Search PubMed⌕ Search

Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 55 records · Page 3Linked to original sources
PubMed2003

Experimental transmission of abnormal prion protein (PrPsc) in the small intestinal epithelial cells of neonatal mice.

Using an immunohistochemical method, we attempted to detect the transmission of abnormal prion protein (PrPsc) to the enterocytes of the small intestine of neonatal mice by oral exposure with sheep brain affected by scrapie. Five 1-day-old neonatal mice were exposed by oral inoculation to the homogenized brain of a scrapie-affected sheep. In the small intestine of all mice 1 hour after inoculation, immunoreactivity with antinormal prion protein (PrPc) antibody was seen in the cytoplasm of villus enterocytes. This finding suggests transmission of abnormal PrPsc into the cytoplasm of enterocytes. In control mice treated with normal sheep brain, no PrPc signal was seen in enterocytes of the small intestine. Immunopositivity for neurofilament protein and glial fibrillary acidic protein was seen in the cytoplasm of enterocytes of mice inoculated with scrapie and normal sheep brain. This suggests that the enterocytes of neonatal mice can absorb PrPsc and other macromolecular proteins of the sheep brain affected by scrapie and may be more important than previously thought as a pathway for PrPsc transmission in neonatal animals.

Animals↗
PubMed2003

Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16.

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.

Animals↗
PubMed2002

Nuclear BAG-1 expression reflects malignant potential in colorectal carcinomas.

BAG-1 is a recently identified Bcl-2-interacting anti-apoptotic protein. The aim of our study was to investigate the immunohistochemical staining pattern of BAG-1 protein in patients with colorectal cancer and examine associations of BAG-1 expression with various clinicopathological factors and patient survival. Tumour samples were collected from 86 patients diagnosed with colorectal cancer. There was significant variation in the immunohistochemical staining patterns for BAG-1, including absent staining and staining of either the cytoplasm, nucleus or both. Twenty-one colorectal carcinomas (24.4%) exhibited a nuclear staining pattern whilst 56 (65.1%) exhibited cytoplasmic staining. The percentage of cases exhibiting nuclear BAG-1 positivity was significantly higher in distant metastasis-positive cases (55.6%) than in distant metastasis-negative cases (20.8%; P=0.036). Overall survival was significantly shorter for patients with tumours exhibiting BAG-1 positive nuclei than those with absent nuclear BAG-1-staining (P=0.011). In addition, the multivariate cox proportional hazard models indicated that nuclear BAG-1 expression was the only independent prognostic variable for mortality (P=0.013). These studies demonstrate that nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer.

Carrier Proteins↗
PubMed2002

Localization of tetrodotoxin in the skin of a brackishwater puffer Tetraodon steindachneri on the basis of immunohistological study.

A monoclonal antibody-based immunoassay for localization of tetrodotoxin (TTX) in the skin of a brackishwater puffer Tetraodon steindachneri is described in this paper. TTX was recognized in the undifferentiated basal cells and succiform cells in the skin under light microscope. Malpighian cells of the skin did not exhibit any TTX antigen. Neither gland nor enclosed gland-like apparatus possessing TTX was apparent in the skin.

Animals↗
PubMed2002

Molecular basis of the alteration in skin collagen metabolism in response to in vivo dexamethasone treatment: effects on the synthesis of collagen type I and III, collagenase, and tissue inhibitors of metalloproteinases.

BACKGROUND: Glucocorticoids are widely used for the treatment of various diseases, despite known side-effects such as skin atrophy. Many studies have shown that the status of collagen fibres in the skin is affected by glucocorticoid treatment. However, the molecular mechanism underlying the alteration of collagen metabolism in the skin by glucocorticoid treatment remains unknown. OBJECTIVES: To characterize the molecular mechanisms related to the deterioration of the dermis in response to glucocorticoids, the status of two major types of collagen, collagenase, and tissue inhibitors of metalloproteinases (TIMPs) in the dorsal skin of rats was studied at the protein and mRNA levels. METHODS: Samples of rat dorsal skin were obtained after daily (1 mg kg-1) subcutaneous injections of dexamethasone (DEX) for 8 days. mRNA levels of two types of collagen and of TIMPs were measured by a lysate RNase protection assay. mRNA levels of collagenase were measured by a quantitative polymerase chain reaction. Protein levels of collagen and collagenase were measured by an immunoblot analysis. RESULTS: Levels of type I tropocollagen and type III tropocollagen were drastically reduced in response to DEX. The effects of DEX treatment were more severe on type III than type I collagen: it also produced a significant decrease in fibril collagen of type III collagen. DEX treatment was found to decrease both active and latent forms of collagenase as well as its mRNA levels. Among TIMPs, mRNA levels of TIMP-1 and TIMP-2 were decreased in response to DEX treatment, whereas those of TIMP-3 were not affected. CONCLUSIONS: These results suggest that DEX treatment strongly interferes with both the synthesis and degradation of type I collagen and, more drastically, type III collagen, the molecule that is known to play a major role in the initiation of wound healing. The present study may provide a molecular basis for the deterioration of skin function, impaired wound healing, and skin atrophy caused by glucocorticoid treatment.

