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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 217 records · Page 12Linked to original sources

[Bronchiolitis obliterans and no radiographic abnormalities in a patient with rheumatoid arthritis].

A 53-year-old woman was given a diagnosis of rheumatoid arthritis in 1988, and begun treatment with D-penicillamine in September 1992. She noticed dry coughing and exertional dyspnea that began in April 1993. Chest X-ray and CT films revealed no abnormal opacities. However, bronchiolitis obliterans was suspected because of a low FEV1% (23%). Examination of specimens obtained by thoracoscopic lung biopsy revealed constrictive obliteration by granulation tissue in proximal bronchioles and follicular bronchiolitis. Alveoli and respiratory bronchioles were intact. After corticosteroid and cyclophosphamide pulse therapy, FEV1% increased to 35%. At the time of this writing she was alive 2.5 years after hospitalization.

Anti-Inflammatory Agents↗

Suppression of Ki-ras p21 levels leading to growth inhibition of pancreatic cancer cell lines with Ki-ras mutation but not those without Ki-ras mutation.

Ki-ras point mutation characteristically occurs frequently in human pancreatic cancer. To clarify the effect of antisense Ki-ras RNA on various pancreatic cancer cell lines, a plasmid expressing an antisense Ki-ras gene fragment (AS-K-ras-LNSX) was transduced into seven human pancreatic cancer cell lines (AsPC-1, MIA PaCa-2, PANC-1, PSN-1, BxPC-3, Hs 700T, and Hs 766T) by liposome-mediated transfection. Western blot analysis showed that transfection of AS-K-ras-LNSX led to a significant reduction in the amounts of Ki-ras p21 protein in all the pancreatic cancer cell lines except BxPC-3. The growth of pancreatic cancer cell lines having Ki-ras point mutations (AsPC-1, MIA PaCa-2, PANC-1, and PSN-1) was suppressed after transduction of AS-K-ras-LNSX, whereas the effect of the antisense construct on the growth was not significant in cell lines with a wild-type Ki-ras gene (BxPC-3, Hs 700T, and Hs 766T). These results suggest that the pancreatic cancer cells with activated Ki-ras depend heavily on a Ki-ras p21-mediated growth signal pathway for their growth because they were far more susceptible to the suppression of the Ki-ras p21 protein than the cells with wild-type Ki-ras. The remarkably increased dependence of the cancer-cell growth circuitry on one or a few crucial regulatory molecules may thus be a common feature of the cancer cells and implies a novel rationale for the targeting of cancer therapy.

Cell Division↗

[Surgical relief of airway obstruction from a double aortic arch associated with corrected transposition of the great arteries, pulmonary atresia and bilateral patent ductus arteriosus in a neonate].

A rare 20-day-old male with double aortic arch, corrected transposition of the great arteries (cTGA), pulmonary atresia and bilateral patent ductus arteriosus (PDA) was transported to our institute because of severe respiratory dysfunction and cyanosis. The patient had been already intubated and ventilated on respirator. A echocardiography and cine-angiography demonstrated that the both sides aortic arch had almost identical sizes, originating common carotid arteries and subclavian arteries and PDAs respectively, and the descending aorta located on the left side of the mid-line. At the first surgery, the distal of the right aortic arch was divided just proximal to the descending aorta after complete tissue dissection around the arch. The divided right sided aortic arch was mobilized from posterior to anterior aspect of the bronchus. Then the right subclavian artery was divided and an original Blalock-Taussig shunt was employed. The right sided PDA was ligated. After the first surgery, respiratory dysfunction lasted for weeks mainly because of the PGE1 dependent left sided PDA. At the second surgery, left sided modified Blalock-Taussig shunt was constructed and the left sided PDA was divided. These procedures resulted in stable respiratory status and oxygen saturation. The patient was extubated three days later and now in satisfactory clinical condition.

Abnormalities, Multiple↗

[Surgical treatment of double outlet left ventricle].

