The role of calcium in collagenase digestion and preservation of islets.
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Biomedical subjects
Publications and source records attributed to T Kanai.
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The efficacy of transarterial immuno-embolization therapy (TIE) was investigated in 7 patients with multiple hepatocellular carcinoma (HCC). We administered OK-432 (10 KE), fibrinogen (30 mg/ml) and thrombin (1 U/ml) as a new treatment for HCC with intrahepatic metastasis. In all patients with a high level of AFP, the AFP level decreased promptly less than the pretreatment level after TIE therapy. High fever in all cases, epigastralgia in 6 cases and appetite loss in 3 cases were observed after TIE therapy. Our results indicate that this therapy may be a safe and effective method in HCC patients with intrahepatic metastasis.
The relationship between postoperative prognosis and plasma level of PIVKA-II (Protein induced by vitamin K absence or antagonist-II) was studied in 56 patients with hepatocellular carcinoma. The survival rate was significantly lower in patients with positive PIVKA-II when compared with that with negative PIVKA-II. Similar results were also obtained in cases with tumor not less than 6cm in diameter (group A, 43 cases). In accordance with these results, the frequency of intrahepatic metastasis or portal tumor thrombus was significantly increased in PIVKA-II positive cases and thereby the macroscopic stage became more advanced although no significant difference was observed in curability. Tumor diameter and frequency of massive type were also increased in PIVKA-II positive patients and all of eight cases with massive type were PIVKA-II positive. Furthermore, all patients with massive type had both intrahepatic metastasis and portal tumor thrombus and their prognosis was extremely poor when compared with that with nodular type, in whom the survival rate was not different between PIVKA-II positive and negative cases. Thus, the poor prognosis of PIVKA-II positive patients might be due to the increased frequency of massive type although the cause-effect relationship remains to be elucidated.
The efficacy of transcatheter arterial infusion chemotherapy was examined for patients with hepatocellular carcinoma (HCC) between April 1986 and May 1992. We investigated the serial serum AFP level in patients with HCC. In 9 of 18 patients, the AFP level decreased promptly to 70% of the pretreatment level after this treatment. In 29 HCC patients with intrahepatic metastasis or portal thrombosis, 10 cases survived more than one year. However, only 3 cases survived more than two years after treatment. Our results suggest that we should carefully select appropriate drugs sensitive to HCC and also give careful consideration to the resistance to anti-cancer drugs.
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The management of late metastases from renal cell carcinoma is often difficult because of multiple organ involvement. We report a case of multiple metastases from renal cell carcinoma in the duodenum, pancreas, intestine, falciform ligament and liver, 18 years after nephrectomy. The patient underwent a total pancreatectomy following a gastroduodenal arterial embolization to control duodenal bleeding, a resection of the ileum and falciform ligament at a second laparotomy and repeated hepatic arterial embolizations to control the growth of liver metastases. Aggressive treatment should be undertaken in cases of late recurrence of renal cell carcinoma after nephrectomy because of the possibly slow-growing biological character of the tumor.
A calcium blocking agent, verapamil, and a beta 1-adrenoreceptor blocking agent, metoprolol, were administered alone or in combination to 4-day-old chick embryos (Hamburger-Hamilton developmental stage 24). Embryos co-administered with verapamil (0.05 nmol) and metoprolol (0.1 or 1.0 nmol), neither of which alone caused significant teratogenicity, showed cardiovascular malformations, including ventricular septal defects associated with or without dextroposition of the aorta (overriding aorta). The alterations of calcium movement into the myocyte and/or the haemodynamic change following impaired calcium transport are suggested to be possible causative factors.
The effects of forskolin on the teratogenicity of ephedrine in the developing chick heart were studied. Forskolin was administered to 4-day chick embryos (Hamburger-Hamilton stage 24) together with ephedrine at doses at which each agent alone caused minimal embryotoxicity. The embryos were examined for malformations on day 14 of incubation. The frequency of malformed embryos exposed to ephedrine (0.5 or 5 mumol) alone was 8 and 26%, respectively, and significantly increased to 47-72% in the presence of 1 nmol forskolin. Forskolin (1 nmol) alone did not induce a significant number of cardiac malformations. These results suggest that the increase in cAMP through stimulation of adenylate cyclase by forskolin is associated with the potentiation of ephedrine-induced cardiovascular malformations in the chick.
