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Biomedical subjects

Tetsuya Yamamoto

Publications and source records attributed to Tetsuya Yamamoto.

At least 109 records · Page 6Linked to original sources
PubMed2003

Effect of exercise and beer on the plasma concentration and urinary excretion of purine bases.

OBJECTIVE: To investigate the effects of exercise and beer ingestion separately and combined on the plasma concentration of purine bases. METHODS: Six healthy men aged 30-39 years participated in 3 different experiments, in which they exercised for 30 min (at 70% of maximum oxygen uptake) and ingested beer (10 ml/kg body weight), or did each activity separately, with each experiment performed at 2 week intervals. RESULTS: The plasma concentration of uric acid was increased by 12% (p < 0.05), 8% (p < 0.01), and 29% (p < 0.01) with exercise, beer ingestion, and a combination of exercise and beer ingestion, respectively, which showed that it increased synergistically in the combination experiment. The fractional excretion of uric acid was decreased by 44% (p < 0.01) and 52% (p < 0.01) with exercise alone and a combination of exercise and beer ingestion, respectively, while it was increased by 15% (p < 0.05) with beer ingestion alone. Creatinine clearance was decreased by 16% (p < 0.01) with both exercise alone and a combination of exercise and beer ingestion, while it was not changed with beer ingestion alone. The increase in the plasma concentration of xanthine during the beer ingestion experiment was 2.1-fold greater than that during the combination (p < 0.05), while the increase in urinary excretion of xanthine caused by beer ingestion was 2.5-fold greater than that caused by a combination of beer and exercise (p < 0.05). Finally, exercise alone as well as a combination of beer and exercise increased the blood concentrations of lactic acid and NH3, whereas beer alone decreased concentration of pyruvic acid. CONCLUSION: These results suggest that the production of uric acid caused by both exercise and beer ingestion, as well as the inhibition of urinary uric acid excretion from a high blood lactic acid concentration, were the main contributors to the synergistic effect on the increase in plasma uric acid concentration. A decrease in creatinine clearance also contributed to the effect. We considered that pyruvic acid and NH3, produced in the muscles following exercise, relieved the beer induced increase of the plasma concentration and urinary excretion of xanthine, which may have played a minor role in the increase in plasma uric acid concentration.

Adult↗
PubMed2003

[Serial topographic changes at the optic disc in normal-tension glaucoma viewed with scanning laser tomography].

PURPOSE: To evaluate topographic changes in normal-tension glaucoma using serial optic disc images obtained by scanning laser tomography. SUBJECTS AND METHODS: Fifty-six eyes of 30 patients with normal-tension glaucoma were imaged using the Heidelberg Retina Tomography (HRT) four or more times during follow-up periods of more than 3 years. Disc progression was determined by regression analysis of global and segmental changes in optic disc parameters. Visual field progression was determined by Humphrey Field Analyzer (HFA) program 30-2 and was compared with disc progression. RESULTS: The global parameters of the optic disc showed progression in 21 of 56 eyes(37.5%). Progression was found in 30 eyes(53.6%) at the superotemporal segment, in 24 eyes(42.9%) at the temporal segment, in 27 eyes(48.2%) at the inferotemporal segment, in 21 eyes(37.5%) at the superonasal segment, in 23 eyes(41.1%) at the nasal segment, and in 27 eyes(48.2%) at the inferonasal segment. The visual field showed progression in 19 eyes (33.9%). The progression in the optic disc parameters did not necessarily agree with that in the visual field. CONCLUSIONS: Glaucomatous disc changes over time can be determined with HRT using regression analysis.

Adult↗
PubMed2002

Cutting edge: tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation.

IFN-alpha inhibits B lymphocyte development, and the nuclear protein Daxx has been reported to be essential for this biological activity. We show in this study that IFN-alpha inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice. In addition, the IFN-alpha-induced up-regulation and nuclear translocation of Daxx are completely abrogated in the absence of tyk2. Therefore, tyk2 is directly involved in IFN-alpha signaling for the induction and translocation of Daxx, which may result in B lymphocyte growth arrest and/or apoptosis.

Active Transport, Cell Nucleus↗
PubMed2002

The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.

