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Biomedical subjects

C Yasunaga

Publications and source records attributed to C Yasunaga.

At least 55 records · Page 3Linked to original sources
PubMed1992

The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium.

Brequinar sodium (BQR) prevents cell proliferation by virtue of its inhibition of de novo pyrimidine biosynthesis. The immunosuppressive activity of BQR is highly effective in prolonging heart, liver, and kidney allograft survival in the rat. In these experiments, we have tested the ability of BQR to prevent the rejection of concordant cardiac xenografts. LEW inbred rats transplanted with heterotopic hamster hearts were treated orally with brequinar sodium as a single agent. The survival of the cardiac xenografts was significantly prolonged with a variety of treatment regimens. The most effective treatment was the daily oral administration of BQR at 3 mg/kg. At this level, the median graft survival was approximately 25 days. Four animals had hamster heart xenografts that functioned for more than 90 days. The prolonged survival of the xenografts was associated with relatively constant plasma drug levels of approximately 1 to 3 micrograms/ml and a marked suppression of IgM production. At rejection, there was a significant rise in IgM levels compared with those of recipients with stable xenografts. In vitro MLR responses were effectively inhibited by BQR, with an IC50 of 0.08 microgram/ml. The results of these experiments demonstrate that BQR is a new immunosuppressive agent that is highly effective as a single agent in prolonging the survival of hamster-to-rat cardiac xenografts. The prolonged xenograft survival is associated with effective suppression of rat antihamster antibody production, suggesting that brequinar sodium may be an important addition to multidrug immunosuppressive regimes designed to prevent B and T lymphocyte-mediated immune responses.

Animals↗
PubMed1992

Endothelial function in thrombosis and thrombolysis.

The localization of tissue factor (TF) in atherosclerotic plaques of human aortas was immunohistochemically examined using rabbit anti-IgG against recombinant TF, which was expressed in E. coli. TF, the initiator of the extrinsic coagulation pathway, was ubiquitously present in atherosclerotic intima, and was expressed mainly by macrophages, but not by endothelial cells. It has been suggested that some macrophages in atherosclerotic intima co-express both molecules of TF and platelet-derived growth factor-B chain. We have developed a morphometrically quantitative in vitro assay for angiogenesis, using endothelial cultures on collagen gel incorporating plasminogen. With this method, we have obtained findings suggesting that plasminogen and plasminogen activators (PAs), especially urokinase-type PA (uPA) derived from endothelial cells, enhance angiogenic activity, probably by increasing endothelial migration. uPA was immunohistochemically observed to be primarily cell-associated on the focal contract areas, probably via its receptors on endothelial cells. These findings may support the hypothesis that the activation and regulation of the pericellular fibrinolysis system is closely related to angiogenesis.

Animals↗
PubMed1992

Fibrinolysis activity promotes tumor invasiveness of B16 melanoma cell lines through a reconstituted gel matrix.

We studied the role of the fibrinolytic function in the invasiveness of murine melanoma B16F1 and F10 cells using a reconstituted matrix on a filter in a modified Boyden chamber. The main species of plasminogen activators (PAs) synthesized in cell lysates and released into conditioned media by these cells was found to be tissue-type PA (t-PA). The invasiveness of these cell lines was enhanced by adding plasminogen to the gel matrix. This enhancing effect of plasminogen was markedly suppressed by adding anti-t-PA IgG and plasmin inhibitors into the gel matrix, but less affected by anti-urokinase-type PA (u-PA) IgG, offering more evidence to the hypothesis that the activation of the fibrinolytic system by PAs plays an important role in the invasiveness of murine melanoma B16 cell lines, and indicating that t-PA contributed more than u-PA to the invasive potential of these cells into the pericellular matrix.

Animals↗
PubMed1991

Extracellular and cell-associated localizations of plasminogen activators and plasminogen activator inhibitor-1 in cultured endothelium.

The extracellular localizations of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were examined in cultured bovine capillary endothelial cells (BCEs) by an immunofluorescence method using BCEs treated with or without saponin and focal contact preparations. The specific immunofluorescence of cell surface uPA showed a patchy or strand-like distribution and was colocalized with vinculin strands indicating that uPA secreted from BCEs was mainly deposited at the cell surface of focal contacts. BCEs at a subconfluent density showed a higher intensity of specific immunofluorescence for uPA than when they were at a confluent density. tPA was observed over the dorsal surface of cultured BCEs and accentuated at their margins, suggesting that tPA was diffusely distributed on the luminal surface of BCEs in vivo. PAI-1 was distributed in the extracellular matrix under cultured BCEs. These findings suggest that uPA and PAI-1 are located under BCEs participating in the regulation of proteolytic activities provoked by plasminogen-PAs-plasmin system in vivo. The localization of tPA appears to be consistent with its function, which is to maintain the fluidity of the blood and to initiate thrombolysis in vivo.

