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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 37 records · Page 2Linked to original sources
PubMed2004

A stable prostacyclin analogue reduces high serum TNF-alpha levels in diabetic patients.

AIMS: To confirm whether a prostacyclin (prostaglandin I (2)) affects the increased TNF-alpha concentration in sera of diabetic patients, we measured serum TNF-alpha concentration and treated these patients with oral administration of the stable prostacyclin analogue (Beraprost). Twelve of 20 type II diabetic patients were investigated for follow up-study and 6 of those patients were for therapy with Beraprost for diabetic neuropathy. SUBJECTS AND METHODS: Serum TNF-alpha concentration was quantified by EASIA using monoclonal antibodies directed against distinct epitopes of TNF-alpha. RESULTS: In diabetic patients, serum TNF-alpha concentration was significantly increased compared with that of healthy subjects. The augmented TNF-alpha concentration in these patients was not decreased by diabetic control using antihyperglycemic agents for 8 weeks but was reduced with oral administration of a stable prostacyclin (prostaglandin I (2)) analogue for 5 weeks without any changes of blood glucose levels. CONCLUSIONS: Stable prostacyclin analogue administration for a short term period reduced increased TNF-alpha levels in diabetic patients, not through the improved hyperglycemic condition but another pathway, probably a cAMP system. These results imply that treatment with the prostacyclin analogue may contribute to the prevention of progression in diabetic complications.

Adult↗
PubMed2004

Possible role of VEGF in the progression of kidney disease in streptozotocin (STZ)-induced diabetic rats: effects of an ACE inhibitor and an angiotensin II receptor antagonist.

Two endothelium-derived factors, endothelin (ET), a vasoconstrictor, and vascular endothelial growth factor (VEGF), an angiogenic factor are thought to be involved in the pathogenesis of diabetic vascular complications. The aim of this study was to determine the effects of an angiotensin II type I (AT-1) receptor antagonist and an ACE inhibitor on the pathogenesis of VEGF and ET-1-mediated kidney disease in STZ-induced diabetic rats. Two days after STZ administration, diabetic rats were treated for 8 weeks with enalapril maleate, an ACE inhibitor, candesartan cilexetil, an AT-1 receptor antagonist, or saline. Urinary albumin and N-acetyl beta-D glucosaminidase (NAG) excretion as well as the VEGF protein content in the kidney were all found to be elevated in diabetic rats. Administration of enalapril maleate or candesartan cilexetil decreased the level of microalbuminuria and NAG excretion in diabetic rats. Administration of enalapril maleate also suppressed the elevated renal VEGF protein content in these animals while candesartan cilexetil treatment had no effect. Serum ET-1 and VEGF levels were unchanged by these treatments. These data support a role for AT-1 receptor antagonists and ACE inhibitors in the prevention of diabetic nephropathy, and suggest that the former may work by reducing renal VEGF levels.

Albuminuria↗
PubMed2004

Helicobacter pylori eradication decreases blood neutrophil and monocyte counts.

BACKGROUND: The effect of Helicobacter pylori infection on systemic disorders is not well understood. AIM: The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori. METHODS: A total of 164 H. pylori-positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed. RESULTS: In the eradicated group (n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non-eradicated group (n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group. CONCLUSIONS: These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Brain activity during distention of the descending colon in humans.

Brain-gut interaction is considered to be a major factor in the pathophysiology of irritable bowel syndrome. However, only limited information has been provided on the influence of gastrointestinal tract stimulation on the brain. Our aim in this study was to determine the specific regions of the brain that are responsible for visceral perception and emotion provoked by distention of the descending colon in humans. Fifteen healthy males aged 22 +/- 1 participated in this study. Using a colonoscope, a balloon was inserted into the descending colon of each subject. After sham stimulation, the colon was randomly stimulated with bag pressures of 20 and 40 mmHg, and regional cerebral blood flow was measured by [(15)O] positron emission tomography. The subjects were asked to report visceral perception and emotion using an ordinate scale of 0-10. Colonic distention pressure dependently induced visceral perception and emotion, which significantly correlated with activation of specific regions of the brain including the prefrontal, anterior cingulate, parietal cortices, insula, pons, and the cerebellum. In conclusion, distention of the descending colon induces visceral perception and emotion. These changes significantly correlate with activation of specific regions in the brain including the limbic system and the association cortex, especially the prefrontal cortex.

Adult↗
PubMed2004

Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses.

