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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 235 records · Page 13Linked to original sources

Reduced adrenomedullin expression in gastric mucosa of portal hypertensive rats after ethanol-induced injury.

OBJECTIVE: To determine the expression and localization of adrenomedullin (AM) and its receptor (AM-R) in portal hypertensive (PHT) gastric mucosa after intragastric ethanol administration. SUMMARY BACKGROUND DATA: The repair of gastric mucosal injury requires reestablishment of the microvascular network. The authors previously demonstrated impaired angiogenesis of PHT gastric mucosa after ethanol-induced injury. Because AM, a potent vasodilatory peptide, is also a novel growth and angiogenic factor, the authors hypothesized that AM is involved in the impaired repair of PHT gastric mucosa and its microvasculature after damage. METHODS: Either PHT or sham-operated rats received intragastrically 100% ethanol, and the stomachs were excised at 1, 6, and 24 hours later. Expression and localization of AM and AM-R mRNA were examined by competitive reverse transcription-polymerase chain reaction and in situ hybridization. AM protein expression was examined by Western blot analysis. RESULTS: One hour after ethanol administration, AM mRNA expression in PHT gastric mucosa was significantly decreased by 81%, especially in the superficial mucosa, compared with the gastric mucosa in sham-operated rats. The significant decrease lasted for 24 hours. AM protein expression was significantly decreased by 43% compared with the sham-operated gastric mucosa. Although AM-R mRNA expression in both groups was significantly increased 1 hour after ethanol administration and lasted for 24 hours compared with baseline, there were no differences between the two groups. CONCLUSIONS: The expression of AM in PHT gastric mucosa after ethanol-induced injury is significantly decreased compared with controls. This finding could explain one mechanism for the impaired angiogenesis after injury of PHT gastric mucosa.

Adrenomedullin↗

Carcinoma in villous adenoma of ascending colon associated with sarcoid reaction in the regional lymph nodes.

A 79-year-old woman was admitted to our hospital due to continuous anal bleeding. Colonoscopy showed a huge villous tumor on the middle area of the ascending colon. A typical right colectomy and lymph node dissection were performed. The resected specimen showed a villous type tumor located on the ascending colon. The histopathologic investigation demonstrated a moderately differentiated adenocarcinoma arising in a tubulovillous adenoma and extending to the submucosa. Although there was no evidence of metastatic carcinoma in the dissected lymph nodes, epithelioid cell granulomas with multinucleated giant cells lacking in the central caseous necrosis suggested sarcoid reaction.

Adenocarcinoma↗

Cancer and adenomatous polyp distribution in the colorectum.

OBJECTIVE: To examine the possible role of adenomatous polyps in colorectal cancer development, this study focused on the relationship of the distribution between adenomatous polyps and cancer in the colorectum. METHODS: The distribution of 753 adenomatous polyps was compared with that of 35 colorectal cancer lesions in 510 male patients ranging from 45 to 55 yr of age who underwent a total colonoscopy. RESULTS: The incidence of cancer significantly increased with a distal shift in the colorectal sites in comparison with that of adenomatous polyps (p < 0.02). CONCLUSION: The different distribution between adenomatous polyps and cancer thus suggested that adenomatous polyps at various colorectal sites appear to have a different malignant potential for cancer development.

Adenocarcinoma↗

Usefulness of preoperative transvaginal ultrasonography for women with advanced gastric carcinoma.

OBJECTIVE: Transvaginal ultrasonography (TVUS) is widely used to diagnose diseases in obstetrics and gynecology. We performed TVUS for diagnosing peritoneal dissemination preoperatively in cases of advanced gastric carcinoma in women. METHODS: Thirty-six female patients with advanced gastric carcinoma were investigated in the current study. TVUS was performed for 24 patients. Computed tomography (CT) was done for all of the women, and the sensitivity and specificity in detecting the existence of ascites were compared between the two in preoperative examinations. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT in detecting ascites were 46.7%, 100%, 100%, 72.4%, and 77.8%, respectively. The results of TVUS were rated as 80%, 100%, 100%, 87.5%, and 91.7%, respectively. CONCLUSIONS: Preoperative TVUS is quite significant for predicting the existence of peritonitis carcinomatosa in women with advanced gastric carcinoma. The aim of the current study was to reduce the use of inappropriate and invasive surgical treatments, including exploratory laparotomy, for women with incurable advanced gastric carcinoma.

Adult↗

Recurrences and relation to tumor growth potential and local immune response in node-negative advanced gastric cancer.

