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Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 649 records · Page 36Linked to original sources

Expression of argyrophilic nucleolar organizer regions in ductal adenocarcinoma of the pancreas and its relationship to prognosis.

The aim of the present study was to investigate the relationship between Ag-NOR count levels and survival in 33 patients undergoing resection for ductal adenocarcinoma of the pancreas at Kanazawa University Hospital from 1985 to 1991. To determine the biologic behavior of invasive ductal adenocarcinoma of the pancreas, 33 tumors were classified into two groups according to the median value of Ag-NOR counts: Group 1, Ag-NOR count > or = 3.25 (higher Ag-NOR count group); Group 2, Ag-NOR count < 3.25 (lower Ag-NOR count group). As a result, we found that tumors with a higher Ag-NOR count were more likely to have liver or peritoneal metastasis than those with a lower Ag-NOR count, although the differences were not statistically significant. Tumors with lower Ag-NOR count levels were associated with favorable prognoses 2 and 3 yr after surgery, whereas those with higher Ag-NOR count levels were related to poor prognosis. Our results indicate that a Ag-NOR count level is a reliable prognostic parameter in resected pancreatic ductal adenocarcinoma.

Adult↗

Long-term therapeutic efficacy of interferon for patients with chronic hepatitis C.

Interferon is being used for therapy of chronic hepatitis C, but its long-term results have not been reported. We studied 65 patients with this disease who were monitored for at least 2 years after completion of the therapy. Almost all patients who had responded to therapy at 6 months after the end of therapy had normal levels of alanine aminotransferase (ALT) when evaluated later. The level of ALT became normal for the first time in some patients more than 6 months after therapy ended. The level of ALT in many of the patients without HCV RNA had become normal 6 months after the end of the therapy. One of three schedules was employed: three times weekly long-term; daily for two weeks and none for two weeks in a cycle; and daily for several weeks; 57%, 29%, and 17% of the patients on these schedules came to have normal ALT levels. Patients without HCV RNA at six months after completion of therapy tended to have higher responses in terms an increased level of 2',5'-oligoadenylate synthetase of mononuclear cells in vitro before therapy began. However, therapy three times per week was effective even for some patients judged not responsive to IFN by this test. The results showed that IFN therapy was effective for chronic hepatitis C when judged by long-term results.

Adult↗

Clinical and histologic features of alcohol drinkers with congestive heart failure.

To clarify the difference between alcoholic cardiomyopathy and dilated cardiomyopathy and to investigate the characteristics of alcoholic cardiomyopathy, right ventricular endomyocardial biopsy was performed, and the two diseases were compared clinically and histologically. Changes in the cardiothoracic ratio, cardiac index, and systolic blood pressure/end-systolic volume index were greater after treatment in patients with alcoholic cardiomyopathy than in patients with dilated cardiomyopathy. Histologically, myocytic hypertrophy, fibrosis, and nuclear change were less significant in the former than in the latter. Among patients with alcoholic cardiomyopathy, the cardiac index in those with less fibrosis was greater than in those with more fibrosis. Thus patients with alcoholic cardiomyopathy had more preserved and reversible cardiac function and fewer histologic changes than the patients with dilated cardiomyopathy. Reversibility of cardiac function in patients with alcoholic cardiomyopathy correlated inversely with the severity of histologic changes.

Adult↗

Stimulation of endothelin-1 release by low density and very low density lipoproteins in cultured human endothelial cells.

To examine the effects of lipoproteins on the secretion of endothelin-1 from endothelial cells, we measured immunoreactive (ir) endothelin-1 release from cultured human umbilical vein endothelial cells in the presence or absence of various concentrations of native low density lipoprotein (LDL), oxidized LDL, and very low density lipoprotein (VLDL). Cultured endothelial cells secreted ir-endothelin-1 into serum-free medium in a time-dependent manner, and the secretion was clearly stimulated following a 15-24-h incubation with 10 micrograms/ml oxidized LDL. The secretion of ir-endothelin-1 increased in a dose-dependent manner after a 24-h incubation with oxidized LDL, while only a high dose of native LDL and VLDL significantly increased ir-endothelin-1 secretion. The release of ir-endothelin-1 stimulated by 20 micrograms/ml oxidized LDL was reproduced by the same concentration of acetylated LDL but not native LDL. These observations indicate that the release of ir-endothelin-1 from endothelial cells is stimulated by lipoproteins, in particular by oxidized LDL, probably through the endothelial scavenger receptor. This increase in ir-endothelin-1 release induced by oxidized LDL may contribute to the development of atherosclerotic vascular lesions.

