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T Noma

Publications and source records attributed to T Noma.

At least 37 records · Page 2Linked to original sources
PubMed2000

Involvement of adrenaline in diazepam-induced hyperglycemia in mice.

Diazepam-elicited hyperglycemia in mice was inhibited by adrenalectomy and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine, although it was unaffected by pretreatment with the corticosterone synthesis inhibitor dexamethasone. Diazepam-induced hyperglycemia was prevented by the alpha2 adrenoceptor antagonist idazoxan, while the beta1 and beta2 adrenoceptor antagonists, metoprolol and ICI 118 551, did not affect it. Furthermore, diazepam increased plasma adrenaline levels in mice. These results suggest that diazepam-induced hyperglycemia is closely related to adrenaline release from the adrenal gland.

Adrenergic beta-Antagonists↗
PubMed2000

cDNA cloning and chromosomal mapping of the gene encoding adenylate kinase 2 from Drosophila melanogaster.

As a step toward understanding of the role of adenylate kinase (AK) in energy metabolism, we analyzed this enzyme in Drosophila melanogaster. The enzyme activities of all three AK isozymes were determined in cell-free extracts of flies, and their proteins were detected by Western blot analysis using polyclonal antibodies against the mammalian isozymes. A cDNA encoding adenylate kinase was isolated from D. melanogaster cDNA library. The cDNA encodes a 240-amino acid protein, which shows high similarity to bovine, human and rat AK2, and hence was named DAK2. Preliminary subcellular fractionation analysis indicated that DAK2 is localized in both cytoplasm and mitochondria. In situ hybridization to salivary gland polytene chromosomes revealed that the Dak2 gene is located at 60B on the right arm of the second chromosome.

Adenylate Kinase↗
PubMed2000

Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads.

Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist.

Adenocarcinoma↗
PubMed2000

Effects of troglitazone on collagen accumulation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats.

We investigated the effect of troglitazone (TG) on aortic distensibility and histopathology at the preclinical stage in the non-insulin-dependent diabetes mellitus (NIDDM) model. Twenty male diabetic and 20 male nondiabetic rats were each divided into two groups: treated-DM, untreated-DM, treated-nonDM, and untreated-nonDM. TG (0.2%) was mixed in chow in the treated groups. From age 5 to 15 weeks, fast blood glucose and insulin were monitored. At 15 weeks, oral glucose tolerance test results, aortic wall histopathology, and collagen content were studied, and intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured during the cardiac cycle, and the stiffness parameter beta was calculated. Blood glucose (mg/dl) 2 h after loading in treated-DM (139+/-20) was normalized (untreated-DM, 188+/-27; p<0.05). Insulin concentration (ng/ml) in treated-DM (3.2+/-0.4) was lower than that in untreated-DM (8.1+/-1.5; p<0.01). At 15 weeks, beta in untreated-DM (2.4+/-0.8) was larger than those in untreated-nonDM (1.5+/-0.4; p<0.0001) and in treated-DM (1.9+/-0.4, p = 0.0081). Aortic wall collagen (mg/g dry weight) increased in untreated-DM (32.8+/-3.3) as compared with treated-DM (28.1+/-3.8; p = 0.048). Histomorphometry showed decreased medial area (mm2) in treated-DM (0.55+/-0.05) compared with untreated-DM (0.78+/-0.12; p<0.0001). This study suggests that TG may prevent metabolic abnormalities and the deterioration of aortic distensibility at an early prediabetic stage.

Animals↗
PubMed2000

Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry.

The purpose of our study has to determine the myocardial protective effects of the angiotensin-converting enzyme (ACE) inhibitor temocapril (TEM, 7 mg/kg/day) simultaneously administered with doxorubicin (Adriamycin). Twenty male Sprague-Dawley rats were intraperitoneally administered a cumulative dose of 15 mg/kg of doxorubicin (each dose of 1.0 mg/kg x 15) for 3 weeks, and divided into TEM-untreated and -treated rats. Seven control rats were injected with saline intraperitoneally. Body weight, hemodynamics, and echocardiographic measurements including quantitative analysis of ultrasonic integrated backscatter (IB) were obtained for 12 weeks after treatment. Finally, rats were killed for histopathologic study. At 6 weeks, end-diastolic left ventricular diameter (LVD) and percentage fractional shortening (%FS) were similar in TEM-treated and TEM-untreated rats, but cyclic variation of IB (dB) significantly decreased in TEM-untreated rats (7.3 +/- 1.2; control rats, 9.7 +/- 0.9; p < 0.01). At 12 weeks, %FS decreased in TEM-untreated rats (26.1 +/- 6.1%: TEM-treated rats, 34.2 +/- 6.2; p < 0.05), and calibrated IB (dB) in TEM-untreated rats (15.5 +/- 0.5) increased as compared with that in TEM-treated rats (12.1 +/- 0.7; p < 0.01). Interstitial collagen accumulation increased in TEM-untreated rats and was inhibited in treated rats. Simultaneous administration of TEM with doxorubicin was beneficial in preventing doxorubicin-induced myocardial damage, and myocardial tissue characterization was useful for the early detection of myocardial damage and the assessment of therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effects of perindopril on left ventricular remodeling and aortic regurgitation in rats assessed by echocardiography.

