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Biomedical subjects

T Takada

Publications and source records attributed to T Takada.

At least 37 records · Page 2Linked to original sources

Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas.

SAP-1 (stomach cancer-associated protein-tyrosine phosphatase-1) is a transmembrane-type protein-tyrosine phosphatase that is abundant in the brain and certain cancer cell lines. With the use of a "substrate-trapping" approach, p130(cas), a major focal adhesion-associated phosphotyrosyl protein, has now been identified as a likely physiological substrate of SAP-1. Expression of recombinant SAP-1 induced the dephosphorylation of p130(cas) as well as that of two other components of the integrin-signaling pathway (focal adhesion kinase and p62(dok)) in intact cells. In contrast, expression of a substrate-trapping mutant of SAP-1 induced the hyperphosphorylation of these proteins, indicating a dominant negative effect of this mutant. Overexpression of SAP-1 induced disruption of the actin-based cytoskeleton as well as inhibited various cellular responses promoted by integrin-mediated cell adhesion, including cell spreading on fibronectin, growth factor-induced activation of extracellular signal-regulated kinase 2, and colony formation. Finally, the enzymatic activity of SAP-1, measured with an immunocomplex phosphatase assay, was substantially increased by cell-cell adhesion. These results suggest that SAP-1, by mediating the dephosphorylation of focal adhesion-associated substrates, negatively regulates integrin-promoted signaling processes and, thus, may contribute to contact inhibition of cell growth and motility.

Animals↗

A repeated pancreatectomy in the remnant pancreas 22 months after pylorus-preserving pancreatoduodenectomy for pancreatic adenocarcinoma.

We report a case of a repeated curative pancreatic resection in the remnant distal pancreas 22 months after pylorus-preserving pancreatoduodenectomy (PpPD). The patient was a 52-year-old woman with a past history of PpPD for adenocarcinoma of the head of the pancreas 22 months prior to the present operation. The original tumor was histopathologically diagnosed as a papillary adenocarcinoma with clear surgical margin at the surgical cut end of the pancreas (R0, International Union Against Cancer [UICC] classification). Twenty months after the PpPD, a follow-up computed tomography (CT) scan showed multiple low-density lesions in the body and tail of the pancreas without any other distant metastasis. A second operation, curative resection of the remnant pancreas, with splenectomy and distal gastrectomy, was performed. The second tumor was a papillary adenocarcinoma, the same diagnosis as that of the first tumor, and it also showed similar histopathological findings, including immunohistochemical staining of Ki-67 and p53 protein, and the same pattern of K-ras point mutation. The patient is considered to have shown a rare, unique pancreatic cancer with metachronous carcinogenesis in the remnant pancreas.

Adenocarcinoma, Papillary↗

Is preoperative biliary drainage necessary according to evidence-based medicine?

Preoperative biliary drainage has been in use for a long time and is still being performed today in some institutions, but there has been a long-standing issue as to whether the necessity of this procedure has been proven medically. Many problems existed previously, such as systemic complications due to the difficulty in diagnosing and differentiating obstructive jaundice from jaundice left untreated for a long time, or surgeon-based problems such as a lack of surgical skill or undeveloped surgical techniques, or even inexperience in perioperative patient management. These problems, however, are being overcome with time, and the advantages of preoperative biliary drainage are now being questioned according to evidence-based medicine. Several recent controlled trials have clearly shown that preoperative biliary drainage is not necessary for lower bile duct obstruction, although it was noted that surgery after reduction of jaundice by percutaneous transhepatic cholangial drainage (PTCD) was very easily performed. It is important to understand that preoperative biliary drainage is unnecessary for lower bile duct obstruction, whether the technique follows a percutaneous approach, an endoscopic apporach, or stenting. Although it is still being debated, there have already been several reports regarding whether preoperative biliary drainage is necessary for upper bile duct obstruction, such as hilar bile duct carcinoma. This also needs to be clarified by randomized controlled trials. Aside from preoperative biliary drainage, the utilization of biliary drainage or stenting has been fully recognized as important for removing intrahepatic stones or choledochal stones, as well as for emergency drainage for acute cholangitis and for the treatment of unresectable malignant biliary stenosis. Additionally, percutaneous transhepatic cholangioscopy (PTCS), using the PTCD. or percutaneous transhepatic biliary drainage (PTBD) route. plays a major role not only in the removal of biliary stones but also in the diagnosis of cases in which it is difficult to differentiate between benign and malignant lesions.

