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Biomedical subjects

T Kuroki

Publications and source records attributed to T Kuroki.

At least 109 records · Page 6Linked to original sources
PubMed1999

Inhibition by 16,16-dimethyl prostaglandin E2 of tumor necrosis factor-alpha and interleukin-1beta production and messenger RNA expression in human monocytes stimulated by Helicobacter pylori.

We investigated the effects of 16,16-dimethyl prostaglandin E2 on the production of tumor necrosis factor-alpha and interleukin-1beta in human monocytes stimulated with Helicobacter pylori. Monocytes isolated from human peripheral blood were incubated for 24 hr with the extract of H. pylori diluted 1:100 to 1:100,000 by volume, a combination of the extract and 16,16-dimethyl prostaglandin E2, or a vehicle alone. The extract stimulated the production of tumor necrosis factor-alpha and interleukin-1beta and the expression of their messenger RNA in a dose-dependent manner. 16,16-Dimethyl prostaglandin E2 inhibited the production of these cytokines and their messenger RNA in the presence of H. pylori at doses higher than 10(-6) M, predominantly with tumor necrosis factor-alpha. These data suggest that antiinflammatory effects of prostaglandins on gastric mucosa are in part related to their effects on inhibition of production of proinflammatory cytokines by monocytes.

16,16-Dimethylprostaglandin E2↗
PubMed1999

Detection of the pancreas-specific gene in the peripheral blood of patients with pancreatic carcinoma.

The prognosis of patients with pancreatic carcinoma remains very poor. To improve the therapeutic results, the early detection of this cancer is needed. The present study was performed to detect the pancreas-specific gene, chymotrypsinogen, in the peripheral blood from patients with pancreatic carcinoma by using reverse transcription polymerase chain reaction (RT-PCR) in order to evaluate the clinical significance of this gene. Ten patients with pancreatic carcinoma, two with acute pancreatitis, three with chronic pancreatitis and ten control subjects were examined for the presence of chymotrypsinogen using RT-PCR techniques in the peripheral blood. To confirm that the chymotrypsinogen gene was expressed in a pancreas-specific manner, the expression of chymotrypsinogen in various types of human adult tissue was evaluated by RT-PCR. The specific band of the chymotrypsinogen gene was detected in the pancreas. Serial dilution studies demonstrated the chymotrypsinogen gene to be detected at a concentration of one pancreatic cell per 10(6) peripheral blood cells. Seven out of the ten (70%) patients with pancreatic carcinoma were found to be positive based on the RT-PCR findings. In contrast, no pancreas-specific gene was detected in the peripheral blood of any patients with acute pancreatitis, chronic pancreatitis or the control subjects. Our observations show that the detection of the pancreatic specific gene, chymotrypsinogen, is therefore useful as a genetic diagnostic marker in pancreatic carcinoma.

Adult↗
PubMed1999

Adenovirus-mediated gene transfer to keratinocytes--a review.

The introduction and expression of a foreign gene provide a powerful tool for investigating functions and regulation of a gene of interest; however, keratinocytes have a major drawback in that foreign genes are hardly transfected by conventional methods and stable transformants are most difficult to establish in normal keratinocytes with a limited short life span. To overcome these problems, we used an adenovirus vector, Ax, developed by Saito et al, which yields desired recombinant viruses at an efficiency about 100-fold that of conventional methods, and by which genes are expressed at a high level under the control of a composite CAG promoter. We established Ax vectors carrying various isoforms of protein kinase C (PKC). Using these vectors, we found that the eta and delta isoforms of PKC, but not the alpha and zeta isoforms, mediate terminal differentiation in normal human keratinocytes. These Ax-vectors are also applicable to organ culture of mouse embryos. Advantages and disadvantages of adenovirus vectors and their use for keratinocyte biology are reviewed.

Adenoviridae↗
PubMed1999

Down-regulation by bucillamine of lamina propria leucocytes in the rat colitis model.

1. The efficacy of bucillamine has been reported in various inflammatory models. 2. In the present study, the effects of 2 weeks administration of bucillamine on hapten-induced experimental rat colitis were analysed. The gross morphological damage score was evaluated and the expression of CD4, CD8, CD11a, CD11b, CD25, CD54 and class II major histocompatibility complex (MHC) antigen was investigated by immunohistochemical methods. 3. Mean bodyweight was significantly increased in colitic rats given 750 micrograms bucillamine compared with colitic rats given vehicle (distilled water). Gross morphological damage was significantly less in colitic rats given 250 or 750 micrograms bucillamine compared with rats given vehicle. 4. Immunohistological studies revealed that CD4, CD11a, CD11b, CD54 and class II MHC antigen expression of infiltrating leucocytes was significantly lower in rat colonic mucosa treated with bucillamine. 5. From these findings, it appears that bucillamine may act through the down-regulation of the activation of lamina propria leucocytes in hapten-induced rat colitis.

Animals↗
PubMed1999

Calcitriol for bone disease in patients with cirrhosis of the liver.

BACKGROUND: Osteoporosis is associated with cirrhosis of the liver, but the effects of therapy for osteoporosis associated with cirrhosis are still controversial. METHODS: We evaluated the effects of calcitriol (1alpha,25-dihydroxyvitamin D3) on bone mineral density (BMD) in 76 patients (26 men and 50 women) with cirrhosis who were assigned randomly to receive calcitriol (0.5 mg twice per day) or not. The BMD of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at least twice, 12-57 months apart. RESULTS: For men, the mean annual change in BMD was 1.1% in the treated group and -0.4% in the control group. The median (25th and 75th percentiles) annual change in BMD was 0.6 (-0.1, 2.1%) in the treated group and -1.4 (-1.9, 1.6%) in the control group. The difference in the median annual change between the two groups was significant (P = 0.013). For women, the mean annual change in BMD was -0.5% in the treated group and -2.3% in the control group. The median (25th and 75th percentiles) annual change in BMD was -0.5 (-1.8, 1.3%) in the treated group and -1.5 (-3.8, -0.7%) in the control group. This difference was significant (P = 0.011). CONCLUSIONS: Our results suggest that calcitriol can prevent bone loss and, therefore, may be useful for the treatment of bone disease in patients with cirrhosis of the liver.

