PubMed Health⌕ Search

Biomedical subjects

S Tsuchida

Publications and source records attributed to S Tsuchida.

At least 127 records · Page 7Linked to original sources

Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor.

We describe novel potent endothelin (ET) antagonists that are highly potent and selective for the ETA receptor (selective to ET-1). Of the synthetic analogs based on ETA antagonist BE-18257A isolated from Streptomyces misakiensis (IC50 value for ETA receptor on porcine aortic smooth muscle cells (VSMCs); 1.4 microM), the compounds BQ-123 and BQ-153 greatly improved the binding affinity of [125I]ET-1 for ETA receptors on VSMCs (IC50; 7.3 and 8.6 nM, respectively), whereas they barely inhibited [125I]ET-1 binding to ETB receptors (nonselective with respect to isopeptides of ET family) in the cerebellar membranes (IC50; 18 and 54 microM, respectively). Associated with the increased affinity for ETA receptors, these peptides antagonized ET-1-induced constriction of isolated porcine coronary artery. However, there was a small amount of ET-1-induced vasoconstriction resistant to these antagonists, which paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the aortic smooth muscle layer. These data suggest that the artery has both ETA and ETB receptors responsible for ET-1-induced vasoconstriction. The antagonists shifted the concentration-response curve to the right for ET-1 in the coronary artery, and increased the apparent dissociation constant in the Scatchard analysis of [125I]ET-1 binding on the VSMCs without affecting the binding capacity, indicative of the competitive antagonism for ETA receptor. In conscious rats, pretreatment with the antagonists markedly antagonized ET-1-induced sustained pressor responses in dose-dependent fashion without affecting ET-1-induced transient depressor action, suggesting that the pressor action is mediated by ETA receptors, while the depressor action is mediated by ETB receptors. In addition, pretreatment with the potent antagonists prevented ET-1-induced sudden death in mice. Thus, these potent ETA antagonists should provide a powerful tool for exploring the therapeutic uses of ETA antagonists in putative ET-1-related disorders.

Amino Acid Sequence↗

Trigeminal neurinoma presenting with intratumoral hemorrhage: report of two cases.

We report 2 cases of trigeminal neurinoma presenting with spontaneous intratumoral hemorrhage. There are only 2 similar cases reported in the literature. Presenting symptoms were headache, diplopia, disturbed consciousness and trigeminal disturbance with sudden onset. CT scan showed a typical fluid-fluid level within low-density mass in the cerebellopontine angle in one case. On MRI, one case showed a typical fluid-fluid level on T2-weighted image and another one had mixed signal intensities including hyper- and hypointensities on both T1- and T2-weighted images. Histologically, increased vascularity, consisting of dilated and thin-walled vessels presenting telangiectatic or cavernous angiomatous appearances were observed in the specimens in both cases. The size of these tumors was about 3 cm each in diameter. Risk factors for hemorrhage appear to be large tumor size and increased vascularity.

Aged↗

Ureteral compliance and histology in partial obstruction in a canine model.

Standardized partial ureter obstruction was achieved in 35 mongrel dogs in whom ureteral compliance and its relationship to histologic changes were studied over a period of 26 weeks. The partially obstructed ureter became dilated with thickened wall and showed muscle hypertrophy and connective tissue proliferation. The normal stellate configuration of the ureteral lumen gradually flattened and became entirely circular by the eighth week. The compliance of the obstructed ureter increased gradually after one, 2, 4, and 8 weeks but decreased thereafter at 12 and 26 weeks. At 8 weeks, the ureter was significantly more compliant than both, the unobstructed control ureter (p less than 0.005) and the 12 week and 26 week partially obstructed ureters (p less than 0.005 & p less than 0.05 respectively). The increase in ureteral compliance was proportional to the amount of muscle hypertrophy during the first 8 weeks while the subsequent decrease in compliance (at 12 and 26 weeks) was proportional to the amount of connective tissue proliferation. This study documents ureteral response, both functional and histologic, to partial obstruction in a canine model over 26 week duration.

