Uterine leiomyoma appearing as an inguinal mass.
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Adult↗
Biomedical subjects
T Obata
Publications and source records attributed to T Obata.
Pyruvate improves deleterious effects of high glucose on activation of pentose phosphate pathway and glutathione redox cycle in endothelial cells.
In our previous study (Diabetes 44:520-526, 1995), endothelial cells cultured in high glucose condition showed impairment of an oxidant-induced activation of the pentose phosphate pathway (PPP) and a reduced supply of NADPH to the glutathione redox cycle. To gain insight into the mechanisms of this impairment, the protective effect of pyruvate was studied in human umbilical vein endothelial cells cultured in either 5.5 mmol/l glucose (normal glucose [NG] condition) or 33 mmol/l glucose (high glucose [HG] condition). Through pretreatment of cells with 0.2 mmol/l pyruvate for 5-7 days in the HG condition, glucose oxidation through the PPP and total cellular NADPH content in the presence of 0.2 mmol/l H2O2 were increased by 54 (P < 0.05) and 34%, respectively, and glutathione-dependent degradation of H2O2 in HG cells was enhanced by 41% (P < 0.01), when compared with those cells to which pyruvate was not added. The addition of pyruvate significantly reduced the fructose 1,6-bisphosphate (FDP) content and free cytoplasmic NADH/NAD ratio, estimated by increased pyruvate/lactate ratio in NG and HG cells exposed to H2O2. Furthermore, the addition of pyruvate also showed a 46% reduction (P < 0.01) of endothelial cell damage induced by H2O2 in HG cells. These results indicate that abnormalities in PPP activation and glutathione redox cycle activity induced by H2O2 in HG cells are compensated, and that the accentuated reductive stress is improved by an addition of pyruvate. These pyruvate effects are associated with protection against an oxidant-induced endothelial cell injury in the high glucose condition.
Adenosine Triphosphate↗
[Abnormalities in lipid metabolism due to alcohol intake].
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Alcohol Drinking↗
[Immunohistochemical study of thymidine phosphorylase in uterine cervical intraepithelial neoplasia].
Studies have shown that thymidine phosphorylase (TdRPase) activity in various tumors is higher than that in normal tissues. We studied the immunohistochemical localization of TdRPase in uterine cervical intraepithelial neoplasia (CIN) using monoclonal antibody against TdRPase. Sixty-nine patients were studied: CIN 1, 14; CIN 2, 15; CIN 3 (severe dysplasia), 23; CIN 3 (carcinoma in situ), 17. Immunoreactivity for TdRPase was found in 29% of CIN 1, 40% of CIN 2, 70% of CIN 3 (severe dysplasia), and 88% of CIN 3 (carcinoma in situ), showing increasing incidence with the progression of tumor grade. Furthermore, in higher grade tumor, more immunoreactive cells were found with increased intensity of immunoreaction. Both nucleus and cytoplasm of atypical cells showed immunoreactivity in most TdRPase positive cases, while either nucleus or cytoplasm was positive in a few cases. The stromal tissues were negative for the antibody except 3 cases of CIN 3 (carcinoma in situ) in which the stromal tissues adjacent to the tumor was positive. Our data suggest that immunoreactivity of TdRPase in CIN may correlate with the grade of CIN.
Biomarkers, Tumor↗
[Measurement of cerebral blood flow using phase-contrast MRI].
The development of phase-contrast magnetic resonance imaging(P-C MRI) provides a noninvasive method for measurement of volumetric blood flow(VFR). The VFR of the left and right internal carotid arteries and basilar artery were measured using P-C MRI, and total cerebral blood flow(tCBF) was calculated by summing up the VFR values in three vessels. We investigated the changes in these blood flows as influenced from age, head size, height, weight, body surface area and handedness. Moreover, regional CBF(rCBF) was measured by combining with the single photon emission computed tomography(SPECT) of 123I. The blood flows were 142 +/- 58 mL/ min(mean +/- SD) in the basilar artery, 229 +/- 86 mL/min in the left, 223 +/- 58 mL/min in the right internal carotid artery, and tCBF was 617 +/- 128 mL/min(Ref. Magn Resn Imaging 14:P. 1143, 1996). Significant increases were observed in head-size-related change of VFR in the basilar artery and height-related change of tCBF. The value of rCBF was easily acquired in combination with SPECT. Phase-contrast MRI is useful for a noninvasive and rapid analysis of cerebral VFR and has potential for clinical use.
Adolescent↗
[Metabolic imaging of human brain tumors: H-1 chemical shift imaging and PET].