In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. In this study, we examined the involvement of the nuclear isoform of TC-PTP in interleukin-6 (IL-6)-mediated signaling pathway. IL-6 is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions, and has also implicated in IL-6-related diseases. Here, we demonstrate that IL-6-induced tyrosine-phosphorylation and activation of STAT3 were suppressed by overexpression of the nuclear isoform of TC-PTP in 293T cells. Tyrosine-phosphorylated STAT3 directly interacted with a substrate-trapping mutant of TC-PTP. Furthermore, retrovirus-mediated overexpression of the nuclear isoform of TC-PTP suppressed the IL-6-induced growth arrest of myeloid leukemia M1 cells. Endogenous TC-PTP complexed with STAT3 in the nucleus of M1 cells. These results strongly suggest that the nuclear isoform of TC-PTP may serve as a negative regulator of IL-6-mediated signaling pathway.

Acute-Phase Proteins↗
PubMed2002

Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect.

To facilitate the repair of articular cartilage defects, autologous mesenchymal cells from bone marrow or periosteum were transplanted in a rabbit model. Two weeks after the transplantation of the mesenchymal cells, the whole area of the original defect was occupied by cartilage. From the deep area of the reparative cartilage, which contacted with host bone, chondrocytes became hypertrophic and the invasion of bone with vasculature started, until the replacement reached the natural junction of the host cartilage and the subchondral bone about 4 weeks after transplantation. Twelve weeks after the transplantation, the repair cartilage in the defect became a little thinner than the adjacent normal cartilage, which became a little thinner 24 weeks after the transplantation (the longest observation period in the study). Large, full-thickness defects of the weight-bearing region of the articular cartilage were repaired with hyaline-like cartilage after implantation of autologous mesenchymal cells. The repair process by mesenchymal cell transplantation was explained as follows: The donor transplanted cell differentiated into cartilage and the defects were completely filled with cartilage. Then, mesenchymal cells that entered the chondrogenic lineage rapidly progressed through this lineage to the hypertrophic state, which was then the target for erosion and vascular invasion. Although this vasculature and the newly formed bone were considered to be host-derived, there was no evidence to that effect. To prove this, suitable experimental marking of these donor cells is needed. In the case of chondrocyte transplantation, the repair cartilage maintained its thickness to the full depth of the original defect; the tissue derived from the implanted chondrocytes was not invaded by vessels or replaced by subchondral bone.

Animals↗
PubMed2002

Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice.

Tyk2 is activated in response to interleukin-12 (IL-12) and is essential for IL-12-induced T-cell function, including interferon-gamma (IFN-gamma) production and Th1 cell differentiation. Because IL-12 is a stimulatory factor for natural killer (NK) cell-mediated cytotoxicity, we examined whether tyk2 is required for IL-12-induced NK cell activity. IL-12-induced NK cell activity in cells from tyk2-deficient mice was drastically reduced compared to that in cells from wild-type mice. IL-18 shares its biologic functions with IL-12. However, the molecular mechanism of IL-18 signaling, which activates an IL-1 receptor-associated kinase and nuclear translocation of nuclear factor-kappaB, is different from that of IL-12. We next examined whether biologic functions induced by IL-18 are affected by the absence of tyk2. NK cell activity and IFN-gamma production induced by IL-18 were reduced by the absence of tyk2. Moreover, the synergistic effect of IL-12 and IL-18 for the production of IFN-gamma was also abrogated by the absence of tyk2. This was partially due to the absence of any up-regulation of the IL-18 receptor treated with IL-12, and it might suggest the presence of the cross-talk between Jak-Stat and mitogen-activated protein kinase pathways in cytokine signaling.

Animals↗
PubMed2002

A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery.

PURPOSE: Postoperative delirium (POD) is known to be one of the most critical complications of major operative procedures in elderly patients. Since disorders of the sleep-wake cycle have been reported to be one of the key factors in POD, we attempted to clarify the effectiveness of improving sleep-wake cycle disorders with medication after surgery to prevent POD, by conducting a prospective randomized study of 42 elderly patients who underwent resection of either gastric or colon cancer through an open laparotomy. METHODS: The delirium-free protocol (DFP) group was given an intramuscular injection of diazepam at 20:00 h each night, as well as a continuous intravenous infusion of flunitrazepam and pethidine administered over 8 h, for the first three nights postoperatively. Two patients were excluded because of failure to complete the DFP. RESULTS: The incidence of POD was 7/20 (35.0%) in the non-DFP group and 1/20 (5.0%) in the DFP group, this difference being significant (P = 0.023). Morning lethargy produced by the DFP was observed in 40% of the DFP group; however, no other side effects were seen. CONCLUSIONS: These findings indicate that DFP treatment is effective for controlling POD in elderly patients after general surgery and does not appear to be associated with severe complications or side effects. To our knowledge, this is the first report proposing artificial control of the sleep-awake rhythm by medication as a means of preventing POD in elderly patients.

