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A Ando

Publications and source records attributed to A Ando.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-dependent formation of a complex containing an 85-kDa subunit of phosphatidylinositol 3-kinase and tyrosine-phosphorylated insulin receptor substrate 1.

Monoclonal antibodies raised against the 85-kDa subunit (p85) of bovine phosphatidylinositol (PI) 3-kinase were found to recognize uncomplexed p85 or p85 in the active PI 3-kinase. Immunoprecipitation studies of Chinese hamster ovary cells, which overexpress the human insulin receptor when treated with insulin, showed increased amounts of p85 and PI 3-kinase activity immunoprecipitable with monoclonal anti-p85 antibody and no increase in the tyrosine phosphorylation of p85. Insulin also induced an association of p85 with the tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and other phosphorylated proteins ranging in size from 100 to 170 kDa but not with the activated insulin receptor. In vitro reconstitution studies were used to show p85 in the active PI 3-kinase associated with the tyrosine-phosphorylated IRS-1 but not with the activated insulin receptor. Competition studies using synthetic phosphopeptides corresponding to potential tyrosine phosphorylation sites of IRS-1 revealed that phosphopeptides containing YMXM motifs inhibited this association with different potencies, whereas nonphosphorylated analogues and a phosphopeptide containing the EYYE motif had no effect. Src homology region 2 domains of p85 expressed as glutathione S-transferase fusion proteins also bound to tyrosine-phosphorylated IRS-1. These results suggest that insulin causes the association of PI 3-kinase with IRS-1 via phosphorylated YMXM motifs of IRS-1 and Src homology region 2 domains of p85.

Amino Acid Sequence↗
PubMed1992

Enhanced insulin-induced mitogenesis and mitogen-activated protein kinase activities in mutant insulin receptors with substitution of two COOH-terminal tyrosine autophosphorylation sites by phenylalanine.

We have studied the function of a mutant human insulin receptor in which two COOH-terminal autophosphorylation sites (Tyr-1316 and -1322) were replaced by phenylalanine (F/Y COOH-terminal 2 tyrosines (CT2)). In addition, we have also constructed a mutant receptor in which Lys-1018 in the ATP-binding site was changed to arginine (R/K 1018). Both the wild type insulin receptor (HIR) and the mutant receptors were expressed in Chinese hamster ovary (CHO) cells by stable transfection. Autophosphorylation of solubilized and partially purified F/Y CT2 was decreased by approximately 30% compared with the HIR. Tyrosine kinase activities of F/Y CT2 and HIR toward exogenous substrates were almost equal. When CHO cells transfected with F/Y CT2 (CHO-F/Y CT2) were stimulated with insulin, autophosphorylation of the beta-subunit of the insulin receptor and the phosphorylation of an endogenous substrate (pp185) in the intact cell were normal compared with cells expressing HIR (CHO-HIR). CHO-F/Y CT2 exhibited the same insulin sensitivity as CHO-HIR with respect to 2-deoxyglucose uptake. However, the dose-response curve of insulin-stimulated thymidine incorporation in CHO-F/Y CT2 was shifted to the left (approximately 5-7-fold) compared with that in CHO-HIR. There was no significant difference in insulin-like growth factor 1-stimulated thymidine incorporation between CHO-F/Y CT2 and CHO-HIR. Furthermore, the dose-response curve of insulin-stimulated kinase activity toward myelin basic protein in CHO-F/Y CT2 was also shifted to the left (approximately 5-fold) compared with that in CHO-HIR. Kinase assays in myelin basic protein-containing gels revealed that both species of MAP kinases (M(r) 44,000, 42,000) were more sensitive to activation by insulin in CHO-F/Y CT2 than in CHO-HIR. This observation was confirmed in immune complex kinase assays toward microtubule-associated protein 2 (MAP2) using specific antibodies against mitogen-activated protein (MAP) kinase. R/K 1018 mutant insulin receptors showed an absence of insulin-stimulated kinase activity and CHO cells transfected with R/K 1018 (CHO-R/K 1018) failed to enhance 2-deoxyglucose uptake or thymidine incorporation in response to insulin. In addition, R/K 1018 kinase-defective insulin receptors were unable to mediate insulin-stimulated MAP kinase activation. These data suggest that: 1) tyrosine kinase activity of the insulin receptor is required for activation of insulin-stimulated MAP kinases and 2) phosphorylation of COOH-terminal tyrosine residues may play an inhibitory role in mitogenic signaling through regulation of MAP kinases.

