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Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

At least 145 records · Page 8Linked to original sources

[Study of complications after endoscopic sclerotherapy for esophageal varices--particularly 2 cases that changed portal circulation after sclerotherapy].

In 116 patients with esophageal varix due to liver cirrhosis who received the endoscopic sclerotherapy, the following complications were observed after the sclerotherapy: 38 ulcer formation; 19 chest pain; 16 hypotension; 15 fever; 12 pleural effusion; 6 esophageal stenosis and so on. Furthermore, two cases with marked changes of portal circulation were experienced after the sclerotherapy. The first case had severe bleeding out of duodenal varix four months after the sclerotherapy and died because of massive bleeding. The second case had hepatic encephalopathy six months after the sclerotherapy. In both cases, angiography revealed the development of collateral veins after the sclerotherapy. Because the abrupt intercept of the esophageal varix by the successful sclerotherapy causes the increase of the other collateral blood flow, the changes of portal circulation must be watched carefully afterward.

Adult↗

Activation mechanism of calcium-activated neutral protease. Evidence for the existence of intramolecular and intermolecular autolyses.

The activation mechanism through limited autolysis of a calcium-activated neutral protease (CANP) with a high sensitivity to calcium ions (microCANP) was analyzed. The rate of autolysis was dependent on microCANP concentration. The reaction was inhibited by high concentrations of digestible substrates but not by a nondigestible substrate. Incubation of microCANP inactivated by N-ethylmaleimide with a small amount of activated microCANP caused the degradation of the former in a manner similar to the autolysis of native microCANP. Immobilized microCANP bound to an anti-microCANP immunoglobulin G column autolyzed on addition of calcium ions. These results show that activation of microCANP through limited autolysis involves both intramolecular and intermolecular reactions.

Animals↗

Effects of retinoic acid on morphological features and biological markers of a neoplastic human salivary intercalated duct cell line in culture.

Retinoic acid has marked effects on the growth, morphological features, and biological markers of a neoplastic human salivary intercalated duct cell clone in culture, whereas the cell clone was not affected by other retinoids such as retinol and retinal. A cell clone with ultrastructure and biological markers specific to the intercalated duct cells of human salivary glands was cultivated in the presence of retinoic acid. Major alterations, such as expression of tonofilaments, Mr 68,000 cytokeratin, and involucrin, were observed in those cells with a phenotype similar to that of keratinizing squamous cells. In addition, the coexpression of Mr 68,000 cytokeratin and carcinoembryonic antigen in these altered cells was found. Both the anchorage-independent and anchorage-dependent growths were markedly suppressed in the presence of retinoic acid. After the removal of retinoic acid from the culture, the treated cells returned rapidly to the phenotype of the untreated cells. These findings indicate that reversible differentiation into the keratinizing squamous cells of a neoplastic human salivary intercalated duct cell clone occurs in growth medium containing retinoic acid.

Adenocarcinoma↗

Tissue distribution of calcium-activated neutral proteinases in rat.

A simple separation method involving a minimum number of essential steps was established to separate the two kinds of calcium-activated neutral proteinase (CANP) activity from each other and from endogenous CANP inhibitor activity. Determination of CANP activity in rat tissues using this method revealed a ubiquitous distribution of two CANPs. The level of CANP activity, however, differs between tissues. Low-calcium-requiring CANP (microCANP) is plentiful in spleen and kidney, while high-calcium-requiring CANP (mCANP) is plentiful in lung and brain. In all of the tissues examined, mCANP activity predominates over microCANP activity.

Animals↗

Systemic hemodynamics in non-cirrhotic portal hypertension--a clinical study of 19 patients.