Biological characteristics and the prognosis for subjects with node-negative advanced gastric cancer have been given little attention in related literature. We analyzed data on 112 patients with serosally invasive gastric cancer who were lymph node metastasis-negative; all had been surgically treated in the Department of Surgery II, Kyushu University Hospital, between 1970 and 1992. Recurrences and relation to the growth potential of the tumor and local immune response were examined. Thirty patients died with a recurrence of the gastric cancer, and in these patients, the tumor was larger, the whole stomach was more frequently involved and infiltrative growth was more common, compared to findings in patients who were recurrence-free. Peritoneal recurrence was evident in half the number of patients and the 5-year survival rate was 74. 5%. Tumor growth potential was evaluated, based on the level of proliferating cell nuclear antigen (PCNA) of the primary tumor and on dendritic cell infiltration into the tumor, determined as a level of local immune function of the host. Higher growth potential and lower immune levels were more frequent in patients with recurrences. Multivariate analysis revealed that tumor size and PCNA labeling index were significant prognostic factors for node-negative gastric cancers. In a subset of advanced gastric cancers, there was no apparent distinct lymph node metastasis and the prognosis was better. However, cancer cells with a higher growth potential and a lower immune response in the host can biologically amplify and mainly infiltrate the gastric wall, extend to the serosa and disseminate transserosally into the peritoneum.

Aged↗

An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group.

5-Fluorouracil (5-FU) or a 5-FU derivative 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) has been widely prescribed for patients with gastrointestinal cancer. However, the phosphorylation of 5-FU in the digestive tract causes gastrointestinal toxicities. 5-FU is also rapidly degraded to alpha-fluoro-beta-alanine after contact with dihydropyrimidine dehydrogenase (DPDase) which is mainly present in the liver. Therefore, to overcome these metabolic events, S-1, an antitumor agent was developed, based on the biochemical modulation of FT by 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo), in a molar ratio of 1:0.4:1. The antineoplastic effect of S-1, was examined in Japanese patients with advanced gastric (G) or colorectal (C) cancer in a multicenter early phase II study involving 24 centers throughout Japan. The patients were prescribed a minimum of 2 courses of S-1 orally, with each course consisting of 75 or 50 mg (in terms of FT) twice a day for 28 days followed by withdrawal for 2 weeks. Thirty-one patients with G and 31 C were entered into this study. The clinical response and extent of toxicity were evaluated in G 28 and C 30 cases, respectively. Nine (32.1%) G patients and 14 (46.7%) C patients had been treated previously with other anticancer drugs. In G patients, there was a 53.6% (15/28) and in C patients a 16.7% (5/30) response rate (90% confidence interval G 38.4-68.1% and C 8.4-30.5%) with 15 (53.6%) (G) and 5 (16.7%) (C) partial responses (PR), and these responses persisted for 79 days (G) and 120 days (C) (median value). In particular, the response rate for the primary lesion was 27.8% (5/18) (G) and 33.3% (1/3) (C). No change (NC) in the disease was observed in 4 (14.3%) (G) and 13 (43.3%) (C) patients, and in 6 (21. 4%) (G) and 7 (23.3%) (C) the disease progressed (PD). At the time of analysis, the median survival was 298 days (G) and 358 days (C). Major adverse effects consisted of gastrointestinal symptoms and myelosuppression while toxicities of grade 3 or more occurred in 35. 7% (10/28) (G) and 33.3% (10/30) (C). Based on these data, S-1 is considered to have positive effects in patients with advanced gastrointestinal cancer.

Adult↗

Invasive thymoma with long-term survival by extensive reoperation.

The recurrence of invasive thymoma is often observed; however, no accepted treatment of recurrent invasive thymoma has yet been established. We herein report a 41-year-old woman with invasive thymoma and pleural dissemination who demonstrated long-term survival after undergoing 4 operations. Based on our findings, reoperation is thus suggested in patients with intrathoracic recurrence and long-term survival can be expected.

Adult↗

Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.

Amino Acid Sequence↗

Role of transforming growth factor-beta 1 in invasion and metastasis in gastric carcinoma.

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-beta1 in invasion and metastasis in gastric cancer. MATERIALS AND METHODS: We detected TGF-beta1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-beta1 levels in the peripheral vein and in the tumor drainage vein were assayed. RESULTS: In the cytoplasm of cancer cells, TGF- beta1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-beta1-negative primary tumor, metastatic lymph nodes were positive for TGF-beta1 staining in 32 cases (54.2%). Positive staining of TGF-beta1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-beta1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-beta1 did not differ between TGF-beta1-negative and -positive groups. There were also no differences in plasma TGF-beta1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings. CONCLUSION: Transforming growth factor-beta1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-beta1 in the tumor does not contribute to the total amount of TGF-beta1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-beta1 alters the biologic behavior of the tumor.