Animals↗
PubMed1992

In vitro association of phosphatidylinositol 3-kinase activity with the activated insulin receptor tyrosine kinase.

We previously have shown that insulin treatment of cells greatly increases the activity of phosphatidylinositol (PI) 3-kinase in immunoprecipitates made with an antibody to phosphotyrosine. However, the association of PI 3-kinase activity with the activated insulin receptor is not significant under these conditions. In the present study, we have attempted to reconstitute the association of PI 3-kinase activity with the activated insulin receptor in vitro. PI 3-kinase activity does indeed associate with the autophosphorylated insulin receptor in our in vitro system. The autophosphorylation of the insulin receptor and/or its associated conformational change appear to be necessary for the association of PI 3-kinase activity with the receptor, since kinase negative receptor failed to bind PI 3-kinase activity. After binding, PI 3-kinase or its associated protein seems to be released from the activated receptor after the completion of its tyrosine phosphorylation by the receptor. Tyr960 in the juxtamembrane region of the insulin receptor beta-subunit seems to be involved in the association of PI 3-kinase activity with the receptor, but not C terminus region of the beta-subunit including two tyrosine autophosphorylation sites (Tyr1316 and Tyr1322). The in vitro assay system for the association of PI 3-kinase activity with the insulin receptor can be utilized to study the mechanism of interaction of these molecules and will be an useful method to detect other associated molecules with the insulin receptor.

Animals↗
PubMed1992

Outcome of patients with lung cancer detected via mass screening as compared to those presenting with symptoms.

We performed lung cancer resection in 721 patients between 1980 and 1989. Cancers were detected via mass screening programs by annual chest X-ray examination in the majority of cases. We evaluated the surgical results in patients with tumors detected by mass screening and compared them to those in whom the malignancy was detected by symptoms. Lesions in the mass screened group were T1 to T2 tumors in 90% of the cases, and NO in 73%. Stage I disease accounted for 65.3% in the mass screened group. The overall 5-year survival rate was 56.2% in the mass screened group, which was significantly better than the 25.3% for the symptom group (P less than 0.001). The surgical results in the lung cancer cases detected by the mass screening program had better results than the cases who presented with symptoms.

Aged↗
PubMed1992

Transsternal thoracotomy for bilateral pulmonary metastasis.

Advances in the surgical treatment of primary malignancies and the recent chemotherapy have led to an expansion of the surgical treatment of metastatic lung tumors. However, multiple pulmonary metastases are often found and may affect both lungs. It is difficult to reach tumors in the posterior parts of the lung when using a common midsternal approach, especially lesions located in the left lower lobe. We performed transsternal simultaneous bilateral thoracotomy on 10 patients with bilateral lung tumors (9 bilateral metastatic pulmonary tumors and 1 bilateral primary lung cancer). This procedure provides a wide operative field and is an effective method of thoracotomy for patients with bilateral lung tumors. In future, this method should be more actively performed for patients in whom it is indicated.

Adolescent↗
PubMed1992

Search for MHC-associated genes in human: five new genes centromeric to HLA-DP with yet unknown functions.

Taking advantage of five mouse genomic or cDNA probes [KE5(probe 14), KE4 (probe 11), KE3 (probe 7), KE2 (probe 5), and SET] mapped on the H-2K region in mouse, we have identified and localized homologues of these five genes in the human major histocompatibility complex region (HKE5, HKE4, HKE3, HKE2, and HSET, respectively). Cosmid cloning and pulsed field gel electrophoresis analyses indicated that a human homologous gene, HKE5, is located 10 kilobases (kb) centromeric of the alpha 2 (XI) collagen (COL11A2) gene followed by HKE4. HKE3, closely linked to HKE2, is located 170 kb centromeric of HKE4. Furthermore, HSET is located 50 kb centromeric of HKE2. This gene organization outside the DP subregion is completely identical to that of the mouse H-2K region centromeric of I-Pb3, a mouse homologue of the DPB gene, except the lack of genes corresponding to the H-2K and -K2 genes in human.

