Biomedical subjects

T Kosuge

Publications and source records attributed to T Kosuge.

At least 37 records · Page 2Linked to original sources

PubMed2000

Cystic liver metastases from colorectal cancer.

BACKGROUND AND OBJECTIVES: Cystic liver metastases from colorectal cancer are rarely reported. METHODS: Clinicopathological and radiological analyses were performed on six cases of cystic liver metastases from colorectal cancer. RESULTS: Computed tomography or ultrasound findings for the tumors were atypical for metastases of colorectal cancer, and the lesions needed to be differentiated from cystadenocarcinoma and benign tumors. The histological findings were peculiar: the central portions of the tumors contained necrotic tissue or areas of hemorrhage, and adenocarcinoma cells were found predominantly outside well-developed fibrous capsules. CONCLUSIONS: Clinicopathological observations suggested that these metastatic tumors had the potential to grow rapidly, but, unexpectedly, the patients had favorable prognoses.

Adenocarcinoma↗

PubMed2000

Surgical results for hepatocellular carcinoma with macroscopic portal vein tumor thrombosis.

BACKGROUND: The longterm results after liver resection for hepatocellular carcinoma with macroscopic tumor thrombus of the portal vein are unclear. STUDY DESIGN: The records of 47 HCC patients with tumor thrombus in the segmental portal branch (n = 33) and the first portal branch or portal vein trunk (n = 14) were reviewed in this study. Survival rates of the patients were calculated with regard to 14 dinicopathologic variables. A log-rank analysis was performed to identify which variables predicted the prognosis. RESULTS: Overall 1-, 3-, and 5-year survival rates were 53.9%, 33.2%, and 23.9%, respectively. The indicators of a favorable prognosis included curative liver resection, tumor size less than 10 cm in diameter, and absence of intrahepatic metastases. CONCLUSIONS: Liver resection should be considered a therapeutic option for hepatocellular carcinoma with macroscopic portal vein tumor thrombus when the tumor is small and curative liver resection can be expected.

Adult↗

PubMed2000

Splenectomy in patients with hepatocellular carcinoma and hypersplenism.

BACKGROUND: Hypersplenism secondary to portal hypertension is common in hepatocellular carcinoma (HCC), but surgeons still face the unresolved problem of how to manage HCC patients with hypersplenism. STUDY DESIGN: The records of 48 patients with HCC and hypersplenism were retrospectively examined and postoperative changes in platelet counts, serum total bilirubin levels, and dinical staging scores were analyzed to evaluate the clinical value of combined splenectomy and liver resection. Hepatectomy and splenectomy were performed as a two-stage operation in 13 patients and synchronously in 35. RESULTS: Postoperative platelet counts were significantly increased, and serum total bilirubin levels were significantly decreased. Clinical staging scores were also reduced after splenectomy in patients who underwent splenectomy before hepatectomy. CONCLUSIONS: Synchronous or metachronous splenectomy can increase the safety of hepatectomy in selected patients with HCC by reducing both the likelihood of bleeding complications and bilirubin overload.

Aged↗

PubMed2000

Analysis of the methionine biosynthetic pathway in the extremely thermophilic eubacterium Thermus thermophilus.

Four DNA fragments that could rescue the mutations of four Met- mutants were cloned from Thermus thermophilus HB27 and their complete nucleotide sequences were determined. Two of the four fragments respectively contained the greater parts of the metF and metH genes, the predicted amino acid sequences of which showed identities of 30.8% and 32.7% with 5,10-methylenetetrahydrofolate reductase (EC 1.7.99.5) and vitamin B12-dependent homocysteine transmethylase (EC 2.1.1.13) of Escherichia coli. The other two DNA fragments, which overlapped one another, contained two open reading frames whose predicted amino acid sequences were respectively similar to those of O-acetylhomoserine sulfhydrylase (EC 4.2.99.10, the product of the MET17 gene) and homoserine O-acetyltransferase (EC 2.3.1.31, the product of the MET2 gene) of Saccharomyces cerevisiae. The metF, metH, MET2, and MET17 genes of T. thermophilus were disrupted by introducing the heat-stable kanamycin nucleotidyltransferase gene into the genome. Each transformant showed methionine auxotrophy. Both the MET2- and MET17-disrupted mutants could grow in a minimal medium containing homocysteine but not in the same medium containing succinylhomoserine or cystathionine. In contrast, the metF- and metH-disrupted mutants could not grow in the minimal medium containing homocysteine. These results suggest that in T. thermophilus, homoserine is directly converted to homocysteine via O-acetylhomoserine and that homocysteine is methylated to synthesize methionine.

