Biomedical subjects

T Takada

Publications and source records attributed to T Takada.

At least 91 records · Page 5Linked to original sources

PubMed1998

Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Roles of Fak and Src family kinases.

SHPS-1 is a receptor-like glycoprotein that undergoes tyrosine phosphorylation and binds SHP-2, an Src homology 2 domain containing protein tyrosine phosphatase, in response to various mitogens. Cell adhesion to extracellular matrix proteins such as fibronectin and laminin also induced the tyrosine phosphorylation of SHPS-1 and its association with SHP-2. These responses were markedly reduced in cells overexpressing the Csk kinase or in cells that lack focal adhesion kinase or the Src family kinases Src or Fyn. However, unlike Src, focal adhesion kinase did not catalyze phosphorylation of the cytoplasmic domain of SHPS-1 in vitro. Overexpression of a catalytically inactive SHP-2 markedly inhibited activation of mitogen-activated protein (MAP) kinase in response to fibronectin stimulation without affecting the extent of tyrosine phosphorylation of focal adhesion kinase or its interaction with the docking protein Grb2. Overexpression of wild-type SHPS-1 did not enhance fibronectin-induced activation of MAP kinase. These results indicate that the binding of integrins to the extracellular matrix induces tyrosine phosphorylation of SHPS-1 and its association with SHP-2, and that such phosphorylation of SHPS-1 requires both focal adhesion kinase and an Src family kinase. In addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, SHP-2 may play an important role, partly through its interaction with SHPS-1, in the activation of MAP kinase in response to the engagement of integrins by the extracellular matrix.

Animals↗

PubMed1998

Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.

SHPS-1 is a receptor-like protein that undergoes tyrosine phosphorylation and binds SHP-2, an SH2 domain-containing protein tyrosine phosphatase, in response to insulin and other mitogens. The overexpression of wild-type SHPS-1, but not of a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region were mutated to phenylalanine, markedly enhanced insulin-induced activation of mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress the human insulin receptor. Mutation of each tyrosine residue individually revealed that the major sites of tyrosine phosphorylation of SHPS-1 in response to insulin are Tyr449 and Tyr473. In addition, mutation of either Tyr449 or Tyr473 abolished the insulin-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Surface plasmon resonance analysis showed that glutathione S-transferase fusion proteins containing the NH2-terminal or COOH-terminal SH2 domains of SHP-2 bound preferentially to phosphotyrosyl peptides corresponding to the sequences surrounding Tyr449 or Tyr473, respectively, of SHPS-1. Furthermore, phosphotyrosyl peptides containing Tyr449 or Tyr473 were effective substrates for the phosphatase activity of recombinant SHP-2 in vitro. Together, these results suggest that insulin may induce phosphorylation of SHPS-1 at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH-terminal SH2 domains, respectively. SHPS-1 may play a crucial role both in the recruitment of SHP-2 from the cytosol to a site near the plasma membrane and in increasing its catalytic activity, thereby positively regulating the RAS-mitogen-activated protein kinase signaling cascade in response to insulin.

Amino Acid Sequence↗

PubMed1998

Solitary splenic metastasis of a carcinoid tumor of the lung eight years postoperatively.

The case of a 49-year-old male who was found to have a solitary splenic metastasis 8 years after undergoing right upper lobectomy for Stage 1 (pT1N0M0) bronchopulmonary carcinoid tumor and was treated by splenectomy is reported. Metastasis of bronchopulmonary carcinoid tumors to the spleen is very rare. However, it is important to bear in mind that there are patients with solitary splenic metastasis who have a favorable outcome.

Carcinoid Tumor↗

PubMed1998

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility.

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 x 10(5) cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing.

Antineoplastic Agents↗

PubMed1998

Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats.

1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.

Acetates↗

PubMed1998

Neocarzinostatin-induced mutations at the hprt locus in exponentially growing CHO cells, compared with spontaneous mutations.

Spontaneous mutations and neocarzinostatin-induced mutations were investigated in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in exponentially growing Chinese hamster ovary cells. Neocarzinostatin (NCS) treatment caused an 4.5-fold increase in mutation frequency. Analysis by multiplex polymerase chain reaction and sequencing of hprt cDNA revealed that spontaneous mutations in this system were characterized by a relatively high rate of large deletions and double-base substitutions, and a low rate of splice mutations compared with data reported in fibroblastic cell lines. NCS hardly affected this spectrum of spontaneous mutations, which indicates the rare incidence of NCS-specific change in the exponential growth phase. This is in contrast to aprt gene mutations reported in plateau phase cells in which base substitutions occur preferentially at sites affected by NCS. These results suggest that differences in the loci assayed or in the processes involved in mammalian mutagenesis in the exponential growth phase and the plateau phase may be the source of the different results.