Aged↗

A significant morphological transformation is recognized in human esophageal cancer cells with an amplification/overexpression of the cyclin D1 gene.

Amplification and expression status of the CCND1 gene in 12 cell lines derived from esophageal cancer was evaluated and the differences in the cell proliferation and morphology were investigated. Amplification was observed in 6 cell lines, all of which consequently overexpressed the mRNA. Although the amplification of the gene did not contribute to an increase of cell proliferation, an in vitro morphological transformation was observed in the colonies with an amplification of the CCND1 gene. An amplification/overexpression of the CCND1 gene plays an important role in the enhancement of cell transformation in esophageal squamous cell carcinoma cells.

Blotting, Northern↗

[Clinical evaluation of S-1, a new anticancer agent, in patients with advanced gastrointestinal cancer. S-1 Cooperative Gastrointestinal Study Group].

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Administration, Oral↗

Increased prostacyclin production after percutaneous transluminal angioplasty of the iliac artery for atherosclerosis obliterans.

BACKGROUND: Endothelial prostacyclin production is modulated by blood flow (wall shear stress). Local plasma prostacyclin concentrations and hemodynamic parameters have therefore been investigated in patients with atherosclerosis obliterans before and after angioplasty. METHODS. DESIGN: Prospective study. SETTING: Department of Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan. PATIENTS: Nine lower limbs in eight patients with significant stenoses of the iliac artery were studied. INTERVENTIONS: blood samples were obtained from the femoral artery and femoral vein of nine lower limbs undergoing percutaneous balloon angioplasty of the iliac artery. MEASURES: Prostacyclin concentrations, radioimmunoassayed as 6-keto-prostaglandin F1 alpha, were measured before and after balloon dilatation. Femoral blood flow and the ankle-brachial pressure index (ABI) were measured using a Doppler velocimeter before and after the procedure. The femoral blood flow waveform was used to calculate the mean blood flow and shear stress variation. RESULTS: Before angioplasty, the mean (+/- SEM) plasma prostacyclin concentration was 21.6 +/- 1.5 pg/ml in the femoral artery and 25.4 +/- 1.1 pg/ml in the femoral vein. After angioplasty, these values increased to 25.6 +/- 2.2 pg/ml (p < 0.05) and 32.8 +/- 1.8 pg/ml (p < 0.01), respectively. The pre-procedural ABI, mean flow rate, and shear stress variation were 0.596 +/- 0.071, 354.1 +/- 63.3 ml/min, and 69.1 +/- 9.9 dyne/cm2, respectively. Both ABI and shear stress variation increased after angioplasty to 0.738 +/- 0.076 (p < 0.05) and 111.1 +/- 24.2 (p = 0.0775) dyne/cm2, but the mean flow rate (287.1 +/- 61.1 ml/min after angioplasty) did not increase (p = 0.2002). CONCLUSIONS: These results suggest that prostacyclin production increases after angioplasty, possibly due to increases in the intraluminal pressure and shear stress variation. This enhanced prostacyclin production may help to maintain arterial or bypass graft patency.

Aged↗

Factors influencing late survival after abdominal aortic aneurysm repair in Japanese patients.

BACKGROUND: To determine the factors influencing the prognosis of patients with abdominal aortic aneurysms (AAA), the clinical characteristics and long-term survival of 366 consecutive patients were examined and compared with those in previous Western studies. METHODS: During the period from January 1979 to December 1995, 376 patients with AAA were admitted to our hospital. Among these, 332 consecutive patients underwent elective reconstruction of infrarenal AAAs. The remaining 44 patients were not surgically treated. With use of the data from the patients who underwent AAA resection, the relationship of various risk factors, such as cardiac dysfunction, hypertension, renal dysfunction, pulmonary dysfunction, and age, to survival rate was investigated by univariate and multivariate analysis. RESULTS: The operative mortality rate was 0.6%. The survival of the patients who underwent the operation at 5 years was 71.0% and at 10 years 51.8%. The survival rate of the patients who were not surgically treated at 5 years was 26.0% and at 10 years 14.9%. There was a significant difference between the 2 groups. A univariate analysis was performed on each possible risk factor affecting survival rates. In relation to the survival rate of 5 and 10 years, there was no statistical significant difference between patients with or without heart disease or hypertension. By contrast, factors influencing long-term survival were associated with renal dysfunction, pulmonary dysfunction, and age at time of surgery. Multivariate analysis of risk factors affecting survival rates demonstrated that renal dysfunction, pulmonary dysfunction, and age at the time of operation were found to be significant, respectively. The main cause of the death for the long-term survival patients with AAA repair was malignancy, whereas that in the patients without repair was rupture. CONCLUSIONS: Risk factors influencing survival after AAA repair were renal dysfunction, pulmonary dysfunction, and advanced age in Japanese patients. In addition, the main cause of death after aneurysmal resection was malignancy. These results were different from outcomes in Western patients. We need to carefully watch out for malignancy during the follow-up period after AAA resection.