Journal Article↗

PubMed2000

Age dependency of neointima formation on vascular prostheses in dogs.

Neointima formed quickly on vascular prostheses implanted in young dogs but not in aged dogs. Previously, we found that impeding neointima formation on vascular prostheses occurred more frequently in aged animals. From these observations, we hypothesized that neointima formation was age-dependent in dogs. To test the hypothesis, 26 fabric Dacron vascular prostheses were analyzed. Half of them were retrieved from aged dogs (more than 13 years old) while the other half were from young ones (less than 1 year old). The grafts were harvested at 8 weeks and 3 months after implantation. The graft surfaces were photographed and analyzed by computer for the ratio of the areas with and without thrombus. Light and scanning electron microscopic observation revealed that most of the thrombus-free areas were lined with endothelial cells. Then the endothelialized areas were calculated. Using data obtained from macroscopic, light microscopic, and scanning electron microscopic observations, the arithmetic means were calculated as the degree of neointima formation. In young animals, the degrees at 8 weeks and at 3 months were 89.1 +/- 8.5% (mean +/- SD) and 95.7 +/- 3.3%, respectively. In old animals, they were 27.9 +/- 5.9% and 31.5 +/- 6. 8%, respectively. From these results, we concluded that neointima formation was age-dependent in dogs.

Aging↗

PubMed2000

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma.

BACKGROUND: Mass-forming type cholangiocarcinoma is a distinct from of cholangiocellular carcinoma, with pathologic and biologic behavior different from those of other types. The clinical consequences of these differences have never been clarified. METHODS: Fifty-two consecutive patients (32 men and 20 women, mean age 62 years) with mass-forming type cholangiocarcinoma that had been treated with curative surgical resection between 1980 and 1998 were retrospectively evaluated. Long-term survival and disease-free survival were calculated, and univariate and multivariate analysis of various prognostic factors was conducted. RESULTS: The 30-day postoperative mortality rate was 2%, and the overall and disease-free 5-year survival rates were 36% and 34%, respectively. Univariate analysis identified 5 significant risk factors for overall survival: surgical margin, lymph node metastasis, lymph node dissection, vascular invasion, and left-side location of the main tumor. Two risk factors were identified for disease-free survival: surgical margin and lymph node metastasis. Multivariate analysis confirmed that surgical margin, lymph node metastasis, and vascular invasion were independently significant variables for overall survival. CONCLUSIONS: This is the first reported study on the effectiveness of liver resection for the treatment of mass-forming type cholangiocarcinoma, showing that surgical therapy can prolong survival if local radicality can be achieved and lymph-node metastases are absent.

Adult↗

PubMed2000

Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results.

OBJECTIVE: To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. SUMMARY BACKGROUND DATA: The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. METHODS: Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. RESULTS: The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). CONCLUSIONS: Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.

Adenocarcinoma↗

PubMed2000

Evaluation of the therapeutic effect of transcatheter arterial embolization for hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum alpha-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level >/=200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.

Adult↗

PubMed2000

Effect of inhibitors of glycoprotein processing on cytokine secretion and production in anti CD3-stimulated T cells.