Animals↗

PubMed1998

Effect of omental lipid fraction on enhancement of skin flap survival.

The effect of an omental lipid fraction on the rate of skin flap survival in the back of the rat was assessed by planimetric and histological examination. Compared with the control group, those rats treated with the omental lipid fraction showed significant improvement of the flap survival area. On histological examination, the flap instilled with the omental lipid fraction showed vasodilatation and neovascularization between the flap and the bed. A topical application of the omental lipid fraction enhanced the skin flap survival area, and showed vasodilatation in the flap and neovascularization between the skin flap and the recipient bed.

Animals↗

PubMed1998

Current surgical trends in Japan for managing chronic pancreatitis.

The main aims of surgery for treating chronic pancreatitis are to relieve the patient's persistent pain and to preserve pancreatic functioning. The indications for surgery include treating complications, such as the presence of pancreatic pseudocysts or biliary stenosis associated with chronic pancreatitis or both. A resection, ductal drainage, or both, may commonly be required. Furthermore, some surgeons recommend pancreatic denervation. We analyze the details of 2,936 patients with chronic pancreatitis who were treated surgically and were listed in the 1985 National Statistics in Japan. We have also evaluated the present surgical methods for treating chronic pancreatitis in Japan. In addition, we discuss a new surgical method being used to treat chronic pancreatitis. This is a recently improved technique involving a complete duodenum-preserving resection of the head of the pancreas, which also preserves the biliary and alimentary tracts.

Chronic Disease↗

PubMed1998

Urinary excretion of podocytes reflects disease activity in children with glomerulonephritis.

The significance of the presence of podocytes in the urine was studied in various renal diseases in children. The podocytes were detected by immunofluorescence using monoclonal antibodies against the podocalyxin that is present on the surface of podocytes which serves as a glycocalyx. They were scored according to the numbers per partitioned area on cytospun urine sediments. Urine podocytes were absent in normal control, nonglomerular diseases such as urinary tract infection and nonglomerular hematuria, and glomerular, non-inflammatory diseases such as minimal change nephrotic syndrome and membranous nephropathy. Conversely, the excretion of podocytes in the urine were detected in various glomerular, inflammatory diseases. A significantly higher level of the podocyte score was found in the acute state of glomerular diseases which was defined as within 6 months after disease onset. Positive correlations were obtained between the presence of urinary podocytes and the histological features of active extracapillary changes and mesangial proliferation. Urinary podocytes were examined monthly for 12 months in 7 cases with IgA nephropathy and 2 cases with Henoch-Schönlein purpura nephritis, and a consistently higher urinary podocyte score was observed in the patients with histological progression. The scoring of urinary podocytes was found to be useful clinically, as a diagnostic tool for glomerular or nonglomerular diseases, inflammatory or noninflammatory diseases, a marker for the estimation of the severity of active glomerular injury and also as a predictor of disease progression.

Adolescent↗

PubMed1998

[Application of genetically engineered animals in pharmacology: the use of green fluorescent protein for selective production of transgenic animals].

Transgenic animals are a very important tool not only for basic science but also for the pharmaceutical industry. The use of genetically engineered farm animals are suitable as a disease model. Production of a therapeutic protein such as human clotting factors by transgenic animals will reduce the risk of infection with human immunodeficiency virus and hepatitis virus. The efficiency of transgenic animal production, however, has been low and thus limited its application. We improved the efficiency using a green fluorescent protein (GFP) as a marker of gene integration. Using this method, we obtained 12 fetuses, and Southern blot analysis showed eight of them were transgenic, indicating transgenic embryos were successfully selected at the preimplantation stage. We also observed similar GFP expression in rat and bovine blastocysts. Application of this GFP selection method should improve the efficiency of transgenic livestock production.

Animals↗

PubMed1998

Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced orthostatic hypotension.

Newly developed alpha1-adrenoceptor antagonists including naftopidil are free from the "prazosin-like" side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the alpha1-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of alpha1d-adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor subtypes, we found that naftopidil was selective for the alpha1d-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the alpha1-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.

