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Biomedical subjects

M Unno

Publications and source records attributed to M Unno.

80 records · Page 5Linked to original sources

Kupffer cell-mediated inhibition of liver regeneration after combined hepatectomy and pancreatectomy.

Recently, simultaneous hepatectomy and pancreatoduodenectomy has been performed for the treatment of some biliary tract cancers in Japan. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduction in the rate of liver regeneration after 70% hepatectomy (Hx) alone or in combination with 70% pancreatectomy (HPx). Male Sprague-Dawley rats underwent hepatectomy or simultaneous hepatectomy and pancreatectomy. The ratio of liver weight to body weight, the labeling index of hepatocytes in vivo, and DNA synthesis of the hepatocytes and/or Kupffer cells in primary culture were analyzed. The ratio of liver weight to body weight and the labeling index in HPx rat were found to be significantly lower than those values in Hx rats. There were no significant differences in plasma alanine aminotransferase levels between the two groups. The inhibitory effect on DNA synthesis was observed with coculture of hepatocytes and Kupffer cells when the portal plasma obtained 1 hour after operation was added. We further observed that the conditioned medium of Kupffer cells stimulated by the addition of the portal plasma that was obtained 1 hour after HPx inhibited DNA synthesis of hepatocytes. This effect was abolished after incubation at 56 degrees C for 30 minutes. These results strongly suggest the existence of a growth inhibitory factor in portal plasma after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells and would appear to act on hepatocytes in a paracrine manner.

Animals↗

Expression of organic anion transporting polypeptide E (OATP-E) in human placenta.

PURPOSE: To examine the expression of multifunctional Na(+)-independent organic anion transporting polypeptide, termed OATP-E, involved in the transport of thyroid hormone in human placenta. METHODS: Western blot analysis was performed using a specific antibody against OATP-E in human placenta to confirm the expression of OATP-E at the protein level. Immunohistochemistry was also performed using the specific antibody against OATP-E on frozen sections of human placenta. RESULTS: By Western blot analysis, a single band for OATP-E was observed in human placenta. Immunohistochemistry revealed that OATP-E was predominantly expressed at the apical surface of the syncytiotrophoblasts in placenta. CONCLUSION: These results reveal that OATP-E is expressed in human placenta, suggesting a functional role for the transplacental transfer of thyroid hormone.

Adult↗

A case of subarachnoid hemorrhage with electrocardiographic and echocardiographic changes simulating transmural myocardial infarction.

A patient with subarachnoid hemorrhage who exhibited changes suggestive of myocardial infarction by electro- and echocardiography and underwent coronary angiography is reported. Echocardiography demonstrated marked hypokinesis in the left ventricular anterior wall to the septum. Since the possibility of concomitant myocardial infarction could not be excluded, coronary angiography was performed with cerebral angiography. No abnormalities were observed in the coronary arteries, and the myocardial damage was considered to be due to subarachnoid hemorrhage. Echocardiograms showed improvements in left ventricular wall motion within a short time after operation of the intracranial lesion.

Cerebral Angiography↗

A case of pelvic lipomatosis presenting with edema of the lower extremities.

We report a 29-year-old male with pelvic lipomatosis that presented with edema of the lower extremities. The patient visited our department because of the marked edema of the lower extremities with body weight gain. The pelvic region was generally radiolucent on plain abdominal radiogram. Excretory urogram and pelvic computed tomography scan revealed compression of the bladder by an adipose tissue mass. On lymphograms, lymph vessels were compressed from the inguinal area in the common iliac region. The edema of the lower extremities was thought to be caused by lymph vessel obstruction.

Adult↗

Detection of perfusion areas of the gallbladder vein on computed tomography during arterial portography (CTAP)--the background for dual S4a.S5 hepatic subsegmentectomy in advanced gallbladder carcinoma.

