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T Kanematsu

Publications and source records attributed to T Kanematsu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance.

Although some previous studies have indicated the possibility of immunosuppression withdrawal in clinical liver transplantation, the mechanism of graft acceptance is not clear. The aim of this study is to elucidate the alloreactivity against the donor and intragraft cytokine profiles in living donor liver transplant (LDLT) recipients with graft acceptance. In October 1999, we had 23 patients who survived without immunosuppression after LDLT with a median drug-free period of 25 months (range: 3-69 months). They consisted of six patients who were electively weaned by an elective weaning protocol and 17 either forcibly or accidentally weaned patients due to various causes but mainly due to infection. We evaluated the alloreactivity against the donor in these patients by a mixed lymphocyte reaction and intragraft cytokine profiles by real-time reverse transcriptase-polymerase chain reaction. The development of donor-specific hyporeactivity was observed in the patients with graft acceptance. The cytokine pattern in the supernatant of the culture medium revealed a down regulation of T helper (Th) 1 cytokine INF gamma against the donor while no significant difference was seen in Th2 cytokine IL-10. Regarding the intragraft cytokine profiles, we could find no amplification of Thl cytokines (IL-2, INF y) and IL-4 while some of the patients revealed a gene expression of IL-10 with no significant difference from that of the normal, untransplanted liver specimen. In addition, no difference was observed in any other cytokines (IL-1beta, IL-8, IL-15, TNFalpha) compared with those of the normal controls. We propose that the down regulation of Th1 cytokine is one possible mechanism of graft acceptance in LDLT recipients.

Administration, Oral↗
PubMed2001

Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGF-I-induced chondrogenesis of the mouse embryonal carcinoma-derived cell line ATDC5.

The embryonal carcinoma-derived cell line, ATDC5, differentiates into chondrocytes in response to insulin/insulin-like growth factor-I (IGF-I) stimulation. In the present study, we examined whether insulin/IGF-I stimulation caused activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway in ATDC5 cells. We also determined whether the insulin-stimulated differentiation of ATDC5 cells into chondrocytes could be mimicked by activation of the PKB pathway alone. ATDC5 cells produced phosphatidylinositol 3,4,5-trisphosphate and the pleckstrin homology domain of PKB was recruited to the plasma membrane in response to insulin stimulation. This was probably a result of activation of PI3K because the PI3K inhibitors, wortmannin and LY294002, inhibited both responses, although the effective concentrations were as high as 10 microM. Insulin stimulation caused the chondrogenic differentiation of ATDC5 cells as assessed by chondrogenic nodule staining with alcian blue. The addition of wortmannin or LY294002, PI3K inhibitors, suppressed the staining, and the suppression was reversible, indicating the effect of the inhibitors is not toxic. Finally, we exogenously expressed a constitutively-activated from of PKB (myristoylated PKB, myr-PKB) in ATDC5 cells, and found the chondrogenic differentiation of ATDC5 cells to form nodules occurred in the absence of insulin stimulation. The kinase-negative mutant of myr-PKB did not caused differentiation, indicating that kinase activity is required. These results support the hypothesis that the PI3K/PKB signaling pathway is involved in the chondrogenic differentiation of ATDC5 cells in response to insulin/IGF-I stimulation. This is the first report that demonstrates the involvement of phosphoinositide signaling in the induction of chondrogenesis from undifferentiated cells.

Androstadienes↗
PubMed2001

Novel immunosuppressive effect of FK506 by augmentation of T cell apoptosis.

We have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.

Animals↗
PubMed2001

Successful treatment of bleeding due to ileal varices in a patient with hepatocellular carcinoma.

This case report concerns a 62-year-old female who was known to have cirrhosis. An endoscopic examination showed no evidence of haemorrhaging due to either oesophageal or gastric varices. Angiographic studies demonstrated extravasation from the ileal varices. There was a prominent arterio-portal shunt in the liver, and the shunt was considered to be a contributing factor to induce portal hypertension and variceal bleeding in the ileum. Therefore, transcatheter arterial embolization was performed, but was unsuccessful. As a result, the patient underwent a laparotomy, and a dilatating ileocaecal vein and a communicating ovarian vein were selectively ligated. Following the procedure, the haemorrhaging stopped and she then recovered. The patient is doing well 21 months after surgery at the time of writing.

Carcinoma, Hepatocellular↗
PubMed2001

Early pancreatic cancer.