Adrenergic alpha-Antagonists↗

PubMed1998

Endogenous immunoreactive ouabain-like and digoxin-like factors in reduced renal mass hypertensive rats.

We evaluated the urinary excretion of immunoreactive endogenous ouabain-like factor (OLF) and digoxin-like factor (DLF) to investigate their pathophysiological roles in sodium metabolism and blood pressure in 5/6-reduced renal mass rats, a model of volume-expanded hypertension. About five-sixths of the kidney mass (5/6 RRM, n = 9) was removed from male Sprague-Dawley rats, or the rats were sham operated (control, n = 10). Both groups were fed regular diets with tap water for 1 wk as a control period, followed by 1% saline solution for 4 wk. Systolic blood pressure (SBP), urine volume (UV), urinary sodium excretion (UNaV), DLF, and OLF were measured on the last 2 d of every week throughout the experimental period. SBP and UNaV were significantly higher in 5/6 RRM rats than in control rats. Urinary DLF significantly increased, reaching peak value in the first week, while OLF increased continuously, reaching peak value in the fourth week. In the first week, there were a significant positive correlations between the change in DLF and the changes in UNaV and SBP. However, the change in OLF was not correlated with changes in either UNaV or SBP. Both SBP and UNaV showed a significant positive correlation with OLF (p<0.001, r=0.547, p<0.001, r=0.658, respectively), whereas DLF significantly correlated with UNaV (p< 0.001, r= 0.584) but not with SBP in 5/6 RRM. These findings suggest that endogenous OLF and DLF coexist in rat urine and that an increased level of OLF, but not DLF, may contribute to the development and maintenance of hypertension. DLF may contribute to renal sodium excretion in this volume-expanded hypertensive rat model.

Animals↗

PubMed1998

Inflammatory cell population and bacterial contamination of membranes used for guided tissue regenerative procedures.

The purpose of this study was to determine the types of inflammatory cells and bacterial contamination on expanded polytetrafluoroethylene (ePTFE) membranes which might affect new tissue formed by guided tissue regeneration (GTR). Forty periodontal bony defects were treated by the flap procedure, which included the use of an ePTFE membrane. Twelve months after the second surgery, the defect sites were re-evaluated for changes in probing depth and clinical attachment level. The ePTFE membranes were retrieved after 4 to 6 weeks of healing and sectioned serially at 3 microm in a coronal-apical plane. The ePTFE membrane was divided into 3 portions: cervical, middle, and apical, each of which was subdivided into outer, central, and inner segments, providing a total of 9 fields. Cells and bacteria were analyzed by light microscopy for their types: mononuclear cell, erythrocyte, fibroblast, neutrophil, plasma cell, T lymphocyte, B lymphocyte, macrophage, and oral bacteria. Both cells and bacteria decreased in number towards the apical portion and were present even in the central part. Most cells were mononuclear cells. Erythrocytes, fibroblasts, neutrophils, and plasma cells were rarely encountered. Bacteria, most of which were Gram-positive, were observed in almost the same number in the outer and inner parts. The results indicate that numerous inflammatory cells adhered to and invaded the ePTFE membranes accompanied by bacterial contamination and that there was a tendency for a negative correlation between the increment number of bacteria and the gain of clinical attachment level.

Adult↗

PubMed1998

Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease.

Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistant to steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.

Aged↗

PubMed1998

[Panhypopituitarism following basilar artery dissection with extensive brainstem and cerebellar infarction: a case report].

We experienced a patient with panhypopituitarism which occurred following extensive brainstem and cerebellar infarction due to dissection of basilar artery (BAD). Panhypopituitarism followed by BAD has not yet been reported in the literature. The patient was a 67-years-old man who was admitted to our hospital because of a sudden onset of consciousness disturbance and vomiting. On the day of admission, he was drowsy and had left IIIrd nerve palsy, skew deviation, occular bobbing, and left hemiparesis. His neurological state was rapidly deteriorated, and fell almost into apneic state, requiring artificial ventilation for a week. Cerebral angiography demonstrated a double lumen sign of the basilar artery confirming the diagnosis of dissection. There were extensive hypodensities in the brainstem and bilateral cerebellar hemispheres on CT. On day 20, he suddenly became shocked following infection. Even after the effective and successful treatment of infection, severe hypotension continued that required administration of chatecholamine agents. Laboratory examinations revealed that he had panhypopituitarism. Supplement therapy with adrenocortical hormones made his circulatory state improved, and could finally be stopped on day 100. In the present case, subclinical hypopituitarism was considered to occur mainly from compression of the pituitary stalk and hypothalamus by the enlarged BAD. Increased intracranial pressure and upward herniation may also have made the pituitary function worse, and the infection finally triggered the adrenal crisis. The BAD occurs more frequently than previously considered, and should be kept in mind as a cause of secondary panhypopituitarism.