BACKGROUND/AIMS: It has been speculated that the veins of the gallbladder join the intrahepatic portal veins supplying the Couinaud's S4a-S5. This has been the theoretical ground for the resection of these 2 hepatic subsegments in advanced gallbladder carcinoma. However, no consensus has been reached on this concept. METHODOLOGY: The current study describes the non-neoplastic perfusion defects in connection with the gallbladder bed in 100 consecutive hepatic CTAP (computed tomographies during arterial portography). The suitability of S4a and S5 subsegmentectomies of the liver for advanced gallbladder carcinoma was also investigated by examining CTAP images of the branches of the portal vein involved in the perfusion defect. RESULTS: Two types of gallbladder venous perfusion were observed: 1) sphenoid distribution from the gallbladder bed into the P4a (37%), P5 (52%) and P6 (3%), and 2) perfusion into the P4 (9%) or directly into the middle hepatic vein (9%) after communicating with the hepatic hilum at the dorsal side of S4. CONCLUSIONS: These results support liver resection at S4a and S5 as the surgical approach for cases of advanced gallbladder carcinoma.

Gallbladder↗

Surgical treatment and postoperative outcomes for middle and lower bile duct carcinoma in Japan--experience of a single institute.

BACKGROUND/AIMS: Recently, the Japanese Classification on Cancer of the Biliary Tract was revised and adopted the new comprehensive staging that is similar to UICC's TNM classification. We should be paying close attention to the significance of newly defined extensive factors of carcinomas on the long-term prognosis. METHODOLOGY: The surgical outcome for 99 patients who underwent resected middle (Bm) and lower (Bi) bile duct carcinomas was reviewed in order to evaluate the suitability of the surgical procedures employed for their treatment, namely, standard pancreatoduodenectomy for Bi carcinoma and bile duct resection with D2 lymph node dissection for Bm carcinoma. RESULTS: The overall 5-year cumulative survival rate (operative death excluded) of Bm and Bi carcinoma patients was 37.4% and the 5-year survival rate of the patients in whom surgical curability (curA) was accomplished was 51.6%. Recently, a new prognostic factor, "t-category", which indicates the degree of pericholedochal neoplastic invasion was proposed in the 4th edition of the Japanese General Rules for Surgical and Pathological Studies on Cancer of the Biliary Tract. The 10-year survival rates by t-category were 49.1% (t1), 19.7% (t2), and 0% (t3 and t4) respectively. For Bm carcinoma, the patients undergoing bile duct resection under the condition of curA showed excellent prognoses. For Bi carcinoma, the patients fulfilling particular histological criteria, i.e., those concerning the histological depth of neoplastic invasion (m, fm, panc1a), duodenal involvement (du0, du1), vascular invasion (pv0), pericholedochal neoplastic invasion (t1), lymph node metastasis (n0), and comprehensive stage I, had good postoperative outcomes. Taking into account the fact that the metastatic rate of paragastric lymph nodes was 1.3%, the cases of panc0,1 should be operated by pylorus-preserving pancreatoduodenectomy. The overall 5-year survival rates including far-advanced cases were 39.9% in Bm carcinoma patients and 36.9% in Bi carcinoma patients. However, these postoperative outcomes are far from satisfactory. CONCLUSIONS: Therefore, we concluded that pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy with extended D3 lymphadenectomy combined with systematic multimodal therapy are indicated in each and every case of Bm and Bi carcinoma.

Bile Duct Neoplasms↗

Correlation between plasma and hepatic phosphatidylcholine hydroperoxide, energy charge, and total glutathione content in ischemia reperfusion injury of rat liver.