Positron Emission Tomography(PET) and Proton Chemical Shift Imaging(1H-CSI) has provided a cerebral metabolism. The glucose analog fluorine-18 fluorodeoxy-glucose(FDG) and amino acid analog 11C-L-methionine is the most commonly used PET tumor tracer. This time we compare with 1H-CSI and PET in gliomas and metastatic brain tumor with computer-assisted fusion images. We experienced some cases of the brain tumor. One case is metastatic brain tumor after radiation therapy, localized in right parietal hemisphere, with hemorrhage, and slightly accumulated Gd-DTPA in tumors. 11C-methionine PET demonstrates defects in tumors, but slight accumulated surrounding tumors. Accumulation of PET lesion is not elevated choline in CSI, but lactate is accumulated in tumors. Choline signal elevation seen in brain neoprasms, associated with increased cellular proliferation. Accumulation of PET and another accumulation of lactate in tumor are not demonstrate recurrence. Fusion image of PET and CSI is useful in understanding metabolism of brain tumor.
Aspartic Acid↗
Protective effect of carbidopa on hydroxyl radical generation in the rat striatum by dopamine.
The effect of L-3,4-dihydroxyphenylalanine (L-DOPA) on the generation of hydroxyl free radicals (.OH) was investigated using striatal microdialysis technique. Salicylic acid in Ringer's solution (0.5 nmol.microliters-1.min-1) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of dihydroxybenzoic acids (DHBA) in the striatum. When L-DOPA (0.1 mM; 1 microliter.min-1) was infused in the rat brain, the level of 3,4-dihydroxyphenylacetic acid (DOPAC) gradually increased in a time-dependent manner. In addition, a marked elevation of DHBA was observed. However, in the presence of carbidopa, a decarboxylase inhibitor, the elevation in DHBA formation was not observed. These results suggest that carbidopa may suppress the .OH generation by dopamine (DA).
3,4-Dihydroxyphenylacetic Acid↗
SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates.
To investigate the role of Janus kinase family (JAK1 and JAK2) in insulin signaling, we assessed their insulin-induced associations with other molecules in the cells overexpressing insulin receptors (HIRc and CHO-IR). After insulin stimulation, pp185 proteins (insulin receptor substrate, IRS) were co-immunoprecipitated with both kinases by alpha JAK1 and alpha JAK2 antibodies. However, JAK2 constitutively associated with pp95 protein (IR beta). Moreover, JAK2 also constitutively bound to a protein tyrosine phosphatase containing Src 2 regions (SHPTP2), but JAK1 did not. In HIRc cells expressing PTPase-negative mutant SHPTP2, no association of JAK2 with either pp185 or pp95 was detected. Thus, SHPTP2 might serve as an adapter protein linking between JAK2 and IRS. These results suggest that JAK1 and JAK2 behave differently and they may constitute a new regulatory component in insulin signaling.
Animals↗
IgE-anti-IgE-induced prostaglandin D2 release from cultured human mast cells.
To elucidate the characterization of cultured human mast cells, the generation of prostaglandin D2 (PGD2) upon stimulation with IgE-anti IgE challenge was determined by using gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) assay. Mononuclear cells obtained from human umbilical cord blood were cultured in the presence of Steel Factor, IL-6, and PGE2. After 8 weeks of culture, approximately 90 to 95% of cultured cells became tryptase-positive and included basophilic granules. At 12 weeks of culture, cells were harvested and incubated with 1 microgram/ml of human IgE for 1 hr and then challenged with 10 micrograms/ml of anti-IgE. The level of PGD2 release into the supernatant was measured by GC/MS/SIM with the stable isotope dilution method. Cyclooxygenase inhibitors affected the PGD2 release from the cell by IgE-anti IgE challenge incubation. Indomethacin inhibited 98% of PGD2 release. Acetylsalicylic acid (aspirin) and NS-398 (potent COX-2 inhibitor) also inhibited PGD2 release by 85 and 45% respectively.
Antibodies, Anti-Idiotypic↗
Cardiac microdialysis of salicylic acid to detect hydroxyl radical generation associated with sympathetic nerve stimulation.
We examined the relationship between norepinephrine (NE) and hydroxyl free radical (OH) generation on cardiac nerve stimulation. Salicylic acid in Ringer's solution (0.5 nmol microliter-1 min-1) was infused directly through a microdialysis probe to detect the generation of hydroxyl radicals (OH) as reflected by the formation of dihydroxybenzoic acid (DHBA) in the myocardium of anesthetized rats. Sympathetic nerve stimulation increased the release of NE and the formation of DHBA. A positive linear correlation between the release of NE and the formation of 2,3-DHBA (R2 = 0.982) or 2,5-DHBA (R2 = 0.976) was observed. These data indicate that the sustained elevation of NE in the extracellular fluid can be auto-oxidized, which in turn leads (possibly by an indirect mechanism) to the formation of cytotoxic OH free radicals.