Aged↗

[Treatment strategy for and clinical results in patients with recurrent esophageal cancer].

In the current study, we evaluate the frequency and pattern of recurrence in patients with esophageal cancer. Among 116 patients who had undergone curative resection for esophageal cancer, recurrence was found in 33 (28.4%). The most frequent pattern of recurrence was lymphatic (54.5%), followed by the mixed type (18.2%), hematogenic (12.1%), locoregional (12.1%), and anastomotic (3.0%) patterns. Recurrence was found within 1 year after surgery in 18 (54.5%), within 2 years in 12 (36.4%), and within 3 years in 3 (9.1%). In patients with recurrence, lymph node metastasis and advanced stage were seen more frequently than in those without recurrence. The prognosis for patients with recurrent disease is poor. However, in some cases surgical resection, systemic chemotherapy, hepatic arterial infusion chemotherapy, and local radiation therapy have proven to be effective. The most appropriate therapy should be selected based on the region of extension and patient performance status to provide optimum treatment of recurrent disease.

Aged↗

Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats.

BACKGROUND: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation. METHODS: Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups. RESULTS: The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group. CONCLUSION: dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats.

Amino Acid Sequence↗

[Usefulness of endovascular grafting for abdominal aortic aneurysm].

The purpose of this study was to determine the usefulness of endovascular grafting for abdominal aortic aneurysm (AAA) compared to conventional open repair. During the period from May 1998 through to April 1999, 16 patients (control group) with AAA underwent conventional open surgery and 6 patients (stent group) underwent endovascular grafting. Surgical data including operative time and intraoperative blood loss did not differ between the two groups. However, the postoperative parameters including the initiation of oral intake, the onset of flatus and the permission to walk were significantly sooner in the stent group than the control group. The postoperative changes of coagulopathy-fibrinolytic factor were comparable between the two groups. We conclude that the endovascular grafting is minimally invasive compared to conventional open surgery. In addition, there was no consumption coagulopathy in the endovascular grafting. However, it was necessary to develop new approach with new devices in order to perform endovascular grafting more safely.

Aged↗

[Factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma: univariate and multivariate analyses of 312 patients].

The purpose of this study was to clarify the factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma (HCC). Three hundreds and twelve patients who underwent hepatectomy for HCC between 1985 and 1994 were observed for at least 5 years. These patients were divided into 2 groups: 160 patients who died within 5 years after hepatectomy and 152 patients who did not die within 5 years. Statistical analysis by chi 2 test showed that the favorable factors linked to 5-year survival were (a) diabetes mellitus (-), (b) albumin > 3.7 g/dl, (c) hepaplastin test > 61%, (d) indocyanine green retention test at 15 minutes < 16%, (e) curative resection (+), (f) alpha-fetoprotein < or = 32 ng/ml, (g) portal vein invasion (-), (h) intrahepatic metastasis (-), and (i) stage I and II. Statistical analysis by stepwise regression test showed that the favorable factors linked to 5-year survival were (a) intrahepatic metastasis (-), (b) diabetes mellitus, (c) indocyanine green retention test at 15 minutes < 16%, (d) curative resection (+) and (e) alpha-fetoprotein < or = 32 ng/ml. When patients diagnosed with HCC, patients selection for hepatectomy should be done, based on the total estimation, such as tumor invasiveness, liver functions, and diabetes mellitus.

Analysis of Variance↗

[Correlation between clinical aggressiveness of thymic epithelial tumors and expression of tumor suppressor gene products (p53, p27)].

It is impossible to predict malignant potential of thymomas by conventional histopathological examination. In order to find a malignant marker of thymoma, we immunohistochemically examined the expression of the products of p53 and p27kip1, potential tumor suppressor genes in thymic epithelial tumors. The thymic epithelial tumors examined in the present study included 13 non-invasive thymomas, 7 invasive thymomas, and 4 thymic carcinomas. The thymic epithelial cells showed abnormal accumulation of p53 protein in 2 of 13 non-invasive thymomas (15.4%), 4 of 7 invasive thymomas (50%), and 3 of 4 thymic carcinomas (75%). The frequency of p53-expression paralleled with clinical aggressiveness. On the other hand, p27 showed no correlation with clinical aggressiveness. In conclusion, the present results suggest that the presence of p53-positive epithelial cells might be a useful indicator to predict malignant potential of thymoma.

Cell Cycle Proteins↗