined by the pulsedamperometric detection method. For each AAG glycoform, significant sex-related differences in carbohydrate content have been observed only for AAG glycoforms two and six, and not for each AAG glycoform. The relationship between the extent of the branch in the glycan chain and the binding capacity to disopyramide were examined. Female AAG contained highly sialylated AAG glycoforms compared to male glycoforms. Conversely, male AAG was rich in the lower sialylated AAG glycoform. Furthermore, it was found that the drug binding capacity decreases with increasing branching of the glycan chain. This suggests that the binding sites of AAG are hindered by a relatively large carbohydrate moiety, such as tetraantennary structures.

Adult↗
PubMed1997

A novel type of binding specificity to phospholipids for rat mannose-binding proteins isolated from serum and liver.

Mannose-binding protein (MBP) belongs to the collectin subgroup of C-type lectins with specificity for mannose and N-acetylglucosamine sugars. We investigated whether rat MBPs isolated from serum (S-MBP) and liver (L-MBP) interact with phospholipids using antibody against each MBP. Both S- and L-MBPs bound to phosphatidylinositol coated onto microtiter wells in a concentration- and a Ca2+-dependent manner. L-MBP also bound to phosphatidylglycerol and weakly to phosphatidylserine. MBPs interacted with liposomes composed of these lipids. S- and L-MBPs bound to phosphatidylinositol 4-monophosphate. L-MBP also bound to cardiolipin. These results provide evidence for a novel type of ligand binding specificity for MBPs, and raise the possibility that phospholipids are ligands for collectins.

Acute-Phase Proteins↗
PubMed1997

Protective protein in the bovine lysosomal beta-galactosidase complex.

Cathepsin A [EC 3.4.16.1], so called protective protein, occurs as an enzyme complex with lysosomal beta-galactosidase [3.2.1.23] and is involved in the stable enzymic expression of lysosomal sialidase [3.2.1.18]. In this study we investigated the enzymatic properties of cathepsin A in the bovine beta-galactosidase complex and how it is involved in the molecular multiplicities of the beta-galactosidase and sialidase complexes. Bovine protective protein homologous to the human protein had a molecular weight of 48 kDa on SDS-PAGE and cathepsin A activity optimum around pH 6.0. It hydrolyzed dipeptide substrates composed of hydrophobic amino acids much faster than any other type of substrate tested. This specificity was found to be conserved from human to a non-mammal, chicken. Immunoprecipitation using an anti beta-galactosidase antibody demonstrated that cathepsin A is a component of both the sialidase and beta-galactosidase complexes. The over 700 kDa sialidase complex depolymerized by a brief incubation at pH 7.5 and the sialidase was inactivated irreversibly via formation of an enzyme active smaller species of sialidase. The 669 kDa beta-galactosidase complex dissociated reversibly into a 120 kDa beta-galactosidase and a 170 kDa cathepsin A, but the 120 kDa beta-galactosidase, free from the cathepsin A, formed a 260 kDa aggregate under the same conditions. Inactivation of cathepsin A by heat treatment did not affect its complex forming activity. The 170 kDa protective protein dissociated into a 50 kDa one at pH 7.5, which no longer formed the complex. These findings indicate that the 170 kDa protective protein could be the minimum unit required for in vitro reconstitution of the complex, and that its complex forming activity is carried in a heat-stable domain. Both beta-galactosidase and cathepsin A activities were labile under the dissociated condition, indicating that it physiologically stabilizes not only beta-galactosidase but also itself by forming the complex.

Animals↗
PubMed1997

Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond acceptors such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)-imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.

Binding Sites↗
PubMed1997

Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha). Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.

Amino Acid Sequence↗
PubMed1997

Effects of nonsedating antihistamine, astemizole, on the in situ canine heart assessed by cardiohemodynamic and monophasic action potential monitoring.

The possible mechanisms of cardiac adverse effects of astemizole were studied using a halothane-anesthetized in vivo canine model under the cardiohemodynamic and monophasic action potential monitoring. A dose of 0.3 mg/kg of iv astemizole (n = 7), which is close to the recommended dose for clinical use, showed a bradycardic effect and a reversed use-dependent lengthening of repolarization. The increase in the repolarization was greater than in the effective refractory period. These effects persisted even when the plasma drug concentration became undetectable. Additional administration of 3.0 mg/kg of iv astemizole (n = 7) decreased the mean blood pressure, suppressed the cardiac contraction and conduction, and induced early after depolarization-like potential in addition to the qualitatively similar effects compared to those observed by the lower dose. The decrease of the plasma concentration of astemizole followed the pattern predicted by the two-compartment theory of pharmacokinetics, but the drug concentration in the cardiac muscle was estimated to be more than 100 times greater than that in plasma. Our study emphasizes that each cardiac consequence of astemizole overdose may be related to proarrhythmic effects and the monitoring of plasma drug concentration will be less helpful in predicting the cardiac adverse effects of astemizole. The results provide some insights into the clinical cardiotoxicity of astemizole. Drugs or interventions inducing positive chronotropic, inotropic, and dromotropic effects can become good candidates for the treatment of astemizole intoxication, which may attenuate the cardiac effects of astemizole including the lengthening of repolarization.

Action Potentials↗
PubMed1997

Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy.

Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori. We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.

Adult↗
PubMed1997

Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity.

Osteoarthrosis, a common pathway of joint deterioration, is caused by mechanical stress loaded on articular cartilage. We previously demonstrated the involvement of protein kinase C (PKC) in the development of osteoarthritis in vitro. In this study, we examined the effect of mechanical stress on chondrocyte metabolism and the activity of PKC in vitro. Low frequency and magnitude of cyclic tensile stretch loaded on chondrocytes increased proteoglycan synthesis. However, high frequency and magnitude of stress decreased its synthesis. In this condition, activity of PKC was reduced. These results suggest an involvement of PKC in the stress-mediated inhibition of proteoglycan synthesis.

Animals↗