Biomedical subjects

F Itoh

Publications and source records attributed to F Itoh.

At least 91 records · Page 5Linked to original sources

PubMed1998

Effects of heat exposure on plasma insulin, glucagon and metabolites in response to nutrient injection in heifers.

Effects of heat exposure on plasma insulin, glucagon, and metabolite responses following injection of various nutrients were investigated in heifers. Four heifers, fed hay wafer and a commercial concentrate, were exposed to thermoneutral (20 degrees C) and hot (30 degrees C) environments. Glucose, arginine and butyrate (each injection at 0.625 mmol/kg) and insulin (0.2 U/kg) were injected intravenously, and then blood samples were collected at regular intervals through jugular vein catheters. Insulin secretion in response to glucose and arginine injection was not affected by heat exposure. However, the insulin response following butyrate injection was inhibited in heifers exposed to heat. In the hot environment, glucagon responses following the arginine and butyrate injections were augmented significantly, however glucagon levels were inhibited following the glucose injection. It is concluded that heat stress causes an inhibition of the insulin response to butyrate injection, and an increase in the glucagon response following arginine and butyrate injection. Plasma metabolite concentrations altered in accordance with the changes in the concentration of pancreatic hormones.

3-Hydroxybutyric Acid↗

PubMed1998

Insulin-independent glucose uptake in growth hormone treated dairy cows.

Our aim was to determine the effect of growth hormone on non-insulin-mediated glucose disposal in lactating dairy cows. Following 5 d of subcutaneous injections of either saline or growth hormone, insulin, somatostatin or insulin plus somatostatin were infused for 2 h each, in a series of experiments. Coincident with this, unlabelled glucose was infused at a variable rate to maintain a constant plasma glucose concentration. Glucose, doubly labelled with deuterium, was also infused for the calculations of glucose turnover. Plasma insulin levels were reduced to nearly zero by the infusion of somatostatin; under such conditions whole body glucose disposal should be non-insulin-mediated. Dairy cows treated with growth hormone, which had significantly increased milk yields on the day before the experimental infusions, did not have different levels of whole body non-insulin-mediated glucose disposal when expressed in absolute terms. Growth hormone did not affect non-mammary non-insulin-mediated glucose uptake estimated by calculation. Growth hormone significantly inhibited insulin-mediated glucose uptake when plasma insulin levels were elevated. Glucose uptake during insulin plus somatostatin infusion was not significantly different from that of the insulin only infusion.

Animals↗

PubMed1998

Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer.

Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Expression of matrilysin mRNA was examined by reverse transcription-polymerase chain reaction combined with Southern blot analysis in 46 human primary gastric cancers. Overexpression of matrilysin was observed in 28 (61%) of gastric cancer tissues. The positive expression ratio of matrilysin was significantly higher in the gastric cancers of subserosa or beyond it than in those within the submucosal layer. Immunohistochemical study with anti-matrilysin monoclonal antibody revealed that matrilysin was mainly expressed on cancer cells but not or very weakly expressed on other cells. In addition, an activated form of matrilysin detected by zymographic analysis was observed in gastric cancer tissues whereas none was detected in non-cancerous tissues, suggesting that matrilysin may directly and powerfully contribute to the invasion step of human gastric cancer. In order to gain more insight into the relationship of this metalloproteinase to invasive activity, we also modulated the expression of matrilysin in gastric cancer cells by DNA transfection using gastric cancer cell lines. Overexpression of matrilysin rendered the gastric cancer cells more invasive in vitro. Concomitant with clinical investigations, matrilysin may be an important metalloproteinase in the progression of gastric cancer.

Adenocarcinoma↗

PubMed1998

Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene.

