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Biomedical subjects

T Kaiho

Publications and source records attributed to T Kaiho.

At least 19 recordsLinked to original sources

Reduced hepatic acute-phase response after simultaneous resection for gastrointestinal cancer with synchronous liver metastases.

Serum cytokines and hepatic acute-phase responses were studied in seven patients undergoing simultaneous resection of primary gastrointestinal cancer and synchronous metastatic liver tumours and in 12 undergoing partial hepatectomy alone for metachronous hepatic metastases. The incidence of postoperative infectious complications was significantly higher after simultaneous resection than after partial hepatectomy alone (P < 0.05). Although the peak interleukin 6 level was significantly higher after simultaneous resection (P < 0.05), plasma levels of acute-phase proteins were significantly lower (P < 0.05). The results suggest that simultaneous resections further reduce the hepatic acute-phase response and render patients liable to infection compared with partial hepatectomy alone, and result in a higher incidence of postoperative infective complications.

Acute-Phase Proteins

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy.

It has been proposed that a major hepatectomy impairs the liver-related host defense mechanism. The changes in the levels of serum inflammatory cytokines and plasma acute-phase proteins synthesized in the liver were measured after partial hepatectomy. Peak levels of serum interleukin-6 were significantly higher after extended lobectomy than after lobectomy or segmentectomy (p < 0.01). Serum interleukin-1 beta and tumor necrosis factor alpha levels showed no significant changes. Plasma levels of acute-phase proteins were significantly lower after lobectomy or extended lobectomy (p < 0.05). A reduced hepatic acute-phase response probably renders patients liable to infection after major hepatectomy.

Acute-Phase Proteins

Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity.

To evaluate liver dysfunction in patients with obstructive jaundice (OJ), morphological and functional hepatic mass was analyzed in comparison with cirrhosis (LC). Total hepatic parenchymal ratio (THPR) was estimated by morphometric analysis and hepatic functional mass by galactose tolerance test (GaTT) in 30 patients who underwent hepatectomy. The value of GaTT in patients with LC was remarkably depressed compared to those with normal liver function (p < 0.001). It was also depressed in OJ (p < 0.05 vs. normal liver), but less than in LC (p < 0.05). However, THPR decreased only in LC (p < 0.05 vs. either normal liver or OJ). A significant correlation between the value of GaTT and THPR was revealed in patients with LC, but not in OJ. These results suggested that liver dysfunction in OJ was independent of the decreased number of hepatocytes, differing from LC.

Adult

Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy.

OBJECTIVE/METHOD: It has been reported that inflammatory cytokines up-regulate human hepatocyte growth factor synthesis in vitro. To demonstrate the relation of this growth factor to interleukin-6 and tumor necrosis factor alpha, the changes in the levels of these cytokines were measured in serum and peritoneal fluid in 22 patients after partial hepatectomy. RESULTS: Serum and fluids levels of cytokines showed a maximum within 3 days after surgery. Cytokines concentrations were much higher in fluid than in serum (p < 0.05). The maximum serum levels of human hepatocyte growth factor were significantly correlated with those of interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not resected liver weights. In fluid level, the growth factor was also correlated with interleukin-6 (p < 0.05) but with tumor necrosis factor alpha. CONCLUSIONS: These results suggest that human hepatocyte growth factor might be locally produced in the injured tissue associated with interleukin-6 and independently of resected liver weights.

Aged

Significance of aminopyrine breath test as a parameter of hepatic functional reserve in 40% partial hepatectomy of rats with CCl4-induced liver injury.

Rats with CCl4-induced liver injury underwent partial (40%) hepatectomy. The [14C]aminopyrine breath test (ABT) values in rats with CCl4-induced liver injury were reduced by 34% compared with those in rats with normal liver. Preoperative ABT values clearly discriminated between survivors and those that died following 40% partial hepatectomy in rats CCl4-induced liver injury (P < 0.05). Hepatic protein synthesis was remarkably enhanced in CCl4-induced liver injury compared with normal liver (P < 0.001), and this was inversely correlated with ABT values (P < 0.001). These data show that the enhanced hepatic protein synthesis could induce a decrease of hepatic functional reserve. ABT seems to be a useful preoperative test for predicting surgical mortality following hepatectomy.

Alanine Transaminase

Inhibition of hepatic regeneration after 70% partial hepatectomy by simultaneous resection of the bowel in rats.