Double outlet left ventricle (DOLV) is an uncommon congenital cardiac defect which was first reported by Sakakibara and associates. We studied anatomical aspects relevant to surgical repair in our 4 cases and additional 28 cases which had been reported on the literatures. The locations of ventricular septal defect (VSD) were subaortic in 20 cases, subpulmonary in 7, doubly-committed in 2 and unknown in 2. The positions of the aorta relative to the pulmonary artery were right or left anterior oblique in 11 cases, right or left side-by-side in 9, right or left posterior oblique in 10 and unknown in 3. The definitive surgery included Rastelli type operation in 18 cases, right ventricular outflow tract repair with closure of VSD in 6, intraventricular conduit repair in 4 and Fontan type operation in 4. In regard to the selection of the procedure, the size of right ventricle, the presence of pulmonary stenosis, the location of VSD and the relationship of the great arteries are very important. Although most of the patients underwent the Rastelli type operation, the right ventricular outflow tract reconstruction or intraventricular conduit repair could be adopted particularly in patients with posterior oblique position of the aorta relative to the pulmonary artery or subpulmonary VSD.

Adolescent↗

[A case of modified Fontan operation with reconstruction of the nonconfluent pulmonary artery].

A three-year-old girl with complex cardiac anomalies and right isomerism successfully underwent a modified Fontan procedure and reconstruction of the nonconfluent pulmonary artery using autologous tissues. These cardiac anomalies included single right ventricle, atresia of the pulmonary trunk with nonconfluent pulmonary artery, atrial septal defect, common atrioventricular valve, bilateral PDAs, and bilateral SVCs. Preoperative cardiac catheterization showed elevated pulmonary artery pressure (mean pressure of 24 mmHg) and a small orifice of common pulmonary vein chamber. Pulmonary arteriographies showed balanced development of the branches. Indication for Fontan procedure was finally determined by measurement of the pulmonary artery and vein pressures and pulmonary vascular resistance before the cardiopulmonary bypass in the operation. Nonconfluent pulmonary artery was reconstructed by direct anastomosis of the right and left branches in the posterior aspect and enlarged with autologous pericardium patch. Intracardiac anomalies were repaired by enlargement of common pulmonary vein orifice (from 5 mm to 15 mm in diameter) and right atrial oblique partition. Furthermore, Fontan circulation was established by pulmonary artery angioplasty, direct anastomosis of left SVC to left pulmonary artery and direct anastomosis of right atrial appendage to pulmonary artery. Postoperative clinical course was uneventful, and cardiac catheterization showed mean right atrial pressure of 14 mmHg, cardiac index of 3.5 l/min/m2, and no pressure gradient at the site of reconstruction of the pulmonary artery.

Child, Preschool↗

[Improving surgical results for cardiovascular anomalies in neonates].

The surgical results for congenital cardiovascular anomalies in neonates between August 1987 and July 1997 were reviewed. Two hundred thirty-four neonates underwent the corrective surgery with the use of cardiopulmonary bypass (CPB) for the cardiac anomalies including transposition of the great arteries (d-TGA) (157 patients), total anomalous pulmonary venous connection (TAPVC) (44 patients), cardiac defects with the aortic arch anomalies (11 patients), and others (22 patients), with an early mortality rate of 12%. The survival rates through the arterial switch operation for d-TGA and correction for TAPVC in 30 days were satisfactory (92% and 89%, respectively). The early mortality rate of palliative surgery done without CPB in 115 neonates due to aortic arch anomalies, pulmonary outflow tract obstruction, or pulmonary hypertension was low (6%). In contrast with these results, the outcome of palliative surgery using CPB for hypoplastic left heart syndrome, the aortic arch anomalies with subaortic stenosis, or TAPVC in asplenia hearts was poor, with the surgical mortality of 80%.

Aortic Coarctation↗

Cardiovascular effects of an ultra-short-acting nitric oxide-releasing compound, zwitterionic diamine/NO adduct, in dogs.

BACKGROUND: This study was conducted to clarify the cardiovascular effects of a new NO-releasing compound, NOC-7, and to compare it with other nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. METHODS AND RESULTS: A bolus injection of NOC-7 decreased mean aortic blood pressure in a dose-dependent manner. The onset was rapid and the recovery quick. Continuous infusion of NOC-7 decreased mean aortic pressure from 115 +/- 3.9 to 84 +/- 2.9 mm Hg and infusion of SNP, from 118 +/- 3.8 to 87 +/- 3.1 mm Hg. The optimum doses of NOC-7 and SNP were determined to be 2.73 +/- 0.77 and 11.5 +/- 6.1 micrograms.kg-1.min-1, respectively. During infusion of NOC-7, heart rate and cardiac output were increased (P < .05), pulmonary artery pressure was not changed, and systemic and pulmonary vascular resistances were decreased (P < .05). Electromagnetic flowmetry showed that portal venous and internal carotid arterial blood flow were increased (P < .05) and that hepatic and renal arterial blood flows were not changed. These hemodynamic changes during NOC-7 infusion were similar to those with SNP. The plasma level of NO2-/NO3 did not change, but methemoglobin increased slightly (P < .05). Comparison between hypotensive responses before and after a 3.5-hour infusion of NOC-7 or nitroglycerin showed that acute tolerance developed to nitroglycerin but not to NOC-7. CONCLUSIONS: The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.