Bile Duct Neoplasms↗

Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a Japanese population.

RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P<0.01) with the frequency of those in AA genotype being elevated (P<0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was significantly increased (P<0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.

Bronchoalveolar Lavage Fluid↗

External venous shunt as a solution to venous thrombosis in microvascular surgery.

We report a case in which venous occlusion occurred after fibular osteocutaneous flap transfer for open tibial fracture. The flap was salvaged using an external venous shunt. The shunt consisted of a Teflon catheter for intravenous infusion, a three-way stopcock, a urokinase-immobilised catheter and a pressurising bag for arterial-pressure monitoring. This method can be used to establish venous drainage when there is no accessible recipient vein. It may improve the success rate of microvascular surgery and extend the indications for surgery.

Adult↗

Antiallergic effect of ardisiaquinone A, a potent 5-lipoxygenase inhibitor.

The antiallergic effects of ardisiaquinone A, a potent 5-lipoxygenase inhibitor, were examined. Pretreatment with ardisiaquinone A (0.1-10 microM) significantly inhibited compound 48/80-induced production of cysteinyl-leukotrienes (cys-LTs; LTC4, LTD4 and LTE4) in rat peritoneal mast cells, but not histamine release. The IC50 value was 5.56 microM. Pre-administration with ardisiaquinone A (0.1-1 mg/kg, s.c.) dose-dependently inhibited rat homologous passive cutaneous anaphylaxis (PCA) and the maximal inhibitory ratio was 22.3 +/- 3.9% at the dose of 1 mg/kg. Ardisiaquinone A (1-5 mg/kg, s.c.) dose-dependently prevented the allergen-induced increase of tracheal pressure in ovalbumin-sensitized guinea pigs, especially during the late phase. In conclusion, the findings of this study show that 5-lipoxygenase inhibitor ardisiaquinone A partially attenuates the allergen-induced increases of vascular permeability and tracheal pressure via the inhibition of cys-LTs production in mast cells.

Animals↗

Blood flow in the left atrial appendage and embolic stroke in nonvalvular atrial fibrillation.

It is unclear if low flow velocity in the left atrial appendage (LAA) is a predisposing factor to stroke in patients with nonvalvular atrial fibrillation (NVAF). We investigated flow velocity in the LAA in NVAF patients in relation to a past history of stroke and other potential embolic sources. We measured and analyzed peak flow velocities into (FV-in) and out of (FV-out) the LAA in a middle portion of the LAA in 35 NVAF patients by transesophageal echocardiography (TEE). We divided the NVAF patients into 3 groups: the Eaf group had a history of embolic stroke without any other potential embolic sources; the Emulti group had other potential embolic sources, and the control group had no embolic history. FV-in and FV-out in the Eaf group (12.3 +/- 6.7 and 10.2 +/- 7.3 cm/s) were significantly lower than those in the control group (24.3 +/- 11.3 and 19.9 +/- 8.8 cm/s; multicomparison Scheffé's test, p = 0.0123 and 0.0395, respectively). The Emulti group varied in those values from less than 5 to above 35. Low flow velocity in the LAA seems to be a predisposing factor for stroke in NVAF patients without any other sources of emboli.

Aged↗

Cardiac imaging in a patient with anomalous origin of the left coronary artery from the pulmonary artery--a case report.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an uncommon congenital heart disease and has a high mortality rate in infancy. However, myocardial ischemia does not develop until adolescence or adulthood in about 10% of patients. Moreover, the diagnosis of ALCAPA is often difficult in cases without heart murmur or cardiac symptoms. The authors report the case of a 31-year-old man with ALCAPA. He was admitted to the hospital for evaluation of mild shortness of breath at exercise, but he had no typical chest symptoms due to myocardial ischemia or heart failure until age 31 and he had no heart murmur. Moreover, electrocardiogram did not show an old myocardial infarction or myocardial ischemia. Therefore, the authors did not suspect ALCAPA until they performed transthoracic echocardiography and exercise-stress single photon emission computed tomography (SPECT) with Tc-99m-tetrofosmin. The final diagnosis was established from the results of coronary arteriography. In the present case, a transthoracic echocardiogram showed abnormal coronary circulation, and exercise-stress SPECT revealed reversible myocardial ischemia. Transthoracic echocardiography and myocardial SPECT imaging could be a useful noninvasive tools for diagnosing the ALCAPA.