This study investigated the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on left ventricular (LV) remodeling and cardiac function in rats with aortic regurgitation (AR). Twenty male Sprague-Dawley rats in which AR was produced by closed-chest aortic valve puncture were divided into untreated and perindopril-treated (5 mg/kg/day) rats. Ten control rats were sham-operated. Blood pressure, body weight, and echocardiographic recordings were followed every 2 weeks for a period of 12 weeks. LV dimension (LVD) and fractional shortening (FS) were calculated. The heart was finally excised for weight, hydroxyproline measurements, and histopathology. At 12 weeks, end-diastolic LVD increased in untreated rats (10.8 +/- 0.2 mm) but did not dilate in treated rats (9.6 +/- 0.3 mm, p < 0.01 vs untreated rats). FS decreased from 6 weeks in untreated rats (27.3 +/- 0.9% at 12 weeks), but did not change in treated rats (33.8 +/- 0.5%, p < 0.001). The ratio of LV weight to body weight in untreated rats (2.62 +/- 0.11 mg/g, p < 0.05) was higher than in sham-operated rats (1.52 +/- 0.02 mg/g) and than in treated rats (1.95 +/- 0.07 mg/g). Interstitial collagen accumulation histopathologically increased in untreated rats and was inhibited in treated rats. LV collagen of untreated rats (1.46 +/- 0.08 mg/100 mg, p = 0.03) was higher than those of treated (1.08 +/- 0.09 mg/100 mg) and sham-operated rats (1.06 +/- 0.14 mg/100 mg). Perindopril inhibited LV remodeling induced by volume overload and preserved LV function in AR rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effects of a nitric oxide synthase inhibitor on hypophagia induced by the peripheral 5-HT receptor agonists, alpha-methyl-5-hydroxytryptamine and 5-carboxamidotryptamine in rats.

We investigated the effects of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on hypophagia in rats elicited by alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) and 5-carboxamidotryptamine (5-CT) which are suggested to be mediated by the peripheral 5-HT2A and 5-HT7 receptor, respectively. Both alpha-methyl-5-HT and 5-CT apparently inhibited food intake in food-deprived rats. L-NAME significantly enhanced alpha-methyl-5-HT-elicited hypophagia, while it inhibited 5-CT-elicited hypophagia. These results suggest that NO is differentially related to alpha-methyl-5-HT and 5-CT-induced hypophagia and that NO may play a role in hypo- and hyperphagia.

Animals↗
PubMed1999

Characterization of the 5'-flanking region of the gene encoding bovine adenylate kinase isozyme 3.

We have characterized the 5'-flanking region of the gene encoding bovine adenylate kinase isozyme 3 (AK3). S1 mapping analysis revealed multiple transcription start points in the bovine AK3 gene. The promoter activities were tested in HeLa cells using the chloramphenicol acetyltransferase (CAT) gene as a reporter. The CAT analysis showed that the basal promoter sequence was located within the region from -189 to +228. In the presence of short DNA fragments of the 5'-flanking region as competitors, the transcriptional activity of the bovine AK3 promoter changed depending on the fragments used. The results identified the basal regulatory elements in the proximal promoter region.

Adenylate Kinase↗
PubMed1999

Cloning and functional characterization of the promoter region of the gene encoding human adenylate kinase isozyme 3.

The 5'-flanking region of the gene encoding human adenylate kinase isozyme 3 was isolated and compared with that of the bovine AK3 gene previously characterized. Four conserved DNA sequences (elements-a, -b, -c, and -d) were found in both the regions. The promoter activities were analyzed in HeLa cells using promoter-CAT reporter constructs. The proximal promoter region (-217 to +261), which contains three of four conserved elements, gave a maximum promoter activity. In a series of electrophoretic mobility-shift assays, DNA fragments and double-stranded oligodeoxyribonucleotides containing sequences of the four conserved elements interacted with nuclear extracts of HeLa cells. The a-element contained the W-element, while the d-element, which had a high G + C content, was a novel regulatory cis-element distinct from the GC box. The b- and c-elements were homologous to each other and had a motif resembling downstream promoter element. Mutations of the c- and d-elements significantly reduced the promoter activity, indicating that the c- and d-elements in the AK3 promoter are crucial. These elements may also be involved in the transcriptional regulation of other TATA-less genes.

