Search PubMed⌕ Search

Biomedical subjects

M Igarashi

Publications and source records attributed to M Igarashi.

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

Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes.

Fibroblast growth factor 10 is a novel member of the fibroblast growth factor family, which is involved in morphogenesis and epithelial proliferation. It is highly homologous to the keratinocyte growth factor (or fibroblast growth factor 7), a key mediator of keratinocyte growth and differentiation. Both fibroblast growth factor 10 and keratinocyte growth factor bind with high affinity to the tyrosine kinase keratinocyte growth factor receptor. Here we analyzed the effect of fibroblast growth factor 10 on primary cultures of human keratinocytes, grown in chemically defined medium, and we compared the proliferative and differentiative cell responses to fibroblast growth factor 10 with those induced by keratinocyte growth factor and epidermal growth factor. Cell counting, 5-bromo-2'-deoxyuridine incorporation, and western blot analysis showed that fibroblast growth factor 10, similarly to keratinocyte growth factor, not only is a potent mitogen for human keratinocytes, but also promotes the expression of both early differentiation markers K1 and K10 and late differentiation marker filaggrin in response to the Ca2+ signal, and seems to sustain the proliferative activity in suprabasal stratified cells. Immunoprecipitation/western blot analysis revealed that fibroblast growth factor 10, similarly to keratinocyte growth factor, is able to induce tyrosine phosphorylation of keratinocyte growth factor receptor and of cellular substrates such as PLCgamma.

Antigens, Differentiation↗
PubMed2001

Characterization of platelet-derived growth factor-induced p38 mitogen-activated protein kinase activation in vascular smooth muscle cells.

BACKGROUND: The mitogen-activated protein (MAP) kinase super-family plays a crucial role in cell growth and differentiation and even in programmed cell death in response to diverse extracellular stimuli. The platelet-derived growth factor (PDGF)-BB is well known to promote the proliferation of vascular smooth muscle cells (VSMC) via extracellular-regulated protein kinases (ERKs), leading to the development of cardiovascular diseases. However, it has not yet been clarified whether PDGFs that include other isoforms can activate the other parallel signal transduction pathways, c-jun NH2-terminal protein kinase (JNK) and p38 MAP kinase (p38), in VSMC. In this study, we investigated the effect of PDGFs on p38 activation in cultured rat VSMC. MATERIALS AND METHODS: After stimulation by PDGFs with SB-203580 or PD-98059, the cells were solubilized, and the expressions of MAP kinases, MAP kinase kinases (MKKs), phosphorylated DNA-binding proteins, and cyclooxigenases (COXs) were examined by immunoblot analysis. RESULTS: PDGFs activated p38 phosphorylation dose-dependently, and the phosphorylations were specifically inhibited by SB-203580 but not by PD-98059. PDGFs also activated the phosphorylation of MKK 3/MKK 6 but not that of either stress-activated protein kinase/ERK kinase or JNK. PDGFs affected the activation of a cyclic AMP response-element binding protein, which was inhibited by SB-203580. However, the activating transcription factor-2 was not activated by PDGFs. Interestingly, the stimulation of PDGFs for 72 h enhanced the level of COX-2, and these levels were decreased by SB-203580. CONCLUSION: These results have clarified that PDGFs activate the p38 cascade via an MKK 3/6 pathway, independently of the ERK cascade, and subsequently regulate the level of COX-2 in rat VSMC, providing that PDGFs influence the inflammatory process in the vascular wall.

Activating Transcription Factor 2↗
PubMed2001

Characterization of an inhibitory effect of pioglitazone on balloon-injured vascular smooth muscle cell growth.