We have investigated the effect of inhibitors of glycoprotein processing on cytokine secretion and production in anti CD3-stimulated T cells to elucidate the role of carbohydrate in the triggering of T cell function. The inhibitors of glycoprotein processing, especially mannnosidase inhibitors, enhanced the anti CD3-induced production of interleukin-2 (IL-2), which is a cytokine without the linkage sequence of N-linked oligosaccharides. On the other hand, N-methyl-1-deoxynojirimycin (NMdNM, an inhibitor of processing glucosidase 1), 1-deoxynojirimycin (dNM, an inhibitor of processing glucosidase I and II) and bromoconduritol (BCD, an inhibitor of processing glucosidase II) inhibited the secretion of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), or interleukin-5 (IL-5) into culture supernatants of anti CD3-stimulated T cells, which had N-linked oligosaccharides. Mannosidase inhibitors, 1-deoxymannojirimycin (dMAN, an inhibitor of processing mannosidase I) and swainsonine (SWN, an inhibitor of processing mannosidase II) did not inhibit the secretion or production of IL-4, IFN-gamma and IL-5. To confirm the inhibition of N-linked oligosaccharide processing in the cytokines by the above inhibitors, the binding of IFN-gamma to lectins with various sugar-binding specificities was investigated. All inhibitors reduced the binding of IFN-gamma to PHA E4, which had a high affinity to bi- or tri-antennary complex type N-linked oligosaccharides with bisecting N-acetylglucosamine. Similarly, all inhibitors reduced the binding of IFN-gamma to PHA L4, which had high affinity to tri- or tetra-antennary complex type N-linked oligosaccharides with beta1-6-linked branching. SWN and dMAN increased the binding of IFN-gamma to concanavalin A (ConA), which had a high affinity to bi-antennary complex type, hybrid type and high-mannose type N-linked oligosaccharides. These results suggest that the processing inhibitors used here inhibit the N-linked oligosaccharide processing of cytokines, and the inhibition of processing enzyme glucosidases I and II induces a decreased secretion of cytokines with N4-linked oligosaccharides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Increased degradation of newly synthesized interferon-gamma (IFN-gamma) in anti CD3-stimulated lymphocytes treated with glycoprotein processing inhibitors.

As described previously (Kosuge T., Toyoshima S., Biol. Pharm. Bull., 23, 1-5 (2000)), inhibitors of the glycoprotein processing enzymes, glucosidase I and II, induce decreased secretion of interferon-gamma (IFN-gamma) into culture supernatants of anti CD3-stimulated lymphocytes, and in the present study the mechanism has been investigated in further detail. The processing inhibitors did not affect intracellular levels of IFN-gamma but enhanced the degradation of newly synthesized IFN-gamma in anti CD3-stimulated lymphocytes. Furthermore, since the stability of N-glycosylated proteins is known to be regulated by lectin family chaperones, such as calnexin, a type I transmembrane protein located in the endoplasmic reticulum (ER), and calreticulin, a soluble protein in the ER lumen, the effect of the processing inhibitors on the interaction of IFN-gamma with calnexin and calreticulin was investigated. It was found that IFN-gamma formed complexes with calnexin and calreticulin in anti CD3-stimulated lymphocytes. Total binding of IFN-gamma to calnexin was not affected but that to calreticulin was increased in anti CD3-stimulated lymphocytes treated with the processing inhibitors. However, binding of newly synthesized IFN-gamma to calreticulin was decreased in the lymphocytes under the same conditions as above. These results suggest that these glycoprotein processing inhibitors block the release of IFN-gamma from already formed calreticulin complexes, which prevents the binding of newly synthesized IFN-gamma to calreticulin and results in the enhancement of IFN-gamma degradation.

Animals↗

PubMed2000

[Effects of psidium components on cytokine productions in helper T cells and type-I allergy].

Psidium genus Myrtaceae (Psidium) is known to be a chinese medicine with an anti-allergy effect. In the present study, to identify active components in Psidium and investigate mechanisms of its anti-allergy effect, effects of several components isolated from Psidium on cytokine production in helper T cell subtypes, Th1 and Th2 cells, were studied. All components, except methyl gallate, suppressed cytokine production in both Th1 and Th2 cells. Then, effects of methyl gallate on IgE production in a model mouse with type I allergy were studied. Methyl gallate suppressed IgE production in the mouse. Only methyl gallate selectively suppressed Th2-cytokine production.

Animals↗

PubMed2000

Long-term survival after multimodality treatment for resectable pancreatic cancer.