Animals↗

Growth of the neopulmonary valve annulus after arterial switch operation in transposition of the great arteries.

BACKGROUND: It is known that supravalvular pulmonary artery stenosis can occur in patients with d-transposition of the great arteries (TGA) after arterial switch operation (ASO). However, little is known about the growth of the neopulmonary valve annulus after the ASO. This study investigated the growth potential of the neopulmonary (old aortic) valve annulus. METHODS AND RESULTS: Annular diameters of the old aortic and neopulmonary valve were measured from cineangiograms in patients who underwent cardiac catheterizations both before and > 1 year after the ASO. Of 71 patients, 13 (18%) had either a small annulus (< 70% of the expected normal value) or no significant growth of the neopulmonary annulus after the ASO, and 4 (6%) had a pressure gradient of > 30 mm Hg across the valve. The small annulus or no growth of the neopulmonary valve was more frequent in patients with a history of pulmonary artery banding. After the ASO, the valve diameter in patients with a ventricular septal defect was 80 +/- 15% of normal (n = 24), and the value was significantly less than in patients with an intact ventricular septum (91 +/- 11%, n = 47). In all patients with an intact ventricular septum who underwent the one-stage ASO, the valve diameters before and after the ASO were within normal limits, and a significant increase in the pulmonary valve annulus was observed. CONCLUSIONS: These data indicate that not only supravalvular pulmonary stenosis but also pulmonary valvular stenosis due to a small annulus can occur in TGA, especially in patients with a history of pulmonary artery banding and in patients with ventricular septal defect.

Humans↗

Use of von Willebrand factor promoter to transduce suicidal gene to human endothelial cells, HUVEC.

Angiogenesis is an essential component of multifactorial carcinogenesis and thus a potential target of therapeutic intervention. To develop a novel cancer gene therapy strategy based on suppression of tumor angiogenesis, we examined the feasibility of targeting and preferential killing of proliferating endothelial cells by use of the von Willebrand factor (vWf) promoter and herpes simplex virus thymidine kinase gene (HSV-TK). Based on previous reports on the vWf promoter, we tested two putative vWf promoter regions. The luciferase assay showed that the shorter region, which encompasses most of the first noncoding exon, had stronger activity in endothelial cells. Although the promoter activity was low when employed as an internal promoter for retroviral and adenoviral vectors, endothelial cell specificity was suggested; the promoter, when used to drive the HSV-TK gene, could preferentially suppress endothelial cell growth in the presence of prodrug ganciclovir, suggesting the feasibility of designing an anti-angiogenesis gene therapy using the vWf promoter and the suicide gene/prodrug strategy.

Cell Division↗

Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family.

The Wnt genes, encoding structurally-related secreted glycoproteins, are implicated in mammary carcinogenesis induced by mouse mammary tumor virus. In search of the Wnt gene(s) expressed in human gastric cancer, a WTGC1 cDNA fragment sharing 66.9% amino-acid homology with human and mouse Wnt-2 was isolated by degenerate polymerase chain reaction. The human gene corresponding to WTGC1 was designated as Wnt-13 and overlapping Wnt-13 cDNAs were cloned. Nucleotide sequence analysis indicated that the Wnt-13 gene encodes the protein of 372 amino acids, including a signal peptide, two potential N-glycosylation sites and 24 cystein residues highly conserved among members of the Wnt gene family. The Wnt-13 mRNA of 2.5 kb in size was detected in heart, brain, placenta, lung, prostate, testis, ovary, small intestine and colon of adult human and also in brain, lung and kidney of fetal human. Among various cancer cell lines, the Wnt-13 mRNA was detected in HeLa (cervical cancer), MKN28 and MKN74 (gastric cancer). The Wnt-13 gene has been mapped to human chromosome 1p13. These results suggest that the Wnt-13 gene may be involved in normal human development or differentiation as well as in human carcinogenesis.