This study investigates whether pioglitazone could suppress an atherogenic process such as balloon-injured carotid intimal thickening and the proliferation of vascular smooth muscle cells (VSMC). We first examined the effect of pioglitazone to determine whether it could suppress intimal thickening induced by balloon catheterization in Sprague-Dawley rats. After 14 days postcatheterization in the left common carotid artery, the neointimal layers were completely occupied by proliferated VSMC, and the area ratio of neointima to media treated with 10 mg/kg/d of pioglitazone was significantly decreased to 57%. Next, we evaluated the effect of pioglitazone on the proliferation of rat cultured VSMC. Piogliotazone dose-dependently decreased the values of DNA synthesis, total cellular protein content, phosphorylations of extracellular signal-regulated protein kinase 1/2 and mitogen-activated protein kinase kinase 1/2, and proliferative cell nuclear antigen in VSMC. Pioglitazone also inhibited the phosphorylation of Pyk2. We conclude that pioglitazone itself could be effective for suppressing the growth of VSMC and consequent carotid intimal thickening.

Animals↗
PubMed2001

Insulin inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically.

Hepatocytes form the hepatic acinus as the unit of microcirculation. Following the bloodstream, at least 2 different zones can be discerned: the periportal and perivenous zones. Two types of hepatocytes, periportal hepatocytes (PPHs) and perivenous hepatocytes (PVHs), have been thought to be functionally heterogeneous, with PPHs being predominantly gluconeogenic and PVHs being glycolytic. We therefore investigated the region-specific functional effects of insulin on glycogen synthesis, glycolysis, glycogenolysis, and gluconeogenesis in isolated PPHs and PVHs prepared by using the digitonin-collagenase method. Glycogen synthesis from 5 to 20 mmol/L glucose did not differ between the PPHs and PVHs of fed rats during 60 minutes of incubation. Lactate release induced by 5 to 20 mmol/L glucose was 3 times greater from PVHs than from PPHs (P <.01). The addition of insulin did not accelerate either glycogen synthesis or lactate release during 60 minutes of incubation. Insulin did not inhibit glucose release from gluconeogenic substrates with or without 0.2 nmol/L glucagon in either the PPHs or the PVHs of fasting rats. Insulin antagonized the 0.1 nmol/L glucagon-induced increase in glucose release from the PVHs of fed rats during 30 minutes of incubation (to 56.1% +/- 7.2%, P <.01) but not that from the PPHs (to 81.8% +/- 7.3%, P =.10). Thus the antagonizing effect was greater in PVHs than in PPHs (P <.01). Insulin binding did not differ between the PPHs and PVHs of fed rats. It was confirmed that PVHs are actually glycolytic. An acute metabolic effect of insulin was observed only in antagonizing glucagon-induced glycogenolysis in PVHs specifically. The specific effect of insulin on PVHs might depend on the differences in intracellular characteristics between PPHs and PVHs rather than hormone binding.

Animals↗
PubMed2001

Age-related changes in cortical and trabecular bone mineral status. A quantitative CT study in lumbar vertebrae.

PURPOSE: To investigate the age and sex dependence of the bone mineral status of human lumbar vertebrae with special regard to differences between cortical and trabecular bone. MATERIAL AND METHODS: The study group comprised 125 normal Japanese healthy volunteers (54 males and 71 females), and was subdivided into adult male and female groups (subjects younger than 40 years), intermediate male and female groups (ages ranging between 41 and 64 years) and old male and female groups (subjects older than 65 years). The cortical bone mineral status was estimated using a single-energy quantitative CT (SE-QCT) technique, whereas trabecular bone mineral density (BMD) was estimated using a dual-energy (DE-QCT) technique. RESULTS: A considerable gender difference in the age-related cortical bone status was found. There was a significant reduction of the mean values of the cortical volume and BMD in the old female group compared with those obtained in the old male group. CONCLUSION: The results suggest that in men, cortical and trabecular bone volume decrease very little with age. In women, cortical volume and BMD and trabecular BMD decrease with age while trabecular bone volume does not. The study showed that all variables had higher values in men than in women and that the difference increased with age.