Aged↗
PubMed2002

Myopia and advanced-stage open-angle glaucoma.

OBJECTIVE: To investigate the effect of myopic refraction on the central visual field in patients with advanced open-angle glaucoma (OAG). DESIGN: Multicenter cross-sectional study. PARTICIPANTS: Three hundred thirteen OAG eyes (176 eyes of 176 primary open-angle glaucoma [POAG] patients and 137 eyes of 137 normal-tension glaucoma [NTG] patients) with clear ocular media and a mean deviation (MD) <-15 dB. Patients with a recorded maximum intraocular pressure (IOP) of 22 mmHg or greater were classified as POAG, and those with an IOP of 21 mmHg or less were classified as NTG. METHODS: Multiple regression analysis was used to study the influence of refraction on 12 central test points of the C30-2 Humphrey program, and the differences in visual field defects between POAG and NTG eyes were examined using logistic discriminant analysis. In the multiple regression analysis, total deviation (TD) of the 12 test points was graded and used as the dependent variable, and MD and the spherical equivalent refraction were the explanatory variables. In the logistic discrimination analysis, TD, MD, and refraction were covariants that determined the OAG subtypes. MAIN OUTCOME MEASURES: TD values of the 12 central test points (C30-2 program). RESULTS: Higher myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point in POAG eyes, whereas it was significantly associated with less damage at test points just temporal and superior to the fixation point in NTG eyes. After correcting for the influence of refraction, POAG eyes had significantly more damage at a test point just temporal and inferior to the fixation point, whereas NTG eyes had significantly more damage at those test points nasal and inferior to the fixation point. CONCLUSIONS: High myopia constitutes a threat to the remaining lower cecocentral visual field and is one of the factors that interfere with the quality of vision in advanced OAG with high IOP but not low IOP.

Cross-Sectional Studies↗
PubMed2002

Expression of cyclooxygenase 2 and cytosolic phospholipase A(2) in the liver tissue of patients with chronic hepatitis and liver cirrhosis.

Cyclooxgenase (COX) and phospholipase A(2) (PLA(2)) are crucial rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H(2), the precursor of various compounds including prostaglandins (PGs), prostacyclin, and thromboxanes in the process of PGs' synthesis. Recent studies have shown increased levels of COX(2) in adjacent cirrhotic tissue of hepatocellular carcinoma. The relationship between the expression of COX(2) or cytosolicPLA(2) (cPLA(2)) and liver fibrosis has not been described previously. We used 45 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsies from patients with chronic hepatitis, consisting of 7 cases of F(0), 10 cases of F(1), 10 cases of F(2), 9 cases of F(3) and 9 cases of liver cirrhosis (LC) according to the New Inuyama Classification of the staging of liver fibrosis. The expression of COX(2) and cPLA(2) was investigated by immunohistochemistry, western blotting and image analysis. The positive signals for COX(2) and cPLA(2) were observed in the cytoplasm of hepatocytes. The signal intensity of COX(2) increased significantly with the progression of liver fibrosis (P<0.001) and no significant difference was observed in the relative amount of cPLA(2) from group F(0) to group LC. According to the New Inuyama Classification of hepatitis activity grading, 45 samples were classified as group A(1) (23 cases), group A(2) (19 cases) and group A(3) (3 cases). No significant differences were found in the relative amount of COX(2) and cPLA(2) between group A(1) and group A(2-3). Significant correlation was observed between the relative amount of COX(2) and hyaluronan (P<0.01). Our findings suggested that COX(2) may be involved in liver fibrogenesis.

Journal Article↗
PubMed2002

Effect of inosine on the plasma concentration of uridine and purine bases.

To examine whether inosine increases the plasma concentration of uridine, 20 mg/kg body weight of inosine was orally administered to 5 healthy subjects. The plasma concentration of uridine was increased by 1.25-fold (P <.05), while that of hypoxanthine, xanthine, and uric acid was increased by 1.26-fold (P <.01), 1.26-fold (P <.01), and 1.2-fold (P <.05), respectively, 2.5 hours after the oral administration of inosine. In addition, the 1-hour urinary excretion of uridine was increased by 1.17-fold (P <.05) and that of hypoxanthine, xanthine, and uric acid by 1.38-fold (P <.05), 1.4-fold (P <.05), and 1.4-fold (P <.05) between 2 and 3 hours after the administration of inosine. We also conducted an in vitro study with Mahlavu cells and found that the addition of inosine (50 micromol/L) inhibited a decrease in the concentration of uridine in medium originally containing 50 micromol/L uridine. Further, we demonstrated that the apparent Km and Vmax values for Na-independent uridine transport were 67.0 +/- 4.3 micromol/L and 7.0 +/- 0.3 pmol/mg protein/s, respectively, and the Ki value of inosine for Na-independent uridine transport was 45.1 +/- 12.1 micromol/L. These results suggest that inosine inhibits uridine uptake via the nucleoside transport pathway, and administered inosine is converted to purine bases (uric acid, hypoxanthine, and xanthine) in the intestine and liver, before entering the systemic circulation via the hepatic vein.