Animals↗
PubMed2002

Effect of SMP-500, a novel acyl-coA:cholesterol acyltransferase inhibitor, on the cholesterol esterification and its hypocholesterolemic properties.

We investigated the effects of SMP-500, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activities in the liver and intestine, and in macrophages. We measured its effects on the serum cholesterol levels and hepatic cholesterol content in mice, rabbits and hamsters. SMP-500 inhibited ACAT activities in rabbit liver and small intestine microsomes with IC(50) values of 72 and 84 nmol/l, respectively, and acted as a competitive inhibitor of rabbit liver ACAT. SMP-500 potently inhibited cholesterol esterification in rat peritoneal macrophages (IC(50) = 15 nmol/l). In high-fat and high-cholesterol diet-fed mice and in high-cholesterol diet-fed rabbits, SMP-500 reduced the serum cholesterol levels and the hepatic cholesterol content. SMP-500 also reduced the serum and hepatic cholesterol in normal chow-fed hamsters in a dose-dependent manner. In all the animal models, SMP-500 reduced the hepatic free cholesterol content as well as the total and esterified cholesterol. Administered orally, SMP-500 had a direct inhibitory effect on hepatic ACAT activity. These results indicate that SMP-500 is a potent and competitive ACAT inhibitor and may have a therapeutic potential for treating hypercholesterolemia and atherosclerosis.

Animals↗
PubMed2002

Obesity and lipid profiles in middle aged men and women in Tanzania.

OBJECTIVE: To examine the relationship between obesity and lipid profiles and to compare the effects of total obesity and central adiposity on lipids in three locations in Tanzania. DESIGN: Cross-sectional epidemiological study. SETTING: Three areas in Tanzania: Dar es Salaam (urban), Handeni (rural) and Monduli (pastoralists), in August 1998. SUBJECTS: Five hundred and forty five men and women from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Mean BMI, waist circumference, WHR, TC, HDL-C, LDL-C, TG and LDL/HDL ratio. Prevalence rates of overweight,obesity, central obesity and dyslipidaemia. RESULTS: As compared to men, women had higher BMI (24.7 versus 22.5 kg/m2, p<0.0001), waist circumference (92.4 versus 89.1 cm, p<0.05), TC (4.9 versus 4.2 mmol/L, p<0.0001) and LDL-C (3.3 versus 2.6 mmol/L, p<0.0001). The urban population demonstrated higher levels of lipid factors than the rural population (TC, men 4.8 mmol/L; women 5.3 mmol/L, p<0.0001; TG, men 3.6 mmol/L; women 3.7 mmol/L, p<0.0001, LDL-C, men 2.8 mmol/L, p<0.0001). BMI and waist circumference correlated positively with serum TC, TG, and LDL-C in both genders. Stepwise regression analysis showed that BMI predicted triglyceride concentration in men (p<0.05) and women (p<0.0001). Waist circumference predicted levels of TC in women only (p<0.0001) and of LDL-C in both genders (men p<0.05, women p<0.0001). The prevalence of overweight, obesity and central obesity were significantly higher in urban than in rural areas in both men and women. Compared to lean subjects, obese men and women had significantly higher mean serum TC, TG, LDL-C and a higher prevalence of dyslipidaemia. The mean levels of TC, TG and LDL cholesterol increased across successive increases in BMI and waist circumference quintiles in both genders. CONCLUSION: Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.

Body Mass Index↗
PubMed2002

Preferential transcription of a gene for alpha amylase in the carcinoid tumor of African rodent Mastomys natalensis.

The carcinoid tumor in Mastomys natalensis provides a useful animal model of tumorigenesis. We investigated preferentially transcribed genes in this carcinoid tumor by differential hybridization. Fourteen clones corresponding to high levels of transcription were isolated from a cDNA library. Sequencing analysis and a homology search revealed that the clones corresponded to genes for chromogranin and alpha-amylase. High-level transcription of a gene for alpha-amylase gene in Mastomys carcinoid tumor was confirmed by Northern blotting analysis. Furthermore, Western blotting analysis confirmed the expression of alpha-amylase in tumors at the protein level. Immunohistochemical staining revealed alpha-amylase in the cytoplasm of Mastomys carcinoid tumors. Our results demonstrated that an exocrine enzyme 'amylase' could be produced ectopically by a neuroen docrine tumor.