Cells, Cultured↗

Effect of endothelin receptor antagonist, BQ-123, on Ca2+ signaling in cultured rat mesangial cells.

Endothelin (ET)-1 causes mesangial cell contraction and proliferation. The present study was designed to evaluate the functional ET receptor subtype in cultured rat mesangial cells by measuring intracellular Ca2+ signaling with the use of a newly synthesized ET receptor type A selective antagonist-BQ123. The ET-1, ET-2 and ET-3 increased intracellular Ca2+ level in a dose-dependent manner. BQ-123 suppressed intracellular Ca2+ elevation in response to ET-1 in a dose-dependent manner with its half maximal inhibition value of 28 nM. BQ-123 (10(-6) M) did not affect ET-3 (10(-7) M)-induced Ca2+ response. The peak Ca2+ levels after addition of ET-3 without BQ-123 were similar to those in response to ET-1, ET-2 and ET-3 in the presence of BQ-123. Northern blot analysis showed that cultured mesangial cells expressed both ETA and ETB receptor mRNA. These results suggest that cultured mesangial cells have, at least, two types of functional receptors, one of which is an ETA receptor.

Amino Acid Sequence↗

Stimulation of brain natriuretic peptide release from the heart by thyroid hormone.

This study was designed to examine the involvement of thyroid hormone in the release of brain natriuretic peptide (BNP) from the heart. We measured plasma immunoreactive BNP (ir-BNP) concentrations in patients with untreated hyperthyroidism. We also measured BNP values in experimental rats with hyperthyroidism induced by thyroxine (T4) and in rats with hypothyroidism induced by propylthiouracil (PTU). The in vitro effects of triiodothyronine (T3) and T4 on the release of BNP were examined in newborn rat atrial and ventricular myocytes in primary culture. Plasma BNP levels were increased in hyperthyroid patients compared with normal control subjects. Plasma BNP levels were increased in hyperthyroid rats and decreased in hypothyroid rats compared with euthyroid rats. Plasma BNP level was correlated with serum T4 level in hyperthyroid patients and hyperthyroid rats. A major component of ir-BNP in plasma from hyperthyroid patients was human BNP-32 and that in plasma from hyperthyroid rats was rat BNP-45. T4 and T3 stimulated release of ir-BNP from both cultured atrial and ventricular myocytes in a dose-dependent manner. Plasma BNP concentration is frequently increased in hyperthyroidism, and thyroid hormone may regulate BNP release from both atrial and ventricular myocytes.

Adult↗

Cosecretion of atrial and brain natriuretic peptides stimulated by endothelin-1 from cultured rat atrial and ventricular cardiocytes.

We examined the secretion of immunoreactive (ir) atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in primary cultures of atrial and ventricular cardiocytes from neonatal rats, and also investigated the stimulatory effect of endothelin-1 (ET-1) on ir-ANP and ir-BNP release from these cells. After 2 days of culture, rat atrial and ventricular cardiocytes secreted both ir-ANP and ir-BNP into serum-free medium in a time-dependent manner. The amount of ir-BNP released per 10(5) ventricular cells was approximately 60% to 70% (1.8 +/- 0.5 pg/h, 2.5 +/- 0.4 pg/2 h, 2.6 +/- 0.4 pg/4 h) of that released from atrial cells (2.8 +/- 0.4 pg/h, 3.5 +/- 0.6 pg/2 h, 4.6 +/- 0.6 pg/4 h), although ir-ANP was secreted almost entirely from atrial cells. ET-1 clearly stimulated secretion of both ir-ANP and ir-BNP in atrial and ventricular cardiocytes. These observations indicate that ir-BNP is cosecreted with ir-ANP not only from atrial cardiocytes, but also from ventricular cardiocytes in the rat, and that ET-1 stimulates the secretion of these natriuretic peptides by a direct mechanism, not through a hemodynamic change.

Animals↗

Effect of neuropeptide Y on human bronchus and its modulation of neutral endopeptidase.