BACKGROUND/AIMS: Oxygen-derived free radicals are believed to be responsible for the hepatocellular injury leading to liver failure following ischemia-reperfusion in liver, endotoxemia and many other life-threatening illnesses. This study was designed to investigate the reactive oxygen species interaction in lipid peroxidation, the adenosine and energy charge levels of liver cells, and total glutathione content in ischemic-reperfusion injury of liver in rat. METHODOLOGY: To prevent intestinal congestion during the clamping of vascular structures, subcutaneous transposition of the spleen was done beforehand. Four to six weeks later, after the development of natural portal-systemic shunts, occlusion of the portal vein, hepatic artery and bile duct was performed for different periods; blood and liver samples were taken at different intervals after the release. On the basis of the ischemia-reperfusion time, the rats were divided into the following 9 groups: 30/0, 30/30, 30/60, 60/0, 60/30, 60/60, 90/0, 90/30, and 90/60. The following parameters were measured: total hepatic glutathione content, adenosine values (ATP, ADP, AMP), energy charge, phosphatidylcholine hydroperoxide (PCOOH) concentrations in liver and plasma, and serum transaminases (AST, ALT). Decreased liver glutathione stores (an indicator of increased oxidative stress), increased serum hepatic transaminases (an indicator of hepatocellular injury), and increased PCOOH (an indicator of cellular-membrane lipid peroxidation) were noted. RESULTS: The ATP level and energy charge diminished significantly with the increase in duration of ischemia and reperfusion. A close correlation between the PCOOH levels in plasma and liver was observed. Extreme damage was noted in the 90-minute ischemia with 60-minute reperfusion group. The hepatic total glutathione level was reduced to the lowest level in the 90/60 group and it correlated with the energy charge level, denoting the highest degree of oxidative stress sustained by the liver cells in this group. CONCLUSIONS: These results indicated that prolonged hepatic ischemia with reperfusion produced bursts of oxygen-derived free radicals which overwhelmed the defense mechanisms of the cells, with a resultant decrease in energy charge associated with an increase in membrane lipid peroxidation. These findings not only provide confirmation of previously reported hepatocellular injury by free radicals generated after reperfusion, but they also establish the use of PCOOH analysis in liver and plasma as a sensitive and specific indicator of the injury process in time. The plasma PCOOH level may be a useful indicator of free radical induced hepatic membrane lipid peroxidation during ischemia-reperfusion, and might be employed in clinical studies of the therapeutic effects of drugs in various liver diseases, as well as for determining the prognosis after different kinds of hepatic operations.

Adenine Nucleotides↗

Interleukin-10 induction after combined resection of liver and pancreas.

BACKGROUND/AIMS: Recently in Japan, combined resection of liver and pancreas is being performed in cases of advanced biliary neoplasms. As we previously reported, in the rat model of combined resection of the liver and pancreas, the potential for liver regeneration after this operation was decreased compared to that after hepatectomy only. Moreover, non-parenchymal cells play an important role in the production of inhibitory factors for liver regeneration. The anti-inflammatory cytokine IL-10, downregulates the release of TNF-alpha, and affects the progressive regeneration of the hepatic parenchyma. To investigate the role of IL-10 and TNF-alpha in hepatic regeneration in the rat, we measured the levels of IL-10 and TNF-alpha in the conditioned medium of non-parenchymal cells stimulated with portal plasma. We also investigated the concentration of IL-10 and TNF-alpha in the portal plasma after combined resection of the liver and pancreas. METHODOLOGY: Adult male Sprague-Dawley rats were used. Rats were divided into 3 groups: group I underwent 70% partial hepatectomy only (Hx), group II underwent 70% partial pancreatectomy only (Px) and in group III both procedures were used, Hx plus Px (HPx). Portal plasma was harvested at 1, 3, 6, 12 and 24 hours after surgery and was used to stimulate the culture medium of non-parenchymal cells. Cytokine concentrations in the plasma and in the conditioned medium were measured by ELISA. Northern blot analysis for IL-10 mRNA was performed on liver, pancreas, kidney, lung and spleen at 1, 3 and 6 hours after surgery. RESULTS: The level of IL-10 released by non-parenchymal cells stimulated with HPx portal plasma was 154.1 +/- 20.3 pg/mL and significantly higher than when stimulated with Hx portal plasma, which was 100.1 +/- 6.4 pg/mL (P < 0.05) during the first hour. Also, the level of TNF-alpha released by Kupffer cells stimulated with HPx portal plasma was 86.6 +/- 13.4 pg/mL, significantly less than when stimulated with Hx portal plasma, which was 138.7 +/- 15.1 pg/mL (P < 0.005) during the first hour. Furthermore, the plasma levels of IL-10 in the HPx group remained significantly higher than those of the other groups from 6 hours up to 12 hours. In northern blot analyses, higher IL-10 mRNA expression were detected in the spleen and moderately high levels in the liver at 1 and 3 hours after HPx, in contrast to those after Hx. CONCLUSIONS: IL-10 expression is induced in the spleen and liver remnant just after HPx. IL-10 released by the spleen and liver might downregulate TNF-alpha production, thereby inhibiting the liver regeneration.

Animals↗