Adult↗

HST-1/FGF-4 stimulates proliferation of megakaryocyte progenitors synergistically and promotes megakaryocyte maturation.

Megakaryocyte (MK) development is dependent on the complex interaction of MK progenitors, various cytokines and stromal elements. We previously reported that an injection of replication-deficient adenovirus containing HST-1/FGF-4 cDNA (Adex1HST-1) into mice caused a twofold increase in peripheral platelet count for 30 days without any other hematological or histological abnormality. In the present study using Adex1HST-1-infected human megakaryocytic Dami cells, we demonstrated for the first time that HST-1/FGF-4 promoted MK maturation, inducing increases in DNA ploidy, cytoplasmic and membrane maturation, and platelet-like particle release. Moreover, HST-1/FGF-4 acted on megakaryocytic cells to induce secretion of IL-6 and TNF-alpha, and increased adhesion of megakaryocytic cells to human endothelial cells primarily via VLA-4 and LFA-1 molecules; both mechanisms have been shown to lead to MK maturation. We also showed that HST-1/FGF-4 stimulates the proliferation of MK progenitors not alone but synergistically with IL-3 via IL-6 and with c-mpl ligand (thrombopoietin) not via IL-6. This result supports the hypothesis of the presence of two distinct populations of MK progenitors: IL-3-dependent and Tpo-dependent. All these results suggest that HST-1/FGF-4 can regulate MK development not only as an MK potentiating factor, but also as an inducer of cytokine secretion from MK, and as a modulator of adhesive interactions with endothelial cells.

Adenoviruses, Human↗

Simultaneous determination of twelve benzodiazepines in human serum using a new reversed-phase chromatographic column on a 2-microns porous microspherical silica gel.

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of twelve frequently used benzodiazepines (BZPs) (bromazepam, clonazepam, chlordiazepoxide, estazolam, etizolam, flutazoram, haloxazolam, lorazepam, nitrazepam, oxazolam, triazolam and diazepam, internal standard) by using commercially available 2 or 5 microns particle size reversed-phase columns and a microflow cell-equipped ultraviolet detector. The separation was achieved using a C18 reversed-phase column (condition 1: 100 x 4.6 mm I.D., particle size 2 microns, TSK gel Super-ODS: conditon 2: 100 x 4.6 mm I.D., particle size 5 microns, Hypersil ODS-C18). The mobile phase was composed of methanol-5 mM NaH2PO4 (pH 6) (45:55, v/v), and the flow-rate was 0.65 ml/min (condition 1 and 2). The absorbance of the eluent was monitored at 254 nm. Retention times under condition 1 were shorter than those of condition 2. When the twelve benzodiazepines were determined, sensitivity and limits of quantification were about four to ten times better under condition 1 than under condition 2. The rate of recovery and linearity in condition 1 were approximately the same as those in condition 2. These results show that a new ODS filler with a particle size of 2 microns was more sensitive, provided better separation and was more rapid than that with conventional ODS filler.

Anti-Anxiety Agents↗

Overexpression of bone morphogenic protein (BMP)-4 mRNA in gastric cancer cell lines of poorly differentiated type.

Gastric cancer is classified as the poorly differentiated and the well differentiated type, depending on its histological, biological, and genetic characteristics. Bone metastasis is more frequently detected in the poorly differentiated type than in the well differentiated type. The prognosis of patients with diffuse osteoplastic bone metastasis of gastric cancer is extremely poor. In this study, we examined the mRNA expression of bone morphogenic proteins (BMPs) in seven gastric cancer cell lines: OKAJIMA, TMK1, MKN45, and KATO-III derived from the poorly differentiated type; and MKN7, MKN28, and MKN74, derived from the well differentiated type. BMP-2 was expressed only in TMK1. BMP-4 mRNA was over-expressed in OKAJIMA, MKN45 and KATO-III, weakly expressed in MKN7, MKN28, and MKN74, but was not expressed in TMK1. Although the biological roles of BMP-2 and BMP-4 expression in gastric cancer remain to be elucidated, these results indicate that BMP-4 mRNA is preferentially overexpressed in the poorly differentiated type of gastric cancer.