BACKGROUND: Neuropeptide Y (NPY) and neutral endopeptidase have been shown to regulate the response of airway smooth muscle. However, their interactions have not been studied. METHODS: To determine the role of NPY and endogenous neutral endopeptidase in regulating the effects of NPY, we investigated the effects of NPY and a neutral endopeptidase inhibitor, phosphoramidon, on the contractile response of isolated human bronchial segments to electrical field stimulation (EFS). RESULTS: Concentrations of up to 10(-6) mol/L of NPY did not change resting tension. NPY inhibited the cholinergic contractions induced by EFS at 5 Hz dose-dependently. Phosphoramidon (10(-5) mol/L) enhanced the inhibitory effect of NPY on EFS-induced contractions at 5 Hz. NPY (3 x 10(-7) mol/L) shifted the frequency-response curve for EFS (1 to 50 Hz) to the right and significantly increased the mean logarithm of frequency that produced 50% of maximal contraction (control: 0.54 +/- 0.07 versus NPY: 0.79 +/- 0.09, p < 0.05). Phosphoramidon (10(-5) mol/L) did not affect the frequency response to EFS, but enhanced the inhibitory effect of NPY (3 x 10(-7) mol/L) on frequency response to EFS, resulting in a significant increase in the mean logarithm of frequency that produced 50% of maximal contraction (NPY: 0.79 +/- 0.09 versus NPY plus phosphoramidon: 1.18 +/- 0.15, p < 0.05). NPY (3 x 10(-7) mol/L) did not affect the response of tissues to exogenously applied acetylcholine. CONCLUSIONS: These observations suggest that NPY inhibits the output of acetylcholine from nerve endings and that endogenous neutral endopeptidase modulates the effect of NPY in the human airway by inactivating this peptide.

Acetylcholine↗

Analysis of myeloid characteristics in acute lymphoblastic leukemia.

We examined myeloid characteristics of myeloid-antigen-positive (My+) and -negative (My-) B-precursor acute lymphoblastic leukemia (ALL) blast cells. Immunophenotyping before and after culture, rearrangements of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) genes, stimulation of DNA synthesis with granulocyte colony-stimulating factor (G-CSF), and G-CSF binding assay were performed. Of My+ ALL blasts, the immunophenotypic staging as B-precursor ALL and rearrangements of IgH and TCR-beta, gamma and delta genes did not differ from findings in My- ALL blasts. Stimulated with G-CSF, cells from one My+ ALL and from one My- ALL patients showed enhancement of DNA synthesis and expression of CD11b and CD13, respectively. G-CSF binding was observed in blasts from 3 My+ ALL patients and one My- ALL child. After culture, blasts from My- ALL children expressed CD13 but showed neither enhanced DNA synthesis with G-CSF nor G-CSF binding. Thus, it would appear that (i) My+ and My- adult ALL blasts are at the same stage of differentiation; (ii) some My+ adult ALL blasts have phenotypic and functional myeloid characteristics; and (iii) induction of CD13 expression in My- ALL after in vitro culture does not correlate with other myeloid characteristics.

Adolescent↗

Effect of a new leukotriene receptor antagonist, ONO-1078, on human bronchial smooth muscle in vitro.

Peptide leukotrienes (LT) have been postulated to play a major role in the etiology of bronchial asthma. The present study investigated the effect of a new peptide LT receptor antagonist, ONO-1078, on isolated human bronchial smooth muscle in vitro. Helical strips of bronchi were suspended in the organ baths filled with 37 degrees C Krebs solution and mechanical responses were recorded isometrically. ONO-1078 produced dose-dependent relaxations, which suggested that the spontaneous basal tone was in part mediated by LT. ONO-1078 caused dose-dependent relaxations of the tissues which were precontracted with LTC4 or LTD4 (3 x 10(-8) M). Pretreatment of bronchi with ONO-1078 (10(-8) M, 10(-7) M) significantly inhibited dose-dependent contractions induced by LTC4 and LTD4. ONO-1078 (10(-6) M) also significantly reduced the antigen-induced contractions in bronchi passively sensitized with atopic serum from mite-allergic patients. Moreover the combination of an H1-receptor antagonist, diphenhydramine (10(-5) M), and ONO-1078 (10(-6) M) completely abolished the antigen-induced contractions. The present findings demonstrate that ONO-1078 is a potent antagonist of exogenous and endogenous LT in the human airway. The selective LT antagonist such as ONO-1078 may be valuable in the therapy of allergic asthma.