KAI1 is a potential metastatic suppressor gene for prostate cancer. We found by Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines exhibited undetectable or very low expression level of KAI1 mRNA. The effects of KAI1 on the adhesion, motility and invasiveness of colon cancer cells was therefore investigated by using two kinds of stable transfectants, i.e., antisense transfectants of BM314 cells whose KAI1 mRNA expression was suppressed by transfer of antisense KAI1 cDNA and sense transfectants of DLD-1 cells with the enhanced KAI1 mRNA by sense cDNA transfer. The following results were obtained: (1) KAI1 gene expression had no significant effect on in vitro cell growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay showed that KAI1 enhanced the Ca++-independent aggregatability of those colon cancer cells; (3) It was revealed by cell motility and invasion assays that KAI1 suppressed both the motility and in vitro invasiveness of those cells and (4) Furthermore, both the binding to fibronectin and the migration on fibronectin-coated plates of those cells were inhibited by KAI1 expression. These suggest that reduced KAI1 gene expression may contribute to the invasiveness and metastatic ability of colon cancer cells.

Antigens, CD↗

PubMed1998

Reduced invasive and metastatic potentials of KAI1-transfected melanoma cells.

KAI1 is a metastasis suppressor gene for human prostate cancer. To reveal the effect of KAI1 on the in vivo metastasis of tumors other than prostatic cancer, we transfected a human KAI1 cDNA into highly metastatic B16-BL6 murine melanoma cells and established stable transfectant clones with different expression levels of KAI1 message. The following results were obtained with the use of those transfectants. (1) Cell aggregation assay revealed a significantly enhanced Ca(2+)-independent aggregation of B16-BL6 cells by KAI1 cDNA transfection compared with mock transfectants (P < 0.01). (2) The in vivo phagokinetic activity and invasive ability of KAI1 transfectants were clearly decreased as compared with those of mock transfectants (P < 0.01). There was no significant effect of KAI1 expression on the in vitro or in vivo proliferation of B16-BL6 cells. (3) Lung colony formation of intravenously injected KAI1 transfectants in nude mice was significantly reduced as compared with mock transfectants or parental B16-BL6 cells (P < 0.01). These data suggest that KAI1 expression gives rise to the suppression of invasive and metastatic potentials of B16-BL6 cells.

Animals↗

PubMed1998

Suppression of natural killer cell activity and interleukin-2 concentration of serum obtained from in vitro fertilization-embryo transfer patients.

PROBLEM: The effect of serum obtained from in vitro fertilization-embryo transfer (IVF-ET) patients on healthy volunteers' natural killer (NK) cell activity was evaluated. We also measured interleukin (IL-2) concentration with IVF-ET patients' serum and clarified the relationship between IL-2 levels and the suppressive effect on NK cell activity. METHOD OF STUDY: A retrospective nonrandomized clinical study was performed. The suppressive effect on NK cell activity and IL-2 concentrations was measured with serum obtained from 30 pregnant and 30 nonpregnant women during an IVF-ET procedure. The suppressive effect of the serum on NK cell activity was evaluated by the formula that we defined in our previous study. RESULTS: The suppression of NK cell activity was significantly higher in the nonpregnant women than in the pregnant women (P < 0.05); however, IL-2 concentration did not differ. There was a positive correlation between the suppression of NK cell activity and IL-2 levels in the pregnant women, but no significant correlation in the nonpregnant women. CONCLUSIONS: These results suggest that the suppression of NK cell activity may be one of the prognostic factors for IVF-ET. In addition, we speculate that an unidentified humoral factor other than IL-2, which could increase NK cell activity, might exist in the serum of the nonpregnant patient.

Adult↗

PubMed1998

Effect of glucose-dependent insulinotropic polypeptide on whole-body glucose utilization in sheep.