Human fetuses are thought to be highly sensitive to radiation exposure because diagnostic low-dose X rays have been suggested to increase the risk of childhood leukemia. However, animal studies generally have not demonstrated a high radiosensitivity of fetuses, and the underlying causes for the discrepancy remain unidentified. We examined atomic bomb survivors exposed in utero for translocation frequencies in blood lymphocytes at 40 years of age. Contrary to our expectation of a greater radiosensitivity in fetuses than in adults, the frequency did not increase with dose except for a small increase (less than 1%) at doses below 0.1 Sv, which was statistically significant. We interpret the results as indicating that fetal lymphoid precursor cells comprise two subpopulations. One is small in number, sensitive to the induction of both translocations and cell killing, but rapidly diminishing above 50 mSv. The other is the major fraction but is insensitive to registering damage expressed as chromosome aberrations. Our results provide a biological basis for resolving the long-standing controversy that a substantial risk of childhood leukemia is implicated in human fetuses exposed to low-dose X rays whereas animal studies involving mainly high-dose exposures generally do not confirm it.

Chromosome Aberrations↗
PubMed2004

Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.

Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening.

Adolescent↗
PubMed2004

The effect of bisphenol A and chlorinated derivatives of bisphenol A on the level of serum vitellogenin in Japanese medaka (Oryzias latipes).

2,2-bis (4-hydroxyphenyl) propane or Bisphenol A (BPA), has been reported to behave as an endocrine disrupter below acute toxic levels, and is widely present in the water environment. Although BPA is easily chlorinated, very little is reported on the effect of chlorinated BPA to the aquatic organisms. In this study, the estrogenic activities of BPA and its chlorinated derivatives were evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka. In addition, the effect of sodium hypochlorite on the decomposition of BPA was tested. The relative potencies of estrogenic activities of chlorinated BPA descended in the order 3,3'-diCIBPA>BPA> or =3-CIBPA>3,3',5-triCIBPA, and no estrogenic activity was observed in 3,3',5,5'-tetraCIBPA. Lowest Observed Effect Concentration (LOEC) and No Observed Effect Concentration (NOEC) for both 3-CIBPA and 3,3'-diCIBPA were 500 microg/L and 200 microg/L, respectively. LOEC for 3,3',5-triCIBPA was >500 microg/L. When BPA was reacted with sodium hypochlorite (24 hours; residual chlorine at 1 ppm), however, complete decomposition of BPA and its chlorinated derivatives was observed. The decrease in BPA and its chlorinated derivatives paralleled the decrease in estrogenic potency evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka.

Animals↗
PubMed2003

Tandem duplication of alkaline phosphatase genes and polymorphism in the intergenic sequence in Bombyx mori.

Alkaline phosphatases are ubiquitous in organisms from bacteria to human. Two alkaline phosphatase genes, Alp-m and Alp-s, were independently cloned from the silkworm Bombyx mori. They were mapped to a small DNA region and shown to be organized in tandem. Exon-intron structures of the two genes were highly conserved, with the exception of the second intron in Alp-m, which has no counterpart in Alp-s. The similarity between the nucleotide sequences of the exons of the two genes was strikingly high (60-79%), suggesting that Alp-m and Alp-s originated from a duplication of their common ancestor gene. The intergenic sequence between the two Alp genes shows length polymorphism in different B. mori strains, which can be explained by presence/absence of two putative insertion sequences. This structural variation suggests a possible scenario for the divergence of the two Alp genes after the duplication event.

Alkaline Phosphatase↗
PubMed2003

Stimulatory effect of prostaglandin F(2alpha) on Na-dependent phosphate transport in osteoblast-like cells.

Prostaglandin F(2alpha) (PGF(2alpha)) has been reported to activate protein kinase C (PKC) through both phospholipase (PL) C and D, resulting in the proliferation of osteoblast-like cells. In addition, it has also been reported that Erk mitogen-activated protein kinase is also involved in the mechanism of PGF(2alpha)-induced proliferation of these cells. Recently, we have reported that several growth factors stimulate Na-dependent phosphate transport (Pi transport) activity of osteoblast-like cells, which has been recognized to play an important role in their mineralization. In the present study, we investigated the effect of PGF(2alpha) on Pi transport in MC3T3-E1 osteoblast-like cells. PGF(2alpha) stimulated Na-dependent Pi transport dose dependently in the range between 1nM and 10 micro M in MC3T3-E1 cells. The effect was time dependent up to 24h. Kinetic analysis revealed that PGF(2alpha) induces newly synthesized Pi transporter. Pretreatment with actinomycin D and cycloheximide suppressed PGF(2alpha)-induced enhancement of Pi transport. Combined effect of PMA and PGF(2alpha) was not additive in Pi transport. Calphostin C, a PKC inhibitor, dose-dependently suppressed Pi transport induced by PGF(2alpha). On the contrary, U0126, which inhibits an upstream kinase of Erk (MEK), did not affect PGF(2alpha)-induced enhancement of Pi transport. In conclusion, PGF(2alpha) stimulates Pi transport through activation of PKC in osteoblast-like cells.

