Biomedical subjects

Y Kawarada

Publications and source records attributed to Y Kawarada.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Three patients with terminal gastric cancer who achieved good QOL through home hospice care].

In our G.I. department, patients with inoperable or recurrent cancer of the digestive organs are treated by chemotherapy and/or radiation therapy. Since the efficacy of these modalities has been poor in our hospital as in others, we have attempted to maintain good quality of life (QOL) in these patients by offering hospice care in the hospital or at home. Home care is provided to those who choose not to have chemotherapy or do not respond well to it. These patients live within 20 km of the hospital and are cared for at home by a visiting nurse or through visits to our outpatient clinic. However, in the latter patients who do not have access to good public transportation, clinic visits are a hardship to both patients and their families even though they do well with home hospice care. Home hospice care is also difficult for those who do not have adequate family support available. We report here three patients with terminal gastric cancer who appeared to experience good QOL through home hospice care.

Adult↗

PubMed1997

Expression of fibronectin and tenascin-C mRNA by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas.

To understand the mechanisms of tissue remodeling during cancer progression, it is important to know the type of cells that actively express extracellular matrix (ECM) proteins. Twenty-nine adenocarcinomas, 5 adenomas and non-neoplastic mucosa samples were therefore investigated to determine their fibronectin (FN) and tenascin-C (TN-C) expression using in situ hybridization (ISH) and immunohistochemical staining. In the non-neoplastic mucosa, no mRNA signals were found. Two of the adenomas demonstrated positive signals in peri-cryptal cells and the vessels. In the cancers, TN-C and FN mRNAs were found in 86% and 96% of the total cases, respectively. The signals were mainly detected in myofibroblasts, labeled with alpha-smooth muscle actin, in the cancer stroma. TN-C mRNA-positive cells were often observed in localized areas, such as in cancer stroma associated with invading edges and/or in host tissues surrounding the invading cancer front, but rarely in the center of the tumors. FN mRNA-positive cells were more widely spread throughout the cancer stroma, although they were also frequently observed at invading edges. Vascular cells in cancer tissues were also labeled. In 10 specimens, cancer cells themselves expressed FN and/or TN-C mRNA. Comparison with histo-pathological findings revealed positive relationships between the degree of mRNA expression of FN and TN-C and the depth of invasion as well as the frequency of metastasis to lymph nodes. The expression of FN and TN-C by myofibroblasts, vascular cells and cancer cells could be important for the remodeling process of neoplastic tissues during cancer development and progression.

Adenocarcinoma↗

PubMed1997

Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.

Copper is an essential trace element in prokaryotes and eukaryotes and is strictly regulated by biological mechanisms. Menkes and Wilson diseases are human disorders that arise from disruption of the normal process of copper export from the cytosol to the extracellular environment. Recently a gene for Wilson disease (WD)(also named the ATP7B gene) was cloned. This gene encodes a copper transporter of the P-type ATPase. We prepared monoclonal and polyclonal anti-(WD protein) antibodies and characterized the full-length WD protein as well as a shorter form that is produced by alternative splicing in the human brain. We found that the WD protein is localized mainly in the Golgi apparatus, whereas the shorter form is present in the cytosol. These results suggest that the alternative WD proteins act as key regulators of copper metabolism, perhaps by performing distinct roles in the intracellular transport and export of copper.

Adenosine Triphosphatases↗

PubMed1997

The effect of silver administration on the biosynthesis and the molecular properties of rat ceruloplasmin.

To examine the cause of the altered ceruloplasmin (Cp) metabolism by silver administration, we analysed the properties of serum Cp by gel filtration chromatography, affinity chromatography and polyacrylamide gel electrophoresis. Metal contents in the Cp fraction from the silver-treated group were estimated as approximately 0.8 atom of silver and 4.2 atoms of copper per molecule, and as 5.9 atoms of copper for the control group. These findings confirm that holo-Cp from rat serum administered with silver nitrate exists as a silver-bound inactive form, suggesting that silver displaces one of Cp's copper atoms associating with oxidase activity. Matured holo-Cp also appeared in the Golgi in both groups, however, the amounts of enzymatically active holo-Cp showed a decrease after silver administration, while the apo-Cp level was hardly changed. These findings suggest that silver-bound holo-Cp is accomplished at Golgi.