Absorptiometry, Photon↗
PubMed1999

Use of scintigraphy with 99mtechnetium galactosyl human serum albumin for staging of primary biliary cirrhosis and assessment of prognosis.

BACKGROUND: Conventional models for prediction of survival in patients with primary biliary cirrhosis (PBC) are based on the results of blood tests and on the clinical condition, which may be affected by treatment. We evaluated the usefulness of hepatic receptor imaging with [99mtechnetium]-diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) for the staging and prognosis of PBC without the need for reference to laboratory test results. METHODS: The subjects were 45 patients with PBC, 10 healthy subjects, 62 patients with chronic hepatitis and 144 patients with cirrhosis. Computer acquisition of gamma-camera data was started just before the injection of 185 MBq [99mTc]-GSA and was stopped 20 min later. Time-activity curves were generated from regions of interest (ROI) for the heart and liver. A receptor index was calculated by dividing the radioactivity of the liver ROI by that of the liver-plus-heart ROI 15 min after the injection. An index of blood clearance was calculated by dividing the radioactivity of the heart ROI 15 min after the injection by that of the heart ROI 3 min after the injection. RESULTS: The median receptor index was higher in patients with PBC than in those with cirrhosis. Among patients with PBC, the receptor index was lower in those with stage IV disease than in those in stages I, II or III. The index of blood clearance was lower in patients with PBC than in those with cirrhosis. Among patients with PBC, the index of blood clearance was higher in those with stage IV disease than in those in stages I, II or III. The receptor index was correlated significantly both to the risk score of the Mayo model and to the prognostic index of the Japanese model. The index of blood clearance was also correlated significantly to this score and prognostic index. CONCLUSIONS: Hepatic receptor imaging with [99mTc]-GSA is useful for the evaluation of hepatic functional reserve, staging of PBC and assessment of prognosis.

Asialoglycoprotein Receptor↗
PubMed1999

Influence of rebamipide on indometacin-induced gastric hemorrhage in rats under restraint stress.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examined in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Severe gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide (3, 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.

Acute Disease↗
PubMed1999

HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway.

Although it is established that growth factors and prostaglandins function in the maintenance of gastric mucosal integrity and in the healing of gastric mucosal injury and ulceration, the regulatory relationship between growth factors and prostaglandins in the gastric mucosa is not well characterized. Therefore, we investigated whether hepatocyte growth factor (HGF) affects expression of COX-2 (the inducible form of the prostaglandin synthesizing enzyme, cyclooxygenase) in gastric epithelial cells and whether this action is mediated through the MAP (ERK) kinase signaling pathway. In RGM1 cells (an epithelial cell line derived from normal rat gastric mucosa), HGF caused an increase in COX-2 mRNA and protein by 236% and 175%, respectively (both P<0.05). This induction of COX-2 expression was abolished by pretreatment with the MAPK kinase (MEK) inhibitor PD98059. HGF also triggered a 13-fold increase in c-Met/HGF receptor phosphorylation (P<0.005) and increased ERK2 activity by 684% (P<0.01). Pretreatment with PD98059 abolished the HGF-induced increase in ERK2 activity, but not c-Met/HGF receptor phosphorylation. The specific inhibitor of p38 MAP kinase, SB203580, had no effect on HGF-induced COX-2 expression. Thus, HGF triggers activation of the COX-2 gene in gastric epithelial cells through phosphorylation of c-Met/HGF receptor and activation of the ERK2 signaling pathway.-Jones, M. K., Sasaki, E., Halter, F., Pai, R., Nakamura, T., Arakawa, T., Kuroki, T., Tarnawski, A. S. HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway.

Animals↗
PubMed1999

Endoscopic resection of two granular cell tumours of the oesophagus.

Granular cell tumour of the oesophagus is rare and usually single. It is diagnosed by endoscopic appearance, results of endosonography, and histological examination of biopsy specimens. Although histological examination is required for diagnosis, it is difficult occasionally to obtain tumour samples by forceps because granular cell tumour is usually located in the submucosal layer. We report the case of a Japanese man with two granular cell tumours of the oesophagus. One lesion was diagnosed as a granular cell tumour by histological examination of a biopsy specimen, but the other was not. Endoscopic resection was performed to obtain the diagnosis and treat the lesions since some granular cell tumours are potentially malignant. Both tumours were completely resected endoscopically, and the diagnosis of granular cell tumour could be established by histological examination of resected tissue. Endoscopic resection is thus useful in the diagnosis and treatment of granular cell tumour of the oesophagus.

Adenocarcinoma↗
PubMed1999

Effects of continuous hepatitis with persistent hepatitis C viremia on outcome after resection of hepatocellular carcinoma.

The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.

Aged↗
PubMed1999

Complete regression of recurrent esophageal carcinoma with reduced expression of glutathione S-transferase-pi by treatment with continuous infusion of 5-fluorouracil and low-dose cisplatin infusion.

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-pi, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-pi might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

Antimetabolites, Antineoplastic↗
PubMed1999

Type 1 T-helper cell predominance in granulomas of Crohn's disease.

OBJECTIVE: The pathogenesis of Crohn's disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC). METHODS: We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12). RESULTS: In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC. CONCLUSIONS: The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.

Adult↗