Aged↗

Cross-mating study on bone mass in the spontaneously osteoporotic mouse (SAM-P/6).

Genetic control of bone mass in the spontaneously osteoporotic mouse (SAM-P/6) was examined by classical cross-mating experiments, in which SAM-P/2 with a high bone mass was used as a control. Femoral bone mass corrected by size (= bone density) was assayed photometrically. F1 hybrids exhibited intermediate values between those of the two parental strains, i.e. higher than SAM-P/6 and lower than SAM-P/2. F2 hybrids showed a more widely distributed pattern with a mean value quite similar to that of F1 hybrids. The values for backcrosses were between those of F1 and the respective parental strains. They did not show segregations expected in cases of a single-gene control. Numerical analysis of data distribution in each generation suggested that strain-specific bone mass in these strains of mice is inherited as a polygenic characteristic and controlled by a relatively small number of genes.

Aging↗

Effects of inotropic stimulation on phosphate compounds in ischaemic canine hearts.

OBJECTIVE: The aim was to evaluate regional coronary blood flow, contractile function, and concentration of phosphate compounds with inotropic stimulation in moderately ischaemic canine hearts. METHODS: Dogs were prepared with instrumentation for the determination of regional coronary blood flow (non-radioactive microsphere method), contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by the phosphorus-31 magnetic resonance spectroscopic technique. RESULTS: In the non-ischaemic condition, dobutamine increased regional coronary blood flow and enhanced contractile function with no significant changes in myocardial phosphate compounds. After constricting the left anterior descending coronary artery, dogs were divided into two groups according to their heart beat response to dobutamine, classified as no pronounced tachycardia with dobutamine (group NT), and pronounced tachycardia (group T). In group NT, dobutamine increased regional coronary blood flow and improved regional contractile function with no significant effect on myocardial phosphate compounds. In group T, dobutamine failed to increase regional coronary blood flow or to improve contractile function, but there was a significant increase in the inorganic phosphate to creatinine phosphate ratio. CONCLUSIONS: Dobutamine increased coronary blood flow and augmented contractile function without significant changes in phosphate compounds in the moderately ischaemic heart, when pronounced tachycardia was not induced. The augmentation of contractile function occurred without prominent improvement in energy metabolism.

Animals↗

Dietary soybean protein compared with casein retards senescence in the senescence accelerated mouse.

The effects of replacing dietary casein with soybean protein on mean life span, mean life span of the last one-tenth of a group, grading scores of senescence and deposition of senile amyloid were investigated in senescence accelerated mice (SAM-P/1) compared with a control strain (SAM-R/1). SAM-R/1 mice fed the soybean protein-containing diet had mean life spans of 618 +/- 42 d (males) and 578 +/- 62 d (females), 58% (males) and 44% (females) longer than those of corresponding casein fed mice (P < 0.01). Similarly, in SAM-P/1 mean life-spans were 265 +/- 16 d (males) and 307 +/- 23 d (females) in the soybean diet group, 27% (males) and 30% (females) longer than in the casein diet groups (P < 0.01). The mean life span of the last one-tenth of each group fed soybean protein was significantly longer than the corresponding group fed casein. In SAM-R/1 mice, pathological studies revealed that severe secondary amyloid deposition (amyloid A protein) in the kidneys, spleen, stomach and liver was significantly suppressed, in males only, by replacing casein with soybean protein (P < 0.01). The occurrence of contracted kidneys caused by the infiltration of amyloid A protein was suppressed in SAM-R/1 mice fed the soybean protein-containing diet (P < 0.05). The deposition of senile amyloid in SAM-P/1 mice with aging was retarded by replacing casein with soybean protein (P < 0.01). These results indicate that dietary protein source is important in modulating the advance of senescence in SAM mice.

Aging↗

Effect of heparin on endothelin-1 production by cultured human endothelial cells.