This study was aimed to evaluate bow simultaneous resection of the bowel influences hepatic regeneration after partial hepatectomy (HTX). Two hundred and sixty-four rats underwent 70% partial HTX, ileocecal resection (ICR), transverse colon resection (TR), colon amputation and simulatenous resection of the liver and the bowel (HTX+ICR, HTX+TR). Hepatic DNA synthesis was remarkably suppressed by simultaneous resection compared with the 70% HTX group (p < 0.01). In simultaneous resection groups, delayed enhanced hepatic protein synthesis (HPS) was observed after the operation as compared with the 70% HTX group, which showed an early postoperative peak of HPS. Postoperative anastomosis leakage occurred more frequently and survival rates were significantly lower in simultaneous resection groups. Higher plasma endotoxin levels of the portal and the peripheral veins were found in simultaneous resection groups as compared with other groups (p < 0.01-0.001). This study suggested that simultaneous resection of the bowel with partial HTX might inhibit hepatic regeneration and result in the increased risk of anastomosis leakage and high surgical mortality rate by increased plasma endotoxin levels and delayed enhanced HPS.

Animals

Handedness trends across age groups in a Japanese sample of 2316.

Hand-preference data of 2316 Japanese were analyzed by age groups, sex, and familial sinistrality. Right-hand preference increased across age groups at least up to 30 years for men, while women showed relatively stable and stronger preference for right-hand use. Unlike some Western studies, no linear trends across age groups were found for both sexes. Declining cultural censorship against left-handedness would not be responsible for the trends, since there was no evidence indicating such a decline in Japan. Hypotheses of reduced longevity and life-long adaptation to the right-handed world are not satisfactory either, since both hypotheses assume a linear trend spanning the entire life span. Thus, it seems that a single-factor hypothesis which explains all the results by resorting to a single cause does not account for the complex results found in this and other studies.

Adolescent

[Intraportal infusion of 5-FU and lipiodol-aclarubicin after hepatic resection for colorectal liver metastasis].

Fifty-five patients with hepatic metastasis from colorectal cancer underwent curative hepatic resection. Postoperative intraportal infusion of 5-fluorouracil (500mg per day) for 14 days from 21 postoperative days (POD) and lipiodol-aclarubicin (40mg) at 35 POD was carried out in twenty-eight patients for reducing the recurrence in the remnant liver and improving the prognosis. Twenty-seven patients had hepatectomy alone as controls. Intraportal infusion chemotherapy did not induce any hepatotoxicity and hematologic severe abnormalities. The cumulative survival rates for the infusion group and the control group, respectively, were 89.3% and 63.0% at 1 year; 55.2% and 43.3% at 2 year; 27.0% and 27.5% at 3 year. The survival rate for the infusion group was significantly higher than that for the control group at 1 year (p < 0.05). No difference of the recurrent rate in the remnant liver was found between the two groups. It is suggested that intraportal infusion chemotherapy after curative hepatic resection for colorectal liver metastasis might improve survival rate at the early postoperative period. Intraportal infusion chemotherapy could be an effective adjuvant therapy especially in the patients with bilateral and multiple hepatic metastasis.

Aclarubicin

Partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura.

OBJECTIVE: The purpose of this study was to assess the effectiveness of partial splenic embolization in the treatment of chronic idiopathic thrombocytopenic purpura. SUBJECTS AND METHODS: Twenty-six patients with chronic idiopathic thrombocytopenic purpura underwent partial splenic embolization and were followed up for 6-61 months. The condition was refractory to steroids in 20 of 26 patients. The other six patients, in whom a response to steroids was shown, could not be withdrawn from steroid therapy because their platelet counts decreased with any decrease in steroid dose. Five of 26 patients underwent splenectomy after partial splenic embolization, and the other patients were followed up without medical treatment until platelet counts decreased below 3 x 10(10)/l. The therapeutic effect of partial splenic embolization was defined on the basis of the platelet count at the last follow-up after partial splenic embolization: complete response, greater than 10 x 10(10)/l; partial response, 5 x 10(10)/l to 10 x 10(10)/l; and no response, less than 5 x 10(10)/l without medication. RESULTS: Partial splenic embolization brought a complete response in seven (33%) of 21 patients, a partial response in eight (38%), and no response in six (29%). In four of five patients, who later underwent splenectomy, response to partial splenic embolization was coincident with the response to splenectomy. No serious complications occurred, but minor complications such as abdominal pain, fever, and nausea were observed in most patients. CONCLUSION: This study suggests that partial splenic embolization might be useful as an alternative to splenectomy in the treatment of chronic idiopathic thrombocytopenic purpura.

Adult

Enhancement of cytotoxicity of doxorubicin by verapamil in the hepatic artery infusion for liver tumors in rats.

