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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 469 records · Page 26Linked to original sources

Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy.

We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress-induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor-specific antagonist), and PD123319 (a type 2 receptor-specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress-induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.

Angiotensin II↗

Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes.

We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90rsk). To clarify the signal transduction pathways from external mechanical stress to nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK), MAPKs, and p90rsk in neonatal rat cardiac myocytes. Mechanical stretch transiently increased the activity of MAPKKKs. An increase in MAPKKKs activity was first detected at 1 min and maximal activation was observed at 2 min after stretch. The activity of MAPKK was increased by stretch from 1-2 min, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10 approximately 30 min after stretch, respectively. Raf-1 kinase (Raf-1) and (MAPK/extracellular signal-regulated kinase) kinase kinase (MEKK), both of which have MAPKKK activity, were also activated by stretching cardiac myocytes for 2 min. The angiotensin II receptor antagonist partially suppressed activation of Raf-1 and MAPKs by stretch. The stretch-induced hypertrophic responses such as activation of Raf-1 and MAPKs and an increase in amino acid uptake was partially dependent on PKC, while a PKC inhibitor completely abolished MAPK activation by angiotensin II. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1 and MEKK, MAPKK, MAPKs and p90rsk, and that angiotensin II, which may be secreted from stretched myocytes, may be partly involved in stretch-induced hypertrophic responses by activating PKC.

Amino Acid Sequence↗

[Long term remission following relapsed CNS lymphoma].

A case of NHL which has been in long-term remission following vigorous treatment for CNS relapse with intrathecal administration of Ara-C and focal irradiation to the brain is presented. The patient was a 61-year-old man, who was successfully treated with CHOP followed by MACOP-B for diffuse large cell NHL in 1988. Five months later he was admitted to our hospital because of loss of visual acquity and numbness in the right upper and lower extremities. The presence of lymphoma cells in CSF, abnormal shadow in the left frontal lobe on a cranial CT scan and MRI scan, and positive Ga scintigraphy yielded a diagnosis of CNS relapse of NHL. Twenty one whole brain and additional 1.0Gy to the left frontal lobe of irradiation were performed. Eight days later the left tumor disappeared. Neurological remission was obtained and has continued until now.

Antineoplastic Combined Chemotherapy Protocols↗

[Neuron specific enolase-producing IgD multiple myeloma with high serum amylase activity].

A 68-year-old man who was admitted to our hospital because of general fatigue and anorexia. He was diagnosed as suffering from neuron specific enolase (NSE)-producing IgD-lambda type multiple myeloma with high activity of serum amylase, based on the detection of monoclonal IgD-lambda M-protein in the serum and urine, markedly high activities of salivary-type amylase and NSE in the serum, and immunohistochemical evidence of NSE and IgD in the myeloma cells. After two courses of alpha-IFN and VMCP chemotherapy, serum IgD, amylase and NSE decreased to normal levels. These observations indicate that NSE was ectopically produced by myeloma cells.

Aged↗

Pancreatic arteriovenous malformation involving adjacent duodenum in a patient with gastrointestinal bleeding.

Gastrointestinal bleeding caused by arteriovenous malformation (AVM) of the pancreas is extremely rare. A 56-yr-old man with AVM of the head of the pancreas who was presented with recurrent episode of melena is described herein. The preoperative diagnosis was confirmed by angiographic study, and he was successfully treated with pancreatoduodenectomy. Histological examination of the resected specimen revealed pancreatic AVM involving the adjacent duodenal wall.

Arteriovenous Malformations↗

Acute aortic dissection, aortic insufficiency, and a single coronary artery in a patient with Turner's syndrome.

A rare case of acute aortic dissection and aortic regurgitation in a patient with Turner's syndrome is reported. A 25-year-old woman with a history of Turner's syndrome presented to our hospital with complaints of chest pain and dyspnea. Emergent surgery was performed after chest roentgenography and two-dimensional echocardiography. Intraoperatively, the patient was found to have a single coronary artery and a bicuspid aortic valve. The patient was treated successfully with a composite graft consisting of a 24 mm woven dacron graft, a 21 mm St. Jude Medical aortic prosthetic valve, and an equine pericardial skirt. The composite graft was inverted into the ascending aorta and connected to a small coronary artery graft. The patient's postoperative course was uneventful. A cardiac catheterization was performed postoperatively and revealed a competent anastomotic site and no evidence of aortic regurgitation. We provide a brief review of coronary anomalies and aortic diseases associated with patients with Turner's syndrome. The most commonly associated complications include coarctation of the aorta and bicuspid aortic valve disease. The incidence of coronary anomalies in patients with Turner's syndrome is maybe rare.

Acute Disease↗

[A case report of corrected TGA with ventricular septal defect, tricuspid valve regurgitation and atrioventricular block].

