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T Noma

Publications and source records attributed to T Noma.

At least 19 recordsLinked to original sources
PubMed2001

Structure and expression of human mitochondrial adenylate kinase targeted to the mitochondrial matrix.

The previously isolated cDNA encoding human adenylate kinase (AK) isozyme 3 was recently renamed AK4. Consequently, human AK3 cDNA remains to be identified and we have little information about the functional relationship between human AK3 and AK4. In pursuit of the physiological roles of both the AK3 and AK4 proteins, we first isolated an authentic human AK3 cDNA and compared their expression. Nucleotide sequencing revealed that the cDNA encoded a 227-amino-acid protein, with a deduced molecular mass of 25.6 kDa, that shares greater homology with the AK3 cDNAs isolated from bovine and rat than that from human. We named the isolated cDNA AK3. Northern-blot analysis revealed that AK3 mRNA was present in all tissues examined, and was highly expressed in heart, skeletal muscle and liver, moderately expressed in pancreas and kidney, and weakly expressed in placenta, brain and lung. On the other hand, we found that human AK4 mRNA was highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain. Western-blot analysis demonstrated expression profiles of AK3 and AK4 that were similar to their mRNA expression patterns in each tissue. Over expression of AK3, but not AK4, in both Escherichia coli CV2, a temperature-sensitive AK mutant, and a human embryonic kidney-derived cell line, HEK-293, not only produced significant GTP:AMP phosphotransferase (AK3) activity, but also complemented the CV2 cells at 42 degrees C. Subcellular and submitochondrial fractionation analysis demonstrated that both AK3 and AK4 are localized in the mitochondrial matrix.

Adenylate Kinase↗
PubMed2001

Quantitative analysis of telomerase activity and telomerase reverse transcriptase expression in renal cell carcinoma.

To investigate the relationship between the telomerase activity levels and clinicopathological features of tumors, we quantified the telomerase activities of 23 renal cell carcinomas (RCCs) and four non-cancerous tissues, using a modified telomeric repeat amplification protocol assay, and assessed the hTERT mRNA levels of these samples by reverse transcription-polymerase chain reaction analysis. Elevated levels of telomerase activity had correlation with tumor stages as well as the degree of nuclear grades. Our findings suggested that telomerase activity is a useful indicator for tumor aggressiveness in RCCs. However, hTERT mRNA levels in RCCs had no correlation with nuclear grades and tumor stages. The telomerase activities and the hTERT mRNA levels in cancer cells were not always in parallel. These results suggested that telomerase activity is regulated in a posttranscriptional manner as well as a post-translational manner in tumor cells.

Adult↗
PubMed2001

Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.

Aged↗
PubMed2001

Effect of roxithromycin on T lymphocyte proliferation and cytokine production elicited by mite antigen.

Clinical evidence suggests that roxithromycin (RXM) may be an effective additional therapy for bronchial asthma. However, how it interferes with allergic responses is unclear. To investigate the mechanisms of action of RXM, lymphocyte transformation and interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 synthesis associated with Dermatophagoides farinae (Df), mite antigen in patients with bronchial asthma were evaluated in vitro in the presence of RXM. T cell proliferation in Df antigen-stimulated patients' lymphocytes was suppressed by 50-100 microg/ml of RXM. Production of IL-4 and IL-5 was similarly decreased by 1-10 microg/ml RXM, whereas, IFN-gamma production, which was reduced by Df-stimulation alone, was increased by 50 microg/ml RXM. Our results suggest that skewed cytokine profiles of patients with mite antigen-induced bronchial asthma may be corrected with RXM, which may mimic those of patients in remission, who are tolerant of Df antigen.

Adolescent↗
PubMed2001

Functional human IgE specific for Dermatophagoides farinae antigen is produced in SCID mice reconstituted with peripheral mononuclear cells derived from healthy persons and patients with asthma.

BACKGROUND: Whether normal peripheral blood mononuclear cells (PBMCs) transferred to severe combined immunodeficient (SCID) mice produce specific IgE remains unclear. METHODS: Mice received injections of Dermatophagoides farinae antigen (Df)-stimulated PBMCs from healthy persons (IgE RAST score of 0). RESULTS: High titers of Df-specific IgE were detected. The Df-specific IgE activity produced was comparable to or higher than that produced by cells from patients with asthma although the time to maximal production was longer. IgE derived from PMBCs of healthy persons or patients with asthma induced histamine release from cultured human basophils that had been stimulated with Df antigen or an anti-IgE antibody. Treatment of Df-stimulated PBMCs with a high dose, but not a low dose, of interleukin-4 stimulated production of Df-specific IgE by PMBCs from healthy persons or patients with asthma. In contrast, intravenous injection of IFN-gamma into reconstituted SCID mice decreased Df-specific IgE production by PBMCs from patients with asthma. In PMBCs from healthy persons, IgE class-switching may occur later and block the effects of treatment with IFN-gamma. CONCLUSIONS: PBMCs from healthy persons and persons with asthma have clones reactive to allergen and produce functional IgE specific for relevant antigens in mite-sensitive bronchial asthma.

