[Cellular immunity of patients with open-heart surgery--with reference to the kinetics of functional subsets of lymphocytes by two color analysis with monoclonal antibodies].
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Biomedical subjects
Publications and source records attributed to T Oka.
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A connective tissue tube containing collagen fibrils and capillary blood vessels is an ideal material for artificial artery, since the collagen fibrils compose an excellent supporting framework for cell migration and proliferation and the endothelial cells of the capillary can be the origin of the endothelialization of the graft. However, its thrombogenicity has remained a problem. This experiment was designed to develop a small caliber (3mm) vascular graft using an autogenous connective tissue provided with temporary antithrombogenicity. A tube knitted of ultra-fine polyesters was implanted subcutaneously in the back of mongrel dogs for three weeks. Thus accomplished connective tissue grafts were heparinized ionically in vitro, using cross-link agents. Then the treated grafts, 5-6 cm in length and 3mm in diameter, were segmentally replaced with bilateral carotid arteries. During the follow-up period up to 55 days, 7 of 8 grafts (88%) were patent. Histological examinations revealed that there was no thrombus and the neointima formation with a lining of endotherial cells was completed, extending overall length of the grafts. Thus, newly devised hybrid type of connective tissue graft is thought to be usefull for a replacement for arteries with a small caliber.
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In primary cultures of adult rat hepatocytes maintained in a salts/glucose medium, a more than 100-fold increase in ornithine decarboxylase (EC 4.1.1.17) activity was caused by asparagine and glucagon in a synergistic manner. The synthesis rate of ornithine decarboxylase was determined by [35S]methionine incorporation into the enzyme protein, and the amount of ornithine decarboxylase-mRNA was measured by hybridization with a cloned rat liver ornithine decarboxylase-cDNA. The synthesis rate of ornithine decarboxylase was stimulated more than 20-fold by asparagine and glucagon together, but the amount of ornithine decarboxylase-mRNA was increased only 3-4-fold, indicating that translational stimulation was involved in the induction process. Asparagine alone stimulated the synthesis of ornithine decarboxylase without substantial effect on the amount of ornithine decarboxylase-mRNA, whereas glucagon alone increased the amount of ornithine decarboxylase-mRNA about 3-fold without a detectable change in either enzyme activity or enzyme synthesis. Asparagine, at least in part, also suppressed degradation of ornithine decarboxylase.
In mouse mammary epithelial cells in primary culture, mechanical stimulation of a cell induced in other cells within the same colony a short depolarization of less than 15 mV with a duration of 1-8 s and a subsequent, prominent hyperpolarization of 6 mV lasting 10-40 s. Epidermal growth factor induces a spontaneous hyperpolarizing response in cultured mammary cells, and in cells treated with EGF mechanical stimulation produced a greater hyperpolarization, while the amplitude of the depolarizing response was not affected. The amplitude of the mechanically induced hyperpolarization was markedly reduced by quinine and tetraethylammonium, blockers of the Ca2+ -dependent K+ channel. The results suggest that the Ca2+ -dependent K+ channel was involved in the hyperpolarization.
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In female nude mice, epidermal growth factor (EGF) was present at a mean concentration of 42.8 +/- 16.9 (SD) ng/mg wet tissue in the submandibular gland and 0.28 +/- 0.13 ng/ml in the plasma. Sialoadenectomy (removal of the submandibular glands) decreased circulating EGF to undetectable levels (less than 0.1 ng/ml). The possible role of EGF in transplantation and growth of mouse mammary tumors in nude mice was examined by sialoadenectomy, anti-EGF treatment, and EGF replacement therapy. The success rate of transplantation of a spontaneous mouse mammary tumor into nude mice was 55% in normal females and 17% in sialoadenectomized animals. Anti-EGF treatment of sialoadenectomized mice completely abolished the implantation of the tumor. Daily administration of EGF at a dose of 5 micrograms per mouse to both normal and sialoadenectomized animals enhanced the success rate of tumor implantation to more than 80%. Sialoadenectomy and/or anti-EGF treatment of tumor-bearing nude mice reduced the growth of implanted mammary tumors. These results suggest that EGF is important for implantation and growth of spontaneous mouse mammary tumor in female nude mice.
