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F Itoh

Publications and source records attributed to F Itoh.

At least 109 records · Page 6Linked to original sources

Expression and identification of aberrant c-kit transcripts in human cancer cells.

We have previously cloned and sequenced a novel 3.5 kb c-kit mRNA expressed in a colon carcinoma cell line Colo201. Here we examined the expression of this truncated form of c-kit in 14 gastrointestinal cancer cells and 16 hematopoieic cancer cells by RT-PCR. Expression of the aberrant c-kit transcript was observed in various cancer cell lines. Furthermore, a new transcript which is 78 bp shorter than the transcript previously described was identified and characterized. These results indicate that two kinds of aberrant c-kit transcript produced by alternative promoter in intron 15 are expressed in human cancer cells.

Adenocarcinoma↗

Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells.

Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.

Antigens, Neoplasm↗

Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma.

BACKGROUND & AIMS: Matrix metalloproteinases have been implicated in invasion and metastasis of various human malignant tumors, but its role in human hepatocellular carcinoma has not been characterized in detail. The aim of the present study was to examine the secretion and activation of metalloproteinases in liver tissues from patients with hepatocellular carcinoma and evaluate its relationship with clinicopathologic characteristics. METHODS: Activity of metalloproteinases was measured in 30 surgical specimen pairs of human primary hepatocellular carcinoma and adjacent nontumoral liver and in five cultured human hepatoma cell lines using zymography. A comparison of this activity with clinicopathological features was made. RESULTS: In the liver tissues, enhanced secretion of active forms of gelatinase A and matrilysin was associated with portal venous invasion (P < 0.05, respectively), intrahepatic metastasis (P < 0.05, respectively), and recurrence within the first postoperative year (P < 0.01 and P < 0.05, respectively). Enhanced messenger RNA expression for membrane type 1-matrix metalloproteinase was observed in 22 of 30 cases and associated with capsule invasion and the activation of progelatinase A (P < 0.05, respectively). CONCLUSIONS: Active gelatinase A, active matrilysin, and membrane type 1-matrix metalloproteinase may play an important role in tumor spread of human hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Non-insulin- and insulin-mediated glucose uptake in dairy cows.

Four mid-lactation Holstein dairy cows (mean milk yield on day of experiments 26.1 kg/d) were used in a series of experiments to establish the contribution of non-insulin-mediated glucose uptake to total glucose uptake at basal insulin concentrations. A secondary objective was to determine whether somatostatin affects the action of infused insulin. In part I of the experiment a primed continuous infusion [6,6-2H]glucose (45.2 micrograms/kg per min) was begun at time 0 and continued for 5 h. After 3 h of [6,6-2H]glucose infusion (basal period) a primed continuous infusion of insulin (0.001 i.u./kg per min) was administered for 2 h. Coincidental with the insulin infusion, normal glucose was also infused in order to maintain the plasma glucose concentration at euglycaemia. Part II of the experiment was the same as part I except that somatostatin was infused for 2 h (0.333 micrograms/kg per min) instead of insulin. In part III of the experiment both insulin and somatostatin were infused for the final 2 h. Plasma insulin levels were increased by insulin infusion (to 0.1476 to 0.1290 i.u./l for parts I and III respectively) and were reduced by somatostatin infusion in part II (to 0.006 i.u./l) relative to the basal periods (mean 0.021 i.u./l). Glucose uptake during somatostatin infusion (2.50 mg/kg per min; part II) was 92.0% of that observed in the respective basal period (2.72 mg/kg per min). Circulating insulin levels were much lower than the dose of insulin that causes a half maximal effect on glucose uptake (0.06-0.10 i.u./l for ruminants); consequently insulin-mediated glucose uptake was probably absent in part II. Secondly, glucose uptake following insulin only infusion (4.05 mg/kg per min) was significantly lower than that observed when insulin plus somatostatin was infused (4.69 mg/kg per min), indicating that somatostatin either directly or indirectly enhanced the action of insulin on glucose uptake.

Animals↗

Growth hormone does not affect non-insulin-mediated glucose uptake in sheep.