Adenylate Kinase↗
PubMed1999

Regulation of NeuroD expression by activation of the protein kinase-C pathway in Y79 human retinoblastoma cells.

To examine the signals that regulate NeuroD expression, we analyzed the effects of activation of two major signal pathways, the protein kinase A (PKA) pathway and the protein kinase C (PKC) pathway, on the expression of NeuroD in Y79human retinoblastoma cells. Activation of PKC resulted in marked induction of NeuroD mRNA and NeuroD protein. NeuroD mRNA induction was inhibited by calphostin C, an inhibitor of PKC. On the other hand, stimulation of PKA by forskolin had a weak suppressive effect on NeuroD mRNA expression. Induction of NeuroD expression was followed by enhancement of expression of the AK1 gene, one of the target genes of NeuroD, which encodes adenylate kinase isozyme 1, an important enzyme in the cellular adenine nucleotide homeostasis. Our results indicate that NeuroD expression is regulated, at least in part, by the PKC pathway and not by the PKA pathway.

Adenylate Kinase↗
PubMed1999

Overexpression of NeuroD in PC12 cells alters morphology and enhances expression of the adenylate kinase isozyme 1 gene.

NeuroD, a basic helix-loop-helix transcription factor, plays an important role in neuronal differentiation. A rat NeuroD cDNA was obtained by the aid of reverse transcription-polymerase chain reaction (RT-PCR) and ligated to an expression vector having a CMV promoter. Transfection of the NeuroD-expression plasmid into PC12 cells, a rat pheochromocytoma cell line, induced morphological changes featured by neurite-like processes and synapse-like structures without a differentiation-inducing reagent such as NGF. In the transfected cells, the overproduced NeuroD was detected by Western blot analysis, and the expression of the gene encoding mid-sized neurofilaments, a neuron-specific marker, was demonstrated by RT-PCR. Adenylate kinase isozyme 1 (AK1) is an enzyme involved in the homeostasis of energy metabolism and appears specifically in neuronal cells during differentiation. The CAT reporter assay of the 5'-flanking region of the AK1 gene suggests that NeuroD activates the AK1 expression through E-boxes in the promoter region. RT-PCR analysis indicated the enhanced level of AK1 mRNA in NeuroD-producing PC12 cells. Electrophoretic mobility shift assays demonstrated that NeuroD was able to interact with a proximal E-box element of the AK1 promoter. The results indicated that NeuroD promoted the PC12 cells to differentiate into neuron-like cells with concomitant activation of the target genes including the AK1 and the neurofilament genes.

Adenylate Kinase↗
PubMed1999

Release of adenylate kinase 2 from the mitochondrial intermembrane space during apoptosis.

The release of two mitochondrial proteins, cytochrome c and apoptosis-inducing factor (AIF), into the soluble cytoplasm of cells undergoing apoptosis is well established. Using spectrophotometric determination of enzyme activity, the accumulation of adenylate kinase (AK) activity in the cytosolic fraction of apoptotic cells has also been observed recently. However, three isozymes, AK1, AK2 and AK3, have been characterized in mammalian cells and shown to be localized in the cytosol, mitochondrial intermembrane space and mitochondrial matrix, respectively, and it is unknown which one of these isozymes accumulates in the cytosol during apoptosis. We now demonstrate that in apoptotic cells only AK2 was translocated into the cytosol concomitantly with cytochrome c. The amount of AK1 in cytosol, as well as the amount of matrix-associated AK3, remained unchanged during the apoptotic process. Thus, our data suggest that only intermembrane proteins are released from mitochondria during the early phase of the apoptotic process.

Adenylate Kinase↗
PubMed1999

IL-12 affects Dermatophagoides farinae-induced IL-4 production by T cells from pediatric patients with mite-sensitive asthma.