A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was selected for investigation in a number of experimental tumor systems because of its efficacy against P388 leukemia. In the initial studies with P388 leukemia (i.p.-i.p.), KW2152 gave an increase in life span of greater than 80%. The activity was schedule dependent and daily administration was the most effective. KW2152 caused marginal activity against L1210 leukemia, B16 melanoma, and M5076 sarcoma. The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC. In tests against human tumors xenografted s.c. in nude mice, KW2152 significantly inhibited the growth of MX-1 mammary carcinoma with all tumors cured at i.v. doses of 4.4 mg/kg/day and p.o. doses of 26.2 mg/kg/day given daily for 7 days. KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days. Against St-4, KW2152 gave a treated versus control percentage of 27, compared to 52 for cis-diamminedichloroplatinum. Against Co-3, KW2152 was at least as effective as MMC, ADM, cis-diamminedichloroplatinum, and bleomycin, giving a treated versus control percentage of 18 at a dose of 8.6 mg/kg/day given daily for 7 days. KW2152 showed growth inhibitory activity against cultured murine tumors and human cells. The order of in vitro efficacy of KW2152 against murine tumors, P388 leukemia greater than L1210 leukemia, B16 melanoma, correlated with the order of the sensitivity on the i.p.-i.p. systems of these tumors. The 50% inhibitory concentrations against P388 leukemia cells were 5.3 X 10(-6) and 1.1 X 10(-7) M after 1 and 72 h exposure, respectively. KW2152 caused significant inhibition of RNA synthesis after a short time exposure. In P388 leukemia cells exposed for 1 h with KW2152, the 50% inhibitory concentration for RNA synthesis was 10(-5) M, 30-fold less than that for DNA synthesis. White blood cell depression or platelet depression was not significant after administration of the i.v. 10% lethal dose given daily for 7 days. Because of its good activity against human mammary tumor MX-1 and some effectiveness against other gastric and colon carcinomas and its water solubility, a novel antitumor antibiotic, KW2152, is being developed as a Phase I anticancer agent.
Epithelioid hemangioendothelioma in a young female is reported. Her symptoms were right upper quadrant pain and low-grade fever. Laboratory examinations showed an increased number of white blood cells and an elevated erythrocyte sedimentation rate. Plasma factor VIII:C was increased. The hepatic lesions were demonstrated as low-density areas by CT scan, and multiple nodules with central depression on the surface of the liver were identified by peritoneoscopy. The biopsy specimens showed spindle-shaped tumor cells set in the fibrous and myxohyalinous tissue. The tumor cells were positive for factor VIII-related antigen and Weibel-Palade bodies. The patient received transcatheter arterial embolization therapy using Gelfoam and mitomycin C following which the plasma level of factor VIII was normalized and regression of the tumors was observed.
Effects of pirenzepine, a newly developed anticholinergic drug, on exocrine and endocrine pancreatic functions stimulated by cholecystokinin octapeptide and secretin were studied in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine did not have any significant effect on cholecystokinin-induced amylase release but caused an inhibition of amylase secretion initiated by secretin and shifted the dose-response curve for amylase secretion to the right. In the isolated perfused pancreas stimulated with 100 pM cholecystokinin octapeptide, addition of 10 microM pirenzepine before as well as after 20 min of perfusion significantly inhibited pancreatic juice flow but not enzyme output. In contrast, pirenzepine caused an inhibition of secretin-stimulated enzyme secretion, but not pancreatic juice flow. The stimulatory effect of both cholecystokinin octapeptide and secretin on insulin secretion was also inhibited by pirenzepine. The present data indicate that pirenzepine may have an influence on pancreatic exocrine and endocrine function by inhibiting endogenous cholinergic activity of the pancreas when a large dose is given.
Outcome, long-term prognosis, growth activity and rehabilitation after kidney transplantation were studied in 25 pediatric patients transplanted with a kidney graft from one-haplotype identical parent. Excellent patient and graft survival with low incidences of acute rejection or serious complications could be achieved in this population, as compared with the results of adult recipients. Growth retardations in height and weight were observed in these patients before transplantation, and were significantly correlated with the duration of low or no kidney function. In 12 recipients who were transplanted at ages of younger than 15 years and followed up over two years, a dramatic increase in weight appeared within one year after transplantation and a greater increase in height was exhibited in the second and third year than in the first. Increase in height was significantly greater in those children transplanted at ages of younger than 10 years than in those transplanted at ages of older than 11 years. Catch-up growth was observed in one-third of these children. Retrospectively, there was no difference in the doses of prednisolone given between the two groups of patients with, and without catch-up growth, but the incidence of acute rejection was higher in the group without catch-up growth. Currently, 18 recipients have functioning grafts and 16 (88.9 per cent) of them are in full-time school or working. From these results it is concluded that kidney transplantation is the first feasible manoeuvre for those children with chronic renal failure and it should be performed as soon an possible in order to preserve their growth activity.