Animals↗

PubMed1997

Regeneration of the un-embolized liver parenchyma following portal vein embolization.

BACKGROUND/AIMS: Portal vein embolization (PVE) induces atrophy of the embolized hepatic parenchyma and hypertrophy of the un-embolized liver. It is important to predict hypertrophy of un-embolized liver following PVE to decide a subsequent tactics in patients with liver tumors. The hypertrophy following PVE was evaluated in reference to embolized liver volume and a preceding use of transcatheter hepatic arterial chemoembolization (HACE) in this study. METHODS: Thirty patients with liver tumors were studied. PVE was performed transhepatically. Ethanol (15-65 ml) was injected into portal veins, which perfused the liver segment bearing the tumor until occlusion. Embolization was performed at subsegmental portal branches in five patients, segmental branches in 11 patients and right portal veins in 14 patients. Twenty-three patients with underlying chronic liver disease and hepatocellular carcinoma (HCC) underwent PVE 2-6 weeks after HACE. The remaining seven patients without underlying chronic liver disease had bile duct cancer (6) or liver metastasis (1), and underwent PVE alone. Segmental volume in the liver was measured with computed tomography before and 4 weeks after PVE. RESULTS: The degree of hypertrophy showed a significant correlation with embolized liver volume (r=0.685, p<0.001). Increase in un-embolized liver volume was 2.4+/-5.8% with subsegmental embolization (NS), 15.2+/-6.4% with segmental embolization (p<0.01) and 46.5+/-18.8% with right PVE (p<0.001). In 14 patients with right PVE, degree of hypertrophy in seven patients with HACE was greater than that in seven patients without HACE (56.7+/-21.6% vs 36.4+/-7.4%; p<0.03). CONCLUSIONS: Hypertrophy of the un-embolized liver parenchyma following PVE was correlated with embolized liver volume and was augmented with combined use of HACE.

Adult↗

PubMed1997

Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver.

Oval cells function as compensatory cells in severe liver injury and are thought to be equivalent to liver stem/progenitor cells. We isolated oval cells from the liver of Long-Evans Cinnamon (LEC) rats by isopyknic centrifugation in a Percoll gradient. The cells were gamma-glutamyl transpeptidase (GGTP)-positive, alpha-fetoprotein-positive, and cytokeratin (CK) 18- and CK 19-positive, but albumin-negative in the cells. When oval cells were transplanted to the liver, they were transformed into hepatocytes. To evaluate albumin biosynthesis, we transplanted oval cells into the liver of Nagase analbuminemic and LEC double mutant rats. The albumin level in the serum of transplanted rats was increased and maintained for up to 10 weeks. These results indicated that the oval cells isolated from LEC rats can differentiate into hepatocytes in vivo.

Albumins↗

PubMed1997

Effect of zinc administration on pancreatic regeneration after 80% pancreatectomy.

We studied the effect of oral zinc administration on functional and morphological regeneration of the remnant pancreas after 80% pancreatectomy in dogs. After 80% pancreatectomy, both endo- and exocrine function (assessed by the sum of plasma immunoreactive insulin on the intravenous glucose tolerance test and amylase output on the cerulein-secretin test) markedly deteriorated, the pancreatic regeneration rate (change in weight of the remnant pancreas between the time of surgery and autopsy) was very poor, and the zinc concentration in pancreatic tissue decreased in dogs fed the standard diet. In dogs fed the high-zinc diet, pancreatic function and regeneration rate were significantly improved, and the zinc concentration in pancreatic tissue was maintained. Early cell proliferation (assessed by ornithine decarboxylase activity. DNA synthesis, and proliferating cell nuclear antigen labeling index in the remnant pancreas) after pancreatectomy was significantly enhanced in the high-zinc diet group compared to the standard diet group. Correlation analyses between parameters of early cell proliferation and zinc concentration in pancreatic tissue yielded significant positive correlations, and the zinc concentration in pancreatic tissue was significantly correlated with both endo- and exocrine function and the pancreatic regeneration rate. These results suggest that a high-zinc diet after major pancreatectomy is effective in maintaining the zinc concentration in pancreatic tissue, which not only enhance early cell proliferation in the remnant pancreas but improves pancreatic endo- and exocrine function in the late period, promoting pancreatic regeneration.

