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Biomedical subjects

K Kotoh

Publications and source records attributed to K Kotoh.

At least 19 recordsLinked to original sources
PubMed2005

Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells.

BACKGROUND: In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. MATERIALS AND METHODS: Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. RESULTS: Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 micromol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. CONCLUSION: These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.

Animals↗
PubMed2005

[New technique to determine graft length using the proximal anastomotic system during off-pump coronary artery bypass grafting].

For determining the graft length for an aortic connector, grafts to the circumflex (Cx) and the posterior descending (PD) regions often present problems. Difficulties in determining the appropriate distance between the aorta and coronary artery have been reported to be due to changes in the morphology of the heart following the evolution of Cx and PD. We set an intermediate point (IMP) in advance and then determine graft distance in 2 steps. When using the IMP method, determination of the graft length in the Cx region is not difficult. However, attention should be paid to determine the distance between the IMP and anastomosed site without deforming the heart, as the graft length becomes shorter if the heart as a whole is pulled up by traction of the diaphragm during evolution to the PD region.

Coronary Artery Bypass, Off-Pump↗
PubMed2004

Movement of a novel serum tumour marker, RCAS1, in patients with biliary diseases.

BACKGROUND: We have demonstrated immunohistochemically that RCAS 1 antigen is expressed in biliary neoplasms. Serum RCAS 1 levels are also elevated in a high percentage of patients with intra-hepatic cholangiocarcinoma. AIM: The study was designed to determine whether serum levels of RCAS1 are of clinical significance as a tumour marker for biliary tract tumour, in comparison to CA19-9. PATIENTS AND METHODS: In 38 patients with biliary carcinoma (gallbladder carcinoma, extra-hepatic and intra-hepatic cholangiocarcinoma and ampullary carcinoma), we measured serum RCAS1 and CA19-9 levels. For control, serum samples from patients with benign biliary disease and healthy volunteers were also examined. RESULTS: We established a threshold value for RCAS1 of 17.5 U/ml, which permitted discrimination between malignant and non-malignant biliary diseases. In comparison to CA 19-9, serum RCAS1 was more sensitive and specific for malignancy, and was not influenced by cholestasis. RCAS1 levels varied with respect to the disease course and the effect of clinical treatment. CONCLUSIONS: Serum RCAS1 appears to be valuable as a diagnostic index for biliary carcinomas, as well as for evaluating the progression of cancers during therapy. We speculate that RCAS1 is a clinically more significant serum marker for biliary neoplasms than CA19-9.

Antigens, Neoplasm↗
PubMed2004

[Beating heart coronary artery bypass grafting for acute myocardial infarction].

We consider that off-pump coronary artery bypass grafting (CABG) [OPCAB], which results in local myocardial ischemia, is more effective for patients with acute myocardial infarction (AMI) than conventional CABG under cardiac arrest with global myocardial ischemia. Twenty-one patients (15 males, 6 females) received OPCAB for AMI, among whom surgery was performed following percutaneous coronary intervention (PCI) failure in 4 and PCI was performed prior to OPCAB in 2, while PCI was not performed in the remaining 15. Preoperatively, 16 patients had intraaortic balloon pumping (IABP), and 4 had IABP and percutaneous cardiopulmonary support (PCPS). The mean interval from onset to surgery was 11.7 (range 3 to 40) hours. In 20 cases, a complete revascularization was performed. The mean number of bypasses was 2.3 and OPCAB was carried out in 14 patients. In 2 cases, OPCAB was converted to on-pump beating CABG for complete revascularization. Fourteen patients (67%), each maintained with preoperative left ventricular ejection fraction (EF), were discharged with an elective bypass. Four patients died after on-pump beating CABG, in whom EF was lower than 10%. In addition, 3 died of low cardiac output syndrome (LOS) under PCPS and 1 of ventricular fibrillation. Based on our results, we considered that complete revascularization using OPCAB was effective for cases of AMI with PCI difficulty. However, in shock cases requiring PCPS, cardiac function was not improved even after revascularization. Therefore, it is necessary to study new procedures for shock cases during the period from onset to surgery.

Aged↗
PubMed2004

[A constrictive pericarditis on oral steroid and immunosuppressant treated with bilateral anterolateral thoracotomy; report of a case].

A successful case of pericardiectomy without median sternotomy for an immunosuppressive 59-year-old man with constrictive pericarditis (CP) was reported. He had a history of invasive thymoma, myasthenia gravis and pure red cell aplasia, and he was on oral steroid and immunosuppressant. Pericardiectomy was performed by the approach of bilateral anterolateral thoracotomy to avoid troubles due to median sternotomy under immunosuppression, and there was no postoperative infection such as mediastinitis. Bilateral anterolateral thoracotomy was considered to be useful for immunosuppressive cases.

Anti-Inflammatory Agents↗
PubMed2003

A novel tumour marker RCAS1 in a case of extramammary Paget's disease.