Blotting, Northern↗

Characterization of subtypes of gamma-aminobutyric acid receptors in an Ascaris muscle preparation by binding assay and binding of PF1022A, a new anthelmintic, on the receptors.

We examined the effect of PF1022A, one of the gabergic anthelmintics newly developed in Japan, on gamma-aminobutyric acid (GABA) receptors using a radioligand binding technique in isolated membrane preparations of the nematode Ascaris suum. Membrane protein was prepared from the homogenate of somatic muscle cells after ultracentrifugation. In addition to the basic binding of [2,3-3H-(N)]-GABA, the radioligand [methyl-3H]-bicuculline is used to identify the GABAA receptor, whereas [butyl-4-3H]-baclofen is employed for GABAB receptor sites. The dissociation constants (Kd values) and the maximal numbers of binding sites (Bmax values) from Scatchard plotting for GABA receptors are close to those obtained in mammalian brain. PF1022A displaced in a concentration-dependent way the binding of [2,3-3H(N)]-GABA and [methyl-3H]-bicuculline as did other specific gabergic agents. In addition, PF1022A decreased the binding of [butyl-4-3H]-baclofen at a higher concentration, although this binding did not represent GABAB sites. In a comparison of the inhibition constants (Ki values) of PF1022A with those of other agents, it is conclusive that PF1022A bound with GABA receptors. A direct effect of PF1022A on GABA receptors can thus be postulated.

Animals↗

Direct cardiotoxic effects of cocaine and cocaethylene on isolated cardiomyocytes.

We investigated the cardiotoxic effects of cocaine and cocaethylene on the Ca2+ flux responsible for excitation-contraction coupling in isolated ventricular rat myocytes. We simultaneously measured intracellular Ca2+ transients and cell length in isolated cardiac myocytes loaded with a fluorescent Ca2+ indicator, indo-1, during electrical field stimulation at 1 Hz. The cell length was estimated by video dimension analysis. We also measured the activities of Ca2+ ATPase and Ca2+ release channels of cardiac sarcoplasmic reticulum membrane vesicles. Both cocaine and cocaethylene produced significant decreases in both peak intracellular Ca2+ and the cell-contraction rate in a dose-dependent manner. The K0.5 for the reduction of peak intracellular Ca2+ was 157.5 microM for cocaine, but 90.0 microM for cocaethylene. Both cocaethylene and cocaine inhibited neither Ca2+ ATPase nor Ca2+ release channel activity. These results demonstrate that cocaethylene has a more potent direct negative inotropic action on cardiomyocytes, without preventing Ca2+ flux through the cardiac sarcoplasmic reticulum membrane.

Animals↗

Myocardial and vascular effects of efonidipine in vitro as compared with nifedipine, verapamil and diltiazem.

1. Effects of efonidipine on isolated myocardial and aortic preparations were compared with those of nifedipine, verapamil and diltiazem. 2. All drugs produced concentration-dependent negative chronotropic effects on isolated guinea-pig atrial preparations. The potency order was efonidipine > or = nifedipine > diltiazem > or = verapamil, EC30 values being 3.08 x 10(-8)M, 3.48 x 10(-8)M, 1.27 x 10(-7)M and 1.47 x 10(-7)M, respectively. 3. Nifedipine, verapamil and diltiazem produced concentration-dependent negative inotropic effects on isolated guinea-pig left atrial preparations. The potency order was nifedipine > verapamil > diltiazem, EC30 values being 4.94 x 10(-8)M, 1.49 x 10(-7)M and 8.03 x 10(-7)M, respectively. Efonidipine, even at 1 microM produced no inotropic effect: 10 microM efonidipine decreased the contractile force by about 20%. 4. All drugs concentration-dependently attenuated the KCl-induced contraction of isolated rat aortic ring preparation. The potency order was nifedipine > efonidipine > verapamil > diltiazem, EC30 values being 2.98 x 10(-9)M, 1.24 x 10(-8)M, 3.96 x 10(-8)M and 2.13 x 10(-7)M, respectively. 5. Thus, efonidipine was demonstrated to be a potent vasodilator with negative chronotropic but minimal negative inotropic activity, which may be of benefit in the treatment of cardiovascular disorders.

Animals↗