Four adult Merino sheep were used in the experiment, which was divided into four parts. For the 5 days before parts 1 and 3 saline was injected and for the 5 days before parts 2 and 4 growth hormone (GH; 4 mg day-1 subcutaneously) was injected. In parts 1 and 2 a primed continuous infusion of [6,6-2H2]glucose and either saline or GH, respectively, were infused for 5 h. The first 3 h was the control period. From 3 to 5 h insulin (0.5 mU kg-1 min-1) was infused. Coincident with the insulin infusion, normal glucose was also infused at a variable rate, dependent on the rapidly determined plasma glucose concentration, in order to keep the plasma glucose concentration constant. Parts 3 and 4 of the experiment were the same as parts 1 and 2, respectively, except for the following: the glucose isotope and saline or GH were infused for 7 h, from 3 to 7 h somatostatin (SRIF; 0.417 microgram kg-1 min-1) was infused, and from 5 to 7 h insulin was infused. Measurements of glucose turnover were made in the last 40 min of the control, insulin-only, SRIF-only and insulin-plus-SRIF infusion periods. Plasma insulin levels were reduced to below the level of detection by the SRIF infusion; under such conditions whole body glucose uptake should be entirely non-insulin mediated (NIMGU). Expressing glucose uptake as glucose metabolic clearance rate revealed that GH had no effect on NIMGU but significantly reduced the level of insulin-mediated glucose uptake (IMGU). Thus a reduction in the rate of NIMGU is probably not part of the mechanism by which GH repartitions glucose to sites of growth and milk production, whilst the present study confirms the antagonistic effect of GH on IMGU.

Animals↗

Infrequent alterations of the p16 (MTS-1) gene in human gastric cancer.

p16 (MTS-1, multiple tumor suppressor gene 1), a putative tumor suppressor gene, is one of the cyclin-dependent kinase inhibitors (CDI) and it regulates the G1/S transition of the cell cycle. To clarify the role of p16 in primary gastric cancer, we have investigated somatic mutations of this gene by using the polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) method. In 23 surgical specimens of primary gastric cancer, none were detected in exon1 and exon 2. Among the 6 human gastric cancer cell lines examined, PCR products were not found in 2, MKN28 and MKN45, suggesting the presence of homozygous deletions. No mutation was found in the other 4 cell lines. Furthermore, decreased expression levels were not observed in 13 gastric cancer tissues by reverse transcription PCR (RT-PCR). Considering the above results of PCR-SSCP and RT-PCR, genetic alterations of the p16 gene are rarely implicated in human gastric cancer tumorigenesis.

Actins↗

Low-molecular-weight heparin (dalteparin) demonstrated a weaker effect on rat bone metabolism compared with heparin.

We studied the pharmacological effects of dalteparin (low-molecular-weight heparin) and heparin on bone metabolism in rats. After their 28 days of consecutive intravenous injections, significant loss of bone weight and mineral contents was observed in the heparin-treated rats, whereas dalteparin slightly reduced bone mass. By the end of the experiment, the femora of 7 out of 8 rats fractured in the heparin (10,000 U/kg/day)-treated group, but none had broken in the control and dalteparin-treated groups. Serum osteocalcin levels were significantly decreased in the former group. The growth plate width of the tibia was increased in a dose-dependent manner, especially in the heparin-treated group. Histomorphometric assessment of tibia showed that the osteoid surface and mineral apposition rates were significantly reduced in the heparin-treated group, whereas the eroded surface was significantly increased in the heparin-treated group. The above results suggest that heparin not only augments bone resorption but also suppressed bone formation and that dalteparin has a weaker suppressive effect on bone formation compared with heparin.

Animals↗

Gene expression of MASH-1, MATH-1, neuroD and NSCL-2, basic helix-loop-helix proteins, during neural differentiation in P19 embryonal carcinoma cells.

We examined the gene expression of MASH-1, MATH-1, neuroD and NSCL-2 during neural differentiation of P19 embryonal carcinoma cells using reverse transcription-polymerase chain reaction and high performance liquid chromatography. These proteins are members of basic helix-loop-helix transcription factor family and their expressions are reported to be transient and restricted in the nervous system during early neurogenesis. Retinoic acid (RA-, 1 microM)-treatment and aggregation for 4 days induced and greatly increased MASH-1, neuroD and NSCL-2 mRNA in P19 cells. The increases peaked at day 3, 4 and 5, respectively. RA-treatment increased MATH-1 mRNA slightly. mRNA of MAP2, a neural differentiation marker, were increased by RA-treatment and the increases reached to the plateau at day 5. The results indicate that the gene expression of MASH-1, MATH-1, neuroD and NSCL-2 during neural differentiation in P19 cells is transient and the order is similar to that in the mouse embryo nervous system as previously reported.