A 66-year-old male, whose primary skin lesion in extramammary Paget's disease had been surgically resected 4 years previously, was hospitalized with liver metastases. Hepatic arterial infusion chemotherapy was carried out and the tumours clearly reduced in size. Serum levels of some common tumour markers were not elevated, even prior to therapy. We measured serum levels of a novel tumour-associated antigen, RCAS1, because its expression was detected in the tumour cells. The patient's serum RCAS1 level was elevated (22.0 U/mL) before therapy and fell during (10.5 U/mL) and after (5.0 U/mL) therapy. Therefore, serum RCAS1 levels may be valuable as a potential biomarker for monitoring therapeutic efficacy against Paget's disease.

Aged↗
PubMed2003

Multiple minimally invasive direct CABG for the complete revascularization: the figure L approach.

BACKGROUND: Coronary artery bypass grafting on the beating heart via median sternotomy causes significant hemodynamic compromise during displacement of the heart, especially in patients with low ejection fraction or those who have potential catastrophic sternal reentry injuries. We have developed an innovative minimally invasive surgical approach (figure L Approach) for the treatment of multi-vessel coronary artery disease; especially in cases with huge hearts (> CTR 50 %) including tracheostomy requiring COLD, and redo cases. The objective of this study was to assess the efficacy and safety of this alternative surgical incision. METHODS: From January 1998 to March 2001, 22 patients underwent complete revascularization using this figure L Approach. Left submammary anterior thoracotomy incisions are made with the medial part of the incision vertically extending downward to the upper abdomen. The costal margin was divided. The pleural and peritoneal spaces were then entered. A chest retractor was placed to elevate the chest wall, exposing the heart and stomach. Two to four arterial grafts including LIT A, RGEA, RA and IEA were harvested. Revascularization of the LAD, LCX and distal RCA were performed in 22 patients without cardiopulmonary bypass on complex performed arterial grafts using this approach. In four patients, triple and quadruple vessel grafting was performed. RESULTS: No early deaths or postoperative complications occurred. The mean coronary clamp time was 12.5 +/- 5.1 minutes for the LAD, 10.8 +/- 1.8 minutes for diagonal branch, 14.1 +/- 2.9 minutes for the LCX and 16.0 +/- 5.1 minutes RCA time. There were no late deaths or angina during the mean follow-up of 37.3 +/- 9.0 months. Postoperative coronary angiography demonstrated widely patent grafts in all but one patient. Hemodynamics did not change significantly during the distal anastomoses. No wound-healing problems were experienced. CONCLUSIONS: Multiple MIDCABG using the figure L Approach represents a novel way of approaching both the LAD, CX and distal RCA in patients with multi-vessel disease, especially in those with low ejection fraction, huge heart (> CTR 50 %), or hemodynamically unstable patients, without any hemodynamic deterioration or sternal related complication.

Aged↗
PubMed2002

[Off-pump coronary artery bypass grafting/beating coronary artery bypass grafting for a patient with low left ventricular ejection fraction].

Beating coronary artery bypass grafting could be performed for a 47-year-old man with left ventricular ejection fraction (LVEF) of 9.3%. Post-operative LVEF was improved to 51.6%. Conventional coronary artery bypass grafting (CABG) used to be contraindicative for patients with LVEF below 20%. Recently, such patients are involved to indication of off-pump CABG (OPCAB) or beating CABG, because we consider OPCAB are lower complications than conventional CABG. We were able to bypass the circumflex for the patient while we had been used percutaneous cardio-pulmonary support (PCPS). We could perform beating coronary artery bypass grafting for a patient of the low LVEF.

Coronary Artery Bypass↗
PubMed2001

Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma.

RCAS1 has been reported as a tumor-associated antigen in uterine and ovarian carcinomas. In vitro studies on RCAS1 indicated that it might function as an apoptosis-inducing factor since binding between RCAS1 and its receptor induced apoptosis in receptor-expressing cells. In this study, 68 surgically resected samples of hepatocellular carcinoma (HCC) were prepared and RCAS1 expression was examined immunohistochemically, because RCAS1 was also positive in all HCC cell lines tested. Clinical and pathological parameters were then compared between RCAS1-positive and -negative HCC cases. As a result, RCAS1 is expressed in 26.5% of HCC cases and vascular invasion is observed at a much higher rate in the RCAS1-positive cases (72.2%) than in RCAS1-negative cases (24.0%). RCAS1 is not an antigen specific for gynecological cancers. In HCC cases, the RCAS1-positive percentage is not high, however, RCAS1-positive HCCs exhibited a trend towards invasive character.

Animals↗
PubMed2001

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma.

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.

Adult↗
PubMed2001

Fas antigen expression on hepatocytes predicts the short- and long-term response to interferon therapy in patients with chronic hepatitis C.