3T3 Cells↗
PubMed2003

Etoposide-mediated sensitization of squamous cell carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced loss in mitochondrial membrane potential.

Squamous cell carcinoma (SCC) cell lines (MIT7-x(L), MIT8, and MIT16) that overexpress Bcl-x(L) have been demonstrated to show resistance to multiple chemotherapeutic drugs. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which belongs to the TNF family of proteins, induces apoptosis in tumor, but not in normal, cells. In the present study, we examined whether etoposide sensitizes tumor cells with multiple-drug-resistance to TRAIL-induced apoptosis. Sequential treatment with etoposide and TRAIL resulted in a synergistically induced cell death in the two resistant lines (MIT7-x(L) and MIT16) but not MIT8, as assessed by WST-8 assay. As expected, MIT7 cells (a drug-sensitive line) were sensitive to the combined treatment. The cell death caused by both etoposide and TRAIL appears to involve apoptosis, since the combined treatment caused a loss in mitochondrial membrane potential (DeltaPsim), which is closely associated with apoptosis induction. The density of the TRAIL-receptors (TRAIL-Rs) was not appreciably modulated by the etoposide treatment, suggesting that etoposide targets molecule(s) downstream of the TRAIL-Rs. Regardless of the molecular mechanisms underlying the cell death, sequential treatment with etoposide and TRAIL could be useful in the design of treatment modalities for patients with SCC, especially those with elevated levels of Bcl-x(L).

Antineoplastic Agents, Phytogenic↗
PubMed2003

The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells.

BACKGROUND: Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin. AIM: Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability. METHODS: Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10-7 M). Trans-epithelial permeability was measured by TER and diffusion rate of 14C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E2 (PGE2) production in culture medium was also measured. RESULTS: Indometacin gradually and significantly decreased TER and increased 14C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor. CONCLUSIONS: COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE2. COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE2 levels in a COX-2 dependent manner.

Alanine↗
PubMed2003

Effects of rebamipide, a gastro-protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double-blind placebo-controlled multicentre trial.

AIMS: To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro-mucosal inflammation after eradication. METHODS: Two hundred and six H. pylori-positive patients with active gastric ulcer underwent 8-week based therapy (OA) consisting of 2-week amoxicillin with omeprazole and subsequent 6-week omeprazole. They randomly received either rebamipide (OA-R) or placebo (OA-P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically. RESULTS: Per Protocol Set analysis showed no significant difference in eradication rate between OA-R (64.6%; 95% confidence interval, 54.3-75.0%) and OA-P (67.9%; 95% CI, 57.6-78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA-R (1.84 +/- 0.41) compared with that in OA-P (2.02 +/- 0.39) after 16-weeks of treatment. This suppressive effect on inflammation was observed even in the OA-R patients unsuccessfully eradicated. CONCLUSION: Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.

Adult↗
PubMed2003

Clinical evaluation of pioglitazone in patients with type 2 diabetes using alpha-glucosidase inhibitor and examination of its efficacy profile.

AIM: Pioglitazone is considered to reduce insulin resistance. This study was conducted to evaluate the efficacy, safety and clinical profile of pioglitazone in patients whose type 2 diabetes were poorly controlled with alpha-glucosidase inhibitor alone or alpha-glucosidase in combination with sulfonylurea. METHODS: Twenty patients with type 2 diabetes were treated with pioglitazone (30 mg q.d.) orally for 16 weeks. RESULTS: There were significant reductions in HbA1C, FPG and postprandial plasma glucose at week 16. As adverse events, oedema, hypoglycaemia-like reaction, increases in LDH, CPK, etc. were noted. There was no significant change in TNF-alpha. Leptin levels increased significantly at week 16 and were still increasing 4 weeks after the treatment. Per cent body fat was almost constant throughout the study period. When efficacy was classified by demographic variables, pioglitazone was found to be more effective in the subjects who had a higher postprandial 2-h plasma glucose level, leptin level or per cent body fat value. CONCLUSION: Pioglitazone was considered to be effective when used in patients whose type 2 diabetes were poorly controlled with alpha-glucosidase inhibitor alone or alpha-glucosidase in combination with sulfonylurea.

Adult↗
PubMed2003

Human infection with Wuchereria bancrofti in Matara, Sri Lanka: the use, in parallel, of an ELISA to detect filaria-specific IgG4 in urine and of ICT card tests to detect filarial antigen in whole blood.