Actins↗

[Emergency coronary artery bypass grafting in elderly patients].

Emergency coronary artery bypass grafting (CABG) in elderly patients still remains to be a therapeutic challenge for cardiac surgeons. The purpose of this study was to review the operative results of our emergency CABG in elderly patients and evaluate it's problems comparing with younger patients. Consecutive forty-three patients underwent emergency CABG for the past ten years were divided into two groups, that is 13 patients aged 75 years or older (group 1) and 30 younger than 75 years old (group 2). There were three in-hospital deaths (mortality rate: 23.1%) in group 1 and three (10.0%) in group 2. The lowest postoperative Ccr (19.1 +/- 8.9 ml/ min) in group 1 was significantly lower (p < 0.02) than that (35.6 +/- 14.4 ml/min) in group 2. Respiratory Index on the first postoperative day, which indicates lung dysfunction when it comes up to 2.0 or more, showed 2.65 in mean value in group 1 compared with 1.31 in group 2 (p < 0.05). Severe infections like sepsis were developed in 4 patients (30.8%) in group 1 and 2 (6.7%) in group 2 (p < 0.05). In conclusion, it was clearly suggested that kidney protection by earlier myocardial revascularization, prevention of severe infection and earlier introduction of respiratory physiotherapy in the postoperative period were advisable to improve the operative results of emergency CABG in elderly patients.

Adult↗

[Clinical efficacy of post-TUR prophylactic chemotherapy for superficial bladder cancer--the result of co-operative prospective randomized trial].

We have performed a prospective randomized clinical trial of post-operative prophylactic therapy for superficial bladder cancer since October in 1991. The criteria were as follows; age < or = 80 y.o., Ta/T1, TCC G1/G2, without CIS lesion and resectable cancer by TUR. The therapeutic arm was divided into three as follows: arm A intracystic instillation with Epirubicin; arm B: oral administration with 5-FU; arm C: combination of arm A and arm B. The number of registered patients were 20 in arm A, 18 in arm B, and 18 in arm C. The patient characteristics in every group were not significantly different. The prophylactic efficacy of arm A was superior to that in the other two groups.

Administration, Intravesical↗

Recombinant Plasmodium falciparum dihydrofolate reductase-based in vitro screen for antifolate antimalarials.

We describe the system for screening the effective antifolate antimalarials that uses the recombinant Plasmodium falciparum DHFR domain of the bifunctional DHFR-TS expressed in Escherichia coli, and were designed with amino acid alterations found in the DHFR genes of the antifolate resistant strains. The validity of the screen was verified by the subsequent examination of several substituted pyrrolo[2,3-d]pyrimidines for their antimalarial activity. Among the 120 chemical derivatives, 5 compounds were identified by their preferential inhibition of the drug sensitive pfDHFR to that of the mammalian isoenzyme. As compared to the sensitive enzyme, the decrease in response of the cycolguanil-resistant and pyrimethamine-resistant enzymes to the selected compounds were relatively moderate. This gave folds decrease in sensitivity of 0.8-7.5 and 3.6-29, respectively, while those for cycloguanil and pyrimethamine were 400 and 308. The compounds inhibited the growth of drug-sensitive cultured P. falciparum with 50% effective concentrations of the ranged 0.17-30 nM. As contrasted with the sensitive strain, the fold decrease in sensitivity of the resistant parasites were 0.9-2 and 15-50 in the case of the test compounds, while those for cycloguanil and pyrimethamine were 690 and 20,500. Moreover, the most selective pyrrolo-pyrimidine (P-1) showed in vivo activity against P. berghei in mice.

Animals↗

Inverse association of cell adhesion regulator messenger RNA expression with metastasis in human colorectal cancer.