Animals↗

PubMed1997

Inhibitory effects of the antiangiogenic agent TNP-470 on establishment and growth of hematogenous metastasis of human pancreatic carcinoma in SCID beige mice in vivo.

Effects on the liver of the antiangiogenesis agent O-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on hematogenous metastasis of a human pancreatic carcinoma cell line were examined. One million PCI-43 cells, a human pancreas carcinoma cell line, were injected into the spleen of SCID beige mice, then TNP-470 at 30 mg/kg was administered subcutaneously every other day. The mice were killed 6 or 10 weeks thereafter and metastatic nodules in the liver were counted and measured microscopically. Metastases were inhibited and an approximately 10% loss of weight was evident in the TNP-470-administered mice. There was no suppression in maximal size of metastatic colonies in mice given the agent for 6 weeks, while inhibition was apparent in mice given the drug for 10 weeks. Suppression of proliferation and an increase in apoptosis were evident in metastatic nodules in the TNP-470-administered groups, following stainings for proliferative cell nuclear antigen and terminal deoxytransferase-mediated dUTP-biotin nick end-labeling, respectively. TNP-470 inhibited the proliferation of human umbilical vein endothelial cells but not PCI-43 in vitro. TNP-470 did not suppress production of vascular endothelial growth factor by PCI-43 cells. Neovascularization in vivo induced by PCI-43 cells was suppressed in the TNP-470-administered mice, using a diffusion chamber placed in subcutaneous tissues of SCID beige mice. These observations suggest that inhibition of angiogenesis is effective in suppressing establishment and subsequent growth of hematogenous micrometastases of pancreatic adenocarcinoma to the liver.

Animals↗

PubMed1997

Clinicopathologic factors influencing the long-term prognosis following hepatic resection for large hepatocellular carcinoma more than 10 cm in diameter.

We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%) cases of large HCC. These 20 cases were divided into group 1 (curative resection, n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic features and long-term survival of the cases were evaluated. In groups 1 and 2, portal vein invasion (Vp+) was noted in 44.4% and 63.3%, intrahepatic metastasis (IM+) in 77.8% and 100%, absence of a fibrous capsule (Fc-) in 55.6% and 63.6%, and stage III or IV in 77.8% and 100%, respectively. The DNA ploidy pattern was aneuploid in 44.4% of group 1 and 100% of group 2. In group 1, the 1-, 3-, and 5-year cumulative survival rates were 75%, 62.5%, and 62.5%, respectively (the longest survivor is alive after 11 years 1 month). Five cases survived more than 3 years in group 1, and all were Vp(-) and nonaneuploid. On the other hand, in group 2, the 1-year survival rate was only 33.3%; none survived more than 2 years. These results suggest that even patients with large HCC have a favorable long-term prognosis if their clinicopathologic factors are Vp(-) and nonaneuploid, and if curative resection can be performed.

Adult↗

PubMed1997

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗

PubMed1997

[Intrahepatic bile duct carcinoma (cholangiocarcinoma)].