Africa↗
PubMed2001

Induction of hepatic tissue-type plasminogen activator and type 1 plasminogen activator-inhibitor gene expressions and appearance of their translation products in the bile following acute liver injury in rats.

BACKGROUND/AIMS: The plasminogen activator (PA)-plasmin system is primarily involved in fibrinolysis, but is also in the patho/physiological events in which breakdown of extracellular matrices is evoked topically. In this present study, we examined the expression of fibrinolytic factors, tissue-type PA (t-PA) and Type 1 PA inhibitor (PAI-1), in acute liver injury. METHODS: Acute liver injury was produced in rats by the intraperitoneal administration of carbon tetrachloride (CCl(4)). Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured to verify the hepatocellular damage. t-PA and PAI-1 gene expressions were measured by Northern blotting, and the cell type(s) expressing these genes was identified by in situ hybridization. t-PA and PAI-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A single intraperitoneal administration of CCl(4) caused severe acute parenchymatous liver injury. Both t-PA and PAI-1 gene expressions were induced by the acute liver injury, and plasma t-PA and PAI-1 concentrations were also increased. In situ hybridization studies demonstrated that the hepatocytes were the cells expressing t-PA and PAI-1 genes during the acute liver injury. t-PA was also augmented in the bile, whereas PAI-1 was decreased there. CONCLUSIONS: t-PA and PAI-1 gene expressions are induced in the hepatocytes of rats with acute liver injury. These fibrinolytic factors induced by liver injury may play important roles in liver regeneration.

Animals↗
PubMed2001

CDK-inhibitors-associated kinase activity: a possible determinant of malignant potential in smooth muscle tumors of the external soft tissue.

There has been accumulating histological observation of leiomyoma and leiomyosarcoma of the external soft tissue regarding their differential diagnosis. The definitive diagnostic tools have not been established, however, nor have the pathological mechanisms of cell proliferation in these tumors been clarified. Herein, expression of the cyclin-dependent kinase inhibitors (CKIs), p21, p27 and p57 and their associated kinase activities were examined in 61 cases of soft tissue smooth muscle tumors. Immunohistochemical staining showed that all 3 inhibitor proteins were expressed in all cases of leiomyoma and leiomyosarcoma, but that the mean values of their labeling indices (LIs) were higher in the cases of leiomyosarcoma. In addition, the LIs of p21 and p27 were inversely correlated in total cases. Immunoblotting revealed that these proteins are expressed at higher levels in tumors, in particular, in leiomyosarcoma. When CKIs were immunoprecipitated from tissue extracts, cyclin/cdk protein complexes associated with, at least, 1 CKI were detectable only in tumor tissues. Furthermore, cdk2 or cdk4 kinase activity manifested by these cyclin/cdk/CKI complexes (CKI-associated kinase activity) was detectable exclusively from leiomyosarcoma, but not from leiomyoma. Among the cases of leiomyosarcoma, cdk2 activity was generally found associated either with p21 or p27, but not both. Statistical analysis indicated that p21- and p27 LIs are predictive of positive or negative clinical outcome, respectively. In conclusion, the participation of CKIs in active cyclin/cdk complexes in a reciprocal and redundant manner and subsequent CKI- associated kinase activity are the characteristic profiles of malignant phenotype in these tumors. Moreover, immunohistochemical detection of CKIs may provide a useful tool for evaluating patients' prognosis.

Cell Cycle Proteins↗
PubMed2001

IL-1beta down-regulates tissue-type plasminogen activator by up-regulating low-density lipoprotein receptor-related protein in AML 12 cells.

Interleukin-1 (IL-1) regulation of tPA in hepatocytes was studied in mouse hepatocyte line AML12. IL-1 induced transient accumulation of tPA mRNA as high as threefold by 2 h after the start of treatment. The cytokine also induced the mRNA for serum amyloid A, a typical acute-phase protein in mice, with more sustained kinetics in a time-dependent manner. In contrast to the induction of mRNA, tPA activity and protein levels in the harvested medium were dramatically diminished by IL-1. IL-1 stimulated the uptake of (125)I-tPA by AML 12. This uptake was inhibited by 39-kDa receptor-associated protein (RAP), but not by the sugar mannan. These results revealed that low-density lipoprotein receptor-related protein (LRP), which is known to be a receptor for tPA and to be blocked by RAP, was up-regulated by IL-1. We also demonstrated, for the first time, that IL-1 transiently increased the mRNA level of LRP threefold by 30 min after the start of IL-1 treatment of AML 12. The receptor-mediated endocytosis of tPA by hepatocytes may thus play a crucial role in the down-regulation of fibrinolysis during the acute-phase response.

Animals↗
PubMed2001

Effects of psychological stress on monoamine systems in subregions of the frontal cortex and nucleus accumbens of the rat.