Aged↗

PubMed1998

[Pure alexia due to a fusiform gyrus lesion].

We present a patient with pure alexia following a hemorrhagic infarction in the left fusiform gyrus. The symptom began with alexia preferentially disturbed for kana, but during the course of recovery slight agraphia for kanji became pronounced. In the earlier phase, alexia was more severe than agraphia and he could write kanji that he could not read. Furthermore, kinesthetic reading was effective. These findings are consistent with the symptoms of pure alexia, although the fact that a writing disturbance for kanji persisted resembles the profile of alexia with agraphia for kanji due to a posterior inferior temporal lesion. Based on the fact that the posterior inferior temporal lesion showed more severe agraphic symptom and more frequent nonresponse writing errors of kanji, and that our patient's lesion was mainly located in the fusiform gyrus that is medial to the inferior temporal gyrus, we believe that alexia occurred when the inferior temporal gyrus was disconnected from the fusiform gyrus, as a result, visual information could not reach the inferior temporal gyrus in which the visual images of individual kanji are stored.

Aged↗

PubMed1998

[The signal transduction of receptor tyrosine kinase].

Polypeptides such as growth factors, differentiation factors, and hormones are crucial components of the regulatory system that coordinates development of multicellular organisms. Many of these factors mediate their pleiotropic actions by binding to and activating cell surface receptors with an intrinsic protein tyrosine kinase activity. The receptor activation due to ligands binding are translated across the membrane barrier into activation of intracellular domain functions. All receptor tyrosine kinase are composed of three major domains; an extracellular domain connected via a single membrane-spanning domain to a cytoplasmic domain. The extracellular domain is responsible for ligand binding and transmission of the biological signal to the cytoplasmic domain, whose role is to transmit the biological signal to intracellular target proteins. The cytoplasmic domain contains, in addition to the catalytic protein tyrosine kinase, distinct regulatory sequences with tyrosine, serine, and threonine phosphorylation sites. It appears that ligand-induced activation of the kinase domain and its signaling potential are mediated by receptor oligomerization. Ligand binding and the subsequent conformational alteration of the extracellular domain induce receptor oligomerization, which stabilizes interaction between adjacent cytoplasmic domains and leads to activation of kinase function and autophosphorylation of themselves. These receptor and substrate phosphorylation create binding sites for SH2 containing signaling molecule, such as Grb2, Shc, PI3 kinase and SHP-2. Binding of SH2 domains to tyrosine-phosphorylated regions of receptors or adaptor proteins, and a number of protein, such as SH3 containing protein, cytosol protein tyrosine kinase, protein tyrosine phosphatase and serine/threonine kinase, mediate intracellular signaling cascade and play critical roles in activated receptor protein tyrosine kinase to downstream signaling pathways.

Animals↗

PubMed1998

[Good response in case of hepatocellular carcinoma; a case report of interdisciplinary local therapy].

A 47-year-old male patient with chronic hepatitis had a high AFP level during the follow-up period. Abdominal CT revealed at S5, which led to a diagnosis of hepatocellular carcinoma. In August 1992, partial resection of S5 was performed, and ethanol was injected into the tumor at S2. In July 1993, recurrent tumors were observed at S5 and S3. PEIT was performed for each lesion. In December 1994, multiple recurrence was observed and 4 mg SMANCS was injected through the proper hepatic artery. In July 1995, another 4 mg of SMANCS was injected into the tumors. In June 1996, only a 20 mm lesion at S5 remained while the other lesions disappeared. Under general anesthesia, the patient underwent percutaneous microwave tumor coagulation. In December 1997, the AFP level was normal, and imaging revealed disappearance of the recurrent tumor. Selection of local therapy for hepatocellular carcinoma achieved long survival in our case considering the QOL and frequent therapy administration.

Antineoplastic Agents↗