Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 235 records · Page 13Linked to original sources

PubMed1999

Differential roles of endothelin-1 in the development of secondary pulmonary hypertension in patients with left heart failure with or without acute exacerbation.

BACKGROUND: The aim of this study was to investigate the contribution of endothelin-1 (ET-1) to the development of secondary pulmonary hypertension (PH) in patients with left heart failure (HF). METHODS AND RESULTS: The subjects were 40 patients with left HF with (group 1; n = 20) and without (group 2; n = 20) acute exacerbation. Before treatment, the ET-1 level in the pulmonary capillary wedge region was three times greater in patients of group 2 than group 1, although there was no significant difference in mean pulmonary artery pressure (mPAP) or pulmonary vascular resistance index (PVRI) between the two groups. Also, the ET-1 level significantly correlated with mPAP and PVRI for both groups, but with different slopes of the regression lines. After treatment of group 1, the extent of reduction in the ET-1 level significantly correlated with that in mPAP and in PVRI, whereas the ET-1 level itself correlated with mPAP, with the regression lines approximating those of group 2. CONCLUSIONS: Our findings suggest that ET-1 may have differential roles in the development of secondary PH in patients with left HF with or without acute exacerbation.

Aged↗

PubMed1999

Interleukin-15 production at the early stage after oral infection with Listeria monocytogenes in mice.

We previously reported that exogenous interleukin-15 (IL-15) induces proliferation and activation of intestinal intraepithelial lymphocytes (i-IEL) in naive mice. To investigate the ability of endogenous IL-15 to stimulate i-IEL in vivo, we monitored i-IEL and intestinal epithelial cells (i-EC) in mice after an oral infection with Listeria monocytogenes. Although the populations of alphabeta and gammadelta i-IEL were not significantly changed after the oral infection, the expression level of interferon-gamma (IFN-gamma) was increased both at transcriptional and protein levels, and a conversely marked decrease in interleukin-4 (IL-4) was detected in the i-IEL on day 1 after infection as compared with before infection. The T helper 1 (Th1)-biased response of i-IEL coincided with a peak response of IL-15 production in the i-EC after oral infection. These results suggested that IL-15 produced from i-EC may be at least partly involved in the stimulation of i-IEL to produce IFN-gamma after oral infection with L. monocytogenes.

Animals↗

PubMed1999

Effects of voluntary exercise and L-arginine on thrombogenesis and microcirculation in stroke-prone spontaneously hypertensive rats.

1. The preventive effects of exercise and L-arginine intake on hypertension and thrombosis in stroke-prone spontaneously hypertensive rats (SHRSP) were studied. 2. Stroke-prone spontaneously hypertensive rats were divided into three groups: (i) the control, sedentary group; (ii) the exercise group, which was allowed to run voluntarily on running wheels; and (iii) the L-arginine intake group, which was given 2.25% L-arginine solution for 8 weeks from 4 to 12 weeks of age. In the control group, one rat died from stroke and symptoms of stroke were observed in the remaining animals. Similar symptoms were recorded in one rat of the exercise group, but not in the L-arginine group. 3. Blood pressure increased in the control group and this increase was suppressed significantly in the exercise and L-arginine groups. Thrombotic potential in cerebral vessels was the lowest at 4 weeks in all groups and was increased significantly at 12 weeks in the control group, but not in the exercise and L-arginine groups. Plasma concentrations of NO2/NO3 were lower in all animals at 12 weeks compared with those at 4 weeks. This reduction was significantly less marked in the L-arginine group. Cerebral arterioles in control rats at 12 weeks of age were significantly smaller in diameter than those at 4 weeks and these changes were less pronounced in the exercise and L-arginine groups. 4. The results provide clear evidence for the beneficial effects of L-arginine intake and voluntary exercise in mechanisms related to hypertension, thrombosis and stroke.

Animals↗

PubMed1999

Microsatellite analysis of childhood leukemia: correlation of 9p and 12p chromosome abnormalities with expression of related genes.