Animals↗

Loss of peroxisomal enzyme expression in preneoplastic and neoplastic lesions induced by peroxisome proliferators in rat livers.

Immunohistochemical staining of enoyl CoA hydratase (ECH), a key peroxisomal enzyme, revealed that the putative preneoplastic lesions induced in livers by administration of the peroxisome proliferator (PP) clofibrate (0.3% in diet) to rats for 60 weeks or more, lacked this enzyme so that they could be detected as ECH-negative foci. ECH and other peroxisomal enzymes such as acyl CoA oxidase, catalase and carnitine-dependent acetyltransferase were also either not or only weakly expressed in most hepatic hyperplastic nodules and hepatomas induced by ciprofibrate (0.025% in diet), Wy-14,643 (0.1%) or BR-931 (0.2%), while being strongly induced in surrounding hepatocytes. These results indicate that the expression of ECH and other peroxisomal enzymes is repressed in putative preneoplastic and neoplastic lesions induced by PPs in rat livers and that these peroxisomal enzymes might therefore be used as negative markers.

Animals↗

Case report of an insulin-dependent diabetes multiplex family with a pair of identical twins.

The following is a case of a family with a pair of identical twins and a family history of insulin-dependent diabetes mellitus (IDDM). A 2 year old identical twin was first admitted to our hospital and diagnosed as IDDM based on diabetic ketoacidosis. His father has been treated with insulin since the diagnosis of IDDM at the age of 17. All family members had the HLA-DR4 and DQA1*0301 alleles, which are strongly associated with IDDM. The DR-DQ haplotypes of the father and both twins were DR4-DQW8 (DQB1*0302), which increases susceptibility to IDDM. Islet cell antibodies were positive only in the index twin at the time of diagnosis. The co-twin was considered to have beta-cell dysfunction based on the result of an intravenous glucose tolerance test.

Adult↗

Characterization of a 28-kD polymorphic polypeptide detected by two-dimensional electrophoresis of human platelets.

A genetic polymorphism of a human platelet polypeptide with a molecular weight of 28 kD detected by two-dimensional electrophoresis was investigated in family and population studies, and cell distribution. The 28-kD polypeptide showed autosomal codominant inheritance of two alleles. The gene frequencies of the two alleles were 0.925 and 0.075, respectively. The 28-kD polypeptide was observed in lymphocytes, neutrophils, eosinophils and monocytes, in addition to platelets. This polypeptide showed good reproducibility in electrophoresis, and appears to be useful as a genetic marker of the human genome in gene mapping and pedigree analysis.

Blood Platelets↗

Pacemaker activity of the pelvicalyceal border recorded by an intracellular glass microelectrode.

Applying intracellular glass microelectrodes to the smooth muscle obtained from the guinea pig pelvicalyceal border, we have succeeded in recording periodic spontaneous action potentials, the so-called slow waves, which are characteristic of a pacemaker. This experiment proved that the pacemaker exists at the pelvicalyceal border. The slow waves originate from the pelvicalyceal border, close to the papilla renalis; they show a biphasic pattern and have the characteristics of a spontaneously excitable cell. The resting potential is 42.3 +/- 1.1 mV, the spontaneous depolarizing potential is 12.1 +/- 0.7 mV, and the depolarizing period is 12/min. The rate of rise of the potential is 22.9 +/- 2.1 mV/s in the first slow depolarization phase, and 50.9 +/- 9.5 mV/s in the following rapid depolarization phase. The rate of decline of the potential is 47.3 +/- 5.4 mV/s in the repolarization phase.

Action Potentials↗

Microwave coagulation therapy on VX-2 carcinoma implanted in rabbit urinary bladders.

