Signal transduction through IL-6 receptor: involvement of multiple protein kinases, stat factors, and a novel H7-sensitive pathway.
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Biomedical subjects
T Takeda
Publications and source records attributed to T Takeda.
Increased nitric oxide production in patients with hypotension during hemodialysis.
OBJECTIVE: To determine the involvement of nitric oxide production in hemodialysis-induced hypotension. DESIGN: Examination of nitric oxide synthesis, cyclic guanosine 3'5'-monophosphate (cGMP) levels, and endothelin-1 levels in plasma before and after hemodialysis. SETTING: Veterans Affairs medical center. PATIENTS: 13 patients with end-stage renal failure who were receiving hemodialysis: Six patients had hypotensive episodes during dialysis and 7 did not. INTERVENTION: Patients received heparin at a bolus dose of 2000 U at the initiation of dialysis followed by 1000 U/h during 4-hour hemodialysis sessions. RESULTS: Nitric oxide production markedly increased during hemodialysis-induced hypotensive episodes; this increase was not seen in patients who did not have a hypotensive episode. In both groups, the plasma cGMP and endothelin-1 levels decreased after hemodialysis. According to multiple regression analysis, standard coefficients of nitric oxide production, plasma cGMP levels, and endothelin-1 levels with mean blood pressure after hemodialysis were -0.743, -0.07, and 0.31, respectively. CONCLUSION: Nitric oxide production increased in patients who had a hypotensive episode during hemodialysis but did not increase in those who did not have a hypotensive episode.
Aged↗
Cloning and expression of cDNA encoding a new type of ascorbate peroxidase from spinach.
A cDNA clone (SAP1) encoding a peroxidase was isolated from a spinach cDNA library using monoclonal antibodies raised against Euglena ascorbate peroxidase. The deduced amino acid sequence of SAP1 had higher homology with the cytosolic ascorbate peroxidases from plant sources than with bacterial peroxidases and classical plant peroxidases. The peroxidase activity of recombinant SAP1 protein expressed in E. coli was 1.6-fold higher with ascorbate than with guaiacol, which was similar to those of endogenous cytosolic ascorbate peroxidases. Here we conclude that SAP1 belongs to a new type of ascorbate peroxidase from spinach.
Amino Acid Sequence↗
Sequence analysis of the gene for a novel superantigen produced by Yersinia pseudotuberculosis and expression of the recombinant protein.
We previously reported that the Gram-negative bacterium Yersinia pseudotuberculosis produces a superantigen (YPM, Y. pseudotuberculosis-derived mitogen) that expands T cells bearing V betas 3, 9, 13.1, and 13.2 in an MHC class II-dependent manner. Based on the previously determined N-terminal 23 amino acids of YPM (T-D-Y-D-N-T-L-N-S-I-P-S-L-R-I-P-N-I-A-T-Y-T-G- (one-letter code)), we cloned the ypm gene and analyzed the nucleotide sequence. The gene encodes a 151-amino acid protein with a 20-amino acid signal peptide at its N terminus. The recombinant YPM expressed by the cloned gene exerted a mitogenic activity on human PBMC at a concentration of approximately 1 pg/ml. T cells bearing V beta 13.3 were preferentially expanded as well as T cells bearing the same V beta repertoires stimulated by native YPM. T cells were stimulated by the recombinant YPM in the presence of either fixed or unfixed HLA class II-transfected mouse fibroblasts. Furthermore, sequence diversity in the junctional region of the TCR beta-chain containing the V beta 3 element could be observed after stimulation by the recombinant YPM. These results indicate that YPM belongs to the category of superantigens and should be included as a novel member. The amino acid sequence of the mature protein showed no significant homology to other superantigens derived from Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes. This observation, together with the substantially smaller m.w. suggest that ypm must have evolved from a different ancestral gene.
Amino Acid Sequence↗
Characterization of a highly toxic, large molecular size heat-stable enterotoxin produced by a clinical isolate of Yersinia enterocolitica.
A novel heat-stable enterotoxin (ST) designated as Y-STc was purified to homogeneity from the culture supernatant of a pathogenic strain of Yersinia enterocolitica serotype O3 and its amino acid sequence was determined. The mature Y-STc was found to consist of 53 amino acid residues, which includes the putative pro-sequence. The molecular weight of Y-STc was 5638 and constituted the largest molecular size in the family of currently known STs. The minimum effective dose of purified Y-STc in the suckling mouse assay was 0.6 ng (0.0 pmol), indicating that, despite the long sequence, Y-STc is the most toxic in the ST family.