There is no high risk group for cholangiocarcinoma as there is for hepatocellular carcinoma, and it has a poor prognosis because many cases are diagnosed after it has become advanced. To date, there is no effective chemotherapy or radiation therapy for cholangiocarcinoma, and extended hepatectomy is the only effective treatment. In Japan, regional lymph node dissection and extended hepatectomy have been performed aiming at curative resection, but the 5-year survival in Japan is still low, only 26.1%. The Committee on the Japanese General Rules for the Clinical and Pathological Study of Primary Liver Cancer has divided macroscopic type into 3 patterns: mass-forming type, periductal infiltrating type, and intraductal growth type, to access prognosis on a common basis. According to these groups, our patients with the intraductal growth type had a good outcome, but patients with the mass-forming type and periductal infiltrating type had a poor outcome. Many papers have reported that the presence of lymph node metastasis makes the prognosis poor. Among our cases, the 5-year survival rate for all patients who underwent hepatectomy was 26.1% and the rate for patients positive for lymph node metastasis was 10.8%, as opposed to 45.1% for patients negative for lymph node metastasis. We examined the outcome according to histological type and found that based on the histological findings, the prognosis was increasingly poor in the following order: papillary adenocarcinoma, macrotubular carcinoma, microtubular carcinoma. To achieve curative treatment in the future it will be important to clearly define the extent of hepatectomy and determine the extent of lymph node dissection required, and clearly identify other prognostic factors.

Bile Duct Neoplasms↗

PubMed1997

[Preoperative estimation of liver injury and operative risk].

We report on preoperative estimation of operative risk, principally rating liver injury in chronic liver disease, c.g., chronic hepatitis and cirrhosis, for liver resection and general surgery. Regarding general surgery, elective and standard operation are possible in Child A and operations with measures to lessen intraoperative blood loss and lymphadenectomy in Child B, but in Child C, surgery is limited to emergency palliative operations, and conservative treatment methods must chosen. In liver resection and major surgery it is important to estimate extent of liver resection and operative risk, primarily by R15 and KICG, and make an overall judgment based on fibronectin, hyaluronic acid, sinusoidal endothelial cell function measured by thrombomodulin, sigma IRI in the 75g OGTT, Fischer's ratio and other indices of lipid metabolism. Generally, surgery limits are: KICG, </ = 0.04/min; serum bilirubin, </- 3.0 mg/dl; prothrombin time, < 50%; R15, =/> 40%. Conventional indices of hepatic reserve should be reviewed. Indices recently attracting interest in liver resection cases are quantitative 99mTC-galactosyl human serum albumin scintigraphy using liver cell surface asialoglycoprotein receptor, and functional hepatic resection rate using 99mTC-GSA SPECT images, which is important in estimating liver regeneration after percutaneous trashepatic portal embolization.

Chronic Disease↗

PubMed1996

Platelet-derived growth factor B-chain homodimer suppressing a convulsion of epilepsy model mouse El.

El mouse is a mutant which has epileptic convulsions after tossing-up stimulations and has a hippocampal dysfunction. Platelet-derived growth factor B-chain homodimer has been reported to be a trophic factor of hippocampal neurons. We found that a recombinant PDGF-BB suppressed the convulsions of El mice in a dose-dependent manner. Furthermore, thrombin-treated mice manifested no convulsions, but thrombin receptor activating peptide-treated ones had convulsions. These findings suggest that an abnormality in PDGF-BB release may make El mice susceptible to tonic-clonic convulsions.

Animals↗

PubMed1996

Overexpression of different members of the type 1 growth factor receptor family and their association with cell proliferation in periampullary carcinoma.

The expression of epidermal growth factor receptor (EGFR), c-erbB-2, and c-erbB-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type I growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c-erbB-3 was significantly higher than with overexpression of c-erbB-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c-erbB-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c-erbB-3 in pancreatic head carcinoma and overexpression of c-erbB-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c-erb-3 in pancreatic head carcinoma, c-erb-2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type I growth factor receptor family are overexpressed in different carcinomas of the periampullary region.

Adenocarcinoma↗

PubMed1996

Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase.

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

Animals↗

PubMed1996

Combined analysis of expression of c-erbB-2, Ki-67 antigen, and tenascin provides a better prognostic indicator of carcinoma of the papilla of Vater.