This study tried to improve the number of viable islets isolated from a pancreas because a sufficient number cannot be obtained when the organ is preserved in the manner used for pancreas transplantation. The mechanism involved in the decrease in islet yield during preservation was studied to try to develop a better method for islet preparation. First, the integrity of the ductal system was compared between fresh and 6-hr simply preserved (in Hanks' balanced salt solution) rat pancreases. The ductal pressure after ductal injection of HBSS reached a plateau earlier and was significantly lower for the preserved pancreases (0.073 +/- 0.026 min, 410 +/- 17 mmHg, n = 5) than for the fresh ones (0.176 +/- 0.086 min, 561 +/- 103 mmHg, n = 7, P less than 0.05). Second, the extent of pancreatic distention was examined following ductal injection of barium gelatin solution. Solution leakage occurred earlier and distention was less in the preserved pancreas. In addition, the gelatin was found in the capillaries within some islets of the preserved pancreas. These results indicated that the preservation led to a rapid loss of integrity of the ductal system before collagenase injection. We therefore tested the efficacy of ductal collagenase injection at the time of harvesting: 15 ml of 1.0 mg/ml collagenase HBSS was intraductally injected and the pancreas was preserved at 4 degrees C for 2, 4, 6, and 24 hr. The isolation procedure was similar to that used for the fresh pancreas. The yield was significantly better than that of the simply preserved pancreas at 4 hr (241 +/- 22, n = 3, vs. 140 +/- 58, n = 3, P less than 0.05) and at 6 hr (171 +/- 58, n = 14, vs. 32 +/- 33, n = 6, P less than 0.01). These isolated islets were spherical-oval and their viability was confirmed by the ability to reverse STZ-induced diabetes in mice. These results indicated that the integrity of the ductal system, which is necessary for distention of the whole pancreas, was lost during preservation. To solve this problem, ductal collagenase injection should be done at the time of pancreas harvesting and then followed by simple preservation. This method is recommended to obtain viable islets from a preserved pancreas.
We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with metastases. Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment. Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases.
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The clinical significance of des-gamma-carboxy prothrombin (PIVKA-II) in hepatocellular carcinoma (HCC) was investigated in 112 patients with and without vitamin K administration. The positivity rate of PIVKA-II was significantly decreased in patients receiving vitamin K (28.5%), compared with those without vitamin K administration (54.5%, p less than 0.05). The plasma levels of vitamin K derivatives [phylloquinone (VK1), menaquinone-4 (MK4), and menaquinone-7 (MK7)] measured were not decreased in patients with HCC, but were significantly increased in MK4 and VK1 + MK4 + MK7. The amount of PIVKA-II in plasma did not correlate with the plasma levels of vitamin K derivatives. However, PIVKA-II was decreased by the administration of vitamin K, and all of the six patients with more than 5.0 ng/ml of VK1 + MK4 + MK7 were within normal limits, whereas half of 32 patients with less than that had abnormal levels of PIVKA-II. Thus, it was suggested that PIVKA-II was not elevated due to vitamin K deficiency, but might result from the impaired metabolism or availability of vitamin K in the tumor. Therefore, PIVKA-II should be measured without vitamin K administration.
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To understand the role of thymic epithelial cells in the development of immature thymocytes, the establishment and cloning of thymic epithelial cell lines must be required. In the present study, we established human and mouse thymic epithelial cell lines through the immortalization by the transfection of cDNA sequences of adenoviral E1a 12S mRNA. This procedure resulted in the isolation of five stable cell lines (one human cell line and four mouse cell lines). These cell lines were positive in cytokeratin demonstrated by immunohistochemistry. Electron microscopic study revealed that they had bundles of tonofilaments and desmosome-like tight junctions. These findings indicate that the cell lines immortalized by E1a gene have retained the properties of epithelial cells. MHC class II antigens were not expressed on these cell lines. When interferon-gamma was added to the cultured epithelial cell lines, MHC class II antigens were induced in their cytoplasm and on their surface membrane, demonstrated by immunohistochemical and immunofluorescent studies. It is suggested that these stable cell lines from human and mouse thymus might serve a good tool for the further study of thymocytes differentiation and of unknown cytokines derived from thymus epithelium.
We evaluated short term clinical effects of intravenous cyclophosphamide (iv CyP) therapy performed by every three month in 7 patients with steroid-resistant lupus nephritis. Significant improvements were observed in daily urinary protein excretion (3.1 to 0.83 g/day), creatinine clearance (65.4 to 95.3 ml/min), CH 50 levels (20.8 to 37.4 U/ml), and anti-DNA antibody titer (26.6 to 7.0 U/ml). In addition, the mean daily dose of prednisolone (PSL) could be markedly reduced from 38.6 mg to 13.9 mg at the final observation. Two patients suffered from Herpes Zoster infection at a few months after ivCyP therapy, however this incidence were not considered as critical side effect which reached to the discontinuation of this therapy. We concluded that ivCyP therapy by every three months were safety and achieved beneficial clinical effects on steroid-resistant lupus nephritis as far as short observation. On the contrary, the long term effect of this mode of therapy is to be defined.