The ICT card test to detect circulating filarial antigen and an ELISA that detects filaria-specific urinary IgG(4) were each used to screen 473 subjects from a community in Sri Lanka where Wuchereria bancrofti is endemic. When the ICT test was used as the gold standard, the ELISA was found to have a sensitivity of 91.2%. However, far more of the subjects were found ELISA-positive than ICT-positive (76.5% v. 31.1%). The youngest children studied (aged 1-10 years) were similar to the adult subjects in terms of the prevalence of antigenaemia (33.8%) and the prevalence (72.1%) and concentration of filaria-specific IgG(4) in their urine. Therefore, especially as urine samples are easier, less painful and safer to collect than blood samples, the ELISA may be particularly useful to screen very young and school-age children, to estimate current levels of transmission in a particular area.

Adolescent↗
PubMed2003

The effect of chlorination of estrogenic chemicals on the level of serum vitellogenin of Japanese medaka (Oryzias latipes).

Mature male medaka were continually exposed to four chemicals, p-n-nonylphenol (p-n-NP), nonylphenol (p-NP), bisphenol-A (BPA) and 17beta-estradiol (E2) to evaluate their estrogenic activities in the laboratory. In order to understand the effect of the chlorination that is applied widely in water and wastewater treatment, the above chemicals were chlorinated and then exposed to mature male medaka. Furthermore, in the case of vitellogenin, a is a female specific protein induced by the exposure to test waters containing the above chemicals after 5 weeks, medaka was returned to uncontaminated tap water to determine whether male medaka have a self recovery function from the effect of estrogenic chemicals. Much greater vitellogenin compared to the background levels were induced in the male medaka by separate exposure to 100 microg/L of p-NP, 1,000 microg/L of BPA and 0.05 microg/L of E2. The levels of vitellogenin increased with increasing exposure periods. The relative potencies of these chemicals descended in the order of E2>>p-NP>BPA. Vitellogenin levels inducible by these chemicals were drastically reduced as a result of the chlorination for 24 hours. However, a moderate increase in hepatocyte somatic index (HSI) meant the hepatic fatness was observed as a result of chlorination. It is not clear at this stage whether or not the formation of chlorination byproducts is responsible for this moderate increase in HSI. The vitellogenin concentration of male medaka exposed to chemicals for 5 weeks decreased gradually after return to the uncontaminated water. However, the vitellogenin concentration did not return to the initial normal levels even after 5 weeks. A clear relationship between the serum vitellogenin concentration and the hepatic vitellogenin concentration was also found. Since quantitative analytical procedures for hepatic vitellogenin are easier than those of the serum vitellogenin, measuring the estrogenic effect using the measurement of vitellogenin in liver is recommended.

Animals↗
PubMed2003

Prevalence and levels of filaria-specific urinary IgG4 among children less than five years of age and the association of antibody positivity between children and their mothers.

An enzyme-linked immunosorbent assay (ELISA) to detect filaria-specific urinary IgG4 was tested in samples from 203 children less than five years old and their parents (165 mothers and 127 fathers) in Sri Lanka. There were four IgG4-positive children within 58 days after birth, suggesting the transfer of the antibody from mothers. No positive children were found between days 65 and 417. After day 1,000, the number of the positive individuals and the level of IgG4 increased quickly. The children of urinary IgG4-positive parents showed a higher IgG4 positive rate than those of negative parents. The children of positive mothers had a higher prevalence than those of negative mothers, whereas, the positivity of the fathers was not associated with that of their children. Collecting urine samples was easy to perform and well accepted because of its non-invasiveness. The ELISA will be useful for monitoring filarial infections in very young children, who are a sentinel population for evaluating the intensity of filariasis transmission and effectiveness of control measures.

Adolescent↗
PubMed2002

Comprehensive sequence analysis of translation termination sites in various eukaryotes.

Recent investigations into the translation termination sites of various organisms have revealed that not only stop codons but also sequences around stop codons have an effect on translation termination. To investigate the relationship between these sequence patterns and translation as well as its termination efficiency, we analysed the correlation between strength of consensus and translation efficiency, as predicted according to Codon Adaptation Index (CAI) value. We used RIKEN full-length mouse cDNA sequences and ten other eukaryotic UniGene datasets from NCBI for the analyses. First, we conducted sequence profile analyses following translation termination sites. We found base G and A at position +1 as a strong consensus for mouse cDNA. A similar consensus was found for other mammals, such as Homo sapiens, Rattus norvegicus and Bos taurus. However, some plants had different consensus sequences. We then analysed the correlation between the strength of consensus at each position and the codon biases of whole coding regions, using information content and CAI value. The results showed that in mouse cDNA, CAI value had a positive correlation with information content at positions +1. We also found that, for positions with strong consensus, the strength of the consensus is likely to have a positive correlation with CAI value in some other eukaryotes. Along with these observations, biological insights into the relationship between gene expression level, codon biases and consensus sequence around stop codons will be discussed.

3' Untranslated Regions↗