BACKGROUND: Loss of heterozygosity (LOH) and DNA replication error (RER) have been thought to be involved in carcinogenesis, but have not been investigated in childhood leukemia and lymphoma. METHODS: Eighty samples from 65 patients with childhood leukemia and lymphoma were examined using seven different microsatellite markers for RER analysis. Additionally, LOH in two chromosome regions (9p and 12p) was investigated. Furthermore, expression of the TEL, TEL/AML1 and p27(KIP1) genes on 12p and the p16 gene on 9p were detected by reverse transcriptase polymerase chain reaction. RESULTS: Replication errors were detected in 5/65 patients (7.7%). Most (4/5 patients) RER were preferentially located in the 9p and 12p regions. There were two patients who had DNA abnormalities in both 9p and 12p, one with common acute lymphoblastic leukemia (ALL) showed 9p LOH and the TEL/AML1 fusion gene on 12p and the other with common ALL and 12p RER had diminished expression of both the p27(KIP1) gene on 12p and the p16 gene on 9p. CONCLUSIONS: Combined DNA alterations on 9p and 12p, involving LOH, RER and/or gene mutation and chromosomal translocation, were found in childhood acute leukemia, especially in common ALL.

Child↗

PubMed1999

The utility of endoscopic screening for patients with esophageal or head and neck cancer.

In a series of 378 patients with esophageal carcinoma, 43 patients with head and neck carcinoma were divided into two groups: 30 patients without symptoms whose esophageal or head and neck second primary carcinomas were incidentally detected by an endoscopic examination for the second carcinoma (group 1) and 13 patients with symptoms whose esophageal or head and neck second primary carcinomas were detected by routine examinations (group 2). Regarding the second primary carcinomas, the incidence of stage 0-I and curability were significantly higher in group 1 than in group 2 (p < 0.001 and p < 0.05 respectively). The 5-year overall survival rates of patients with the second primary carcinomas were significantly higher in group 1 (60.4%) than in group 2 (0%) (p < 0.01). We suggest that a routine endoscopic screening of the upper aerodigestive tract in patients with esophageal carcinoma or head and neck carcinoma contributes to the improvement of the prognosis and the patient's quality of life.

Adult↗

PubMed1999

Expression of two dead box genes (DDX1 and DDX6) is independent of that of MYCN in human neuroblastoma cell lines.

To examine whether two DEAD box genes, DDX1 and DDX6, would have some roles in the progression of tumors, we investigated the correlation of the expression of these genes with that of MYCN in neuroblastomas either with or without MYCN amplification. The mRNA of MYCN was observed only in the cell lines with amplification of MYCN. The mRNAs of DDX1 and DDX6 were found in all the cell lines examined, but the correlation between the mRNA levels of DDX1 or DDX6 and MYCN was poor. These findings suggest that the expression of neither DEAD box gene is correlated with the gene expression of MYCN.

DEAD-box RNA Helicases↗

PubMed1999

Genomic organization and promoter analysis of a mouse homeobox gene, Hex.

A homeobox gene, Hex, is mainly expressed in haematopoietic cells and hepatocytes. It is assumed to play a role in the early stage of differentiation of these cells. To understand the mechanisms involved in the regulation of the Hex gene expression in hepatocytes, we cloned and characterized the mouse Hex gene. The gene consists of four exons and three introns, and spans about 5.7 kb. All the exon-intron boundaries are consistent with the "GT-AG" rule. A single transcription start site was identified by primer extension and S1 mapping analyses. Although the 5'-flanking region is G/C rich (69%), it contains probable "TATA and CCAAT" boxes. Potential binding sequences for transcriptional regulatory proteins including Sp1 and AP-2 are also present in this region. Functional analysis of the Hex promoter was performed by transfecting MH1C1, HeLa, COS-7, and Caco-2 cells with Hex promoter region-luciferase constructs. We found three possible positive regulatory regions, comprising of nucleotides -199 and -172, -154 and -133, and -105 and -68, respectively, required for Hex gene expression in MH1C1 cells by analyses of a series of 5'-deletion constructs of the fusion genes. The activities of these constructs were extremely low in HeLa, COS-7, and Caco-2 cells suggesting that they possess cell-type specificity. Further analysis revealed two GC boxes, GC box1 and GC box2, at nucleotides -197 to -188 and -176 to -167, respectively, necessary for Hex gene expression. Thus, multiple regulatory elements contribute to the Hex gene expression in hepatocytes.

Animals↗

PubMed1999

Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients.