The results of surgical treatment for ordinary carcinoma of the pancreas, even now considered the only means for cure, have been dismal. In order to define early pancreatic cancer, aiming amelioration of surgical results, early pancreatic cancer has been seeked. It may be readily conceivable that the smaller the tumor size, the earlier the lesion. The relationship between tumor size and surgical results was reviewed from the literature, some of which included articles written in Japanese. Tumor size < or = 2 cm in diameter is not always an early cancer. Tumor < 1 cm could be an early cancer but does not definitely reveal long-term survival. An increase of pancreatic cancer in Japan may be strongly related with the increased elderly population. Small cystic lesions which develop in elderly persons seem to indicate carcinogenesis of ordinary ductal cancer of the pancreas. Carcinoma in situ may be an early pancreatic cancer. Early pancreatic cancer is defined as an intraductal adenocarcinoma without any invasion or with minimal invasion to the stroma, regardless of size or extent of the lesion.

Adenocarcinoma, Papillary↗
PubMed2001

In vivo assessment of the regulatory mechanism of cholinergic neuronal activity associated with motility in dog small intestine.

Intestinal motor activity associated with acetylcholine (ACh) release was assessed in the small intestine of anesthetized dogs by simultaneous measurement of motor activity and local ACh concentrations within the intestinal wall with in vivo microdialysis. Basal concentration of ACh measured in the dialysate was 1.12 +/- 0.08 pmol/15 min (n = 10), a value that remained constant until 3 h after perfusion. Intra-arterial infusion of tetrodotoxin reduced dialysate ACh concentration, while the motor activity accelerated at the early phase after infusion of tetrodotoxin and then decreased, thereby suggesting that the motor activity is regulated by not only excitatory cholinergic neurons, but also inhibitory neurons. Intraarterial infusion of atropine increased dialysate ACh concentration but reduced motor activity, thereby indicating that the cholinergic neurons are tonically active and the muscarinic autoreceptors operate to inhibit the ACh release. Intraarterial infusion of norepinephrine reduced, but yohimbine increased both motor activity and dialysate ACh concentration, thereby indicating that the adrenergic neurons regulate the motor activity due to control of cholinergic neuronal activity. This in vivo microdialysis method demonstrated in the whole body of animals that the activity of cholinergic neurons was physiologically regulated by itself and adrenergic neurons.

Adrenergic alpha-Agonists↗
PubMed2001

Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.

We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study.

Adolescent↗
PubMed2001

[Bullous sarcoidosis--a case report].

A 37-year-old man was admitted to our hospital complaining of dry cough and dyspnea. His chest radiographs showed severe bullous changes in the upper lobes and scattered small nodules in the lower. During the course of further examination, a spontaneous left pneumothorax developed in the lung, and video-assisted thoracic surgery was performed to remove a bulla. Multiple noncaseous granulomas were seen and sarcoidosis was diagnosed. Here we report a case of pathologically investigated bullous sarcoidosis, which is rarely seen to generate bullae due to granulomatous lesions. Therefore, it is important to consider sarcoidosis in making a differential diagnosis when a diffuse lung disease with cystic change is encountered.

Adult↗
PubMed2000

Inhibition of Ca(2+) signalling by p130, a phospholipase-C-related catalytically inactive protein: critical role of the p130 pleckstrin homology domain.

p130 was originally identified as an Ins(1,4,5)P(3)-binding protein similar to phospholipase C-delta but lacking any phospholipase activity. In the present study we have further analysed the interactions of p130 with inositol compounds in vitro. To determine which of the potential ligands interacts with p130 in cells, we performed an analysis of the cellular localization of this protein, the isolation of a protein-ligand complex from cell lysates and studied the effects of p130 on Ins(1,4,5)P(3)-mediated Ca(2+) signalling by using permeabilized and transiently or stably transfected COS-1 cells (COS-1(p130)). In vitro, p130 bound Ins(1,4,5)P(3) with a higher affinity than that for phosphoinositides. When the protein was isolated from COS-1(p130) cells by immunoprecipitation, it was found to be associated with Ins(1,4,5)P(3). Localization studies demonstrated the presence of the full-length p130 in the cytoplasm of living cells, not at the plasma membrane. In cell-based assays, p130 had an inhibitory effect on Ca(2+) signalling. When fura-2-loaded COS-1(p130) cells were stimulated with bradykinin, epidermal growth factor or ATP, it was found that the agonist-induced increase in free Ca(2+) concentration, observed in control cells, was inhibited in COS-1(p130). This inhibition was not accompanied by the decreased production of Ins(1,4,5)P(3); the intact p130 pleckstrin homology domain, known to be the ligand-binding site in vitro, was required for this effect in cells. These results suggest that Ins(1,4,5)P(3) could be the main p130 ligand in cells and that this binding has the potential to inhibit Ins(1,4,5)P(3)-mediated Ca(2+) signalling.