The features of systemic hemodynamics were analyzed in 19 non-cirrhotic patients with prominent esophageal varices. The patients were divided into two groups; Group I comprised 8 patients with an occluded extra-hepatic portal vein and Group II comprised 11 patients with a patent extra-hepatic portal vein whose histopathological diagnosis was idiopathic portal hypertension or hepatic fibrosis. An increase in the cardiac index and a decrease in the total peripheral resistance were significant in both groups when compared with 12 control patients (p less than 0.01). There was a significant correlation between the cardiac index and plasma volume in the 14 non-cirrhotic patients with portal hypertension (r = 0.537, p less than 0.05), but no significant relationships were identified between the cardiac index and liver functional values. These results reveal that the systemic hemodynamics in non-cirrhotic portal hypertension are significantly hyperdynamic, as in cirrhotic portal hypertension. They also suggest that the expanded plasma volume secondary to the enlargement of the portal bed might be closely related to the mechanism of hyperdynamic systemic circulation in non-cirrhotic portal hypertension.

Adolescent↗

Effects of a competitive antagonist of bradykinin on blood pressure and renal blood flow in anesthetized rats.

To examine a possible role of endogenous bradykinin in the regulation of blood pressure (BP) and renal blood flow (RBF), a newly synthesized competitive antagonist of bradykinin (B4147) was studied in anesthetized rats. Also, the question of whether the hypotensive effect of the converting enzyme inhibitor, captopril, is mediated partly by an accumulation of endogenous bradykinin was considered. The intravenous infusion of B4147 (25 micrograms/min) inhibited the depressor effect of exogenous bradykinin (0.5 microgram, i.v.) by 69%. After an intravenous injection of B4147 at doses of 25, 50 and 100 micrograms, BP increased and RBF decreased in a dose-dependent fashion. The increase in BP was not blocked by pretreatment with an angiotensin II antagonist (1-Sar-8-Ile angiotensin II; 20 micrograms/kg per min) or an alpha 1-blocker (prazosin; 0.1 mg/kg). The administration of captopril (1 mg/kg) decreased mean BP from 110 +/- 3.5 to 71 +/- 1.9 mmHg (P less than 0.001). However, the injection of B4147 (50 micrograms) after the administration of captopril elicited an increase in BP of 43% of the initial decrease induced by captopril. These results suggest that the effects of B4147 on BP and RBF are not mediated through angiotensin II or sympathetic alpha 1-stimulation. Endogenous bradykinin could contribute to the maintenance of BP and RBF in anesthetized rats, probably counter-balancing the vasoconstrictor mechanisms. It is also suggested that bradykinin may partly participate in the acute hypotensive effect induced by the converting enzyme inhibitor captopril.

Animals↗

Contribution of bradykinin to maintenance of blood pressure and renal blood flow in anaesthetized spontaneously hypertensive rats.

We used a newly synthesized competitive antagonist of bradykinin (B 4147) to determine whether bradykinin contributes to the maintenance of blood pressure and renal blood flow in anaesthetized Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The injection of B 4147 (50 micrograms, intravenously) caused an increase in blood pressure and a decrease in renal blood flow in both strains. However, the magnitude in the change in blood pressure was significantly lower in SHR than in WKY. The reduction of renal blood flow was greater in WKY than in SHR, but there was no significant difference in the basal renal blood flow. These results indicate that bradykinin contributes to the maintenance of blood pressure and renal blood flow in both strains. However, bradykinin antagonist produced a more prominent systemic effect in WKY than in SHR. This suggests that a deficiency in the bradykinin system in SHR contributes to the development or the maintenance of hypertension.

Animals↗

Cloning and sequencing of the Escherichia coli chlEN operon involved in molybdopterin biosynthesis.

The nucleotide sequence of a HinPI-HpaII restriction nuclease fragment which complemented a delta chlE strain of Escherichia coli was determined. Two open reading frames were deduced to be the structural genes for ChlE and ChlN proteins, which have molecular weights of 44,067 and 26,719, respectively. Both proteins were required for complementing a chromosomal deletion of the chlE locus. The chlE and chlN genes were transcribed from a common promoter, chlEp, located upstream of chlE. Transcriptional and translational signal sequences were recognized in this region.

Amino Acid Sequence↗

[Clinical study of controlled-release preparation of mitomycin C in the treatment of inoperable cancer patients].