Actins↗
PubMed1991

Successful surgical treatment of hepatocellular carcinoma invading into biliary tree.

A 41-year-old woman was admitted to hospital with obstructive jaundice. Computed tomography showed a large mass in the right hepatic lobe and marked dilatation of the biliary tree in the left lateral segment of the liver. Angiography showed evidence of neovascularity. Percutaneous transhepatic cholangiography revealed complete obstruction of the common bile duct just below the bifurcation. The serum level of alpha-fetoprotein on admission was 1,080,000 ng/ml. These findings suggested to us a primary hepatocellular carcinoma invading the intrahepatic bile duct. Extended right lobectomy and hepaticojejunostomy for bile drainage was carried out. The patient is doing well 3 years after surgery. Hepatocellular carcinoma (HCC) invading to the portal vein is not so rare, but invasion into the bile duct is much less common. In 1947, Mallory described a single case of HCC invading the gallbladder and obstructing extrahepatic bile ducts. In 1975, Lin termed this HCC "Icteric type hepatoma". The incidence of such HCC in Japan was reported to be 1.9-9%. Obstructive jaundice is a clinical manifestation of the terminal stage in HCC. We describe here our treatment of a woman with HCC invading the common bile duct. Right extended lobectomy and reconstruction of hepaticojejunostomy were effective.

Adult↗
PubMed1990

Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis.

To search for possible untoward effects of surgical manipulation of a malignant tumor, a series of experiments was carried out using VX2 carcinoma of rabbits. Fourteen days after inoculation of VX2 carcinoma into the liver, the rabbits were separated into two groups: Group I, manual manipulation during relaparotomy; and Group II, relaparotomy alone without manual manipulation of the tumor. After these procedures, the tumor was surgically removed and histologic examinations were made. The incidence of vascular permeation of liver tumor cells into the hepatic vein was significantly higher in Group I (P less than 0.01). On the 14th day after resection of the tumor, the number of metastatic nodules in the lungs was significantly increased in Group I (P less than 0.01). Survival time of rabbits after resection of tumor was significantly shorter in Group I (P less than 0.01). These results are taken to mean that manual manipulation of a tumor may well enhance metastasis.

Animals↗
PubMed1990

Sustained arterial injury and progression of atherosclerosis.

In this paper the following findings were described: 1) Murine arteriosclerosis induced by immune challenge was ultrastructurally characterized by intimal monocyte-macrophage recruitment and minor endothelial alterations; 2) Atherosclerotic lesions of human coronary arteries exhibited frequently segmental or patchy neovascularization, probably representing a response to intimal injury as an example of repair process. Newly formed blood vessels in the intima were derived from both adventitial and luminal endothelial growth; 3) Angiogenesis in vitro was related to the activation of fibrinolytic system especially via the autocrine production of u-PA from endothelial cells, and this process was modulated by cytokines and TGF beta. These findings add more evidence for the hypothesis that the chronic inflammation-repair process plays an essential role in the initiation and progression of atherosclerosis.

Animals↗
PubMed1990

[Hypoxemia of liver cirrhosis--an autopsy case study].

41 year-old male with liver cirrhosis accompanying severe hypoxemia was presented. Shortly after the diagnosis of liver cirrhosis, he suffered from exertional dyspnea and cyanosis. Though home oxygen therapy had been prescribed for 2 years, hypoxemia gradually progressed accompanied by persistent cough, mucous sputa and intermittent fever. The chest X-ray revealed bilateral interstitial shadow particularly localized in lower lung fields. The arteriovenous shunt ratio was shown to be 24% by oxygen method. Perfusion lung scan using 99mTc-labeled MAA revealed perfusion defects in bilateral lung fields and radionuclide uptake was strongly demonstrated in the kidneys. These clinical data suggested that severe hypoxemia was probably due to multiple arteriovenous shunt. With further progression of hypoxemia for 4 months, he died of hepatic failure and pulmonary infection. Autopsy showed Miyake's type B cirrhosis. Multiple pleural and subpleural arteriolar nevi were demonstrated grossly and microscopically. There were no arteriovenous malformations demonstrated after injection of barium-gelatin solution into the pulmonary artery. Histologically, irregularly dilated vessels were found in the lung parenchyma beneath the pleura and filled with blood and injection material. These clinical and pathological findings provided evidence that the mechanism of arterial desaturation was pulmonary arteriovenous shunting due to liver cirrhosis.