Adult↗

Effect of nitric oxide on mouse clonal osteogenic cell, MC3T3-E1, proliferation in vitro.

Nitric oxide (NO) is a very small lipophilic molecule which rapidly diffuses and reaches the cytoplasmic components, and results in the activation of diverse biological function. It has been already reported that cultured osteoblasts synthesize NO in response to proinflammatory cytokines and lipopolysaccaride. In terms of the action of NO on bone metabolism, cytokine-induced NO by osteoblast inhibits bone resorption through inducing the apoptosis of osteoclast progenitor cells and suppressing the osteoclast activity. Also, NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine is reported to induce a dose-dependent inhibitory effect on the proliferation of osteoblast-like cell lines MG63 and ROS 17/2.8, which indicate that NO may stimulate cell proliferation. On the other hand, cytokine-induced NO is reported to reduce osteoblast activity significantly in high concentration, as was evidenced by inhibition of DNA synthesis, cell proliferation, alkaline phosphatase activity, and osteocalcin production. Thus, the effect of NO on osteoblast activities is still controversial. In the present study, S-nitroso-N-acetyl-dl-penicillamine(SNAP), NO donor enhanced DNA synthesis of MC3T3-E1 in vitro. This activation seems to be mediated by NO directly because specific NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) partially attenuated the osteoblast proliferation induced by SNAP. On the other hand, the guanylate cyclase inhibitor, LY83583, failed to abolish the effect of SNAP on DNA synthesis of osteoblasts and 8-bromo cyclic guanosine 3',5'-monophosphate(cGMP), substituting for the accumulation of intracellular cGMP in osteoblasts, did not enhance the incorporation of 3H-thymidine(3H-TdR). It is, then, suggested that osteoblast proliferation might be enhanced by NO independently apart from the activation of cytoplasmic guanylate cyclase and cGMP-dependent mechanisms.

Animals↗

[A case of pulmonary inflammatory pseudotumor with hypergammaglobulinemia, elevated ANA, and uveitis].

A 63-year-old man presented with a chronic myeloproliferative disorder complicated with left pneumonia. His pneumonia was cured with antibiotics, but a nodular lesion remained in his chest radiographs together with hypergammaglobulinemia, a high titer of anti-nuclear antigen, and uveitis with secondary glaucoma. Specimens obtained by transbronchial lung biopsy showed a mixed accumulation of plasma cells, lymphocytes, and histiocytes as well as a spindle cell proliferation diagnosed as pulmonary inflammatory pseudotumor. The specimen did not show any recombination indicative of a heavy or a light chain of immunoglobulin in Southern blotting analysis. Oral prednisolone treatment improved the pulmonary nodular lesion, the abnormal laboratory data, and the uveitis. These findings suggest that much of the gammaglobulin produced by plasma cells in the inflammatory pseudotumor caused a variety of clinical symptoms.

Administration, Oral↗

[Pulmonary hyalinizing granuloma with massive infiltration of lymphocytes].

A 39-year-old man was admitted to our hospital for examination of multiple nodules and infiltrates on a chest radiograph. His chest HRCT revealed multiple nodules with or without thick- or thin-walled cavities. Specimens obtained by video-assisted thoracoscopic biopsy showed bundles of hyalinized collagen fibers, some of which contained accumulated plasma cells in the center. The nodules were surrounded by massive lymphoid cells which formed germinal centers. These findings are compatible with pulmonary hyalinizing granuloma. The lymphoid cells looked uniform in some areas and had infiltrated along the bronchioles and small vessels and into the intralobular septa in a manner resembling pulmonary lymphoma or pseudolymphoma. The findings suggested that pulmonary hyalinizing granuloma may overlap pulmonary lymphoma. The disease has shown no progression for four years although no treatment has been given.

Adult↗

[A case of spontaneous intracranial hypotension with simultaneous CSF leaks at the upper and lower thoracic levels].