The composite substance of Mitomycin C (MMC) and polymer by low temperature radiating polymerization has a characteristic of slow release, the possibility of applying it to local chemotherapy was clinically studied. Buttom-formed preparation (MMC 20 mg) and needle-formed preparation (MMC 5 mg) were applied to the lesions, respectively, by sewing and piercing in 220 cancer patients with non resectable infiltrative lesions. The treatment had a pain-relieving effect in 70 out of 117 cases (60.0%) of painful cancer in the pancreas, biliary duct, liver, etc, and improved the symptoms of digestive organs in 31 out of 93 cases (33.3%). However, the tumor-reducing effect was recognized only in minute localized lesions of hepatic cancer, etc., and the survival period was not prolonged. The treatment caused no severe side effects. From the above results, the local chemotherapy with slow-releasing MMC preparation was concluded to be a useful means of palliative therapy in non-resectable, though its formulation may to be further improved.

Clinical Trials as Topic↗

[A case of colon cancer with pulmonary metastasis treated effectively by uracil futraful].

A 57-year-old female was admitted for advanced ascending colon cancer with a solitary pulmonary metastasis measuring 1.5 cm in diameter. As laparotomy revealed an absolute noncurable tumor of stage V (H0, p2, s2 n1 (+], palliative right hemicolectomy was performed. A pathological diagnosis of well differentiated adenocarcinoma was made postoperatively. A daily dose of 400 mg of UFT was given orally. After 8 months, plain chest film and tomography revealed a reduction in the size of the pulmonary metastasis to 1.0 cm in diameter. The metastatic lung tumor was controlled for a period of 1 year and 9 months. It was suggested that UFT was rather effective for pulmonary metastasis from colon cancer.

Adenocarcinoma↗

[A cooperative study of surgical adjuvant chemotherapy of colorectal cancer (second report): 3-year survival rate. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

To evaluate the efficacy of surgical adjuvant chemotherapy for patients with curatively resected colorectal cancer (excluding m and sm cancer), a randomized controlled study was performed from January 1982 to October 1983. The schedules for drug administration were different in four districts, and four randomly assigned protocols were studied using tegafur (FT), ACNU, MMC and ADM. A total of 4,906 cases from 491 institutions were entered and 4,206 cases were varied for the study. There were no significant differences in 3-year survival rate in each district protocol. According to Dukes C for rectal cancer patients, ADM + FT group was higher than the FT only group in 3-year survival rate (p = 0.092) and had a significantly longer survival than FT only group in 3-year disease-free rate (p = 0.011). The rate of local recidivation in colon cancer resected curatively was higher in ACNU + FT group than in FT only group (p less than 0.05). A tendency for decreased liver metastasis was observed in FT group compared with the control group, and liver metastasis of ADM + FT group was lower than that of FT only group. No serious adverse effects were observed in any protocol.

Antineoplastic Combined Chemotherapy Protocols↗

General pharmacological properties of muroctasin.

General pharmacological effects of N2-[(N-acetyl-muramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-ly sine MDP-Lys(L18), muroctasin) were examined and the following results were obtained. 1. Central nervous system: MDP-Lys(L18) had no effect on behavior, spontaneous motor activity, electroshock- and chemoshock-induced convulsions, hexobarbital sleeping time, pain threshold (mice), conditioned avoidance response (rats) at a dose of 0.4 mg/kg, s.c. and EEG as well as spinal reflex (cats) at a dose of 0.4 mg/kg, i.v. It produced a significant elevation in body temperature (rabbits) at doses of 13 micrograms/kg, s.c. and greater. 2. Respiratory and cardiovascular system (dogs): MDP-Lys(L18) did not show any significant effect on respiratory and cardiovascular functions at a dose of 0.4 mg/kg i.v. 3. Autonomic nervous system: MDP-Lys(L18) induced a miosis (rabbits) at doses of 13 micrograms/kg s.c. and greater. It did not affect norepinephrine-induced pressor and acetylcholine-induced depressor responses (dogs) and contraction of the nictitating membrane induced by electrical stimulation (cats) at a dose of 0.4 mg/kg i.v. 4. Smooth muscles: In the experiments using the isolated ileum, vas deferens, trachea (guinea pigs) and uterus (rats), MDP-Lys(L18) showed neither spasmogenic nor spasmolytic activity at a concentration of 4 x 10(-6) g/ml. Gastrointestinal propulsion (mice), gastric mucosa, gastric emptying rate and gastric secretion (rats) were not affected by this drug at a dose of 0.4 mg/kg s.c. MDP-Lys(L18) did not influence gastrointestinal motility (dogs) at a dose of 0.4 mg/kg, i.v. 5. Miscellaneous: MDP(L-18) suppressed carrageenan-induced edema (rats) at doses of 0.13 mg/kg s.c. and greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗

Preferential localization of calcium-activated neutral protease in epithelial tissues.

Immunohistochemical localization of calcium-activated neutral protease (CANP) in rabbit organs was determined using a monoclonal antibody against CANP. In most organs, epithelial tissues reacted intensely: these tissues include great alveolar and squamous alveolar cells in lung; interlobular artery, vein, and bile duct in liver; small vessels in skeletal muscle; glomeruli, juxtanglomerular cells, distal and collecting tubules in kidney; mucous epithelium in gallbladder; interstitial cells in testis; and cuboidal epithelial cells in brain choroid plexus. On the other hand, hepatocytes, epithelial cells which have ill defined basal lamina, were stained very faintly. These observations suggest that the physiological function of CANP is involved with transport systems in epithelial tissues through basal lamina.

Animals↗

Renal kallikrein activity in spontaneously hypertensive rats.

To assess possible roles of the renal kallikrein-kinin system in the development of spontaneous hypertension, we determined daily excretion of urinary total and active kallikrein in 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for up to 2 weeks. We also evaluated the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension in the 6-week-old SHR on ordinary intakes of sodium or on sodium loading with 1% NaCl for up to 2 weeks. Active kallikrein was determined by its kininogenase activity, and the generated kinins were radio-immunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in 7-week-old SHR (1.5 +/- 0.2 microgram/day compared to 2.8 +/- 0.3 micrograms/day in WKY, P less than 0.05) and in 8-week-old SHR (1.6 +/- 0.2 microgram/day compared to 3.2 +/- 0.4 micrograms/day in WKY, P less than 0.01). Urinary total kallikrein excretion was also reduced in the 7- and 8-week-old SHR whereas the ratio of active to total kallikrein did not change. In addition, renal contents of total and active kallikrein were significantly lower in the 8-week-old SHR than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term effects of aldosterone on kallikrein, prostaglandin E2 and sodium in rats.

To assess the long-term effects of mineralocorticoids on the regulation of the synthesis or release of kallikrein and prostaglandin E2 in the renal kallikrein-kinin-prostaglandin E system, we studied the effects of chronic infusion of aldosterone (50 micrograms/kg/day) on urinary excretion of total and active kallikrein, and prostaglandin E2 for 10 days in conscious rats on regular intakes of sodium and on sodium loading with 1% NaCl as a drinking water. Chronic infusion of aldosterone induced a prompt and transient decrease in the ratio of sodium to potassium and a sustained increase in urinary prostaglandin E2 excretion in rats on regular diets, whereas urinary total and active kallikrein excretion did not increase significantly until the 4th day of aldosterone infusion. In rats loaded with sodium, aldosterone did not induce any changes in urinary total and active kallikrein excretion, whereas it induced similar changes in the ratio of sodium to potassium and urinary prostaglandin E2 excretion to those in rats on regular diets. Thus, the present results suggest that aldosterone might stimulate the synthesis or release of renal prostaglandin E2 independent of sodium balance. Furthermore, it is also suggested that aldosterone might stimulate the synthesis or release of kallikrein, at least partly, via the same pathway as sodium loading does.

Aldosterone↗

No evidence on significant roles of the prostaglandin-thromboxane and kallikrein-kinin system in the antihypertensive effect of MK 421 in rats made hypertensive by norepinephrine or vasopressin.

Inhibition of angiotensin converting enzyme by MK 421 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induced any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressin-infused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100,000 units/kg/day sc) did not affect the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.

Animals↗