Adult↗
PubMed2002

Effects of angiotensin II infusion on renal excretion of purine bases and oxypurinol.

The effect of angiotensin II infusion on the renal transport of purine bases and oxypurinol (a metabolite of allopurinol) was investigated in 5 healthy subjects who were orally given allopurinol (300 mg) 9 hours prior to the study. Angiotensin II was intravenously administered at 8 ng/min/kg for 2 hours. The fractional clearances of uric acid, xanthine, and oxypurinol were significantly decreased during angiotensin II infusion; however, that of hypoxanthine did not change. The urinary excretion levels of uric acid, xanthine, and oxypurinol were also significantly decreased during angiotensin II infusion. These results suggest that angiotensin II infusion affected the renal clearances of uric acid, xanthine, and oxypurinol through direct tubular transport and/or hemodynamic changes. Accordingly, the hypouricemic effect of allopurinol may be exaggerated in hypertensive gout patients with an enhanced renin-angiotensin system, since an increased biological half-life of oxypurinol is expected in these patients.

Administration, Oral↗
PubMed2002

Effect of beer on the plasma concentrations of uridine and purine bases.

We conducted the present study to determine whether beer, both with and without ethanol content, increases the plasma concentration and urinary excretion of purine bases and uridine. Because 10 mL of regular beer (with ethanol) was found to contain 0.34 g of freeze-dried beer (without ethanol) and 0.5 mg of uridine, 5 healthy males were given regular beer (10 mL/kg of body weight) and freeze-dried beer (0.34 g/kg of body weight) or uridine (0.5 mg/kg of body weight). The plasma concentrations of hypoxanthine, xanthine, and uridine increased by 3.5-fold (P <.05), 4.7-fold (P <.05), and 1.8-fold (P <.05), respectively, 30 minutes after regular beer ingestion, and the urinary excretion of hypoxanthine, xanthine, and uridine increased by 4.0-fold (P <.05), 4.5-fold (P <.01), and 1.7-fold (P <.05), respectively, when measured 1 hour after ingestion. The plasma concentrations of uric acid and total purine bases increased by 6.5% (P <.05) and 7.6% (P <.05), respectively, 30 minutes after regular beer ingestion, whereas the urinary excretion of uric acid did not increase, while that of total purine bases increased by 1.3-fold (P <.05) when measured 1 hour after ingestion. As for freeze-dried beer, the plasma concentrations of uric acid total purine bases increased by 4.4% (P <.05) and 4.6% (P <.05), respectively, and that of uridine by 1.5-fold (P <.01) 30 minutes after ingestion, while the urinary excretion of uridine increased by 1.4-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine and xanthine and the urinary excretion of uric acid and total purine bases did not change significantly. As for uridine ingestion, the plasma concentration of uridine increased by 1.37-fold (P <.01) 30 minutes after ingestion, and the urinary excretion of uridine increased by 1.3-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine, xanthine, uric acid, and total purine bases did not change significantly. These results suggest that the purines in beer played a major role in the increase in the plasma concentration of uric acid, while both uridine and ethanol in beer had a significant effect on the increase in plasma concentration of uridine.

Adult↗
PubMed2002

Specificity and sensitivity of glaucoma detection in the Japanese population using scanning laser polarimetry.

AIMS: To investigate the usefulness of the scanning laser polarimeter (GDx; GDx Nerve Fiber Analyzer) for glaucoma detection in the Japanese population, and to investigate the difference in the thickness of retinal nerve fibre layer (RNFL) between normal tension glaucoma (NTG) and primary open angle glaucoma (POAG). METHODS: 69 eyes of 69 normal subjects and 115 eyes of 115 chronic open angle glaucoma patients (60 NTG and 55 POAG patients) were studied. The thickness of RNFL was measured with GDx. An eye was diagnosed as glaucomatous, if at least one original GDx variable showed p <5%. The difference in thickness of RNFL between the NTG and POAG groups was then investigated. RESULTS: 46 normal eyes (66.7%) were diagnosed as not glaucomatous (no variables showing p <5%), and 93 glaucomatous eyes (46 NTG and 47 POAG eyes) (80.9%) were diagnosed as glaucomatous. Actual values of average thickness, ellipse average, superior average, and superior integral were significantly lower in the POAG group than those in the NTG group. CONCLUSIONS: New variables which elucidate focal RNFL defects or early changes are needed to improve the moderate detection ability found in this present study. The pattern of the change in RNFL may differ in NTG and POAG groups.