BACKGROUND: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV) -induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short-and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. METHODS: Ten million units of recombinant IFN-alpha2b were administered daily for the first 2 weeks, and three times a week for another 22 weeks. The short-term efficacy of IFN therapy was evaluated after 12-month follow-up from cessation of treatment. We also examined the long-term response to IFN at 56.6 +/- 10.8 (mean +/- s) months after termination of IFN therapy in 55 of 72 patients. RESULTS: Univariate analysis showed that serum HCV-RNA levels, HCV genotype and Fas expression significantly correlated with the short-term efficacy of IFN therapy (P = 0.005, 0.006, and 0.04, respectively). Fas antigen expression did not correlate with serum HCV-RNA levels (P = 0.286), but significantly correlated with HCV genotype (P = 0.003). Multivariate analysis indicated that Fas expression and serum HCV-RNA levels were independent determinants of the short-term response to IFN therapy. Combined together, Fas expression and serum HCV-RNA levels accurately predicted the short-term response to IFN therapy. On the other hand, in 55 patients who were examined the long-term response to IFN, about 60% of Fas-positive patients were HCV-RNA negative, whereas 30% of Fas-negative patients were HCV-RNA negative (P = 0.04). Among Fas-positive patients, the percentage of those with serum ALT levels persistently lower than twice the normal upper limit in long-term study (81.8%; 9/11) was significantly higher than those in short-term study even among patients who failed to show elimination of HCV-RNA (36.4%; 4/11, P = 0.03). CONCLUSION: Our results indicate that Fas expression on hepatocytes is a good predictor of the short-and long-term response to IFN therapy.

Adult↗
PubMed2001

Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats.

We studied the preventive effects of dimethyl sulfoxide (DMSO) on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral DMSO (2 ml/kg daily for 4 weeks) essentially prevented this DMN-induced body and liver weight loss with no major side effects. DMSO suppressed the induction of hepatic fibrosis, as determined by histological evaluation, and reduced hepatic hydroxyproline. It also suppressed the expression of mRNA for type I collagen in the liver. Because hepatic stellate cells (HSC) are the major cellular source of the collagen in hepatic fibrosis, we examined the effects of DMSO on collagen production in vitro using rat primary HSC culture. However, it was found that DMSO did not inhibit the collagen production in vitro. We next evaluated the effects of DMSO on tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production by Kupffer cells, because these factors represent major activator of HSC, and because monocyte-macrophage infiltration has been implicated as being pathogenetically important for hepatic fibrosis induced by DMN. DMSO inhibited lipopolysaccharide (LPS)-induced TNFalpha and NO production, and reduced TNFalpha mRNA levels. DMSO also suppressed the LPS-induced nuclear factor kappa B activation in a murine macrophage-like cell line. These results suggest that the inhibitory effects of DMSO on hepatic fibrosis may be primarily exerted via blocking of DMN-induced inflammation. These results also implied that DMSO may be potentially useful for preventing the development of hepatic fibrosis.

Animals↗
PubMed2001

[Evaluation of cases of off-pump CABG with mid-sternotomy].

Off-pump CABG was utilized on patients who had multivessel coronary artery disease and other organ diseases. A total of 79 patients who underwent off-pump CABG were evaluated. Of these, 66 suffered from OMI and AP, 4 form AP, 6 from u-AP, and 3 from AMI. LITA was used in 75 cases, RA in 48, GEA in 45, RITA in 13, IEA in 3, and SVG in 38. Revascularization was performed at # 2 in 3 cases, # 3 in 11, 4 PD in 37, 4 PL in # 7 or # 8 in 79, # 9 in 27, # 12 in 51, and # 14 in 17. A time of 10.3 min was spent on LAD revascularization, 9.8 min on D 1, 10.2 min on Cx, anf 11.5 on RCA. Seven patients were transferred to on-pump beating CABG because of hemodynamic instability. One patients suffered postoperative CVA, and 2 had wound infection. Complete revasculization was accomplished in 78 patients, and hospital death was not reported.

Aged↗
PubMed2000

Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C.

BACKGROUND/AIMS: To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodell's histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS: HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferroni's inequality method=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferroni's method=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7 Meq/ml vs. 3.1 Meq/ml, p=0.0007). CONCLUSION: These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the host's immune reaction regulated by HLA DR.

Adolescent↗
PubMed2000

Malignant melanoma in the thymus.

A case of malignant melanoma in the thymus is reported. Diagnostic imaging demonstrated a left anterior mediastinal mass in a patient with giant pigmented nevus without malignant change. Histologic and cytologic specimens obtained from the tumor revealed that the tumor was malignant melanoma. Surgery revealed malignant melanoma in the left lobe of the thymus. Many cell nests of pigmented nevi were observed throughout the thymus. The malignant melanoma was thought to have originated from the nevocellular nevus in the thymus. This is the first report of malignant melanoma in the thymus.

Adult↗