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Biomedical subjects

T Sano

Publications and source records attributed to T Sano.

At least 523 records · Page 29Linked to original sources

Impaired induction of prolactin secretion from the anterior pituitary by suckling in streptozotocin-induced diabetic rat.

Prolactin (PRL) secretion in streptozotocin-induced diabetic rats postpartum was examined to elucidate the reason for the reduced milk secretion of diabetic mothers. Pregnant Wistar rats were given citrate buffer (control group) or streptozotocin only (DM group) or with insulin (insulin group). Growth of pups was significantly lower in the DM group than in the control group, but similar in the insulin and control groups. Suckling-induced PRL secretion was significantly lower in the DM group than in the control group, and intermediate in the insulin group. TRH-induced PRL secretion was significantly lower in the DM group than in the control group, but the same in the insulin and control groups. Histologically, the mammary glands in the DM group were relatively less developed than those in the control group. The results suggest that reduced milk secretion in diabetic mothers is due to impaired induction by suckling of PRL secretion from the anterior pituitary as well as poor development of the mammary gland.

Animals↗

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. I. Taxonomy, fermentation, isolation and structural elucidation.

A new series of antifungal antibiotics, Ro 09-1470 and its 6 congeners were isolated from the fermentation broth of Penicillium sp. NR6564. Their structures were determined as tetrahydropyran derivatives with an alkenyl side chain on the basis of their spectroscopic and physico-chemical properties. Among these compounds, Ro 09-1470 and Ro 09-1545 possessing a glycyl N-substituted glycyl ester residue had high antifungal activity. Ro 09-1469, one of the congeners, was found in the fermentation broth of several strains of Aspergillus sclerotiorum Huber.

Antifungal Agents↗

Pharmacological profile of HS-142-1, a novel nonpeptide atrial natriuretic peptide (ANP) antagonist of microbial origin. II. Restoration by HS-142-1 of ANP-induced inhibition of aldosterone production in adrenal glomerulosa cells.

Atrial natriuretic peptide (ANP) is known to inhibit the aldosterone production by adrenal glomerulosa cells stimulated by angiotensin II. However, the mechanism of the inhibitory action is still somewhat uncertain. In this study we used HS-142-1, a novel nonpeptide antagonist for ANP receptor, to examine the role of cyclic GMP in the inhibition of aldosterone production by ANP. Aldosterone production by isolated bovine adrenal glomerulosa cells was stimulated by angiotensin II at a concentration of 10(-8) M. The angiotensin II-stimulated aldosterone production was inhibited by rat ANP in a dose-dependent manner at concentrations ranging from 10(-9) to 10(-7) M. HS-142-1, at concentrations of 0.1 to 100 micrograms/ml, reversed the inhibition by ANP of the angiotensin II-stimulated aldosterone production. On the other hand, intracellular concentration of cyclic GMP increased rapidly as early as 1 min after the exposure of the cells to 10(-8) M ANP in the presence of angiotensin II. This increase of intracellular cyclic GMP level was again reduced by HS-142-1 at concentrations similar to those that reversed the inhibition by ANP of the aldosterone production. These results suggest that ANP inhibits the aldosterone production through a guanylyl cyclase-coupled pathway in adrenal glomerulosa cells.

Adrenal Glands↗

Pharmacological profile of HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin. I. Selective inhibition of the actions of natriuretic peptides in anesthetized rats.

HS-142-1, a novel polysaccharide, isolated from the culture broth of Aureobasidium pullulans var. melanigenum, has been found to inhibit selectively the binding of [125I]atrial natriuretic peptide (ANP) to the guanylyl cyclase-linked ANP receptor (ANP-B receptor) and production of cyclic GMP by ANP. The effect of this compound on renal and vascular actions evoked by exogenously administered natriuretic peptides was examined in anesthetized rats. The increase in urine flow and in the urinary excretion of sodium elicited by human ANP or porcine brain natriuretic peptide was prevented by pretreatment with HS-142-1. The prevention was accompanied by the inhibition of increase in urinary cyclic GMP excretion. In addition, these renal responses were rapidly reversed by an injection of HS-142-1 during ANP infusion. Higher doses of HS-142-1 did not alter the increase in urine flow and in the urinary excretion of sodium evoked by furosemide, and HS-142-1 alone showed no significant change in these renal parameters. Hypotensive action elicited by human ANP was also prevented by the pretreatment with HS-142-1 and rapidly reversed by treatment with HS-142-1 during ANP infusion. These results clearly demonstrate that HS-142-1 acts as an antagonist for ANP-B receptor in vivo. HS-142-1, then, provides a new tool for the study of the physiological and pathophysiological roles of ANP.