Allergens↗
PubMed2001

Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence.

IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.

Adenoviridae↗
PubMed2001

Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat.

This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two groups: diabetic treated and untreated. Pioglitazone was mixed in rat chow fed to the diabetic treated group (0.01%). Treatment duration was 5 weeks. At baseline (15 weeks) and 20 weeks of age, blood glucose, lipid, insulin, and plasma malondialdehyde-thiobarbituric acid (MDA) levels were measured and Doppler echocardiography was tracked. At 20 weeks of age, left ventricular collagen content was studied. Blood glucose, plasma insulin, and triglyceride levels in the diabetic treated group were significantly lower than those in the untreated diabetic group. Deceleration time (ms) of early diastolic inflow in the treated diabetic group decreased significantly compared with the untreated diabetic group (65 +/- 8 vs. 77 +/- 8, p < 0.01). Ratio of left ventricular weight to body weight (mg/g) and ratio of left ventricular collagen content to dry weight (mg/100 mg) were decreased in the treated diabetic group (1.5 +/- 0.1, 1.3 +/- 0.3) compared with the untreated diabetic group (1.7 +/- 0.2, p < 0.01; 1.7 +/- 0.3, p < 0.05). Plasma MDA concentration (nmol/ml) significantly decreased (2.9 +/- 0.3 at baseline to 2.3 +/- 0.3 at 20 weeks, p = 0.001) in the treated diabetic group, and was lower than that in the untreated diabetic group (3.2 +/- 0.7 at 20 weeks, p < 0.05). Pioglitazone improved glucose and lipid metabolism and reduced oxidative stress in the left ventricle, which decreased left ventricular collagen accumulation and improved left ventricular diastolic function of prediabetic rat hearts.

Animals↗
PubMed2001

Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment.

Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 +/- 3 vs untreated 64 +/- 5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 +/- 7 vs untreated 86 +/- 8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage.

Animals↗
PubMed2001

The 5-HT2C/2B receptor agonist m-chlorophenylpiperazine (mCPP) inhibits 2-deoxy-D-glucose (2-DG)-induced hyperphagia in rats.

Effects of the 5-HT2C2/2B receptor agonist m-chlorophenylpiperazine (mCPP) on hyperphagia elicited by 2-deoxy-D-glucose (2-DG) were investigated in rats. mCPP apparently reduced 2-DG-induced hyperphagia. Suppressive effects of mCPP on hyperphagia induced by 2-DG were inhibited by the 5-HT2A/2B/2C receptor antagonist, ritanserin, although the 5-HT2, receptor antagonist ketanserin was without effect. Thus, inhibitory effects of mCPP on 2-DG-induced hyperphagia are mediated by the 5-HT2C/2B receptor. Our results demonstrate that mCPP can inhibit the bulimia model, 2-DG-induced hyperphagia.

Animals↗
PubMed2001

Acute effect of human cardiotrophin-1 on hemodynamic parameters in spontaneously hypertensive rats and Wistar Kyoto rats.

There is considerable evidence to indicate that humoral factors play an important role in the development of left ventricular hypertrophy. Cardiotrophin-1 (CT-1) is a cytokine that has been shown to induce cardiac hypertrophy in a dose-dependent manner. The aim of the present study was to investigate the acute effect of CT-1 on hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) and to study the relationship between the plasma concentration of CT-1 and its hemodynamic effect. Ten-week-old SHR and age-matched WKY were used. Blood pressure (BP), heart rate (HR) and plasma concentration of CT-1 were measured both before and for 60 min after intravenous bolus injection of human CT-1 (10 microg/kg). CT-1 injection significantly decreased BP and significantly increased HR in SHR and WKY. There were significant differences in BP and HR between the two groups at all time points after injection. The lowest BP, highest HR and maximal plasma concentrations of CT-1 were observed in both groups within 10 min after injection. However, after converting the values into the percentage change from their respective baselines, there were no significant differences between the two groups in BP or HR at any time point. There was also no significant difference between the two groups at any time point in the plasma concentration of CT-1. This study indicates that CT-1 decreases BP and increases HR in both SHR and WKY. The most obvious change occurred within 10 min after injection. However, there was no significant difference in the hypotensive effect of CT-1 on 10-week-old SHR and WKY.

Animals↗
PubMed2001

Inverse correlation between macrophage-colony stimulating factor, cholesterol and high density lipoprotein cholesterol in Kawasaki disease.