Expression of the molecular biological factors (MBFs) c-erbB-2, Ki-67 antigen, and tenascin (TN) was assessed immunohistochemically in specimens from patients who had undergone surgery for carcinoma of the papilla of Vater. The MBFs were then analyzed by histological factors (v, d, panc, n, Stage), which have been demonstrated to be outcome predictors, and by patient outcome. None of the MBFs showed any significant correlation with the histological factors. There were significant differences (p < 0.05) in the expression of c-erbB-2, Ki-67 antigen, and TN between patients who survived >5 years and those who survived <5 years. The patients with greater expression of c-erbB-2, Ki-67 antigen, and TN had a poor prognosis, whereas those with less expression had a good prognosis. They were therefore considered independent predictors of outcome for carcinoma of the papilla of Vater. Combined analysis of both histological factors and MBFs was also performed, with the result that the combined analysis of MBFs yielded a better prediction of outcome in carcinoma of the papilla of Vater than analysis of either one histological factor or MBF.

Adult↗

PubMed1996

Therapeutic effects of continuous intraarterial antibiotic infusion in preventing pancreatic infection in experimental acute necrotizing pancreatitis.

To determine the efficacy of antibiotics in the prevention of pancreatic infection and the process of aggravation after induction of acute pancreatitis, antibiotic was administrated intravenously or intraarterially, starting 6 h after acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. Flomoxef, recognized as an antibiotic able to penetrate well into pancreas tissue, was selected for the present study. Animals were divided into three groups: no antibiotic given (Group A), antibiotic given intravenously as a bolus injection of 25 mg/kg every 6 h (Group B), and antibiotic infused continuously into the celiac trunk (4 mg/kg/h) (Group C). Compared with Group A, continuous intraarterial infusion of antibiotic (Group C) significantly improved the survival rate and decreased the serum levels of phospholipase A2(PLA2) activity and endotoxin. Furthermore, it completely prevented the occurrence of pancreatic infection, not only ameliorating the severity of pancreatic necrosis but also reducing the activity levels of amidase, trypsin-like enzyme, and PLA2 in pancreas tissue. Group B showed little beneficial effect. Antibiotic concentration in peripheral blood and pancreas tissue was significantly higher in Group C than in Group B. These results suggest that continuous arterial infusion of antibiotics into the feeding artery of the pancreas is an effective modality for preventing pancreatic infection and aggravation of severe acute pancreatitis.

Amidohydrolases↗

PubMed1996

Pathophysiological changes caused by occlusion of blood flow into the liver during hepatectomy in dogs with obstructive jaundice: effects of intestinal congestion.

Obstructive jaundice was produced in adult mongrel dogs by cholecystectomy and ligation of the common bile duct. Two weeks later 40% hepatectomy was performed during 10 min occlusion of hepatic inflow (group I). Liver tissue lipid peroxide levels increased significantly and superoxide dismutase activity decreased. The portal endotoxin (Et) concentration increased markedly after reperfusion and peripheral blood Et and serum beta-N-acetyl hexosaminidase levels increased markedly, beginning 3 h after reperfusion. The phagocytic index increased transiently after reperfusion, but decreased markedly thereafter. Hepatocyte degeneration and necrosis became severe, intestinal villi were damaged and the 1 week survival rate was 23.1%; deaths were due to liver failure. These changes were prevented by construction of a portosystemic bypass and a 1 week survival rate of 70% (group II) was achieved. When the ischaemic time was prolonged to 20 min with the portosystemic bypass (group III), the pathological changes resembled those seen in group I, although no changes were observed in portal or peripheral blood Et levels. These findings suggest that major hepatectomy in the presence of severe jaundice should be carefully performed so that the ischaemic time is minimized during portosystemic bypass in an attempt not only to prevent production of Et in portal venous blood due to intestinal congestion, but also to reduce ischaemia-reperfusion injury.

Animals↗