3T3 Cells↗
PubMed2000

Direct influences of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6) on the proliferation and cell-surface antigen expression of cancer cells.

Pro-inflammatory cytokines, e.g. interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha), IL-6 produced by surgical intervention or non-specific immunotherapy may directly affect both the growth and the metastasis of tumour cells. It is therefore important to clarify the direct influence of pro-inflammatory cytokines on tumour cells in order to obtain a better knowledge of anti-tumour therapy. Four human lung cancer cell lines were used. The tumour cells were incubated for 72 h in the presence of various concentrations of IL-1beta, TNF-alpha, or IL-6 and then the proliferative response was assessed by an MTT assay. After 14 days of culture with each pro-inflammatory cytokine, the cell-surface antigen expressions (HLA-class I, HLA-class II, CEA, sialyl Lewis(x)) were assessed by an immunocytochemical staining method. Among the various combinations of tumour cells (PC-9, PC-12, QG-56, QG-95) and cytokines (IL-1beta, TNF-alpha, IL-6), only TNF-alpha significantly exhibited an antiproliferative effect against PC-9 cells. However, various modulations of the cell-surface antigen expression by the cytokines were observed. The HLA-class I antigen expression of PC-9 was augmented by either TNF-alpha or IL-1beta. Furthermore, IL-1beta was able to induce CEA in PC-9, QG-56, and QG-95 cells while TNF-alpha was able to enhance the expression of sialyl Lewis(x)in QG-95 cells. Although the influence of pro-inflammatory cytokines on the growth of tumour cells was only slight, some modulations of the cell-surface antigen expression were notable. The augmentation of HLA-class I expression can thus improve the immunogenicity of tumour cells while the induction of CEA or sialyl Lewis(x)may therefore be associated with the promotion of metastasis.

Adenocarcinoma↗
PubMed2000

A method for culturing and transplanting biliary epithelial cell from syrian golden hamster.

The present paper describes the establishment of a method for simultaneous culturing of biliary epithelial cells (BECs) from the gall bladder (GB), extrahepatic bile duct (EBD) and intrahepatic bile duct (IBD) of the hamster. GB, EBD and IBD were cut from the biliary tree after collagenase perfusion of the liver. These biliary segments were minced into fragments. The fragments were embedded in collagen gel and cultured in Dulbecco's modified Eagle medium/HamF12 medium containing 10% fetal bovine serum. The various cells subsequently spread from the fragments and formed cellular sheets. After the fragments and flattened cells were removed with the aid of a Pasteur pipette under phase-contrast microscopy, the sheets remaining were found to be composed of cuboidal cells. These cuboidal cells were shown to express gamma glutamyl transpeptidase and cytokeratin 7, which are known to be specific markers of BECs. Ultrastructurally, a large number of microvilli were observed on the luminal surface and junctional complex and interdigitation was identifiable on the lateral surfaces. BEC cultures were subcultured by digestion with collagenase and dispase and then dissociated by subsequent digestion in trypsin and ethylenediaminetetraacetic acid and then maintained on collagen gel for up to 8 weeks. After several passages, the BECs in culture eventually increased in size and showed vacuoles in the cytoplasm. They demonstrated irreversible growth arrest at 9 weeks. The BECs tended to form cystic structures when the BECs with collagen gel were transplanted into the interscapular fat pads of syngeneic hamsters. We established a method for culturing and transplanting biliary cells from syrian golden hamsters. This method may help to clarify the mechanism of hepatobiliary diseases.

Adipose Tissue↗
PubMed2000

Small-cell carcinoma of the gallbladder: report of a case.

We report herein the case of an 81-year-old woman in whom a mass in the gallbladder was revealed by an ultrasound examination conducted as part of a follow-up study for a silent gallstone. The mass showed evidence of invasion into the adjacent liver parenchyma. Under the tentative diagnosis of malignant neoplastic disease originating in the gallbladder, a cholecystectomy with partial hepatectomy was performed. Histological examination of the tumor confirmed a diagnosis of small-cell carcinoma of the gallbladder, which is considered to be a rare type of neoplasm.

Aged↗
PubMed2000

Tauroursodeoxycholate and cholestyramine enhance biliary carcinogenesis in hamsters.