Four adult Corriedale sheep were used in an experiment divided into three parts. In part 1 a primed continuous infusion of [6, 6-2H2]glucose was infused for 7 h. The first 3 h was the control period, from 3 to 7 h glucose-dependent insulinotropic polypeptide (GIP) was infused, and from 5 to 7 h somatostatin was infused. Part 2 of the experiment was the same as for part 1 except that insulin was infused between 3 h and 7 h and GIP was infused between 5 and 7 h. Coincident with the insulin infusion, normal glucose was also infused at a variable rate in order to keep the plasma glucose at basal levels. In part 3 of the experiment [6,6-2H2]glucose was infused for 5 h and somatostatin was infused between 3 and 5 h. Measurements of glucose turnover were made in the last 40 min of the control, GIP only, insulin only, somatostatin only, GIP plus somatostatin and GIP plus insulin infusion periods. Plasma insulin levels were reduced to the limit of detection by the somatostatin infusion; under such conditions whole-body glucose uptake should be entirely non-insulin-mediated (NIMGU). Expressing glucose disposal as glucose metabolic clearance rate demonstrated that elevated, but still physiological GIP levels had no effect on NIMGU but significantly increased insulin-mediated glucose uptake when plasma insulin levels were similar to levels typically observed after a meal. These results indicate that in sheep, GIP may enhance insulin action with respect to glucose disposal following a meal, but has no effect on glucose disposal pathways not responsive to insulin.

Animals↗

PubMed1998

Synthesis and structure-activity relationships of TAN-1511 analogues as potent hematopoietic agents.

A series of TAN-1511 analogues bearing a non-peptide spacer in place of the Gly-Gly-Gly sequence in the peptide moiety was synthesized, and the effects of these compounds on the proliferation of bone marrow cells in culture and experimental leukocytopenia in mice were examined. The structure-activity relationships obtained were as follows. As the substituent at the 2-position of the 4-thiaheptanoic acid framework, an amino group, methyl group or hydrogen was preferable; as a spacer in place of the Gly-Gly-Gly sequence, a 4-aminobenzoyl or 4-aminomethylbenzoyl group was suitable; and as the fatty acids bonded to the 6,7-dihydroxy groups, C16 fatty acid was best. Compounds 12f, 30d and 30i potently promoted the proliferation of bone marrow cells in culture and the restoration of leukocyte counts in a murine leukocytopenia model.

Animals↗

PubMed1998

[Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats].

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day.

Animals↗

PubMed1998

Insulin and glucagon secretion in lactating cows during heat exposure.

Heat stress affects endocrine systems in cows. This study investigated changes in insulin and glucagon secretion between thermoneutral (TN; 18 degrees C, relative humidity [RH] 60%) and hot (28 degrees C, RH 60%) environments in lactating cows. Glucose, arginine, and butyrate were administered i.v. to four cows (mean, at 83 d postpartum) in each environment. Blood was collected via a jugular catheter at regular intervals. Heat exposure resulted in a marked increase in respiration rate and rectal temperature. A decrease in milk yield was also observed during heat exposure. Basal insulin concentrations were elevated, and basal glucose concentrations tended to be lower in the hot environment. Peak values of insulin and glucagon following the arginine injection were significantly higher in the hot than in the TN environment. The insulin peak value in response to the butyrate infusion was also higher during the heat exposure. However, insulin and glucagon responses to the glucose load were not affected by heat stress. The increase in plasma glucose concentration following arginine injection was inhibited by the heat exposure. In conclusion, heat stress resulted in a higher insulin secretion in lactating cows. Glucagon secretion in response to the arginine injection was enhanced, but the rise in plasma glucose was inhibited by heat exposure. These changes would be related to a reduction in milk yield during heat stress.

Animals↗

PubMed1998

Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers.

Matrilysin is one of matrix metalloproteinases, which is supposed to have a specific role in tumor progression. Expression of matrilysin was investigated in gastric and esophageal cancers by an immunohistochemical examination. Matrilysin was expressed in all esophageal squamous cell carcinomas (13/13) and in the majority of gastric adenocarcinomas (31/35, 89%). The positive staining was observed in tumor cells of cancerous tissues. In gastric cancers, there were significant statistical correlations between matrilysin expression at the invasive front and nodal metastasis or advanced stage. These results suggest that overexpression of matrilysin has an important role in the progression of upper gastrointestinal cancers.

Disease Progression↗

PubMed1998

Immunohistochemical detection of MUC2 mucin core protein in ulcerative colitis.