Anesthesia↗

Inhibition by HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin, of atrial natriuretic peptide-induced relaxation of isolated rabbit aorta through the blockade of guanylyl cyclase-linked receptors.

HS-142-1, a specific nonpeptide antagonist for the atrial natriuretic peptide (ANP) receptor, equally blocked rat ANP (rANP)-, porcine brain natriuretic peptide-, or porcine C-type natriuretic peptide-stimulated GMP production in cultured bovine aortic smooth muscle (BASM) and bovine aortic endothelial (BAE) cells in a concentration-dependent fashion, at concentrations of 1-300 micrograms/ml. But, even at 300 micrograms/ml, HS-142-1 only weakly inhibited the specific binding of 125I-rANP to the BASM and BAE cells, where only a small portion of the binding sites are linked to guanylyl cyclase. Further, with BAE cell membranes, HS-142-1 recognized only the 135-kDa ANP receptor, which is thought from 125I-rANP affinity cross-linking studies to be the guanylyl cyclase-linked receptor. HS-142-1 also, if anything, inhibited the labeling of 135-kDa ANP receptors in the affinity cross-linking studies with BASM membranes, suggesting that a major portion of the 135-kDa ANP receptors are HS-142-1 insensitive and only a small portion of the 135-kDa ANP receptors are responsible for the blockade by HS-142-1 of GMP production in BASM cells. At a concentration of 100 micrograms/ml, HS-142-1 reversibly prevented ANP-induced relaxation of the isolated rabbit thoracic aorta induced to contract with 3 x 10(-7) M phenylephrine, but not the relaxation induced by sodium nitroprusside, isoproterenol, or papaverine. These results suggest that HS-142-1 specifically inhibits natriuretic peptide-induced vasorelaxation through the blockade of guanylyl cyclase-linked natriuretic peptide receptors. HS-142-1 thus will be a powerful tool for understanding the physiological roles, in vasculature, of natriuretic peptides, which contribute to the homeostasis of blood pressure and intravascular volume.

Animals↗

Evaluation of right ventricular function by regional wall motion analysis in patients after correction of tetralogy of Fallot. Comparison of transventricular and nontransventricular repairs.

Right ventricular function was assessed by regional wall motion analysis and by global function in 62 patients after repair for tetralogy of Fallot. Its relation to surgical procedures, with special attention to right ventriculotomy, was investigated. Patients were classified as follows: group Ia (n = 17), transpulmonary-transatrial repair without right ventriculotomy; group Ib (n = 22), transpulmonary-transatrial repair with minimal right ventriculotomy and small transannular patch; and group II (n = 23), transventricular repair with or without transannular patch. For regional wall motion analysis, fractional area change was used for three anterior parts obtained from hemiaxis area analysis of the lateral right ventriculogram. Ejection fractions were used for global right ventricular function. Functional assessment was done both at rest and during isoproterenol infusion, which is a stress test to evaluate cardiac functional reserve. At rest, group Ia showed better right ventricular anterior wall motion as well as global ejection fraction than did group II. Group Ib showed a global ejection fraction comparable to group Ia, with better regional wall motion in the middle anterior part of the right ventricle despite the depressed upper and lower anterior parts of the right ventricle. Group II showed depressed wall motion of the middle anterior part and the resultant impaired global ejection fraction. During isoproterenol infusion, group Ia showed significant increase in fractional area change of all anterior parts and in global ejection fraction. Group Ib showed significant increases in fractional area change at the middle and lower parts and in global ejection fraction comparable with group Ia. Otherwise, group II showed no significant change in fractional area change, or in global ejection fraction, at the upper and middle parts. These results indicated that transpulmonary-transatrial repair for tetralogy of Fallot provided better postoperative global right ventricular function and its reserve, with less impaired regional wall motion, than did the transventricular repair.

Cardiac Catheterization↗

[Assessment of Blalock-Taussig shunts in children with complex cardiac anomalies associated with reduced pulmonary blood flow and total anomalous pulmonary venous drainage].