A 61-year-old woman was admitted for heart failure. She was diagnosed as corrected TGA with tricuspid regurgitation, perimembronous ventricular septal defect and atrioventricular block by echocardiography and cardiac catheterization. We chose tricuspid valve replacement with preservation of valve leaflet and subvalvular apparatus, direct closure of ventricular septal defect and implantation of permanent pacemaker (myocardial lead). Although IABP was needed for 24 hours, after that postoperative course was uneventful. It is preferable that tricuspid valve replacement with preservation of valve leaflet and subvalvular apparatus is applied to similar adult cases from standpoint of morphological structure.

Cardiac Pacing, Artificial↗

Interaction of cardiac myocytes and non-myocytes in mechanical stress-induced hypertrophy.

It is known that mechanical stress directly changes the conformation of the functional proteins, or directly activates enzymes such as phospholipase in the plasma membrane. The integrin-cytoskeleton complex may be an alternative candidate structure for a mechanoreceptor and a transducer. The cytoskeleton has been also shown to play an important role in secretion. Mechanical stress may stimulate the secretion of some cytokines or angiotensin II, which may generate multiple intracellular signals as a secondary event. External stimuli are generally transduced into the nucleus through the activation of protein kinase cascade. Stretching of cardiac myocytes stimulates the activity of PKC, Raf-1 kinase, MAP kinase kinase. MAP kinase and S6 kinase. In cardiac myocytes, mechanical stress directly induces gene expression as well as protein synthesis. Immediate early genes are first induced, and then fetal-type genes are reinduced. Both in hypertrophied hearts and in the experimental model of cardiac hypertrophy induced by pressure overload. Ca(2+)-ATPase content of cardiac myocytes is depressed. Reduced function of sarcoplasmic reticulum causes insufficient decrease of intracellular calcium in diastole and induces slowing of ventricular relaxation. In the interstitium of pressure overloaded hearts, the accumulation of collagen fiber is increased. The abnormal deposit leads to increased chamber stiffness and diastolic dysfunction. Furthermore, TGF-beta and tissue renin-angiotensin system are up-regulated in pressure overloaded hearts, both of which accelerate the interstitial fibrosis.

Animals↗

[Molecular biological analysis of hereditary thrombophilia--genetic characterization of protein S deficiency].

Protein S is a plasma glycoprotein, which functions as a cofactor for activated protein C in the protein C pathway and also directly inhibits factors Va and Xa, independently of protein C. In plasma, protein S circulates as a free molecule (40%) or in a complex with C4b-binding protein (60%). Only a free protein S acts as an anticoagulant and its activity is lost by binding to C4b-binding protein. The physiological importance of protein S has been established by observations in patients with hereditary protein S deficiency who have an increased risk of developing thrombosis. Several previous studies reported that hereditary protein S deficiency was as common as protein C deficiency and that approximately 5% of hereditary thrombophilia was caused by protein S deficiency. But molecular biological analysis of protein S deficiency is not as advanced as protein C deficiency because the genetic characterization of protein S deficiency is limited by the presence of the inactive pseudogene that is highly homologous to the active true gene. Only a few previous studies have examined the genetic features of hereditary protein S deficiency. Further investigation is needed to characterize the pathophysiology and molecular basis of hereditary protein S deficiency.

Humans↗

[Normal-sized ovary carcinoma syndrome: histopathological analysis of 14 cases].

Fourteen cases of "normal-sized ovary carcinoma syndrome" (diffuse metastatic malignant disease of the abdominal cavity of the female, with normal-sized ovaries, with no origin assigned definitively by intraoperative or preoperative evaluation, Feuer et al., 1989) were analyzed histologically, histochemically, immunohistochemically and ultrastructurally. Through these studies, 14 cases were divided into 11 primary peritoneal tumors (4 diffuse malignant mesotheliomas and 7 serous surface papillary carcinomas) and 3 metastatic peritoneal tumors (2 ovarian tumors and 1 appendicular tumor). To distinguish serous surface papillary carcinomas from epithelioid diffuse malignant mesotheliomas, examinations such as hyaluronidase digestion test, electron microscopy, and immunohistochemical studies using antibodies for Ber-EP4 and Vimentin were found to be useful. In order to achieve an accurate prognosis of normal-sized ovary carcinoma syndrome, it seems necessary for us to accumulate more information on this syndrome.

Carcinoma, Papillary↗

[Quantification of renal function with 99mTc-MAG3--quantification of tubular extraction rate using Bubeck's method].

99mTc-mercaptoacetyltriglycine (MAG3) is a new agent for dynamic renal scintigraphy. It provides not only superior quality of imaging to conventional agents such as 131I-orthoiodohippurate or 99mTc-demethylenetriaminepantaacetic acid but also quantification of renal function as do the latter agents. The aim of the present study was to evaluate the value of the tubular extraction rate (TER) using 99mTc-MAG3 calculated by Bubeck's method, a simple technique for quantifying renal function. In 31 patients with renal disorders, we compared the TER thus obtained with laboratory data, plasma paraaminohippurate clearance, effective renal plasma flow calculated by Tauxe's method, and plasma 99mTc-MAG3 clearance calculated according to the two-compartment model. TER was easily applicable in clinical settings, and showed close parallels with the other indexes of renal function. We believe, therefore, that it can serve as a useful parameter of renal function.