MUC2 mucin is predominantly expressed in the colon and is considered to play an important role in the protection of that organ. Recent findings suggested that MUC2 protein levels are significantly decreased in active ulcerative colitis (UC). We therefore performed an immunohistochemical study to reveal if the expression of MUC2 protein is altered in UC. Seventy-nine biopsy tissue specimens from 31 UC patients, along with normal colon tissues, were immunostained with anti-MUC2 mucin core protein monoclonal antibody (MoAb) CCP58 (IgG1). UC tissue specimens were divided into two groups based on the histological severity of inflammation, i.e., 64 with active inflammation (grades 2-5) and 15 without (grade 1). In the former group, 52 out of 64 (81.3%) tissue specimens contained sections of glands with a few cells positive for MoAb CCP58. These glands were small and consisted of MUC2 negative-short cells and a few positive cells without apparent mucus formation, considered to be immature regenerative glands. In contrast, the staining pattern was almost the same as that of the normal colon and no immature glands were seen in the group without active inflammation. The sections of immature regenerative glands with a few MUC2-positive cells were exclusively found in the UC tissues with active inflammation, but not in those without it, suggesting that the expression of MUC2 protein may be decreased in active UC.

Adolescent↗

PubMed1998

Changes in morphology of neuroblastoma cells treated with all-trans retinoic acid combined with transfer of the C-terminal region of the amyloid precursor protein.

Alzheimer disease is a progressive neurodegenerative disorder that is characterized by a loss of cognitive and memory functions. Amyloid fibrils deposited in neuritic plaque is mainly beta-amyloid protein (Abeta) that is derived from amyloid precursor protein (APP). The secreted form of APP, which is corresponded to N-terminal portion of APP, shows neurotrophic activities. On the other hand, Abeta and cytoplasmic domains of APP are thought to be neurotoxic. In order to investigate the effect of C-terminal fragment of APP covering Abeta and the cytoplasmic domain upon cell growth and differentiation, we established a stably transfected cell line producing the C-terminal 100 amino acid peptide of APR The transfected clones stained positively with anti-Abeta monoclonal antibody, TB-1. The growth rate of the transfected cells was not significantly different from that of mock-transfected cells or native NB39 cells. After treatment with all-trans retinoic acid (ATRA), mock-transfected cells extended neurite processes and showed neuronal-like differentiation, while a transfected clone overexpressing C-terminal fragment did not present neuronal-like morphology. These results suggest that ATRA-induced neurite extension may be suppressed by overexpression of the C-terminal fragment of APP.

Amyloid beta-Peptides↗

PubMed1998

[Regulation of integrin function in the metastasis of colorectal cancer].

Alterations in several classes of adhesion molecule 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 the 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. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. 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 metastases than in those without (p < 0.01) and in patients with distant metastases than in those without (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.

Animals↗

PubMed1998

[Recent advance of prognostic factor in human colorectal cancer].

It has become clear that cancers develop and progress through the accumulation of various genetic alterations. Among various human malignancies, none is better understood at the molecular genetic level than colorectal cancer. Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. Recent advances in the molecular genetics of colorectal cancer have stimulated attempts to evaluate the prognostic significance of specific genetic alterations in this tumor. Although conventional pathological staging has served as the standard measure of prognosis in colorectal cancer, certain molecular genetic markers are now considered to be useful for predicting the behavior of cancer and the clinical outcome of patients. We have described the recent advances in prognostic factors of colorectal cancer, such as oncogenes, tumor suppressor genes, chromosomal deletions, adhesion molecules, proteinases, DNA replication error, and others. The latest improvements in detecting these molecular markers have made it possible to apply them to the clinical setting with relative ease. Some of these markers are considered to be susceptible to, or modifiable by, direct therapeutic intervention. For instance, matrix metalloproteinases could be targets for therapeutic intervention using their inhibitors. We hope that these molecular genetic markers with prognostic significance play an important role in disease management of patients with colorectal cancer in future.

Cell Adhesion Molecules↗

PubMed1997

A novel gastric-cancer-associated mucin antigen defined by a monoclonal antibody A3D4.

