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Biomedical subjects

A Hayakawa

Publications and source records attributed to A Hayakawa.

At least 73 records · Page 4Linked to original sources

Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study.

Lipiodol injection is a useful method for detecting liver tumors, especially hepatocellular carcinoma (HCC). We therefore prepared and tested a new emulsion of lipiodol containing epirubicin and cis-diammine-dichloroplatinum (CDDP), drugs that are very effective against HCC. This CDDP-epirubicin-lipiodol suspension (CELS) was injected into 18 HCC patients via a celiac angiographic catheter. In 11 of these patients, CELS was followed by transcatheter arterial embolization (TAE) therapy. Clinical and pharmacological investigations were performed in all 18 patients, and the following results were obtained. CELS is pharmacologically and chemically stable, and both the results of the dissolution test and the serum levels of these two drugs indicate that slow release can be obtained. After the injection of CELS, serum levels of AFP and PIVKA-II decreased immediately, and no fatal clinical side effects were encountered. Although no statistically significant difference was observed, the survival (Kaplan-Meier method) of patients injected with CELS in the presence or absence of TAE therapy can be estimated to be much longer than that of patients receiving CDDP-lipiodol suspension injection in the presence (16 patients) or absence (6 patients) of TAE therapy. A combination of CELS injection and TAE therapy might be effective and useful for the treatment of HCC.

Aged↗

Immobilization of proteases to porous chitosan beads and their catalysis for ester and peptide synthesis in organic solvents.

alpha-Chymotrypsin (CT), subtilisin BPN' (STB), and subtilisin Carlsberg (STC) were immobilized by adsorption to porous chitosan beads (Chitopearl, CP). The immobilized enzymes showed higher catalytic activities than free enzymes for amino acid esterification in many hydrophilic organic solvents except for methanol and DMF. In ethanol, the initial rate of the esterification increased with water content, whereas in ethyl acetate, the maximum rate was obtained at 2%-3% water. CP-immobilized CT also catalysed transesterification of Ac-Tyr-OMe in ethanol and peptide synthesis in acetonitrile from Ac-Tyr-OH or its ethyl ester and amino acid amides. The immobilized enzymes are highly stable in organic solutions, and can easily be separated from the reaction solutions. Repeated esterifications of Ac-Tyr-OH in acetonitrile by a CP-immobilized CT gave almost constant yields of the ester for more than 3 weeks.

Catalysis↗

Small cell carcinoma of the uterine cervix showing Cushing's syndrome caused by ectopic adrenocorticotropin hormone production.

A uterine cervical cancer is reported in a woman who developed Cushing's syndrome. The tumor measured 1.3 x 0.7 cm, and was a pure small cell carcinoma, identical to that in the lung. The primary tumor cells showed argyrophilia with Grimelius staining and reacted positively to the anti-chromogranin antibody. Clinically, the neoplasm behaved in an aggressive manner in spite of adjuvant chemotherapy and radiotherapy, and the patient died of widespread metastasis. Cushing's syndrome was noted after the occurrence of liver metastasis with an elevation of the serum adrenocorticotropin hormone (ACTH) level. At autopsy, metastatic tumor cells from the liver reacted immunohistochemically positively not only to anti-ACTH but also to antichromogranin, anti-gastrin and anti-calcitonin antibodies. This is the first report of an immunohistochemical analysis of, and comparison of primary and metastatic sites in cervical carcinoma showing Cushing's syndrome.

ACTH Syndrome, Ectopic↗

[Clinical significance of antibodies against calmodulin in patients with various liver diseases].

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.

Autoantibodies↗

Protease-catalyzed synthetic reactions and immobilization-activation of the enzymes in hydrophilic organic solvents.

The catalytic feature of serine proteases for synthetic reactions in hydrophilic organic solvents and effects of immobilization by complexation with polysaccharides are described. Free alpha-chymotrypsin and subtilisin Carlsberg catalyze esterification, transesterification, and peptide synthesis in hydro-organic cosolvents with less than 10% water. Subtilisin BPN' is catalytically less active. The medium effects on the reaction kinetics and product yield were investigated in terms of the nature of solvent and water content in the reaction systems. The substrate- and stereo-specificities of the enzymes suggest that the enzymes maintain their native conformations in these low-water organic solvents. The catalytic activities of the proteases markedly increase by immobilization or complexation with polysaccharides, such as chitin or chitosan. The results of the rate measurements suggest that the primary role of the support materials is the activation of the enzymes and the increase in substrate concentration at reaction sites.

Catalysis↗

Excitatory cholinergic innervation in canine portal and mesenteric veins.

A possibility that the canine portal and mesenteric veins may have an excitatory cholinergic innervation similar to that observed in the middle segment of the inferior vena cava (IVC) was investigated. After adrenergic blockade with prazosin, contractile responses of isolated longitudinal strips of the portal and mesenteric veins to transmural electrical stimulation were greatly diminished. Subsequent anticholinesterase (neostigmine or physostigmine) treatment, however, revealed in the nerve-evoked contraction a component that was antagonized by atropine. The same phenomenon was also observed in circular strips of the portal and mesenteric veins but was absent in those of the external jugular, saphenous, and splenic veins. In accord with the results of nerve stimulation, concentration-response curves of acetylcholine-induced contraction were shifted leftward by neostigmine in strips of the portal and mesenteric veins as well as of the middle segment of IVC. In contrast, no shift was observed in 12 other different sites of the venous system. Cholinesterase staining demonstrated positively stained smooth muscle and nerve fibers in the portal and mesenteric veins and in the middle segment of IVC. These findings indicate the existence of excitatory cholinergic innervation in the portal and mesenteric veins, which may reflect the common embryological origin of smooth muscle of these veins with the intestinal muscle.