The impact of smoking on plasma haloperidol (HAL) concentrations was investigated in 66 Japanese male schizophrenic inpatients treated orally with HAL. The subjects consisted of 22 nonsmokers and 44 smokers each smoking ten cigarettes per day. Plasma concentrations of HAL were determined by an enzyme immunoassay method. There were significant positive correlations between the plasma HAL concentration and the daily dose of HAL per kg body weight (Y = 58.1X-0.01 (r = 0.86)). Smokers had significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 54.3+/-16.6 vs. 70.6+/-23.2 ng/mL/mg/kg). In doses less than 0.2 mg/kg of HAL, smokers showed significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 55.1+/-14.4 vs. 79.5+/-27.1 ng/mL/mg/kg), whereas no significant difference in HAL concentrations per daily dose of HAL/kg body weight was observed between smokers and nonsmokers when treated with more than 0.2 mg/kg (smokers vs. nonsmokers = 52.9+/-20.7 vs. 60.0+/-11.1 ng/mL/mg/kg). Our results indicate that smoking may induce the enzyme(s) metabolizing HAL, which results in lower plasma HAL concentrations in smokers than in nonsmokers, particularly at low doses of HAL.

Administration, Oral↗

PubMed1999

The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis.

Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism.

Alleles↗

PubMed1999

Arabidopsis det2 is defective in the conversion of (24R)-24-methylcholest-4-En-3-one to (24R)-24-methyl-5alpha-cholestan-3-one in brassinosteroid biosynthesis.

Previously, we have shown that the Arabidopsis det2 (deetiolated2) mutant is defective in the biosynthesis of brassinosteroids (BR) and that DET2 (a steroid 5alpha-reductase) acts early in the proposed BR biosynthetic pathway. In this paper we present further biochemical characterization of det2. We have undertaken metabolic experiments with 2H-labeled substrates of intermediates involved in the formation of campestanol from campesterol, and quantitative analysis of intermediates in Arabidopsis wild type and det2. The results of these studies indicate the early operating steps of BR biosynthesis as: campesterol --> 4-en-3beta-ol --> 4-en-3-one --> 3-one --> campestanol in Arabidopsis, with det2 deficient in the conversion of 4-en-3-one to 3-one. We have also detected these intermediates in the formation of campestanol from campesterol and their metabolic conversions using cultured cells of Catharanthus roseus. These studies confirmed the biosynthetic sequence of events from campesterol to campestanol as was found in Arabidopsis. As such, the originally proposed biosynthetic pathway should be modified.

Arabidopsis↗

PubMed1999

Brassinosteroid-insensitive dwarf mutants of Arabidopsis accumulate brassinosteroids.

Seven dwarf mutants resembling brassinosteroid (BR)-biosynthetic dwarfs were isolated that did not respond significantly to the application of exogenous BRs. Genetic and molecular analyses revealed that these were novel alleles of BRI1 (Brassinosteroid-Insensitive 1), which encodes a receptor kinase that may act as a receptor for BRs or be involved in downstream signaling. The results of morphological and molecular analyses indicated that these represent a range of alleles from weak to null. The endogenous BRs were examined from 5-week-old plants of a null allele (bri1-4) and two weak alleles (bri1-5 and bri1-6). Previous analysis of endogenous BRs in several BR-biosynthetic dwarf mutants revealed that active BRs are deficient in these mutants. However, bri1-4 plants accumulated very high levels of brassinolide, castasterone, and typhasterol (57-, 128-, and 33-fold higher, respectively, than those of wild-type plants). Weaker alleles (bri1-5 and bri1-6) also accumulated considerable levels of brassinolide, castasterone, and typhasterol, but less than the null allele (bri1-4). The levels of 6-deoxoBRs in bri1 mutants were comparable to that of wild type. The accumulation of biologically active BRs may result from the inability to utilize these active BRs, the inability to regulate BR biosynthesis in bri1 mutants, or both. Therefore, BRI1 is required for the homeostasis of endogenous BR levels.

Alleles↗

PubMed1999

Fimbria-mediated coaggregation between human oral anaerobes Treponema medium and Porphyromonas gingivalis.