In order to evaluate the effectiveness of microwave coagulation therapy on urinary bladder carcinoma, we conducted a series of experiments using carcinoma VX-2 cells designed for the application on animal hosts. Three days after implantation of VX-2 cells into the bladder of the rabbits, microwave coagulation therapy was performed. The antitumor effect, i.e. the survival rate, the histological study and the immunological response of the microwave therapy was examined in comparison with the control group (no treatment), the partially cystectomized group and the sham-operated group (no tumor cell implantation). The results were obtained as follows. (1) The survival rate in the microwave group was greater than that in the control group. (2) The stimulation index value (SI), which represents humoral immunity, decreased postoperatively in all groups. In the microwave group, SI increased gradually beginning 21 days after the transient decrease. (3) Histological findings revealed severe degeneration, necrosis and complete eradication of the cancer cells of the bladder wall in the microwave group, however, perforation of the urinary bladder could not be detected. The results indicate that microwave coagulation therapy is an effective procedure for urinary bladder tumors. Furthermore, microwave therapy may also accelerate the inactivation of immunological suppressors in the carcinoma host, an additional benefit of the microwave procedure.

Animals↗

Neurinomas presenting as spontaneous intratumoral hemorrhage.

Massive intratumoral or subarachnoid hemorrhage from neurinomas is very rare. The authors report on six patients, four men and two women, with neurinomas that presented as spontaneous intratumoral hemorrhage. The average age of the patients was 56.8 years (range, 31-74 years). Neurinomas originated from the acoustic nerve in four patients and from the trigeminal nerve in two. Four cases were accompanied by the sudden occurrence of clinical symptoms such as headache, double vision, and hemisensory or motor disturbance. The maximum diameter of the tumors ranged from 2.8 to 3.8 cm (average, 3.1 cm). Histological examinations showed massive hemorrhage and increased vascularity, with dilated, thin-walled vessels, in all cases. The size of the tumor and the increase in vascularity with dilated, thin-walled vessels within neurinomas are important pathogenetic factors of hemorrhage. When sudden onset of symptoms or rapid worsening of chronic symptoms occurs in neurinomas, intratumoral or subarachnoid hemorrhage should be considered as a possible cause, and magnetic resonance imaging can be an important tool in obtaining correct diagnosis.

Adult↗

Mitochondrial DNA polymorphism in dogs.

Mitochondrial DNA (mtDNA) polymorphism was studied in 20 mongrel dogs using 14 restriction enzymes. The polymorphism was observed in the cleavage patterns of Apa I, EcoR I, EcoR V, Hinc II and Sty I. Three morphs using EcoR I and Apa I and two morphs using EcoR V, Hinc II and Sty I were found. However, no polymorphism was detected in the cleavage patterns of BamH I, Bgl II, Hae II, Hind III, Pst I, Sca I, Stu I and Xba I. The examined dogs were classified in seven types using five restriction endonucleases which recognized six nucleotide sequences. The value of nucleotide diversity was estimated to be 0.0055. A phylogenetic tree constructed by genetic distances among seven restriction types showed at least two clusters of mtDNA.

Animals↗

Simultaneous recording of urethral pressure and cross sectional area profile.

A new technique for simultaneously recording urethral closure pressure and cross sectional area profile is described. The cross sectional area of the urethra could be measured using the field gradient principle. The procedure was performed readily in male patients and the recordings can be graphically presented during measurement. A high degree of reproducibility using this method was obtained. Typical recordings of control subjects was well as patients with pathology were obtained using this technique. The results of this study show that the maximum urethral closure pressure obtained was 60.8 + 3.4 mmHg and functional profile length, 4.8 + 0.4 cm. Internal meatus cross sectional area was 0.67 + 0.04 cm2 and the minimum urethral cross sectional area was 0.12 + 0.02 cm2. This method has been shown to be readily applicable in measuring urethral closure pressure in males and can potentially be used as a tool of comparing the functional parameters of pressure with the anatomical value of diameter.

Adult↗

The effect of alpha-2 agonists and antagonists on the upper urinary tract of the rat.