We investigated the effects of two types of psychological stress, novelty stress and psychological stress using the communication box, on dopamine and serotonin systems in subregions of the frontal cortex and nucleus accumbens of rats. Placement of rats into a compartment of the communication box (novelty stress) increased both dopamine and serotonin metabolism in medial precentral, anterior cingulate, and prelimbic subregions of the frontal cortex as evaluated by the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid for dopamine, and 5-hydroxyindoleacetic acid for serotonin. In contrast, novelty stress had no effect on these monoamine systems in infralimbic and sulcal subregions of the frontal cortex. In the nucleus accumbens, novelty stress increased both dopamine and serotonin metabolism in the shell, but decreased dopamine metabolism in the core. On the other hand, psychological stress using the communication box augmented dopamine metabolism in the anterior cingulate and prelimbic subregions. This stress, however, failed to affect the dopamine system in the medial precentral, infralimbic and sulcal subregions. In the nucleus accumbens, the stress selectively decreased dopamine metabolism in the shell but showed no effect in the core. The serotonin system showed little change due to the stress. These results demonstrate that psychological stress causes distinct changes in both the dopamine and serotonin systems in the frontal cortex and the nucleus accumbens. These changes vary with the subregions of these areas, suggesting that the region-specific responsiveness to psychological stress reflects the functional differences among these subregions. In addition, our results also suggest that changes in brain monoamine systems induced by psychological stress are quite different from those induced by physical stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Flecainide reverses neuropathic pain and suppresses ectopic nerve discharge in rats.

We investigated effects of flecainide, a Class IC sodium channel blocker, in the rat chronic constrictive injury (CCI) and ectopic nerve discharge models. In the behavioral evaluation, 2, 6, and 12 mg/kg flecainide were intravenously given to the CCI model, and a dose-dependent analgesic effect was shown on both thermal hyperalgesia and tactile allodynia. In the electrophysiological evaluation using the ectopic nerve discharge model produced by saphenous neurectomy, i.v. administration of 2, 6, and 12 mg/kg flecainide suppressed spontaneous discharge at the peripheral nerve level in a dose-dependent fashion as with the behavioral evaluation, but flecainide did not affect nerve conduction at the dose of 12 mg/kg.

Action Potentials↗
PubMed2001

Cardiovascular risk factors in Tanzania: a revisit.

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMI > or = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P < 0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure > 160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P < 0.001) for men and to 38.7% (P < 0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol > 5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P < 0.0001) and women (54.0%, P < 0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P < 0.0001; women 5.1, P < 0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

Blood Pressure↗
PubMed2001

Important role of tetrahydrobiopterin in no complex formation and interdomain electron transfer in neuronal nitric-oxide synthase.

Neuronal nitric-oxide synthase (nNOS) is composed of a heme oxygenase domain and a flavin-bound reductase domain. Ca(2+)/calmodulin (CaM) is essential for interdomain electron transfer during catalysis, whereas the role of the catalytically important cofactor, tetrahydrobiopterin (H4B) remains elusive. The product NO appears to bind to the heme and works as a feedback inhibitor. The present study shows that the Fe(3+)-NO complex is reduced to the Fe(2+)-NO complex by NADPH in the presence of both l-Arg and H4B even in the absence of Ca(2+)/CaM. The complex could not be fully reduced in the absence of H4B under any circumstances. However, dihydrobiopterin and N(G)-hydroxy-l-Arg could be substituted for H4B and l-Arg, respectively. No direct correlation could be found between redox potentials of the nNOS heme and the observed reduction of the Fe(3+)-NO complex. Thus, our data indicate the importance of the pterin binding to the active site structure during the reduction of the NO-heme complex by NADPH during catalytic turnover.

Anaerobiosis↗
PubMed2001

Polyphosphate:AMP phosphotransferase and polyphosphate:ADP phosphotransferase activities of Pseudomonas aeruginosa.

In Pseudomonas aeruginosa PAO1, we have found massive polyphosphate:AMP phosphotransferase activity and polyphosphate:ADP phosphotransferase activity known as the reverse catalytic activity of polyphosphate kinase which participates in polyphosphate synthesis in the bacterium. Biochemical analysis using the partially purified polyphosphate:ADP phosphotransferase has revealed that it is independent of polyphosphate kinase and can function as polyphosphate-dependent nucleoside diphosphate kinase which most prefers GDP to the other three nucleoside diphosphates as a phospho-acceptor. It has been also demonstrated that polyphosphate:AMP phosphotransferase activity marked in the bacterium mainly originates from the combined action of the polyphosphate:ADP phosphotransferase described above and adenylate kinase. Both of the polyphosphate-utilizing activities require short polyP as a phospho-donor whose chain length is <75.

Base Sequence↗
PubMed2001

Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors.

Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.

Animals↗