Bacterial binding phenomena among different bacterial genera or species play an important role in bacterial colonization in a mixed microbiota such as in the human oral cavity. The coaggregation reaction between two gram-negative anaerobes, Treponema medium and Porphyromonas gingivalis, was characterized using fimbria-deficient mutants of P. gingivalis and specific antisera against purified fimbriae and bacterial whole cells. T. medium ATCC 700273 strongly coaggregated with fimbriate P. gingivalis strains ATCC 33277 and 381, but not with afimbriate strains including transposon-induced fimbria-deficient mutants and KDP98 as a fimA-disrupted mutant of P. gingivalis ATCC 33277. In the P. gingivalis-T. medium coaggregation assay, the presence of rabbit antiserum against the purified fimbriae or the whole cells of P. gingivalis ATCC 33277 produced different "aggregates" consisting predominantly of P. gingivalis cells with few spirochetes, but both preimmune serum and the antiserum against the afimbriate KDP98 cells did not inhibit the coaggregation reaction. Heated P. gingivalis cells lost their ability to bind both heated and unheated T. medium cells. This T. medium-P. gingivalis coaggregation reaction was inhibited by a cysteine proteinase inhibitor, leupeptin, and also by arginine and lysine, but not by EDTA or sugars including lactose. A binding assay on nitrocellulose membranes and immunoelectron microscopy demonstrated that a heat-stable 37 kDa surface protein on the T. medium cell attached to the P. gingivalis fimbriae.

Animals↗

PubMed1999

Uptake and intracellular distribution of amrubicin, a novel 9-amino-anthracycline, and its active metabolite amrubicinol in P388 murine leukemia cells.

Amrubicin, a 9-aminoanthracycline anti-cancer drug, and its C-13 hydroxyl metabolite amrubicinol, were examined for growth-inhibitory activity as well as cellular uptake and distribution in P388 murine leukemia cells and doxorubicin-resistant P388 cells. Also discussed are the differences in the mechanisms of action among amrubicin, amrubicinol and doxorubicin in terms of their cellular pharmacokinetic character. In P388 cells, amrubicinol was about 80 times as potent as amrubicin, and about 2 times more potent than doxorubicin in a 1-h drug exposure growth-inhibition test. A clear cross-resistance was observed to both amrubicin and amrubicinol in doxorubicin-resistant P388 cells, though the resistance index was lower for amrubicin. The intracellular concentration of amrubicinol was about 6 times and 2 times higher than those of amrubicin and doxorubicin, respectively. Compared to doxorubicin, amrubicin and amrubicinol were released rapidly after removal of the drugs from the medium. A clear correlation was found between the growth-inhibiting activity and the cellular level of amrubicin and amrubicinol in P388 cells. About 10 to 20% of amrubicin or amrubicinol taken up by the cells was detected in the cell nuclear fraction, whereas 70 to 80% of doxorubicin was localized in this fraction. These results suggest that amrubicin and amrubicinol exert cytotoxic activity via a different mechanism from that of doxorubicin.

Animals↗

PubMed1999

A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer.

BACKGROUND/AIMS: Endoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer. A prospective blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed. METHODS: Findings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently reviewed and the results of 52 early gastric cancer lesions analysed. RESULTS: The overall accuracy rates in invasion depth staging of early gastric cancer were 63% for endoscopy and 71% for endoscopic ultrasonography. No statistically significant differences were observed in overall accuracy. Endoscopic ultrasonography tended to overstage, and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely (95%) to be limited to the mucosa on histological examination. All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa. CONCLUSIONS: Endoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer.

Adult↗

PubMed1999

IL-1beta mediates induction of hepatic type 1 plasminogen activator inhibitor in response to local tissue injury.

Type 1 plasminogen activator inhibitor (PAI-1), a major physiological inhibitor of plasminogen activation, is an important component of the hepatic acute phase response. We studied the acute phase regulation of murine hepatic PAI-1 in response to systemic toxicity and local tissue injury in both wild-type mice and in mice in which the interleukin (IL)-1beta gene had been inactivated by gene targeting. Endotoxin induced plasma PAI-1 antigen levels and PAI-1 mRNA accumulation in liver to the same extent in both wild-type and IL-1beta-deficient mice. In contrast, turpentine increased plasma PAI-1 and hepatic PAI-1 mRNA accumulation in wild-type mice but not in IL-1beta-deficient mice. Intraperitoneal injection of murine IL-1beta rapidly increased plasma PAI-1 and hepatic PAI-1 mRNA in both wild-type and IL-1beta-deficient mice. These results suggest that IL-1beta is a critical inducer of hepatic PAI-1 gene expression during the acute phase response to local tissue injury. In situ hybridization studies revealed that hepatocytes are the cells primarily responsible for the hepatic expression of the PAI-1 gene induced by lipopolysaccharide and turpentine.

Acute-Phase Reaction↗

PubMed1999

Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans.

The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2 consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.

Adult↗

PubMed1999

Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. Significance of its inhibitory effect on cytosolic phospholipase A2.

IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer's solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

Animals↗

PubMed1999

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.

Aged↗