We examined the effect of the selective alpha-2 agonist dexmedetomidine and antagonist atipamizole on the upper urinary tract, renal pelvic pressure and ureteral peristalsis. Experiments were performed on twelve Sprague-Dawley female rats weighing 275-323 grams, with administration of urethane (1.2 micrograms/kg). Ventilatory support was provided through a tracheotomy. A continuous normal saline infusion was maintained through the left iliac vein at a rate of 2.5 ml/hr. Arterial pressure was measured at the left iliac artery, which was cannulated with a PE-100 tube connected to a pressure transducer. A mid-line incision was then made from the xyphoid to the symphysis to expose the left kidney, both ureters, and the bladder. The bladder was intubated and drained to avoid bladder pressure increase. Measurements of urine output rate were made from the right ureter and renal pelvic or ureteral pressure was measured using a nephrostomy placed into the pelvis. A ureterostomy was produced by introducing another catheter, into the upper segment of the left ureter for ureteral pressure measurements. The rats were divided into two groups as follows: 1) dexmedetomidine group (n = 6); injected intravenously with 2 micrograms/kg of dexmedetomidine dissolved in 0.5 ml saline. 2) atipamizole group (n = 6); injected intravenously with 2 micrograms/kg of atipamizole dissolved in 0.5 ml saline. Ureteral peristaltic frequency, baseline pressure, and contraction amplitude were compared before, after, and between the bolus injections of 2 micrograms/kg dexmedetomidine (n = 6) or 2 micrograms/kg atipamizole (n = 6) in 0.5 ml saline. The results showed that dexmedetomidine at 2 micrograms/kg produced a significant decrease in arterial pressure and an increase in urine output from 1.2 + 0.8 to 3.6 + 1.2 ml/min. There was no effect on the baseline pelvic pressure of 6.8 + 1.2 cmH2O or amplitude of the renal pelvic contractions: 3.5 + 0.6 cmH2O. The frequency of pelvic contractions was reduced from 0.37 + 0.03 to 0.27 + 0.02 Hz. Atipamizole at 2 micrograms/kg produced a significant reduction in urine flow rate of 1.1 + 0.8 to 0.6 + 0.2 ml/min. Atipamizole also showed no significant effects on baseline pelvic pressure or frequency, but increased the amplitude of pelvic contractions from control values of 3.0 + 0.9 to 3.4 + 0.9 cmH2O. Dexmedetomidine reduced both the baseline ureteral pressure of 8.5 + 2.4 and peristaltic contraction pressure of 11.5 + 2.3 cmH2O in 4/6 rats. Atipamizole reduced base-line ureteral pressure and increased peristaltic rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗

[Effect of terazosin on lower urinary tract function in the male decerebrate dog].

The effect of terazosin on the lower urinary tract function was studied by combined recording of bladder and urethral pressures and external sphincter electromyogram in 8 male decerebrate dogs. Reflex micturitions were induced by bladder filling before and after terazosin. The statistical analysis was carried out on the urodynamic parameters. During the collecting phase, terazosin at doses of 10, 30 and 100 micrograms/kg produced a significant decrease in maximum urethral pressure in the dose dependent manner. Threshold pressure was significantly shown to decrease at doses of 30 and 100 micrograms/kg. In the urodynamic parameters of the emptying phase there was a significant decrease in maximum contraction pressure at 10 and 30 micrograms/kg, and in voided volume at 100 micrograms/kg. Terazosin seems to facilitate an initiation of the bladder contraction with a decrease in threshold pressure. In concludes that alpha 1 adrenergic activity seems to take an important role for the maintenance of the urethral pressure and to control the initiation of bladder contraction in modulation with threshold pressure.

Animals↗

Effect of methylene blue on the vesicourethral function in the rats.