Adult↗
PubMed2001

Suppressive effect of Lactobacillus gasseri OLL 2716 (LG21) on Helicobacter pylori infection in humans.

To examine the efficacy of Lactobacillus gasseri OLL2716 (LG21) as a probiotic for Helicobacter pylori in humans, 31 subjects infected with the bacterium ingested yogurt containing LG21 daily for an 8 week period. The [(13)C]urea breath test and assays of serum pepsinogens revealed a significant improvement following LG21 treatment. LG21 was thus determined to be effective in both suppressing H. pylori and reducing gastric mucosal inflammation.

Female↗
PubMed2001

The occurrence of various collagen diseases in one family: a sister with ISSc, PBC, APS, and SS and a brother with systemic lupus erythematosus.

We encountered siblings who had collagen diseases and related symptoms. Case 1 was a 53-year-old woman who had limited cutaneous systemic sclerosis (ISSc) associated with primary biliary cirrhosis (PBC), antiphospholipid antibody syndrome (APS), and subclinical Sjögren's syndrome (SS). Case 2 was a 48-year-old man, her younger brother, with systemic lupus erythematosus (SLE) that developed at 32 years of age. Investigation of their family revealed that their mother had Raynaud's phenomenon, arthritis, and subclinical Sjögren's syndrome, and that another younger brother of Cases 1 and 2 had Raynaud's phenomenon and general fatigue. HLA analysis revealed that the sister and brother had some identical HLA antigens in common, including A2, A33 (19), B67, B44 (12), Cw7, DR2, DR6, DR52, and DQ1. The sister, brother and their mother had common HLA antigens including A2, B67, Cw7, DR2, and DQ1. Although Cases 1 and 2 shared the same HLA system, they presented different phenotypes of collagen disease.

Antiphospholipid Syndrome↗
PubMed2001

Ammonia as an accelerator of tumor necrosis factor alpha-induced apoptosis of gastric epithelial cells in Helicobacter pylori infection.

The mechanism by which Helicobacter pylori induces apoptosis remains unclear. In a previous study using biopsy samples, we found a significant correlation between the urease activity of an H. pylori strain and the apoptosis level induced by this strain. Therefore, in this study, we investigated whether urease and/or the ammonia generated by urease can induce apoptosis. Human gastric epithelial cell lines were cocultured with H. pylori, and the levels of apoptosis and ammonia production were measured. The medium was supplemented (or not supplemented) with urea and cytokines. While a large amount of ammonia (>30 mM) accumulated in the coculture containing urease-positive H. pylori and urea, no significant degree of apoptosis occurred. In the presence of tumor necrosis factor alpha (TNF-alpha), however, a marked acceleration of apoptosis was found in this coculture. Such enhancement of apoptosis was also induced by the addition of 4 to 8 mM ammonia to the cell culture without either H. pylori or urea but containing TNF-alpha. These results suggested that ammonia accelerates cytokine-induced apoptosis in gastric epithelial cells, while ammonia or urease molecules alone are unable to induce a significant degree of apoptosis.

Ammonia↗
PubMed2001

Association between job strain and prevalence of hypertension: a cross sectional analysis in a Japanese working population with a wide range of occupations: the Jichi Medical School cohort study.