Alterations in several classes of adhesion molecules have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored a possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon cancer cell lines. To further study the biological significance of CAR expression in colon cancer cells, a CAR expression vector was introduced into HT-29 cells, in which CAR is not expressed. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. In spite of similar growth properties with the controls, CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated CAR expression in 30 surgical specimen pairs of human colorectal cancer and adjacent noncancerous tissue using semiquantitative reverse transcription-PCR. In 14 of 30 cases (46.7%), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor:normal ratio of CAR expression was significantly lower in patients with lymph node metastasis than in those without it (P < 0.01) and in patients with distant metastasis than in those without it (P < 0.05). CAR expression was significantly lower in more advanced Dukes' stage tumors (P < 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.

ATPases Associated with Diverse Cellular Activitie↗

Enhanced secretion and activation of matrilysin during malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cancer cells.

BACKGROUND: Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Matrilysin mRNA has been reported to be overexpressed in colorectal cancer. The aim of this study was to evaluate the enzyme activity of this protein during colorectal cancer. The aim of this study was to evaluate the enzyme activity of this protein during colorectal carcinogenesis and its relationship with the invasiveness of colorectal cancer cells. METHODS: We have examined the levels of secreted matrilysin in various epithelial disorders of the colon using casein zymography. We have also examined the effect of matrilysin on the in vitro invasiveness of colorectal cancer cells using a modified Boyden Chamber method. RESULTS: The enzyme activities of matrilysin were detected in cancer tissue and adenoma tissue, whereas they were hardly detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis, and normal colon tissue. Enhanced secretion and enhanced activation of matrilysin were observed in cancer. An in vitro invasion assay revealed that the levels of secreted matrilysin-transfectants correlated positively with invasiveness. CONCLUSIONS: Our data suggest that the secretion and activation of matrilysin may be up-regulated during malignant conversion of colorectal epithelium. Matrilysin appears to contribute to in vitro invasiveness of colon cancer cells. Inhibitors of the enzyme may be of value in preventing colorectal cancer progression.

Cell Transformation, Neoplastic↗

Expression of CD10/neutral endopeptidase in normal and malignant tissues of the human stomach and colon.

The expression of common acute lymphoblastic leukemia antigen (CALLA; CD10), which is identical to neutral endopeptidase (NEP, EC3.424.11), was examined in the malignant and adjacent noninvaded tissues of the human stomach and colon (n = 27). All of 27 normal and 18 well or moderately differentiated adenocarcioma tissue specimens were positive for monoclonal antibody (mAb) NL-1 against CD10/NEP, whereas the expression level was clearly decreased in all of 9 specimens of poorly differentiated adenocarcinoma. In addition, all of 7 gastric or colorectal carcinoma cell lines tested showed decreased expression of CD10/NEP. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis of the crude antigen J5 from the normal colon tissue lysate by mAb J5 detected a single band of approximately 100 kDa that was consistent with that of NALM-6 cells used as a positive control. These findings suggest that CD10/NEP is expressed in normal epithelial cells of the human stomach and colon, whereas the expression level is decreased in the poorly differentiated type of adenocarcinoma.

Adenocarcinoma↗

Rheumatoid arthritis associated with ulcerative colitis.

This report describes a 58-year-old man with rheumatoid arthritis (RA) and interstitial pneumonia who suffered from low-grade fever, abdominal pain, and bloody diarrhea 16 months after the diagnosis of RA. Ulcerative colitis (UC) was diagnosed, based on endoscopic and histological findings. RA associated with UC is rare and the underlying mechanism is unknown. We discuss here whether vasculitis and HLA class may play some role in the association of RA with UC.

Arthritis, Rheumatoid↗

Subcapsular hematoma of the liver and pylethrombosis in the setting of cholestatic liver injury.

We describe a subcapsular hematoma of the liver and pylethrombosis in a patient who developed cholestasis 4 days after severe burn injury. On the 44th hospital day, severe anemia suddenly appeared with no determinable cause. This was the initial manifestation of hepatic hematoma. Cholestatic liver injury of unknown cause lasted throughout the clinical course. The patient subsequently died of hepatic failure 27 months after the burn injury. An autopsy confirmed pylephlebitis and pylethrombosis, which were considered to have contributed to the hepatic failure. This was a rare case of hepatic hematoma and pylephlebitis and pylethrombosis that developed after burn injury.

Aged↗