Amino Acid Sequence↗
Angiotensin II stimulates production of nitric oxide in guinea pig airways via AT1 receptor activation.
Angiotensin II (Ang II) and nitric oxide (NO) regulate a variety of physiological functions. In this study, we suggest that inhaled Ang II produces an initial bronchodilation apparently by stimulating NO production via AT1 receptors. Also, we demonstrate that following the initial bronchodilation, Ang II causes bronchoconstriction in the guinea pig, also via AT1 receptors. Both of the findings are important for our understanding of airway functions induced by Ang II.
Angiotensin II↗
The role of extrinsic nervous system in jejunal absorption during elevation of intraluminal pressure in anesthetized dogs.
The aim of this study was to investigate the role of the extrinsic nervous system in jejunal absorption under elevated intraluminal pressure of the jejunum. Increase in intraluminal pressure from 0 to 70-100 mmHg decreased net absorption of fluid, Na+ and Cl-, from 7.6 +/- 0.5 to 5.6 +/- 0.3 ml/15 min, 1.1 +/- 0.1 to 0.7 +/- 0.1 mEq/15 min, and 1.2 +/- 0.1 to 0.8 +/- 0.1 mEq/15 min, respectively. To examine the role of the extrinsic nervous system in the depressed net jejunal absorption induced by the increase in intraluminal pressure, jejunal afferent and efferent nerve activities were measured in response to the increase in intraluminal pressure. Both afferent and efferent nerve activities increased to 224 +/- 14 and 236 +/- 18% in response to the increase in intraluminal pressure. In the extrinsic denervated jejunal loop, the responses of net absorption to the elevation of intraluminal pressure were quite different from those in innervated jejunum. That is, in the denervated jejunal loop the elevation of intraluminal pressure converted jejunal absorption to jejunal secretion. These results indicate that elevation of intraluminal pressure elicits the jejuno-jejunal reflex, and this mechanism counteracts jejunal secretion.
Anesthetics↗
Dietary alpha-linolenate/linoleate balance influences learning and memory in the senescence-accelerated mouse (SAM).
The senescence-accelerated mouse (SAMP8) is a model of age-related deterioration of memory and learning ability. A semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate) was fed to SAMP8 mouse dams and their pups. The offspring (males from several mothers) at 28 weeks of age were used for behavioral tests. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets. The learning and memory abilities of the two dietary groups were tested with the Sidman active avoidance task and the light and dark discrimination learning test. The group given perilla oil showed much greater improvement in learning in the Sidman active avoidance task than did the group fed safflower oil. In the light and dark discrimination learning test, the total number of responses to positive and negative stimuli was lower in those fed perilla oil, and their responses to positive stimuli were higher than to negative stimuli after the 10th session. Consequently, the correct response ratios of discrimination were higher in the perilla oil group than in the safflower oil group. In the open field test, the total amount of locomotor activity during 5 min was lower in the perilla oil group at 7 months of age than in the group fed safflower oil.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Femoral peak bone mass and osteoclast number in an animal model of age-related spontaneous osteopenia.
BACKGROUND: SAMP6 was developed as a murine model of age-related spontaneous osteopenia characterized by low peak bone mass. A morphometric study of the growing femur in SAMP6 and sex-matched SAMP2 at 10 days to 4 months of age was done to examine the pathogenic process related to osteopenia. METHODS: Age-related changes in cortical bone thickness, femur score, trabecular bone volume, thickness of epiphyseal growth plate, number of osteoclasts, and osteoclast surface were measured with a computerized image analyzer. Osteoclasts were examined cytomorphometrically after TRAP (tartrate resistant acid phosphatase) staining of the femoral sections. RESULTS: Cortical bone thickness and femur score increased significantly with age, while trabecular bone volume decreased significantly. Comparing mean values of cortical bone thickness, femur score and trabecular bone volume, we noted significantly lower mean values in SAMP6 than in SAMP2 mice. These significant inter-stain differences first became evident in 20-40-day-old mice, but there was no significant difference in thickness of the epiphyseal growth plate between the two strains. The mean values of the number of osteoclasts per unit bone surface length and of the osteoclast surface in SAMP6 were significantly greater than in age- and sex-matched SAMP2. Histograms of distribution of size of osteoclasts of 40-day-old male mice revealed that larger ones were more frequently seen in SAMP6. Furthermore, the ratio of osteoclasts/TRAP positive cells free in the bone marrow cavity was significantly higher in SAMP6 than in SAMP2. CONCLUSION: Activated bone resorption may play a role in the osteopenia seen in SAMP6.