BACKGROUND: The prognosis of pancreatic adenocarcinoma after radical pancreatectomy is poor, especially in advanced-stage disease. STUDY AIM: To determine the survival rates and evaluate the effectiveness of multimodality treatment for advanced pancreatic cancer. METHODS: From November 1983 to January 1993, 30 patients with pancreatic adenocarcinoma including 9 with carcinoma of the body and tail were treated by a multimodal approach consisting of extended pancreatectomy, intraoperative radiotherapy (IORT), and hepatic artery or portal vein infusion of mitomycin C (MMC) followed by systemic bolus injection. All surviving patients were followed for more than 8 yr and survival rates were calculated by the Kaplan-Meier method. RESULTS: There were no operative or hospital deaths. Eight patients survived for more than 5 yr, 3 of whom survived more than 10 yr. The 5-yr survival rate for 27 patients excluding 3 with metastasis to the liver, peritoneum, or lung was 31%, with a median survival of 31.1 mo. Among them, the 1-, 3-, and 5-yr survival rates for 19 patients with regional nodal metastasis were 95, 50, and 28%, respectively, with a median survival of 36.0 mo. CONCLUSION: The multimodality treatment combined with IORT and MMC chemotherapy appeared to have a benefit for prognosis of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Selective intraarterial contrast-enhanced CT of pancreaticoduodenal tumors: early clinical experience in evaluating blood supply and detectability.

OBJECTIVE: The purpose of this study was to compare CT with selective intraarterial contrast enhancement with IV contrast-enhanced CT for diagnostic usefulness in the detection of tumors in the pancreaticoduodenal region. SUBJECTS AND METHODS: intraarterial contrast enhanced CT was performed in 36 patients with tumors of the pancreaticoduodenal region. Feeding arteries of the tumors and distribution of hyperattenuating areas on intraarterial contrast-enhanced CT were analyzed with various routes of contrast material injections. The intraarterial contrast-enhanced CT scans were compared with the IV contrast-enhanced CT scans. RESULTS: In all 29 patients with standard vascular anatomy, the right cephalic portion of the pancreatic head was enhanced on CT during common hepatic or gastroduodenal arteriography and the left caudal portion was enhanced on CT during superior mesenteric arteriography. The enhanced areas were complementary to each other in the whole pancreatic head, including the tumor. Tumor conspicuity from the surrounding pancreatic tissue on intraarterial contrast-enhanced CT was not superior to that on IV contrast-enhanced CT in all but four patients with cystic tumors. After intraarterial contrast-enhanced CT, three patients with tumors less invasive than pancreatic ductal carcinoma underwent local resection of their lesions. CONCLUSION: Intraarterial contrast-enhanced CT for pancreaticoduodenal tumors has potential technical problems and is not valuable in improving the detectability of tumors other than cystic lesions because the enhancement of the wall and septa of the tumor is emphasized. However, the feeding artery of the tumor and its surrounding tissue were clearly depicted.

Adult↗

PubMed1999

Should hepatomas be treated with hepatic resection or transplantation?

BACKGROUND: The aim of this collaborative study was to compare the long term results of hepatic resection (Hx) with those of orthotopic liver transplantation (OLTx) in large numbers of cirrhotic patients with hepatocellular carcinoma (HCC) and to delineate the roles of these two surgical treatments. METHODS: The databases of the National Cancer Center Hospital in Japan and the University of Pittsburgh Medical Center in the U. S. were exchanged and 294 cirrhotic patients who underwent curative Hx and 270 cirrhotic patients who underwent curative OLTx were selected for comparison. RESULTS: The mortality rate within 30 days and that within 150 days after Hx were significantly lower than those after OLTx (P = 0.001 and P = 0.00007, respectively). Overall survival was similar between the Hx group and the OLTx group (P = 0.40). When compared in the HCC patients without macroscopic vascular invasion and lymph node metastases, the overall survival rate after OLTx was significantly higher than that after Hx (P = 0.006). However, this difference was not significant between the patients with Child-Pugh Grade A tumors in the Hx group and all patients (majority with Child-Pugh Grade C tumors) in the OLTx group (P = 0.25). Tumor free survival after OLTx was significantly higher than that after Hx (P < 0.0001), particularly in HCCs measuring </=5 cm, unilobarly distributed tumors, and HCCs with either no or only microscopic vascular invasion. In HCCs measuring > 5 cm and those with macroscopic vascular invasion, the tumor free survival rate was similar between the Hx group and the OLTx group. CONCLUSIONS: In the face of organ shortage, HCC developing in a well compensated cirrhotic liver initially may be treated with Hx. However, the authors believe OLTx should be applied selectively to those patients with tumor recurrence and/or progressive hepatic failure.