OBJECTIVES: To explore the association between the prevalence of hypertension in a Japanese working population and job strain (a combination of low control over work and high psychological demands), and to estimate this association in different sociodemographic strata. METHODS: From a multicentre community based cohort study of Japanese people, sex specific cross sectional analyses were performed on 3187 men and 3400 women under 65 years of age, all of whom were actively engaged in various occupations throughout Japan. The baseline period was 1992-95 [corrected]. The association between job characteristics--measured with a Japanese version of the Karasek demand-control questionnaire--and the prevalence of hypertension defined by blood pressure and from clinical diagnoses were examined. Adjustments were made for possible confounders. The analyses were repeated for stratified categories of occupational class, educational attainment, and age group. RESULTS: In men, the level of job strain (the ratio of psychological job demands to job control) correlated with the prevalence of hypertension. In a multiple logistic regression model, job strain was significantly related to hypertension (odds ratio 1.18; 95% confidence interval 1.05 to 1.32), after adjustment for age, employment (white collar v blue collar), marital status, family history of hypertension, cigarette smoking, alcohol intake, physical activity, and body mass index. The stratified analyses showed significant excess risks in the subordinate groups compared with managers, blue collar workers, less educated workers, and the older age groups. This association was not significant in women. Multiple linear regression analyses, with systolic and diastolic blood pressures as dependent variables, did not show any significant association. CONCLUSIONS: The findings provided limited proof that job strain is related to hypertension in Japanese working men. Older men in a lower social class may be more vulnerable to the hypertensive effects of job strain.

Adult↗
PubMed2001

Characterizations of recombinant human tartrate-resistant acid phosphatase from osteosarcoma: comparison study between recombinant and placental proteins.

We cloned the human tartrate-resistant acid phosphatase (TRAP) gene from human osteosarcoma cells (Saos-2), and produced recombinant human TRAP (rhTRAP) using a baculovirus vector expression system. RhTRAP from Sf9 culture medium was purified by cation exchange chromatography, gel filtration and affinity chromatography. The molecular mass and amino acid composition of the rhTRAP were consistent with the deduced amino acid composition from the TRAP gene. The N-terminal amino acid sequence of rhTRAP was identical to that of TRAP purified from osteoclastoma and hairy cell leukemia spleen. The monoclonal antibodies generated against rhTRAP also reacted to human placental TRAP (pTRAP). The optimum pH of rhTRAP and pTRAP were pH 5.0-5.5 and pH 6.0-6.5, respectively. The enzymatic activities of rhTRAP and pTRAP were activated by reducing agents such as 2-mercaptoethanol, dithiothreitol and ascorbic acid. The activities of rhTRAP and pTRAP were enhanced by Fe2+ ions, but were inhibited by Fe3+ ions. The present results indicate that rhTRAP has similar properties to the native human TRAP, and suggest that the enhancement of TRAP activity by reducing agents might be expressed via the reduction of Fe ions at the metal center.

Acid Phosphatase↗
PubMed2001

Platelet-derived growth factor BB-induced p38 mitogen-activated protein kinase activation causes cell growth, but not apoptosis, in vascular smooth muscle cells.

The aim of this experiment was to examine the regulation of p38 mitogen-activated protein (MAP) kinase by platelet-derived growth factor (PDGF)-BB and its biological effects on rat cultured vascular smooth muscle cells (VSMCs). VSMCs were obtained from aortae of male Wistar rats by the media explant technique. After being stimulated by PDGF-BB with or without the p38 MAP kinase-specific inhibitor, SB-203580, the cells were solubilized, and the levels of phosphorylated p38 MAP kinase were examined by immunoblot analysis. The amounts of DNA synthesis and content were measured by using [3H]-thymidine and Hoechst-33258 dye, respectively. The detection of apoptotic cells was evaluated by the TUNEL method. PDGF-BB could phosphorylate p38 MAP kinase dose-dependently, and the phosphorylation was specifically inhibited by SB-203580 in a dose-dependent manner. However, PDGF-BB did not affect the protein level of p38 MAP kinase. Both [3H]-thymidine incorporation and total cellular DNA content were increased by PDGF-BB, and these elevations were prevented by SB-203580. In contrast, PDGF-BB-stimulated VSMCs did not show apoptotic change in spite of the presence or absence of SB-203580. These results established that PDGF-BB activated p38 MAP kinase and subsequently regulated cell growth in VSMCs, providing a molecular mechanism by which p38 MAP kinase can cause the development of cardiovascular diseases, including atherosclerosis.

Animals↗
PubMed2001

Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample.