The aim of this study was to examine whether tauroursodeoxycholate (TUDC) and cholestyramine resin (CR) enhance biliary carcinogenesis in the hamster model. A cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct was performed on Syrian hamsters. The hamsters were then divided randomly into 3 groups: control group, TUDC-treated group, and CR-treated group. All animals received N-nitrosobis(2-oxopropyl)amine (BOP) to initiate pancreaticobiliary cancer. The experiment was terminated at week 16 and the number of neoplastic lesions was counted microscopically. In the TUDC group, the intrahepatic biliary carcinogenesis was more accelerated than that observed in the control group, but no promoting effect was seen in the pancreas, gallbladder, or extrahepatic bile duct. In the CR group, both the intrahepatic biliary and the gallbladder carcinogenesis were inhibited compared with that observed in the control group and the TUDC group. TUDC enhanced the intrahepatic bile duct carcinogenesis, whereas CR inhibited both the intrahepatic bile duct and the gallbladder carcinoma. Bile acids were suggested to promote biliary carcinoma in the hamster model.

Administration, Oral↗
PubMed2000

Hepatic resections for bilobar liver metastases from colorectal cancer.

The present study was performed to assess survival benefits in patients who underwent a hepatic resection for isolated bilobar liver metastases from colorectal cancer. Thirty-eight patients underwent a curative hepatic resection for isolated colorectal liver metastasis. Among them, 11 patients had bilobar liver metastases and 19 had a solitary metastasis. The remaining 8 patients had unilobar multiple lesions. We investigated survival in two groups those with bilobar and those with solitary metastatic tumors. Survival and disease-free survival were 36% and 18% at 5 years, respectively, in the patients with bilobar liver metastases, while these survivals were 43% and 34% in the patients with solitary liver metastasis. In the 38 patients, repeated hepatic resections were performed in 15 patients with recurrent liver disease. The 5-year survival and disease-free survival rates for these patients were 38% and 27%, respectively, after the second hepatic resections. Of the 11 patients with bilobar liver metastases, 5 underwent a repeated hepatic resection, and they all survived for over 42 months. Based on our observations, a hepatic resection was thus found to be effective even in selected patients with either bilobar nodules or recurrence in the remnant liver.

Adult↗
PubMed2000

MRI facilitated a diagnosis of endometriosis of the rectum.

A 51-year-old pre-menopausal Japanese woman suffering from chronic lower abdominal pain was referred to our hospital. A barium enema showed a stenotic lesion in the recto-sigmoid region, and a pelvic computed axial tomography (CAT) scan revealed a thickened rectal wall. A colonoscopic examination showed the rectum to be constrictive, but the mucosa appeared to be intact. Magnetic resonance imaging (MRI) with T1 high-intensity revealed a cystic lesion in the thickened wall of the rectum, which led us to suspect possible bowel endometriosis. Part of the biopsy specimen showed endometrial epithelium within the interstitial layer of histologically normal mucosa; finally, endometriosis of the rectum was diagnosed. The patient became asymptomatic after the initiation of hormonal treatment and later experienced spontaneous menopause. MRI was effective for diagnosis and the patient did not undergo unnecessary laparotomy. Although bowel endometriosis is generally diagnosed by means of resected specimens, in our patient, diagnosis was made using MRI and biopsy, and hormonal therapy had an effective role as a bridge to menopause.

Biopsy↗
PubMed2000

Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility.

The multiple 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes are distinguished. In this article, we described mainly the 5-HT4 receptor of four subtypes of functional 5-HT receptors, 5-HT1, 5-HT2, 5-HT3, and 5-HT4, recognized in the gastrointestinal tract. In-vivo microdialysis experiments determined that activation of the 5-HT4 receptor stimulated intestinal motor activity associated with a local increase in acetylcholine (ACh) release from the intestinal cholinergic neurons in the whole body of dogs. The 5-HT4 receptor-mediated response of ACh release in the antral, corporal, and fundic strips isolated from guinea pig stomach corresponds to the presence of 5-HT4 receptor in the myenteric plexus. In-vitro receptor autoradiograms of the stomach and colon indicate that the distribution of 5-HT4 receptors in human tissues is similar to that in the guinea pig, although density of 5-HT4 receptors in the myenteric plexus of human tissues is lower than that in guinea pig tissues. The 5-HT4 receptors located in the myenteric plexus may participate in gastrointestinal motility, and thus the 5-HT4 agonists and antagonists may be available for treatment of dysfunction of gastrointestinal motility.

Animals↗