Aging↗
Treatment combined with bone marrow transplantation for advanced neuroblastoma: an analysis of patients who were pretreated intensively with the protocol of the Study Group of Japan.
One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.
Antineoplastic Combined Chemotherapy Protocols↗
Gas-forming liver abscess following transcatheter hepatic arterial embolization for an iatrogenic intrahepatic pseudoaneurysm: report of a case.
We herein describe a case of gas-forming pyogenic liver abscess following transcatheter hepatic arterial embolization (THAE) for an iatrogenic intrahepatic pseudoaneurysm in a 74-year-old woman. Hemobilia developed 19 days after percutaneous transhepatic cholangio-drainage was performed for the purpose of percutaneous cholangioscopic lithotripsy for the treatment of post-gastrectomy choledocholithiasis. Celiac arteriography disclosed a saccular aneurysm in the right hepatic artery. The pseudoaneurysm was successfully occluded by THAE with gelatin powder and a stainless steel coil of the Gianturco type. Ten days after successful THAE, abdominal computed tomography revealed a gas-containing cavity, which suggested the presence of a gas-forming abscess, in the posterior hepatic segment, and percutaneous transhepatic abscess drainage was performed. Thus, impaired hepatic perfusion following effective THAE and coexisting cholangitis may play an important role in the development of a gas-forming pyogenic liver abscess.
Aged↗
Clinicopathological findings and p53 expression of thyroid cancer in children.
Although thyroid cancer tends to metastasize early in children, it is generally associated with a good prognosis. In this study, the expression of p53, mutations of which are found in many cancers, including anaplastic thyroid cancer, was examined to determine the relationship between cell proliferation and the clinical course of thyroid cancer. The clinicopathological findings and clinical courses of 15 children who underwent surgery before the age of 18 years at our hospital between 1972 and 1992 were examined, and the expression of p53 was studied using immunohistochemical techniques and an RNase protection assay. Postoperative follow-up ranged from 1 to 20 years, with a median of 12 years. No abnormal expression of p53 was detected in the thyroid cancer of any of the children tested, and none of them have died. The findings of this study therefore strongly suggest that p53 may play a role in the regulation of cell proliferation, and in this capacity slow the growth of and be related to the prognosis of differentiated thyroid cancer in children.
Adolescent↗
Evaluation of portal circulation through the superior mesenteric vein with an enteric capsule of [123I]iodoamphetamine.
We report a method by which the contribution of the superior mesenteric vein to the portal blood flow can be evaluated noninvasively. An enteric-coated capsule containing [123I]iodoamphetamine is given by mouth 3h before the examination. The data obtained are treated by computer to calculate the portal shunt index (SI) through the superior mesenteric vein. The SI was higher for more severe liver disorders, Increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis. The SI was higher in cirrhotic patients than in chronic hepatitis patients or healthy volunteers (both, P < 0.0001). The SI was higher in cirrhotic patients with esophageal varices than in such patients without varices (P < 0.05). The SI was higher in cirrhotic patients with ascites than in such patients without ascites (P < 0.001). The SI was higher in cirrhotic patients with encephalopathy than in those without encephalopathy (P < 0.01). Correlation was significant between the SI and classical indicators of functional reserve. This method is clinically useful.
Administration, Oral↗
Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-I tax gene.
To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of the lyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.
Animals↗
Primary biliary cirrhosis complicated by severe hypoxemia.
The case reported here is of a 61-year-old woman diagnosed with hepatopulmonary syndrome. She had had severe hypoxemia for 5 years. In room air, her arterial oxygen tension was low, and although we anticipated that treatment with oxygen would increase it, the treatment failed to do so. Pulmonary perfusion imaging with Tc-99m-labelled macroaggregated albumin showed an arterio-venous shunt in the lungs. Blood tests and liver scanning with Tc-99m-labelled galactosyl human serum albumin showed abnormalities of liver function, and per-rectal portal scintigraphy with Tc-99m pertechnetate showed severe portal hypertension. Inspection of a biopsy specimen taken under ultrasonographic guidance showed primary biliary cirrhosis of Scheuer stage I. The causes of hepatopulmonary syndrome are unknown, but seem to include a decrease in hepatic functional reserve, portal hypertension, or other factors. The development of hepatopulmonary syndrome due to portal hypertension in this patient is of interest.