Animals↗
Effect of iron (II) on the generation of hydroxyl free radicals in rat myocardium.
We examined the effect of iron (II) on the generation of hydroxyl radicals (.OH) in the extracellular fluid of rat myocardium. Salicylic acid in Ringer's solution (0.5 nmole x microliter(-1) x min(-1)) was directly infused through a microdialysis probe to detect the generation of OH as reflected by the formation of dihydroxybenzoic acid (DHBA) in the myocardium. Iron clearly produced a dose-dependent increase in .OH formation. A positive linear correlation between iron (II) and the formation of 2,3-DHBA (R2 = 0.970) or 2.5-DHBA (R2 = 0.983) was observed. However, when desferrioxamine (DES) was infused through a dialysis probe, a marked increase in DHBA formation was obtained. The present results suggest that iron (III) may reduce .OH formation by the Fenton reaction.
Animals↗
Eosinophil chemotactic activity in Leishmania amazonensis promastigotes.
Tissue eosinophilia was observed in the subcutaneous tissue of mice shortly after their inoculation not only with living but also with lysed promastigotes of Leishmania amazonensis. Intraperitoneal inoculation of lysed promastigotes from five different Leishmania species (L. donovani, L. chagasi, L. tropica, L. amazonensis, and L. braziliensis) induced eosinophil accumulation in the mouse peritoneum. This eosinophil infiltration was also detected in C5-deficient AKR mice, indicating complement independent eosinophil chemotaxis by the parasite. The induced eosinophils were hypodense, suggesting activation of the cells. Finally, we demonstrated in vitro eosinophil chemotactic activity in the promastigote lysates using purified eosinophils and blind well chambers. These results suggest the presence of an eosinophil chemotactic factor in Leishmania, a protozoan parasite.
Animals↗
Noninvasive analysis of water movement in rat testis using deuterium magnetic resonance imaging.
To measure water movement in the testis without the effects from the blood-testis barrier, we performed in vivo deuterium magnetic resonance imaging (2H MRI) of rats administered with deuterated saline. Alcohol was injected into one testis of each animal and the other was administered with normal saline as a control. Dynamic 2H MRI was obtained at 2 T by FLASH pulse sequence (TR, 300 ms; TE, 10 ms; alpha = 90 degrees) using a surface coil (3 cm in diameter). The variation in 2H signal intensity between the two testes as a function of time after deuterated saline injection was examined every 1.1 min up to 20 min. The signal intensity in the testis receiving the alcohol treatment was lower than that in the normal control. Thus, deuterium MRI can be used to analyze functional disorders of the testis.
Animals↗
Evaluation of antitumour effects of docetaxel (Taxotere) on human gastric cancers in vitro and in vivo.
In vitro antitumour effects of docetaxel (Taxotere) were examined in nine cultured human gastric cancer cell lines and 18 clinical gastric cancer specimens. In vivo antitumour effects were examined in human gastric cancer xenografts in nude mice. The activity was compared with paclitaxel (Taxol). Docetaxel was more effective than paclitaxel in six of the nine cell lines and the effectiveness rates of docetaxel and paclitaxel were 56% (10/18) and 6% (1/17), respectively, in the clinical gastric cancer specimens. In vivo docetaxel showed superior antitumour effect on well differentiated (MKN-28), poorly differentiated (MKN-45) and undifferentiated (KKLS) gastric cancer xenografts. We conclude that docetaxel promises to be clinically active against gastric carcinomas.
Animals↗
Three-vessel study of cerebral blood flow using phase-contrast magnetic resonance imaging: effect of physical characteristics.
The development of phase-contrast magnetic resonance imaging (P-C MRI) provides a noninvasive method for measurement of volumetric blood flow (VFR). We performed P-C MRI to study the effects of physical characteristics on cerebral blood flow. VFR of the left and right internal carotid arteries and basilar artery were measured using P-C MRI and total cerebral blood flow (tCBF) was calculated by summing up the VFR values in the three vessels. Moreover, we investigated the changes in these blood flows as influenced by age, head size, height, weight, body surface area, and handedness. The blood flows were 142 +/- 58 ml/min (mean +/- standard deviation) in the basilar artery; and 229 +/- 86 ml/min in the left, and 223 +/- 58 ml/min in the right internal carotid artery; and tCBF was 617 +/- 128 ml/min. Significant increases were observed in head size-related change of VFR in the basilar artery (p = .028) and height-related change of tCBF (p = .045). The other characteristics did not significantly influence any VFR. The results suggest that head size and height may reflect CBF, and that these effects should be considered when changes of CBF are diagnosed. Phase-contrast MRI is useful for a noninvasive and rapid analysis of cerebral VFR and has potential for clinical use.