Heparin shows a blood pressure-lowering effect in various hypertensive rat models. This study was designed to examine the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production by cultured human umbilical vein endothelial cells (HUVECs). ET-1 and cyclic GMP levels in the medium were determined by radioimmunoassay. ET-1 mRNA was quantified by densitometric Northern blot analysis. ET-1 was released into the medium in a time-dependent manner, and its release was augmented by thrombin (10 U/ml). Heparin suppressed both basal and thrombin-stimulated ET-1 secretion and its mRNA expression in a dose-dependent manner. Heparin suppressed ET-1 mRNA expression in a time-dependent fashion. Heparin did not suppress both basal and thrombin-stimulated ET-1 production in the presence of NG-monomethyl-L-arginine (L-NMMA) (10(-5) M). The production of cGMP stimulated by thrombin was significantly enhanced by heparin, but not in the presence of L-NMMA (10(-5) M). Heparin may suppress vasoconstrictor ET-1 production mediated by the enhancement of endothelium-derived nitric oxide in HUVECs.

Blotting, Northern↗

Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation.

Using hepatocytes injected into prevascularized polymer sponge devices, we studied hepatocyte survival and function after delivery of a whole liver-equivalent of cells into rats. LEW rats and enzyme-deficient Gunn rats served as recipients, respectively. Totally, 28.5 cm2 (0.5-cm thick) of polyvinyl alcohol sponges were implanted per animal. Hepatotrophic stimulation was induced by portacaval shunt and partial (70% or 30%) hepatectomy. Recipient rats received 5 x 10(8) hepatocytes (equivalent to whole rat liver) which were harvested from LEW and Wistar donors, respectively. After engraftment, histologic examination revealed hepatocyte remodeling in the device with capillaries lining plates of hepatocytes, and also tubular structures resembling early biliary radicles. BrdU staining revealed DNA synthesis in hepatocytes, providing evidence of regeneration within the grafts. Quantification of viable hepatocyte area at various time points was performed using computer-assisted morphometry. We then estimated a range of cell numbers from the quantitated cell area. The number of hepatocytes viable at day 7 was estimated at 27.5-46.0% and 6.6-11.0% in the mesentery and subcutaneous site, respectively. Thus the average number was estimated between 10.8% and 18.0% of initially injected hepatocytes. In the Gunn rat experiment, experimental rats that received normal Wistar hepatocytes showed a significantly greater decrease in total serum bilirubin compared with the concurrent control Gunn rats (P < 0.01). At week 1, serum bilirubin in experimental rats decreased to 74.7% (6.80 +/- 0.46 mg/dl) of pretransplantation level (9.10 +/- 0.47 mg/dl) and this was 71.4% of the control rats' bilirubin level (9.53 +/- 0.37 mg/dl). In conclusion, a hepatocyte mass equivalent to a whole rat liver can be delivered into prevascularized polymer sponge devices. At day 7 between 10.8% and 18.0% of these hepatocytes were estimated to be engrafted and functioning. Further optimization of this technique is necessary before clinical application is considered.

Animals↗

Virulence patterns of Vibrio cholerae non-O1 strains isolated from hospitalised patients with acute diarrhoea in Calcutta, India.

A collection of 28 strains of Vibrio cholerae non-O1 isolated during a 3-year period (1989-1991) from hospitalised patients with acute diarrhoea in Calcutta, India, were examined with regard to virulence-associated factors. Of the 28 isolates (each representing a case), 18 were isolated as the sole infecting agent; the remaining 10 were recovered as co-cultures from cases infected with V. cholerae O1. Of the strains isolated in this study, 82% could be serotyped, with serovars O5 (32.1%), O11 and O34 (14.3% each) predominant. Serovars O7, O14, O34, O39 and O97 were associated exclusively with sole infections. Two strains of V. cholerae non-O1 produced anti-cholera toxin IgG-absorbable cholera toxin (CT). Both CT-producing V. cholerae non-O1 strains hybridised with the DNA probe specific for the zonula occludens toxin (ZOT) but none of the remaining 26 strains hybridised with the ZOT probe. The majority of the strains were cytotoxic for CHO, HeLa and Vero cells, with end-point titres of 4-512. Fewer strains produced a cytotonic effect, with end-point titres of 2-16. Of the 28 strains of V. cholerae non-O1 examined, 75%, 75%, 25% and 14.3% produced haemolysin that was active against erythrocytes of rabbit, sheep (Eltor haemolysin), chicken and man, respectively. Strains that produced a haemolysin active against both rabbit and sheep erythrocytes were dominant (35.7%). Ten (35.7%) of the 28 strains examined showed cell-associated haemagglutinating activity on human blood. Of the 10 strains, nine were isolated as sole pathogen and only one strain was associated with mixed infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