Blotting, Southern↗
PubMed1992

HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.

To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.

Adult↗
PubMed1992

Cluster of fibronectin type III repeats found in the human major histocompatibility complex class III region shows the highest homology with the repeats in an extracellular matrix protein, tenascin.

Walking and sequencing a genome portion centromeric of CYP21B in the human MHC class III region disclosed a cluster of fibronectin type III repeats in an approximately 50-kb DNA segment. Fibronectin type III repeats are known to consist of ca. 90 amino acid residues and exist in a wide range of protein species. Homology searches in protein databases showed that the repeats found had the highest homology with the repeats of human tenascin, an extracellular matrix protein. One cDNA sequence located immediately centromeric of CYP21B, the 3' portion of which is transcribed by the opposite strand of CYP21B, was found also to have six type III repeats followed by a fibrinogen domain. Pairwise homology comparison of these repeats in the MHC locus with those of human tenascin showed a general parallelism in their gene organization, indicating that the newly found repeats are elements of certain tenascin-like genea.

Amino Acid Sequence↗
PubMed1992

Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth.

Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.

Animals↗
PubMed1992

[Mixed acid-base disorders].

Maintenance of the acid-base balance is critical for keeping cellular and whole body integrity, and acid-base disturbances are commonly encountered in critically ill patients. In this chapter, the classification and the pathogenesis of mixed acid-base disorders are reviewed in order to understand and manage these abnormalities. First of all, the compensatory reactions to the primary acid-base state must be evaluated. Careful examination of the physical findings and medical history are also essential for making a correct diagnosis and to treat the patients effectively.

Acid-Base Imbalance↗
PubMed1992

The surgical treatment of invasive thymoma. Resection with vascular reconstruction.

We have treated 96 patients with thymoma during the past 27 years; 57 of them had invasive thymoma. Surgical resection was undertaken in 45 of the 57 patients with invasive thymoma, including 14 patients in whom tumors were extirpated with vascular reconstruction. In addition, six patients with other thymic malignancies were treated in the same way. In six patients only angioplasty was performed, whereas artificial grafts were used in the other 14 patients. Ten of the 20 patients are still alive and well. One has probably been cured, since no signs of recurrence have been noted during the postoperative follow-up period of 8 years. No complications or occlusive symptoms were observed in these patients postoperatively, except in one who died after gastrointestinal hemorrhage. In one patient long-term patency of the vascular graft was confirmed by angiography and magnetic resonance imaging 5 years after operation. This intensive surgical procedure improved the quality of life for patients with the superior vena caval syndrome and may also have improved the prognosis of the patients with invasive thymoma.

Adult↗
PubMed1992

[Congenital lobar emphysema successfully treated by right upper lobectomy at five hours after delivery: a case report].

Lobar emphysema is a rare disease and one of the causes of respiratory disturbance in the newborn and infancy. A case report is presented and compared with related data in the literature in Japan. Maternal echographic findings indicated the cystic lung disease of the fetus. The cystic space was punctured and aspirated three times. The baby was delivered by caesarean section after having taken sufficient precaution to prevent respiratory failure. Since the baby developed dyspnea gradually, at five hours following the delivery, right upper lobectomy was performed and the major symptoms were eliminated. The pathological diagnosis was congenital lobar emphysema and the etiology was concluded to be bronchiectasis.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1991

Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells.

Interleukin 6 (IL-6) is one of the potent autocrine growth factors for mesangial cells. We investigated the signal transduction mechanism of IL-6 in cultured rat mesangial cells. IL-6 induced a transient increase of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) followed by a transient and sustained increase of intracellular calcium concentration, suggesting that IL-6 stimulates phosphoinositide turnover. IL-6 also stimulated prostaglandin E2 (PGE2) production. The IL-6-concentration dependency in PGE2 production was similar to that in Ins 1,4,5-P3 production. We concluded that the action of IL-6 on mesangial cells is exerted at least partially through the enhancement of phosphoinositide turnover and PGE2 production.

Animals↗