Adult↗

A quantitative protein S deficiency associated with a novel nonsense mutation and markedly reduced levels of mutated mRNA.

A 50-year-old Japanese man who had experienced recurrent episodes of venous thrombosis was found to have a hereditary protein S deficiency. The amount of total protein S antigen in plasma was reduced by approximately 50% in the patient and his two sons. DNA sequence analysis revealed a novel nonsense mutation, TAG for Gln 522 (CAG), in exon 14 of the protein S gene. Family studies performed by mutagenic PCR followed by restriction enzyme digestion showed that the proband and his two sons were heterozygous for this mutation. An mRNA-based analysis indicated that transcripts of the mutated allele were markedly reduced in the platelets of the affected individuals. Immunoblot analysis failed to detect the truncated mutant of protein S in the plasma or platelets of affected members. Our results demonstrated that this novel nonsense mutation was responsible for the quantitative deficiency of protein S.

Amino Acid Sequence↗

[Carrier detection and prenatal diagnosis for hemophilia A using the inversion analysis of the factor VIII gene].

Hemophilia A is an X-linked hemorrhagic disorder caused by heterogeneous mutations in the factor VIII gene. Recently, it was reported that approximately 50% of the cases of severe hemophilia A may be caused by a common inversion in the factor VIII gene. In this study, we analyzed 33 Japanese patients with severe hemophilia A for the presence of this inversion mutation using the non-RI Southern blotting, and detected inversion mutations of the factor VIII gene in 12 patients (36.4%). We also showed that the inversion analysis of the factor VIII gene was useful for carrier detection and prenatal diagnosis in a hemophilia A family, which we had not been able to diagnose by the analysis of restriction fragment length polymorphisms (RFLPs) of the factor VIII gene. The detection of inversion mutations in the factor VIII gene using non-RI Southern blotting analysis appears to be very useful for the genetic counseling for severe hemophilia A.

Adult↗

Synthesis of oligopeptides as polynucleotide analogs.

Several dipeptides which have a nucleic acid base in their side chains were designed as water-soluble nucleotide analogs. Amino acids having a uracil or adenine moiety in the gamma-position were synthesized and were connected with another amino acid (spacer) to afford dipeptides. The oligopeptides were prepared from the dipeptides as monomer units. Although all the oligopeptides having uracil moieties examined were water-soluble as expected, these exhibited no hypochromic effect with poly A or poly dA. Contrary, the oligopeptides with adenines exhibited large hypochromicity (ca. 30%) base-specifically with poly dT or poly U.

Molecular Structure↗

Over-expression of membrane-bound cytochrome c-551 from thermophilic Bacillus PS3 in Bacillus stearothermophilus K1041.

Cytochrome c-551 is a lipoprotein of about 10500 Da, found in thermophilic Bacillus PS3 grown under air-limited conditions. An expression vector was constructed from a structural gene of PS3 cytochrome c-551, synthetic oligonucleotide as a promoter for Bacillus stearothermophilus and a shuttle vector for Escherichia coli and B. stearothermophilus. The transformed cells of B. stearothermophilus K1041 expressed cytochrome c-551 as much as 5 nmol/mg membrane protein. The effects of over-expression on the host cells are analyzed; a slightly slower growth rate and an increased synthesis of cytochrome oxidase (about twofold) occurred. Over-expressed (4-10-fold) cytochrome c-551 were purified and its properties were examined to know whether the protein is processed as in PS3 cells grown under air-limited conditions. The molecular mass determination and treatment with Rhizopus lipase suggested that the same processes, cleavage of signal peptidase, blocking of the N-terminal group and acylation of glycerol residue by two fatty acids, took place in the over-expression system. Fatty acylation seems useful for the cytochrome c to be effectively oxidized.

Acylation↗

Energy migration in allophycocyanin-B trimer with a linker polypeptide: analysis by the principal multi-component spectral estimation (PMSE) method.

Energy migration processes in allophycocyanin-B trimer with a linker polypeptide were analyzed using the principal multi-component spectral estimation (PMSE) method, which does not require assumption of component number, decay function, or the spectral band shape. We determined the number of spectral components showing independent kinetic behavior by the eigen-value of an auto-correlation matrix, and further the spectra of the components and their rise and decay curves. Two decay components were resolved at 20 degrees C: one corresponded to the decay of one type of beta-84 chromophore, and the other to the decay from the thermally equilibrated state between another type of beta-84 chromophore and the alpha-allophycocyanin B chromophore. An additional slow decay process was resolved at -196 degrees C. We also compared the component spectra obtained using the PMSE method with the decay-associated spectra obtained using the global analysis.

Cyanobacteria↗