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Biomedical subjects

M Mito

Publications and source records attributed to M Mito.

17 recordsLinked to original sources

[A study of hepatocellular transplantation].

Clinical liver transplantation has been done for patients with irreversible hepatic diseases, but the shortage of donor livers from heart beating cadavers has become very serious. Hepatocyte transplantation requires no vascular anastomosis and donor hepatocytes are easy to obtain from living donors and easy to preserve for a long time. In the animal experiments, transplanted hepatocytes survived in the spleen for long periods of time, and cytochemical investigation revealed differentiated liver functions, such as gluconeogenesis, albumin synthesis, bilirubin conjugation. Intrasplenic transplantation of hepatocytes relieved congenital disorders of liver enzymes in rats. Moreover, transplanted hepatocytes re-composed normal cord structures with hepatic sinusoids in the spleen of rats. Hepatocytes could also be isolated from human cirrhotic livers by a multi-perfusion method, and the viability was almost 80%. After the success in transplantation of human hepatocytes into the spleen of athymic mice, 6 patients have undergone clinical trial of intrasplenic hepatocyte transplantation without any complications. In the future, the progress of gene manipulation techniques may make possible rapid growth of transplanted hepatocytes. Intrasplenic transplantation of isolated hepatocytes provides an in-vivo experimental model to study cellular growth and functions in detail.

Animals

Stress platelets in normal individuals and patients with idiopathic thrombocytopenic purpura.

To test the hypothesis that stress platelets (SPs) described by Tong et al. in rats may be a parameter of young platelets in humans, we examined and characterized SPs in normal individuals and in patients with idiopathic thrombocytopenic purpura (ITP). Our results indicated that SPs comprise about 1.2% of the circulating platelets in normal individuals and 2.6% in ITP patients. The configuration of SPs as well as of various irregular forms of circulating platelets was found to be supported by synergism of both the platelet microfilaments and microtubules. SPs showed some segmentation, the degree of which was similar in normal individuals and ITP patients, and they underwent further segmentation during in vitro incubation, mainly promoted by microtubules, so that they sometimes appeared like discoid platelets in a chain. These observations suggest a new mode of production of discoid platelets in the circulation. Thus, identification and enumeration of SPs may be useful for evaluating thrombocytopoiesis in humans.

Adult

[A study of progression in hepatocarcinogenesis using cell transplantation system].

It is important to distinguish a precancerous lesion and hepatocellular carcinoma (HCC) with diploidy or aneuploidy nuclear DNA pattern, not only in clinical cases but also in experimental carcinogenesis models. Using liver perfusion technique, we detected early HCC from persistent hyperplastic nodules (HN) which were induced in Wistar rats by intermittent 5-6 months administration of 2-acetylaminofluorene. This investigation was undertaken to assess both promotive and progressive effects of liver regeneration following partial hepatectomy (PH). Results are as follows: 1) Isolated hepatocytes of precancerous HN, which were transplanted into the spleen, didn't develop to HCC by 2 months after 70% PH of host liver. 2) Diced tissues of HCC, which were transplanted into the liver via portal vein, grew many metastasis in 10/10 by 7 weeks after PH, while 5/19 in control. 3) Nuclear DNA patterns of early HN-late HCC in rat liver were diploidy at the rate of more than 90% each. But it changed to aneuploidy, when inoculation of HCC for one month was repeated 7 times in the spleen.

Animals

[Hemostatic control in platelet dysfunction and abnormality by DDAVP].

DDAVP infusion shortens the bleeding time in patients with some types of platelet dysfunction and may be useful for hemostatic control. In order to clarify the mechanism of DDAVP to correct or bypass the release defect, we examined the effect in 17 patients with prolonged bleeding time, i.e., 11 with various kinds of platelet dysfunction, 4 with idiopathic thrombocytopenic purpura (ITP), 1 with chronic myelocytic leukemia (CML), and in an aspirin-ingested volunteer. DDAVP shortened the bleeding time in 9 patients with platelet dysfunctions, one with ITP, and the one aspirin ingested volunteer. No improvement was found in the aggregability and the retention rates, and no signs of activation occurred in the platelet shape. The RCof was elevated in all of the patients after the infusion. Our data suggests that DDAVP improves the hemostasis through primary aggregation and release of dense bodies, and not directly through an increase of RCof.

Bleeding Time

Morphology and function of isolated hepatocytes transplanted into rat spleen.

Hepatocytes isolated by the collagenase digestive method were transplanted into the spleens of syngeneic rats. Morphology and function of the hepatocytes in the spleen were investigated for 12 to 17 months after transplantation. The transplanted hepatocytes proliferated and reconfigured in the spleen without direct perfusion of portal venous blood and with the presence of an intact host liver. Fourteen to 17 months after transplantation, the hepatocytes which had formed a demarcated nodule occupied approximately 40% of the area of the splenic parenchyma without undifferentiation on microscopic examination. However, the weight of the hepatized spleen did not increase beyond the weight of a normal spleen and the weight of the host liver that had normal morphology also did not differ from a normal liver. Light and electron microscopic studies demonstrated differentiated cord structure and normal architecture for each heptocyte. Furthermore, the hepatized spleen synthesized albumin and glycogen as demonstrated by immunofluorescence and histochemical studies. Ammonia tolerance and indocyanine green clearance tests revealed functioning hepatocytes in the spleen proper. These results indicate that our experimental model lends itself well to investigations in cell growth mechanism and that hepatocellular transplantation has potential clinical application to compensate for impaired hepatic function.

Animals

Hepatocellular transplantation --morphological study on hepatocytes transplanted into rat spleen--.

Hepatocellular transplantation into the spleen was investigated as a new attempt in utilizing isolated hepatocytes to compensate for impaired liver function. Present study was undertaken to evaluate morphological and histochemical alterations up to 6 weeks following transplantation in hepatocytes transplanted into the splenic parenchyma. Light microscopic studies revealed viable hepatocellular islets in the splenic parenchyma up to 6 weeks, although minimal cytoplasmic changes were observed. Electron microscopic studies demonstrated moderate changes in organelles, which developed gradually as the time after transplantation proceeded. Distortion and fragmentation of the membranes around the cytoplasm and organelles were not recognized. Moreover, newly formed bile canaliculi and tight junctions which indicate reconstruction of hepatic plates were observed between adjacent cell membranes, and enzyme activities were detected by cytochemical determination of glucose-6-phosphatase in the hepatocytes even 6 weeks after transplantation. The transplanted hepatocytes preserved their characteristic enzyme and fine structures as hepatocytes up to 6 weeks. Our present study based on the persistence of cellular viability suggests that inoculated hepatocytes do maintain their hepatocellular functions after transplantation.

Animals