Carcinoma, Hepatocellular↗

PubMed1999

A novel splicing mutation (894-9 G --> A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1.

Germline MEN1 gene mutations are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited cancer syndrome. We identified a MEN1 germline mutation 894-9 G --> A in three MEN1 patients from two unrelated families. This mutation was not present in any of the 100 blood samples from normal volunteers. The wild type MEN1 sequence was lost in the patient's pancreatic tumor. Abnormal mRNA was identified in the tumor, which retained an intronic sequence indicating aberrant mRNA splicing at a newly created splicing acceptor site. These findings indicate that this nucleotide substitution is, though previously reported to be a polymorphism, a causative splicing mutation.

Adult↗

PubMed1999

Blood supply to the pancreatic head, bile duct, and duodenum: evaluation by computed tomography during arteriography.

HYPOTHESIS: Blood supply to the peripancreatic region is derived from the celiac and superior mesenteric arteries, complementary to each other. DESIGN: Cohort analytic study. SETTING: Tertiary care public hospital. PATIENTS AND METHODS: Computed tomography (CT) during superior mesenteric artery arteriography (SMAA-CT) and during celiac artery arteriography (CEAA-CT), in which a catheter tip was inserted into the common hepatic or gastroduodenal artery, was performed in 25 patients. MAIN OUTCOME MEASURE: Distribution and correlation of these areas of marked enhancement on SMAA-CT and CEAA-CT were analyzed. RESULTS: The right cephalic part of the pancreatic head that is derived from the dorsal bud was enhanced on CEAA-CT, and the left caudal part of the pancreatic head that is derived from the ventral bud was enhanced on SMAA-CT. Blood supply to the intrapancreatic bile duct, including the ampulla of Vater, is derived from the CEA. The boundary between the areas of the duodenum supplied from the CEA and SMA was in the second or third portion. CONCLUSION: The pancreatic head can be separated into 2 segments by the arterial supply, and each segment may be removed separately.

Angiography↗

PubMed1999

Treatment of mediastinitis arising after replacement of the ascending aorta.

Mediastinitis due to graft infection is a serious and potentially lethal complication associated with replacement of the ascending aorta. We present the case of a 67-year-old man with this condition for the aneurysm and chronic dissection. Mediastinitis and sepsis were diagnosed and debridement, irrigation with povidone solution and omental transposition were performed successfully. Continuous closed irrigation prior to omental transposition without replacement of the infected graft is useful for treating mediastinitis after ascending aortic or arch replacement.

Aged↗

PubMed1999

Anterior transhepatic approach for isolated resection of the caudate lobe of the liver.

We have devised a new technique for isolated caudate lobe resection in which we access the caudate lobe by separating the liver parenchyma along the interlobar plane. The safety and radicality of the procedure were evaluated in five patients: four with hepatocellular carcinoma (HCC) and one with metastatic rectal cancer. All of the tumors were located mainly in the paracaval portion of the caudate lobe. The patients with HCC (three of four) underwent an anatomic caudate lobe resection by identification of the right margin of the caudate lobe. Two patients required red blood cell transfusion, and one showed bile leakage after surgery. All of the patients are alive without recurrence more than 4 years after surgery, except one with rectal carcinoma who developed lung metastases. The anterior transhepatic approach is a safe and potentially curative surgical option for a tumor in the paracaval portion of the caudate lobe.

Aged↗