OBJECTIVE: Despite a large number of studies, no association of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS: A total of 1,685 subjects (935 women and 750 men, aged 58.7 +/- 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI > or =30 kg/m(2) were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The chi(2) test and analysis of variance were used for the association studies and to assess the differences in the traits' values, respectively. RESULTS: More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84 vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS: Genotype Arg/Arg, but not Trp/Arg, of the beta(3)-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.

Aged↗
PubMed2001

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities.

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Anti-Bacterial Agents↗
PubMed2001

Some biological and biochemical activities of resormycin, a novel herbicidal antibiotic.

Biological and biochemical activities of resormycin were studied using unicellular green algae, Selenastrum capricornutum (abbreviated as Selena.), as a test organism. Resormycin inhibited the growth in vitro of Selena. more strongly in the dark than in the light. A weaker but more photo-stable derivative, (+/-)-2,3-dihydro-resormycin, showed more long-lasting activity against Selena. in the light. Resormycin started killing Selena. only after exposure for 2 days and longer, even at high concentrations. Resormycin at concentrations near IC50 rapidly inhibited incorporation of 3H-leu, but not 3H-UR or 3H-TdR, into the TCA insoluble fraction of Selena. Herbicidal activity of resormycin was confirmed using some crops and weeds.

Antifungal Agents↗
PubMed2001

Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse transcriptase messenger RNA in pancreatic juice with sample qualification.

PURPOSE: We evaluated the diagnostic efficacy of detection of human telomerase reverse transcriptase (hTERT) message, a catalytic domain of human telomerase, in endoscopic retrograde pancreatography (ERP)-derived pancreatic juice. EXPERIMENTAL DESIGN: Both hTERT and CD25 expression were detected by reverse transcription-PCR (RT-PCR) in 17 patients with pancreatic adenocarcinoma (PC), 12 patients with chronic pancreatitis (CP), and 7 patients with no ERP abnormality (N). In the same patients, beta-actin message was semiquantified by competitive RT-PCR. K-ras codon 12 mutations were concomitantly analyzed by enriched PCR-SSCP in 11 and 7 PC and CP cases, respectively. RESULTS: Expression of hTERT was detected in 88% of PC cases and 17% of CP cases but not in the normal control (N). Alterations in K-ras were detected in 73% of PC cases and 57% of CP cases, respectively. beta-Actin mRNA was expressed in >3.0 x 10(1) copies/microl in all but two PC cases in which hTERT mRNA was not detected. CD25-positive and -negative peripheral lymphocytes were isolated from a normal volunteer using a fluorescent activating cell sorter. The hTERT message was detected in CD25-positive peripheral lymphocytes and in 18, 25, and 0% of the pancreatic juice samples from PC, CP, and N cases, respectively. All CP cases expressing hTERT message were also CD25 positive. CONCLUSIONS: These results suggest that detection of hTERT mRNA in pancreatic juice is a powerful tool to discriminate PC from CP, particularly when the samples are qualified against beta-actin mRNA levels and contaminating CD25-positive lymphocytes.

Actins↗
PubMed2000

E-73, an acetoxyl analogue of cycloheximide, blocks the tumor necrosis factor-induced NF-kappaB signaling pathway.

Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1 activate the NF-kappaB signaling pathway which induces the expression of a variety of genes such as the encoding intercellular adhesion molecule (ICAM)-1. We have found that E-73, an acetoxyl analogue of cycloheximide, specifically blocks TNF-induced ICAM-1 expression even at concentrations unable to affect protein synthesis. By contrast, cycloheximide inhibited both TNF- and IL-1-induced ICAM-1 expression primarily due to the blockage of protein synthesis. The nuclear translocation of NF-kappaB as well as the IkappaB degradation induced by TNF, but not by IL-1, was significantly prevented by E-73. These observations suggest that E-73 blocks the TNF-induced NF-kappaB signaling pathway upstream of IkappaB degradation.

Blotting, Western↗