BACKGROUND: The calcium channel blocker has been demonstrated to be effective in the accumulation and retention of chemotherapeutic agents in tumor cells. METHODS: The effect of verapamil on cytotoxicity of doxorubicin was investigated in a hepatic artery infusion (HAI) for liver tumors of Walker 256 carcinosarcoma in rats. Doxorubicin was infused by way of a hepatic artery by a bolus injection intra-arterially (IA) (1 mg/kg) and a continuous infusion intra-arterially (CIA) (6 mg/kg/day for 6 days). RESULTS: Doxorubicin increased 90% and 66% in tumor tissue following HAI of verapamil by a bolus and continuous infusion (P < 0.05), respectively. However, no enhancement of the accumulation of doxorubicin in the tumor tissue was found in an intravenous administration of verapamil. The CIA infusion of verapamil with doxorubicin inhibited the tumor growth by 73% in comparison with doxorubicin only (P < 0.05). Verapamil administered intravenously (IV) could not induce this inhibitory effect. The CIA administration of verapamil reduced the serum concentration by 45% (P < 0.001) in comparison with the CIV route. Furthermore, the administration of verapamil did not increase the accumulation of doxorubicin in the normal liver and heart tissues. No enhancement of bone marrow suppression and hepatic biochemical influence by doxorubicin was revealed by the concomitant use of verapamil. CONCLUSIONS: The continuous HAI of verapamil remarkably enhanced the cytotoxicity of HAI with doxorubicin for the treatment of hepatic tumor without aggravating the side effects induced by doxorubicin.

Animals

Portal vein infusion of cancer chemotherapeutic agent emulsified with Lipiodol in regenerating liver after partial hepatectomy in rats.

Portal vein infusion of aclarubicin (ACR) emulsified with Lipiodol (LP) in regenerating liver after 70% partial hepatectomy in rats was evaluated for its safety and usefulness. DNA synthesis in regenerating liver was transiently suppressed by LP, ACR or LP+ACR, but no obvious inhibition was seen in aminopyrine N-demethylase activity and liver weights. LP significantly enhanced hepatic tissue levels of ACR and its active metabolites by long-term retention in the sinusoidal space. This study demonstrates that in rats LP has a powerful effect on the long-term retention of anticancer agents in the sinusoidal space after infusion into the portal vein, without aggravating hepatic damage by anticancer agents.

Aclarubicin

[Hepatic protein synthesis in regenerating liver after partial hepatectomy].

The process of hepatic protein synthesis was studied in the regenerating liver after partial hepatectomy (HTX). Hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were determined in the regenerating liver of rats after 68% HTX. The serum levels of the following items were determined in 10 patients before and after HTX: interleukin-6 (IL-6), acute-phase proteins (APP), and negative acute-phase proteins (NAPP). HPS has markedly increased after HTX, with the peak occurring at 48 hours. The regenerating rat liver showed an increase of 80% over normal livers in HPS and 200% in SPS 48 hours after HTX. A remarkable increase in IL-6 levels occurred on the first day after HTX. In all patients transient falls in APP levels occurred on the first day. Values appeared to return rapidly toward preoperative values by 3 or 5 days after HTX but failed to show any significant increase compared to preoperative values. In contrast to APP, prolonged decreases in NAPP levels occurred after HTX. Values declined to a nadir on the first or third day after HTX and remained suppressed for 14 days. These results suggest that the production of APP is activated at an early stage of liver regeneration after partial hepatectomy.

Acute-Phase Proteins

[Long-term prognosis of idiopathic thrombocytopenic purpura treated by partial splenic embolization].

The therapeutic effect of partial splenic embolization (PSE) was evaluated in 13 patients with idiopathic thrombocytopenic purpura (ITP). Eight patients were treated by PSE and followed up over 6 months after the treatment. Two patients were treated by splenectomy following PSE. (1) PSE achieved complete remission in one case, partial response in 3 cases, minimal response in one case and no change in 3 cases. PSE resulted in 62.5% of the effective rate. (2) The effect of PSE did not depend on age, sex, the duration of disease, platelet count and PA-IgG level before the treatment and the splenic infarcted rate. The platelet count after PSE increased more remarkably in the effective cases than in the non-effective ones (p < 0.01), which could predict the prognosis after PSE. (3) One patient whose platelet count increased enough after PSE had splenectomy later and resulted in complete remission. However another patient whose platelet count did not increase enough after PSE revealed no effect by splenectomy. PSE for the treatment of ITP could prevent some patients from non-effective splenectomy and achieve the same effective rate as splenectomy. Therefore, PSE could be an alternative therapy of splenectomy because of the less invasive one.

Adolescent

[Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis].

In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers.

Adult

Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.

A series of 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)- pyrimidinedione derivatives were synthesized and studied for their class III electrophysiological activity and class II (beta-blocking) effects in in vitro and in vivo models. Structure-activity relationships are discussed for a series of compounds. Several members of this series prolonged the action potential duration at 75% repolarization of isolated canine Purkinje fibers and were 10-30-fold more potent than d-sotalol. 1,3-Dimethyl-6-[[2-[N-[3-(4-nitrophenyl)propyl]-N- (hydroxyethyl)amino]ethyl]amino]-2,4-(1H,3H)-pyrimidinedione (40), is one of the most potent compounds in this series.

Animals

[Hepatic protein synthesis and cytokines in obstructive jaundice].

UNLABELLED: To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). THE RESULTS: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.

Acute-Phase Proteins