De-glycosylation of mucins may expose new tumor-associated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MAbs was shown to react with gastric cancer with high frequency, but not with normal gastric epithelium. Among normal digestive organs, only the colon and gall bladder were positive for MAb A3D4. The incidence of positivity in gastric cancer was 75% for intestinal-type adenocarcinoma (n = 28), 40% for solid-type adenocarcinoma (n = 5) and 33% for signet/scirrhous-type adenocarcinoma (n = 15). Interestingly, adenoma and intestinal metaplasia (IM) with chronic gastritis or peptic ulcer were negative for MAb A3D4, whereas 8 out of 13 cases (62%) of IM with gastric cancer was positive. Western-blot analysis using the lysate from normal colon tissues revealed a high-molecular-weight (> 300-kDa) smear-like band. Immunohistochemical analysis indicated that the reactivity of MAb A3D4 was clearly increased when tissue sections were pre-treated with periodic acid or O-glycanase, while it was decreased by pre-treatment with trypsin or protease V8. There was no reactivity with the synthetic peptide encompassing the tandem-repeat sequence of MUC2 or MUC3. These data suggest that MAb A3D4 detects a novel gastric-cancer-associated mucin antigen whose epitope may be peptide in nature.

Adenocarcinoma↗

PubMed1997

Decreased sensitivity of carcinoembryonic antigen cDNA-transfected cells to adriamycin.

Carcinoembryonic antigen (CEA) is a heavily glycosylated protein and is expressed at a high frequency in adenocarcinomas, which are known to be one of the cancers most resistant to chemotherapeutic agents. In this study, with the aim to elucidate whether CEA participates in drug resistance or not, we tested the adriamycin (ADR) sensitivity of CEA transfectants of H-ras-transformed NIH 3T3 cells in vitro and in vivo. The ADR sensitivity of CEA transfectants in vitro was evaluated as growth (% of control) when incubated with various concentrations of ADR, and showed that they were higher than those of mock transfectants. The decreased ADR sensitivity of CEA transfectants in vivo was also observed as an increase in tumor size after intraperitoneal administration of ADR into SCID mice. To define the mechanisms for resistance, the accumulation and efflux of ADR in transfectants was examined. The rate of ADR accumulation in CEA transfectants was reduced compared to mock transfectants, caused at least partly by an increased efflux out of the cells. Furthermore, the modification of N-glycan on CEA by deoxymannojirimycin, an N-glycosylation processing inhibitor, partially restored ADR sensitivity of CEA transfectants, suggesting an involvement of sugar chains. Our data suggest that CEA expression may decrease ADR sensitivity of cancer cells.

Animals↗

PubMed1997

Association of reduced cell adhesion regulator messenger RNA expression with tumor progression in human hepatocellular carcinoma.

The recently identified cell adhesion regulator (CAR) modulates the process of integrin-mediated cell adhesion. The CAR gene is located on 16q, a locus at which high levels of allelic losses have been demonstrated in advanced human hepatocellular carcinoma (HCC). We studied the possible involvement of the CAR gene in the progression of HCC. With this aim, we determined the expression of CAR mRNA in 30 cases of HCC. Matching pair samples of tumor and adjacent nontumoral liver were analyzed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The results were compared with the clinicopathological features of the patients. Every nontumoral liver tissue sample analyzed, expressed CAR mRNA. All tumor samples showed amounts of expression that were equal or lower, compared with those found in their matching controls. Thus, in 16 out of 30 cases (53.3%), CAR mRNA expression in tumor was diminished to less than one tenth of that observed in nontumoral tissue. This group of patients exhibited higher amounts of alpha-fetoprotein, and comprised tumors with poor histological differentiation (Edmondson-Steinert's grades III-IV), higher rates of intrahepatic metastasis and recurrence within the first postoperative year (p < 0.05, respectively). Tumors exhibiting low levels of CAR mRNA were also found to be diagnosed at more advanced TNM stages (p < 0.01). We conclude that downregulation of CAR mRNA expression may play an essential role in the progression of HCC.

ATPases Associated with Diverse Cellular Activitie↗