The bladder and urethral activities during the rhythmic bladder contractions were evaluated before and after the intraarterial administration of methylene blue, which prevents the activation of soluble guanylate cyclase. The methylene blue produced an increase in the bladder activity and a decrease in the urethral smooth muscle relaxant response induced with bladder contraction. The L-arginine/nitric oxide pathway seems to modulate the vesicourethral function.

Anesthesia↗

Specific expression of glutathione S-transferase Pi forms in (pre)neoplastic tissues: their properties and functions.

The detection of preneoplastic cells is very important for the analysis of carcinogenic processes and for developing strategies for prevention and treatment of cancer. We have been investigating enzyme alterations occurring during rat chemical hepatocarcinogenesis, especially to find more specific enzyme markers for preneoplastic hepatic lesions. We identified the placental form of glutathione S-transferase (GST-P; GST 7-7) as a new marker enzyme for preneoplastic hepatocytes. We also found human placental form, GST-pi, to be a possible tumor marker for various human tissues except liver. In this article, their properties and possible functions are reviewed on basis of our recent investigations. A peroxisomal enzyme, enoyl CoA hydratase, in also described as a possible negative marker for rat preneoplastic hepatic foci/nodules and hepatomas induced by peroxisome proliferators.

Animals↗

Glutathione transferases and cancer.

The glutathione transferases, a family of multifunctional proteins, catalyze the glutathione conjugation reaction with electrophilic compounds biotransformed from xenobiotics, including carcinogens. In preneoplastic cells as well as neoplastic cells, specific molecular forms of glutathione transferase are known to be expressed and have been known to participate in the mechanisms of their resistance to drugs. In this article, following a brief description of recently identified molecular forms, we review new findings regarding the respective molecular forms involved in carcinogenesis and anticancer drug resistance, with particular emphasis on Pi class forms in preneoplastic tissues. The rat Pi class form, GST-P (GST 7-7), is strongly expressed not only in hepatic foci and hepatomas, but also in initiated cells that occur at the very early stages of chemical hepatocarcinogenesis, and is regarded as one of the most reliable markers for preneoplastic lesions in the rat liver. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-responsive element-like sequences have been identified in upstream regions of the GST-P gene, and oncogene products c-jun and c-fos are suggested to activate the gene. The Pi-class forms possess unique enzymatic properties, including broad substrate specificity, glutathione peroxidase activity toward lipid hydroperoxides, low sensitivity to organic anion inhibitors, and high sensitivity to active oxygen species. The possible functions of Pi class glutathione transferases in neoplastic tissues and drug-resistant cells are discussed.

Animals↗

[Vesical ultrasonography and internal examination of female patients with urethral syndrome].

Transabdominal ultrasonography of the bladder and internal examination were performed in 80 female patients without pyuria. They were divided into 3 groups: urethral syndrome with trigonitis (49 cases), asymptomatic trigonitis (16 cases) and normal bladder (15 cases) by cystoscopy. Ultrasonography of trigonitis with or without symptoms showed focal dilation of the submucosal low echo zone and mucosal irregularity around the bladder neck. On the sagittal view, the thicknesses from the surface of mucosa to that of muscle layer within 2 cm from the bladder neck were 4 +/- 1 mm (mean +/- standard deviation) in the group with urethral syndrome and in that with asymptomatic trigonitis, and 3 +/- 1 mm in the normal bladder group. Mucosa of the trigonitis with or without symptom is patients with significantly thicker than that of those with normal bladder (p less than 0.01). On internal examination, tenderness at the upper frontal wall of the vagina was present in 10 of 11 cases (91%) with urethral syndrome, in 2 of 8 cases (25%) with asymptomatic trigonitis and in one of 9 cases (11%) with normal bladder. There was a significant difference (p less than 0.005) between the degree of inflammation and the number of cases with tenderness at the frontal wall of the vagina. From these results, transabdominal ultrasonographic measurement of mucosal thickness around the bladder neck and internal examination for tenderness at the frontal wall of vagina are thought to be useful methods for diagnosis and follow-up of urethral syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