BACKGROUND: IL-12 is a critical cytokine in the regulation of immune responses produced by phagocytic cells exposed to microorganism infection. OBJECTIVE: We sought to study the effect of low doses and high doses of IL-12 on TH1 versus TH2 cytokine expression to elucidate the etiology of mite antigen-sensitive bronchial asthma in infants. METHODS: We studied the effect of IL-12 on Dermatophagoides farinae (Df) antigen-induced IL-4 production and subsequent production of IgE by PBMCs from pediatric patients with asthma. RESULTS: Simultaneous addition of 1 to 10 ng/mL IL-12 to cultures enhanced Df-induced IL-4 production, although low doses (0.05 to 0.1 ng/mL) of IL-12 downregulated IL-4 production. Endogenous IL-12 is required for such production. These phenomena were not observed in Df-stimulated control PBMCs. In contrast, on stimulation with the same dose of Df, IFN-gamma production by patient PBMCs was enhanced in a dose-dependent fashion by addition of IL-12. Quantification analysis of RT-PCR-amplified DNA fragments by laser-induced fluorescence showed that a high dose of IL-12 augments mRNA expression for IL-4 protein synthesis, whereas a low dose of IL-12 inhibits IL-4 mRNA expression, and that the signal of mRNA for IFN-gamma protein synthesis was increased on Df stimulation in a dose-dependent fashion. Df-induced in vitro production of IgE and Df-specific IgE in serum from severe combined immunodeficient mice reconstituted with PBMCs were increased by treatment with high doses of IL-12, whereas low doses of IL-12 inhibited that production. The combined results indicate that at a low dose of IL-12, IL-4 and IFN-gamma production was regulated reciprocally; however, at high doses of IL-12, cells produced IL-4 and IFN-gamma simultaneously, and neither cytokine was regulated. CONCLUSION: Low-dose and high-dose IL-12 induce TH1 responses, and high-dose IL-12 induces both TH1 responses and TH2 or TH0 responses. Consequently, the IL-4 production may overcome TH1-type cell activation of IgE production in patients with mite-sensitive bronchial asthma.

Animals↗
PubMed1999

Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo.

We examined the effect of interleukin-15 (IL-15) gene transfer into tumour cells on the host's anti-tumour response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T-cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8* T-cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells. These results demonstrate that IL-15-secreting tumour cells can stimulate local and systemic T-cell-dependent immunity and therefore may have a potential role in cancer therapy.

Animals↗
PubMed1999

The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma.

Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisense-transfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy.

Aged↗
PubMed1999

Functional interleukin-5 activity in peripheral blood mononuclear cells from adolescents with mite antigen asthma in remission.

BACKGROUND: Asthma improves in most children during adolescence such that a small minority of patients exhibit clinically significant symptoms by the age of 20 years. OBJECTIVE AND METHODS: To investigate late allergic reactions, including eosinophil inflammation, associated with outgrowing mite antigen-induced bronchial asthma during adolescence, the relationship between clinical status and functional activity of interleukin (IL)-5 produced by Dermatophagoides farinae (Df)-stimulated peripheral mononuclear cells (PBMCs) in culture was assessed in mouse IL-3-dependent cells transfected with the human IL-5 receptor gene. RESULTS: Activity of IL-5 spontaneously produced by PBMCs from either patients with mite-sensitive bronchial asthma or nonatopic control subjects was low. The activity of IL-5 produced by PBMCs stimulated with concanavalin A was significantly higher. Upon challenge with specific allergens, such as Df antigen, but not with irrelevant antigens, including ovalbumin, the in vitro activity was increased in patients with active disease and decreased in patients in remission. CONCLUSION: Results suggest that the antigen-specific up-regulation of functional IL-5 activity in late allergic reactions is reduced in patients in remission and likely to result in an improvement in clinical status. The Df antigen may suppress Df-induced responses in patients with asthma in remission.

Adolescent↗
PubMed1999

Alteration in aortic wall stiffness and accumulation of collagen during the prediabetic stage of type II diabetes mellitus in rats.

Aortic damage during the prediabetic stage of diabetes mellitus (DM) was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II DM. In 30 OLETF and 30 nonDM rats, an oral glucose tolerance test was performed at 10, 20 and 30 weeks of age. At 15 and 30 weeks, intravascular ultrasound images and aortic pressure were recorded and the stiffness parameter beta was calculated. The aortic walls were excised at 5, 15 and 30 weeks for histopathology and the measurement of hydroxyproline. At 10 weeks, blood glucose (mg/dl) and insulin concentrations (ng/ml) of the OLETF rats (2h; 168+/-30 and 0.82+/-0.15) were significantly high (nonDM: 118+/-15; p = 0.02 and 0.16+/-0.64; p = 0.003). At the prediabetic stage (15 weeks), beta in the OLETF rats (2.5+/-0.9) was larger than in nonDM rats (1.4+/-0.4; p = 0.0006), and the collagen (hydroxyproline) content/dry weight (mg/g) of the aortic wall was significantly higher in OLETF (33.5+/-3.1) than in nonDM rats (28.7+/-3.5; p<.05). Histopathological examination showed that from 15 weeks of age the medial wall thickness increased gradually. In the prediabetic stage, collagen accumulation may contribute to impairment of aortic wall stiffness in the OLETF rats, which would accelerate the aging process in the aortic wall.

Animals↗