Adult↗
PubMed2002

Cross-talk between bone morphogenic proteins and estrogen receptor signaling.

Bone morphogenic proteins (BMPs) play central roles in differentiation, development, and physiological tissue remodeling. Estrogens have key roles in a variety of biological events, such as the development and maintenance of numerous target tissues. Previous studies demonstrated that estrogens suppress BMP functions by repressing BMP gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on BMP function. BMP-2-induced activation of Sma and Mad (mothers against decapentaplegic)-related protein (Smad) activity and BMP-2-mediated gene expression were suppressed by 17beta-E2 in breast cancer cells and mesangial cells. E2-mediated inhibition of Smad activation was reversed by tamoxifen, an ER antagonist. We provide evidence that the inhibitory action of ER on Smad activity was due to direct physical interactions between Smads and ER, which represents a novel mechanism for the cross-talk between BMP and ER signaling pathways.

Blotting, Northern↗
PubMed2002

Effect of octreotide acetate on the plasma concentration and urinary excretion of uridine and purine bases.

To determine the effect of octreotide acetate on urinary excretion of uric acid and plasma concentration of uridine, we subcutaneously administered octreotide acetate (1 microg/kg of body weight) to 5 healthy subjects. Ninety minutes after administration, octreotide acetate increased the plasma concentration of uridine by 15% and decreased the plasma concentration of glucagon by 24% and that of insulin to below the detection limits. In addition, octreotide acetate decreased the urinary excretion of uric acid, sodium, and chloride by 60%, 40%, and 38%, respectively, at 1 hour after administration. However, octreotide acetate did not affect the concentrations of hypoxanthine, xanthine, uric acid, cyclic AMP in plasma, lactic acid and pyruvic acid in blood, urinary excretion of hypoxanthine and xanthine, or creatinine clearance. From these results, we speculated that octreotide acetate decreases the urinary excretion of uric acid by decreasing the concentration of glucagon and/or urinary excretion of sodium, and increases the plasma concentration of uridine via decreased concentrations of glucagon and insulin.

Adult↗
PubMed2002

Effect of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism in healthy subjects.

OBJECTIVE: The acute effects of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism were evaluated. METHODS: Losartan (50 mg) was administered orally to 6 healthy males. Blood and urine samples for uric acid and oxypurine were collected before and up to 6 hours after losartan administration. The same examinations were performed later using enalapril (5 mg). RESULTS: Losartan decreased the serum uric acid concentration (from 5.9 +/- 0.9 to 5.2 +/- 1.0 mg/dl) and increased its fractional clearance, which reached a maximum after 2 hours, while enalapril did not. Losartan also induced an increase in the plasma concentration of hypoxanthine, peaking in the fourth hour, and a decrease in its urinary clearance, while the plasma xanthine concentration and its urinary clearance were unchanged. The extent of uric acid excretion was much greater than that of the oxypurines. CONCLUSIONS: Losartan, which has a high affinity for the urate/anion exchanger, has a transient uricosuric effect. Our data indicate that losartan induces a significant decrease in the urinary excretion of hypoxanthine without changes in xanthine.

Adult↗
PubMed2002

Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR imaging and inductively coupled plasma atomic emission spectroscopy in rat brain tumors.

BACKGROUND AND PURPOSE: After the advent of extracellular contrast media, hepatobiliary-specific gadolinium chelates were developed to improve the diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is a new paramagnetic contrast agent with partial biliary excretion that produces prolonged enhancement of liver parenchyma on T1-weighted images. However, whether Gd-BOPTA is useful as a contrast agent in central nervous system disease, particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a brain tumor-selective contrast agent was compared with that of gadopentetate dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two contrast agents was performed, and tissue concentrations were measured with inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd-BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at every time course until 2 hours after administration and no enhancement in peritumoral tissue and normal brain. Corresponding results with ICP-AES showed significantly greater uptake of Gd-BOPTA in tumor samples than that in peritumoral tissue and normal brain 5 minutes after administration. Gadolinium was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging in brain tumors and possibly an effective absorption agent for neutron capture therapy.

Animals↗