Kawasaki disease (KD) is a childhood-onset vascular disease. We assessed the concentrations of macrophage-colony stimulating factor (M-CSF) and those of lipids in sera from patients with KD. The M-CSF concentration in patients with acute-phase KD was 2,914+/-159 U/ml, significantly higher than that in control subjects with Infectious diseases (1,241+/-96 U/ml). The elevated levels of this cytokine in the acute phase fell to 1,319+/-138 U/ml in the convalescent phase. Total and high-density lipoprotein cholesterol concentrations in acute phase KD (113.8+/-8.4 and 21.5+/-2.3 mg/dl, respectively) were lower than in the infectious disease controls (195.8+/-7.0 and 62.5+/-1.8 mg/dl). The elevation of M-CSF correlated with the decrease of total and high-density lipoprotein cholesterol. Overproduction of macrophage-colony stimulating factor activates macrophages and monocytes and may disturb the lipid metabolism. Both effects could contribute to vasculitis in KD.

Child Welfare↗
PubMed2001

Fatal buckwheat dependent exercised-induced anaphylaxis.

Cases of food-dependent exercise-induced anaphylaxis (FEA) caused by buckwheat have been rare. Clinical, laboratory, and autopsy findings are present on an 8-year old girl with FEA caused by Japanese buckwheat. The patient consumed buckwheat noodles called "zaru soba" and immediately thereafter swam vigorously. Approximately 30 minutes later, she complained of abdominal pain, vomiting, coughing, and chest discomfort. Another ten minutes later her consciousness level deteriorated and she experienced cardiorespiratory arrest. The heart beat was restored and she was admitted to the hospital. She never regained consciousness and expired after another arrest 13 days later. Her IgE level was high (2,840 IU/ml) and the IgE-radioallergosorbent test (RAST) score was 2 for soybeans, 3 for buckwheat, 2 for rice, and 3 for wheat. An exaggerated hematemesis that occurred immediately after hospital admission indicated an inflammatory condition of the digestive tract that was caused by buckwheat. Marked ulceration accompanied with hemorrhage and necrosis was noted at the ileum. Extensive hemorrhage involving the endotracheal pulmonary field and lymphocyte infiltration of the alveolar space likely appeared after the inflammation. The analysis of buckwheat-specific IgE antibody by immunoblotting showed 7 bands that reacted with the IgE of the patient's serum, 4 bands: 16, 20, 24, and 58 kDa, were specific to the patient as compared to subjects not allergic to buckwheat. A first case of fatal FEA by buckwheat is reported with reference to specific IgE.

Anaphylaxis↗
PubMed2000

Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats.

Oxidative stress is involved in the initiation and development of atherosclerosis in diabetes. We tested the hypothesis that oxidative stress is already increased in early stage type II diabetes, and that troglitazone may prevent the increase. Three groups of 20 week old rats were studied: untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II diabetes, OLETF rats treated with troglitazone, and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma lipid hydroperoxides (LOOH) concentration, as an indication of lipid peroxidation, and superoxide dismutase (SOD) activity in the thoracic aorta were measured. Plasma LOOH concentration was significantly higher in non-treated OLETF rats compared to LETO rats and treatment with troglitazone completely prevented this increase. SOD activity was significantly decreased in non-treated OLETF rats compared to LETO rats and troglitazone attenuated the diminution of it. These observations demonstrate oxidative stress is already increased in the early stage of type II diabetes and we confirmed troglitazone has the effect of an antioxidant in vivo.

Animals↗
PubMed2000

Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model.

BACKGROUND: Considerable controversy exists regarding impairment of cardiac function in diabetes mellitus (DM). We investigated the serial changes in left ventricular (LV) histopathology and LV filling dynamics in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of type II DM. METHODS AND RESULTS: In 54 OLETF and 54 non-DM rats, body weight, blood pressure, heart rate, and transmitral pulsed Doppler examinations were performed from 5 to 47 weeks of age. An oral glucose tolerance test was performed at 10, 20, and 30 weeks of age. The hearts were excised for histopathology, including immunohistochemistry and histomorphometry of collagen, and measurement of hydroxyproline at baseline and each stage of developing DM. In the prediabetic stage (15 weeks of age), in which fast blood glucose remained normal, OLETF rats manifested mild obesity, postprandial hyperglycemia, and hyperinsulinemia, and early diastolic transmitral inflow exhibited prolonged deceleration time (OLETF, 59+/-10 ms versus non-DM, 49+/-8 ms, P<0.01) and low peak velocity (OLETF, 73+/-11 cm/s versus non-DM, 88+/-11 cm/s, P<0.01). Histopathology revealed extracellular fibrosis and abundant transforming growth factor-beta(1) receptor II in LV myocytes of OLETF rats. At 15 weeks of age, the ratio of collagen area/visual field of LV wall in OLETF rats (8.3+/-1.3%) was larger than that in non-DM rats (4.9+/-1.8%, P<0.0001), and the collagen content/dry tissue weight ratio of heart was significantly higher in OLETF (2. 0+/-0.5 mg/g) than non-DM (1.3+/-0.2 mg/g, P<0.01) rats. CONCLUSIONS: A metabolic abnormality present in the prestage of type II DM may produce LV fibrosis and alteration in cardiac function.

Animals↗
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↗