Biopsy↗
Study on the primary visual cortex of visually impaired subjects by means of 123I-IMP SPECT and MRI.
We conducted a study of rCBF in the primary visual cortex of visually impaired subjects who have not been subjected to external stimulation for a long period, by means of 123I-IMP SPECT and MRI. The four subjects had lost their sight due to brain tumors (n = 2), glaucoma (n = 1) and trauma (n = 1). 123I-IMP SPECT showed no differences between the visually impaired group and a visually sound control group on visual analysis as well as semiquantitative analysis. MRI of the visually impaired subjects showed no organic changes, such as atrophy, in the occipital cortex. In conclusion, visually impaired subjects have no decrease in rCBF and no anatomical changes in the primary visual cortex.
Adult↗
The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy.
The accuracy of measurement of the functional hepatic volume by single photon emission computed tomography (SPECT) with 99mTc-galactosyl serum albumin (99mTc-GAS) was evaluated. 99mTc-GSA planar scintigraphic images were obtained dynamically and the hepatic SPECT imaging was then performed in 25 patients with hepatobiliary tumors. The patients were divided into 4 groups with normal hepatic function, and mild, moderate and severe hepatic dysfunction. The functional hepatic volume determined by SPECT was compared with the morphological hepatic volume determined by compute tomography. The ratio of the hepatic volumes obtained by the two methods was calculated. The mean hepatic volume ratio was 96.6 +/- 2.3% in the normal hepatic function group and 95.9 +/- 2.2% in the mild dysfunction group (n.s.). In both the moderate and severe hepatic dysfunction groups, the hepatic volume ratio was smaller than that in the normal group (87.9 +/- 5.2%, p < 0.0001, and 71.9 +/- 7.6%, p < 0.0001, respectively). There was a linear correlation between the hepatic volume ration and various indices of reserve hepatic function, such as LHL15 (r = 0.83, p < 0.0001), HH15(r = 0.74, p < 0.0001), and ICG15 (r = 0.75, p < 0.0005). These results indicate that the hepatic volume ratio is proportional to the severity of hepatic dysfunction, and suggest that the functional hepatic volume measured with 99mTc-GSA faithfully reflects the functioning hepatocyte mass. 99mTc-GSA scintigraphy and hepatic SPECT therefore provide information regarding global and regional reserve hepatic function.
Adult↗
Inhibition by angiotensin II type 1 receptor antagonist of cardiac phenotypic modulation after myocardial infarction.
The purpose of this study was to examine the cardiac phenotype and remodeling after myocardial infarction and the effect of the angiotensin II type 1 (AT1) receptor antagonist (TCV-116) on the gene expression. Myocardial infarction in rats was produced by ligation of the coronary artery. TCV-116 (10 mg/kg/day) was administered orally to rats from 1 day after myocardial infarction. At 1, 2 and 3 weeks after myocardial infarction, blood pressure and heart rate were measured, and the heart was removed. The left ventricle was measured for infarct size and weight, and then the total RNA from the non-ischemic left ventricle was extracted. mRNAs in the non-ischemic left ventricle were measured by Northern blot analysis. The weight of the non-ischemic left ventricle was significantly increased 3 weeks after infarction. This was completely prevented by TCV-116 treatment. mRNA levels for beta-myosin heavy chain (beta-MHC), atrial natriuretic polypeptide (ANP), collagen types I and III and transforming growth factor-beta 1 (TGF-beta 1) in the non-ischemic left ventricle were increased by a factor of 3.0, 6.7, 7.9, 4.0 and 1.4 (P < 0.01), respectively, 1 week after infarction. There was no increase in alpha-skeletal actin mRNA at 1 and 2 weeks, but it was increased by a factor of 2.9 (P < 0.05) at 3 weeks. On the other hand, there was no change in alpha-MHC mRNA during the 3 weeks. TCV-116 significantly suppressed the increased gene expression of beta-MHC and alpha-skeletal actin in the non-ischemic myocardium at all time points, and also suppressed the expression of ANP at 2 and 3 weeks. However, TCV-116 failed to inhibit the expression of collagen I and III mRNAs at 1 and 3 weeks. These results show that myocardial infarction causes a rapid shift of myocytes to fetal phenotype and a rapid activation of collagen genes in the non-ischemic myocardium. AT1 receptor may be responsible for the phenotypic modulation of myocytes following myocardial infarction.
Actins↗