Adult↗
PubMed1989

Myelolipoma of the liver. A case report.

We treated a 56 year-old woman with myelolipoma originating from the liver. Hepatic imagings, including ultrasound and computed tomography (CT), demonstrated characteristic features of a fat-enriched tumor. Since this tumor was symptomatic, hepatic resection was done, with good results. The histology revealed tissues mainly composed of fat and bone marrow elements. The diagnosis was hepatic myelolipoma.

Female↗
PubMed1989

Heterogenous expression of endothelial cell markers in infantile hemangioendothelioma. Immunohistochemical study of two solitary cases and one multiple one.

Three cases of infantile hemangioendothelioma were immunohistochemically studied with the use of antibodies against von Willebrand factor (vWF), Ulex europaeus I lectin (UEA I), vimentin, thrombomodulin (TM), and actin, as endothelial cell (EC) markers. Because of a broad variety of histologic features, the growth pattern of the tumor cells was subclassified into the following four subtypes: capillary, sinusoidal, cavernous, and myxomatous parts. The solitary tumor from patients 1 and 2 was composed of these four components, but the multiple tumor in the patient 3 consisted of capillary and sinusoidal parts. Immunohistochemically, vWF and vimentin were dominantly expressed in the ECs of the cavernous and myxomatous parts. UEA I had strongly positive results in all histologic types, except the myxomatous part. Expression of vWF and vimentin in neoplastic EC suggests that functional differentiation of the tumor tissue occurs in the myxomatous and cavernous parts and may be related to the spontaneous regression of the infantile hemangioendothelioma.

Actins↗
PubMed1989

Morphologic and functional changes in the remnant liver following resection for cirrhosis or chronic hepatitis.

We studied the late effects of hepatic resection on the remnant liver in patients with cirrhosis or chronic hepatitis. Data were obtained from 15 patients who underwent primary resection for hepatocellular carcinoma, followed by a second operation for recurrence. The mean interval between primary and second operations was 21.5 months (range, 7-39 months). When we compared the histologic features of the resected specimens obtained at the two operations, no apparent changes were noted in 14 of the 15 patients who had had an uneventful perioperative course. However, in the remaining patient, who had experienced postoperative intraperitoneal bleeding, the histologic diagnosis was changed from chronic inactive hepatitis to cirrhosis 7 months later. With regard to serum chemistry, there was no statistically significant difference in values between the two operations. We conclude that hepatic resection does not derange morphologic and functional status of the remnant liver and that advancement of chronic liver disease may occur in case of perioperative complications leading to liver cell damage.

Adult↗
PubMed1989

A role of fibrinolytic activity in angiogenesis. Quantitative assay using in vitro method.

The functional role of the fibrinolytic system in capillary growth was investigated using bovine capillary endothelial cells (BCEs) cultured on a Type I collagen gel matrix, into which the cells migrated to form capillary-like tubular structures. The length of the tubes formed were measured morphometrically using an image analyzer in the absence and presence of fibrinolytic proteases, namely plasminogen, plasminogen activators (PAs) and PA inhibitor (PAI). The addition of plasminogen (25 micrograms/ml) to the gel matrix significantly increased the length of BCE tubes found on the 9th day of culture (p less than 0.01), with a dose-dependent tendency. The simultaneous addition of a basic fibroblast growth factor (bFGF, 10 ng/ml) enhanced this tube formation as early as the 3rd day of culture (p less than 0.01). Cultured BCEs secreted both tissue-type and urokinase-type PAs (tPA and uPA) and PAI-1 into the culture medium, and the secretion of both PAs was enhanced by the addition of bFGF. However, the secreted tPA was composed mostly of an inactive form of tPA.PAI-1 complex, and the PA activity was derived mostly from uPA. Inhibitors of plasmin suppressed the enhancing effect of plasminogen on angiogenesis. In addition, anti-uPA IgG markedly inhibited the enhancing effect of plasminogen on the 4th and 7th days of culture (p less than 0.01), whereas anti-tPA IgG showed an inhibitory tendency only on the 4th day of culture (p less than 0.05). These findings indicate that the plasminogen-PAs system, especially uPA synthesized and secreted by BCEs, plays an important role in regulating angiogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