We presented a patient of spontaneous intracranial hypotension (SIH), in which radionuclide cisternography demonstrated multiple CSF leaks. A 51-year-old previously healthy woman awoke with a severe headache and nausea that were almost completely relieved by lying flat (day 1). The headache was not relieved by analgesics. On day 10, she visited our clinic. Neurological examination showed no abnormalities. A lumbar puncture revealed an opening pressure of 50 mmH2O, protein level of 64 mg/dl, 21 erythrocytes 21/microliter, and 4 lymphocytes/microliter. Cranial MRI on day 11 with gadolinium infusion demonstrated diffuse thickening and enhancement of the meninges. No signs of venous sinus thrombosis were identified. There was no downward displacement of the cerebellar tonsils. Indium-111 radionuclide cisternography demonstrated early accumulation of the tracer in the urinary bladder and CSF leakage at the upper thoracic level on the left side, at the lower thoracic level on both sides, and at the lumbar level. It is noteworthy that the scintigram taken 4 hours after tracer injection demonstrated CSF leakage at the injection site but not in the upper thoracic area. The patient kept sitting for about 20 minutes just before the images were obtained. Spinal MRI did not show meningeal diverticulum and epidural fluid collection. Ten days of bed-rest and transfusion failed to relieve the headache. Epidural patching with 7 ml of autologous blood performed at the Th2/3 interspace partially relieved the headache. Five days later, a second epidural patching was performed at Th11/12, which was slightly effective. A third epidural patching at L3/4 was ineffective. On day 32, a fourth epidural patching was performed at Th1/2 while the patient was lying down on her left side. The postural headache disappeared. Repeated cranial MRI with gadolinium infusion performed on day 47 showed resolution of the abnormal findings. To our knowledge, this is the second case report of SIH with double CSF leaks. To localize multiple leaks, radionuclide cisternography should be performed with a patient in various positions just before images are obtained.

Cerebrospinal Fluid↗

SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility.

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced signaling, its biological role has remained unknown. Fibroblasts homozygous for expression of an SHPS-1 mutant lacking most of the cytoplasmic region of this protein exhibited increased formation of actin stress fibers and focal adhesions. They spread more quickly on fibronectin than did wild-type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion-induced activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras-extracellular signal-regulated kinase signaling pathway and of c-Jun N-terminal kinases by growth factors was either unaffected or enhanced in the mutant fibroblasts. These results demonstrate that SHPS-1 plays crucial roles in integrin-mediated cytoskeletal reorganization, cell motility and the regulation of Rho, and that it also negatively modulates growth factor-induced activation of mitogen-activated protein kinases.

Animals↗

Alexia caused by a fusiform or posterior inferior temporal lesion.

We evaluated the alexia and agraphia of three patients with different lesions using Japanese kanji (morphograms) and kana (phonograms) and made a lesion-to-symptom analysis. Patient 1 (pure alexia for both kanji and kana and minor agraphia for kanji after a fusiform lesion) made more paragraphic errors for kanji, whereas patient 2 (alexia with agraphia for kanji after a posterior inferior temporal lesion) showed severe reading and writing disturbances and more agraphic errors for kanji. Brodmann Area 37 was affected in both patients, but in patient 2 the lesion was located lateral to that in patient 1. Patient 3 showed agraphia without alexia after restricted lesion to the angular gyrus. We believe that pure alexia (patient 1) results from a disconnection between the medial fusiform gyrus and posterior inferior temporal area (the lateral fusiform and inferior temporal gyri), whereas alexia with agraphia for kanji (patient 2), corresponding to lexical agraphia in Western countries, results from damage to the posterior inferior temporal area, in which whole-word images of words are thought to be stored. Furthermore, restricted lesion in the angular gyrus (patient 3) does not produce alexia; the alexic symptom of "angular" alexia with agraphia may be the result of damage to the adjacent lateral occipital gyri.

Aged↗

Characterization of 5'-flanking region of human MRP3.

We previously cloned MRP3, which is responsible for the cellular extrusion of organic anions, as an inducible transporter in the liver under cholestatic conditions. In the present study, we investigated the mechanism for the expression of human MRP3. The cap site hunting method revealed that the transcription starts at -25 and -27 nt upstream of the initiation codon. Luciferase assay with a series of truncated 5'-flanking regions indicated that the region from -127 to -23 nt is important for MRP3 expression. Moreover, carrying out a gel shift assay indicated that Sp1 binds to the sequence between -92 and -58 nt. Collectively, it was demonstrated that human MRP3 is under the control of TATA-less promoter and Sp1 binding sites may be involved in the transcription.

5' Untranslated Regions↗