The concentration of epidermal growth factor in the submandibular gland and plasma of female mice increased substantially during pregnancy. Pregestational sialoadenectomy (removal of the submandibular glands) attenuated the rise in plasma epidermal growth factor during gestation and reduced the number of mice completing a term pregnancy by approximately 50%. Epidermal growth factor replacement therapy given to these mice during pregnancy improved the outcome of complete pregnancy to 86%. The administration of anti-epidermal growth factor antiserum in a daily dose of 50 or 100 microliter to sialoadenectomized pregnant mice increased the percentages of abortion to 67 and 100, respectively. These results suggest that epidermal growth factor may be necessary for the normal course of pregnancy.
The physiological importance of EGF in the development of the mouse mammary gland during pregnancy and in spontaneous mammary tumorigenesis has been documented by a series of experimental results presented herein. In our study, we have taken a variety of experimental approaches including radioimmunoassay of EGF in the submandibular gland and plasma, mammary gland organ/cell culture, EGF receptor assay, sialoadenectomy and treatment with EGF and EGF antibodies to assess the role of EGF in the mammary gland. In particular, studies employing sialoadenectomy and EGF replacement have provided valuable information concerning the function of EGF in the body. These studies are possible in the mouse system because the submandibular gland serves as a major source of circulating EGF and also because purified mouse EGF is available commercially. Our work on the biological, endocrinological, and physiological aspects of EGF in normal and neoplastic growth of the mammary gland should be useful for the study of the regulation of mammary gland growth at the molecular level as well as for clinical investigations of mammary tumors. Finally, our findings of a mammary growth factor in embryonic mesenchymal cultures suggest the possible involvement of paracrine growth factor(s) in mammary cell growth. Further progress in this area is needed for better understanding of the complex process of mammary gland growth and development.
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Twenty-two cases of primary hepatic tumors consisting of 11 hepatocellular carcinomas, 6 cholangiocarcinomas, 3 mixed hepatocellular and cholangiocellular carcinomas, and 2 biliary cystadenocarcinomas together with 8 cases of metastatic adenocarcinoma from various sites were studied by immunoperoxidase technic to demonstrate tissue polypeptide antigen. All of the tumors presumably derived from the epithelial lining of the bile duct, including cholangiocarcinoma, cholangiocarcinomatous portion of the mixed hepatocellular and cholangiocellular carcinoma, and biliary cystadenocarcinoma showed strong positive reaction. The hepatocellular carcinoma and the metastatic adenocarcinoma exhibited negative to weakly positive reactions. These results indicate that TPA can be of use in differentiating bile duct carcinomas from hepatocellular carcinoma and, to a lesser extent, from hepatic metastases of various adenocarcinomas.
Neuromedin-B and neuromedin-C are novel decapeptides which have recently been isolated from porcine spinal cord and canine intestinal muscle, and show striking sequence homology with gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin-B and neuromedin-C on exocrine pancreatic function were examined using isolated rat pancreatic acini. Neuromedin-B and neuromedin-C were able to cause full stimulation of amylase release. The relative efficacy of neuromedin-B and neuromedin-C was the same as that of GRP-27. Neuromedin-C was about twofold more potent, whereas, neuromedin-B was about 10-fold less potent than GRP-27. Both neuromedin-B and neuromedin-C potentiated the stimulation of amylase release caused by vasoactive intestinal peptide, secretin, or forskolin. Potentiation of amylase secretion did not occur with neuromedin-B or neuromedin-C plus cholecystokinin (CCK), carbamylcholine, or Ca2+ ionophore A23187. The effects of neuromedin-B and neuromedin-C on enzyme secretion were inhibited neither by dibutyryl cyclic GMP, nor atropine. The present study suggests that neuromedin-B and neuromedin-C act on different receptors than CCK and cholinergic agents, but appear to activate a common intracellular mechanism.