Acetylcholine↗

Distinctive characteristics of the splenic vein in the dog. Its morphological and pharmacological discontinuities with the portal vein and splenic capsule.

Vascular characteristics of the splenic vein are entirely different from the portal vein in the dog. We compared the responsiveness of the splenic capsule, which contains abundant smooth muscle with the portal and splenic veins. With respect to potentiation of acetylcholine-induced contraction by neostigmine, the relaxation response to isoproterenol and the contractile response to 5-hydroxytryptamine, the splenic capsule differed from the splenic vein, but was rather similar to the portal vein. A site of morphological and pharmacological discontinuity between the portal vein and the splenic vein occurred at the junction of the splenic vein and the left gastric vein to form the gastrosplenic vein. This junction may coincide with the site of connection of the embryonic splenic vein, a newly formed efferent vein of the spleen, with the portal vein, which was reported by Miki [cf. Bevan et al.: 4th Int. Symp. on Vascular Neuroeffector Mechanisms; Raven Press, New York 1983]. On the splenic side, histological examination revealed that smooth muscle of the splenic capsule and trabeculae are interconnected, but did not extend to the splenic vein. At openings of the trabecular veins into the 'intrasplenic' portion of the splenic vein the trabecular smooth muscle continued to the extended capsule. The site of change in pharmacological responses was also found to be located between the trabeculae and the intrasplenic portion of the splenic vein. Thus the splenic vein can be regarded as a distinct segment of vessel inserted between the portal vein and the spleen. This may reflect differences in embryogenesis of their smooth muscle.

Animals↗

Distribution of cholinesterase in canine venous system.

Cholinesterase (ChE) activity was examined in 15 veins from dogs by pharmacological and histochemical procedures. Potentiation of acetylcholine (ACh)-induced contractile response by neostigmine was observed in helical and longitudinal strips of portal, mesenteric veins and middle segment of the inferior vena cava, but not in the other 12 veins. Histochemical studies with an electron-microscope (the method of Karnovsky-Roots) revealed that ChE activity was identified as high density granules around the smooth muscle cells only in the former three veins. The visible ChE activity was abolished by pretreatment with neostigmine.

Animals↗

Heterogeneity in vasorelaxant effects of alpha-human atrial natriuretic polypeptide in the dog.

Effects of alpha-human natriuretic polypeptide (ANP) on isolated canine vascular strips were examined in 6 arteries and 5 veins. Under the preconstriction with either methoxamine, prostaglandin F2 alpha or KCl, ANP relaxed the vascular strips to various degrees, depending on the region removed from the circulatory system. The largest relaxation was obtained in the pulmonary artery, suggesting that the pulmonary artery may be an important site of action of ANP.

Anesthesia↗

Pharmacokinetics of pirenzepine in patients with gastric or duodenal ulcers.

1. The pharmacokinetics of pirenzepine (Gastrozepin) was studied after single and multiple oral administration in gastric ulcer and duodenal ulcer patients. 2. With a dose of 50 mg of pirenzepine, plasma levels reached a maximum 2 h after the administration in both groups (gastric ulcer patients: 57.2 +/- 31.8 ng/ml, duodenal ulcer patients: 48.0 +/- 18.0 ng/ml), and decreased bi-phasically with an elimination half-life (t1/2 beta) of 13.9 +/- 4.0 and 17.9 +/- 4.5 h, respectively. The area under the plasma level curve were 844 +/- 319 ng X h/ml and 663 +/- 151 ng X h/ml in the respective group. 3. The plasma levels of pirenzepine after multiple administration (50 mg was given as a loading dose, and thereafter 25 mg was given as a maintenance dose at an interval of 12 h for 7 days) maintained certain steady state levels from just after the start of administration. 4. It can be concluded that there is no significant difference in the pharmacokinetics of pirenzepine between gastric and duodenal ulcer patients. It can be judged that twice-daily administration of pirenzepine is enough for ulcer treatment.

Administration, Oral↗

[Two cases of papillary tumor of the pancreas].

Two patients with papillary tumors of the pancreas are reported. In both cases, the tumors occurred in women (62 and 60 years of age) who presented with upper abdominal mass and abdominal fullness. The resected tumors were 14 X 16 cm and 13 X 10.5 X 8.3 cm, respectively. Their histology resembled that of the papillary tumor of the pancreas reported by Frantz (1959). The ultrastructural details, including numerous mitochondria, basement membrane and no evidence of secretory or zymogen granules, suggest pancreatic duct cell origin. The first patient died of colon cancer six years and 10 months postoperatively. The second patient is without signs of recurrence five months after resection.

Carcinoma, Papillary↗