Adolescent↗
Insulin signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscle cells.
Hyperinsulinemia has been recognized as an independent risk factor for atherosclerosis. However, its exact mechanisms are still unclear. In our previous work, we showed that 10 nmol/L insulin stimulated neither mitogen-activated protein kinase (MAP kinase) activity nor [3H]thymidine incorporation but did stimulated S6 kinase through the specific insulin receptors in cultured rat vascular smooth muscle cells (VSMCs). In this study, we observed that > or = 1 nmol/L insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and activated IRS-1-dependent phosphatidylinositol 3'-kinase (PI 3'-kinase) and p70 S6 kinase (p70S6K) but not MAP kinase (extracellular signal-regulated kinase 2) and p90 S6 kinase (p90RSK). However, 10 nmol/L insulin-like growth factor I stimulated all these pathways. Finally, 10 nmol/L insulin stimulated alpha-amino-isobutyric acid (AIB) uptake, and wortmannin (100 nmol/L) completely inhibited insulin-stimulated AIB uptake, whereas rapamycin (20 nmol/L) had no such effect. Furthermore, cycloheximide (10 micrograms/mL) completely inhibited insulin-stimulated AIB uptake, but actinomycin D (5 micrograms/mL) failed to inhibit this. Thus, we reached the following conclusions: (1) Insulin (1 nmol/L) induced phosphorylation of IRS-1 and activated the PI 3'-kinase and p70S6K pathways in VSMCs, even though 10 nmol/L insulin did not significantly stimulate MAP kinase or p90RSK. (2) Stimulation of AIB uptake by insulin was regulated at the translational level via wortmannin-sensitive pathways but not p70S6K pathways.
Aminoisobutyric Acids↗
Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury.
Because excessive neutrophil elastase (NE) activity is involved in the pathogenesis of acute lung injury, we speculated that administering anti-NE might prevent lung injury. In a guinea pig model of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]), we investigated the effect of ONO-5046, a low-molecular-weight and specific inhibitor of NE. ONO-5046 produced concentration-dependent inhibition of guinea pig NE, whereas there were no inhibitory effects on neutrophil chemotaxis or the expression of adhesion molecules in endothelial cells. Detectable NE activity in bronchoalveolar lavage (BAL) fluid was present in the LPS-alone group. No NE activity in BAL fluid was detected in the LPS+ONO-5046 groups. Neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio, and the lung tissue or BAL fluid to plasma ratio of 125I-albumin were increased in the LPS-alone group as compared with the saline group (p < 0.05). In the LPS+ONO-5046 group, neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio and BAL fluid to plasma ratio of 125I-albumin were decreased as compared with the LPS-alone group (p < 0.05). These data suggest that ONO-5046 can attenuate LPS-induced acute lung injury.
Acute Disease↗
Major Dermatophagoides mite allergen, Der 1, in soft toys.
BACKGROUND: Allergen avoidance is recommended when treating atopic asthma. OBJECTIVES: Soft toys are often kept in close proximity to children and may serve as a source of exposure. Due to the potential danger from the mite allergen content of these toys, Der 1 from toys was measured. METHODS: We quantified the level of Der 1 (Der p 1 + Der f 1) in both 30 new and 174 old soft toys (weight 216 +/- 2.5 g, height 26.5 +/- 3.4 cm), as well as in washed and in vacuumed soft toys. Dust was collected using an electric vacuum cleaner. Der 1 was measured by monoclonal antibody-based enzyme-linked immunosorbent assay (MoAb-ELISA). RESULTS: In brand new toys Der 1 was 0.1 microgram/g of dust, and in toys used for 1 year, 9.0; 2 year, 22.2; 3 year, 18.9; and more than 4 year, 22.7 micrograms/g of dust. Der 1 in new toys was measured every 4 months for 1 year. Der 1 rapidly increased 10- to 20-fold in the first 4 months, but there was no clear seasonal change. In toys washed using a chemical detergent or cleaned using a vacuum cleaner, there was a stastistically significant (P < 0.001) decrease in Der 1 in the washed group, but not in the vacuumed group. CONCLUSION: These results confirm that mite allergens accumulate rapidly in toys to form a potentially important source of allergens and that washing toys with a chemical detergent is effective in the reduction of allergens.
Allergens↗