Eleven patients with syndromes of asplenia and polysplenia associated with total anomalous pulmonary venous drainage (TAPVD) were underwent Blalock-Taussig (B-T) shunt operation for reduction of pulmonary blood flow. The age of patients at operation were 6 days to 5 years (average 19.5 +/- 18.7 month). There were seven patients in supracardiac type and four in cardiac type of TAPVD. All patients didn't present obstruction to pulmonary venous return (PVO) before B-T shunt operation. There were one early (9%) and two late deaths (20%) after surgery. Although the hospital death was related to perioperative errors. Two late deaths were not due to the PVO. One of infants had moderately pulmonary congestion and cardiac failure after shunt procedure. Two patients were measured pressure gradient (3 to 4 mmHg) between common pulmonary vein to atrium chamber before shunt procedure. Repeated catheterization revealed that 6 of them could be measured pressure gradient, 3 to 7 mmHg, and no patients had clinical sign of the PVO. Our results demonstrated that B-T shunt operation could be satisfactory for syndromes of asplenia and polysplenia associated with reduced pulmonary blood flow and TAPVD.

Anastomosis, Surgical↗

[A case of gold-induced pneumonitis showing a positive reaction in the drug lymphocyte stimulation test (DLST) for gold].

A case of acute interstitial pneumonia developing during gold therapy is reported. A 67-year-old female with rheumatoid arthritis for about twenty years who received a total dose of 80 mg of gold thiomalate (Shiosol) for about two months, developed high fever and dry cough. Exertional dyspnea developed and chest roentgenogram showed diffuse small nodular and reticular shadows. RA and RAPA tests were positive. Drug lymphocyte stimulation test (DLST) for Shiosol was positive. The dyspnea resolved on administration of methylprednisolone. Chest roentgenogram and CT-scan showed improvement. A total dose of 80 mg of gold thiomalate, as administered in this case, is the minimum dose previously reported in Japan. It has been recently reported that allergic reaction is the mechanism of gold lung. In the present case, positive DLST indicated the existence of many activated lymphocytes, and was very useful in the diagnosis of gold lung.

Aged↗

[Complications and their management in intraarterial infusion chemotherapy].

Complications and its management were evaluated in intraarterial infusion chemotherapy for 188 patients with advanced carcinoma of the digestive organs from 1975 to Sept. 1991. Subjects were divided into four groups: Group I was 62 patients in whom the tip of the catheter without knots was established in the abdominal aorta via celiac axis, Group II consisted of 72 patients with the tip of the catheter without knots in the common hepatic artery. Group III had 35 patients with the tip of the catheter with knots (Anthron catheter) in the common hepatic artery. Group IV was 19 patients with the tip of the anthron catheter connected to the Infuse A-Port in the common hepatic artery. The most frequent complications seen among Group I, II and III were caused by catheter thrombosis (11.3%) in Group I, spontaneous dislodgement of catheter (26.4%) in Group II and extravasation (20%) in Group III. By using 16 gauge Toray Anthron catheter with Heparin coating on its inner and outer surfaces, the number of complications in Group I and II was kept smaller. Extravasation, on the other hand, has been less frequently seen in Group III by establishing the tip of the catheter at the branching site of the gastroduodenal artery from the common hepatic artery. Complications in Group IV (19 patients) were noted only in 3 patients, i.e., extravasation, subcutaneous necrosis and subcutaneous abscess, respectively. Therefore, we concluded that Group IV showed the most favorable intraarterial infusion chemotherapy with the most infrequent complications.

Aorta↗

[Effect of growth hormone on immune function in normal and hypophysectomised rats].

The effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age. In hypophysectomised rats, the counts of peripheral white blood cells (5,513 +/- 813/microliters), lymphocytes (4,838 +/- 737/microliters), Th/i cells (2,237 +/- 329/microliters), and B cells (1,400 +/- 509/microliters), Th/i/Ts/c ratio (1.78 +/- 0.27), splenic T cell subsets (pan T: 51.0 +/- 4.3%, Th/i: 31.6 +/- 3.0%, Ts/c: 23.9 +/- 2.7%), and serum IgG level (2,148 +/- 470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8 +/- 4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1 +/- 15.7, PHA: 51.6 +/- 12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850 +/- 840/microliters), lymphocytes (6,211 +/- 731/microliters), Th/i cells (2,909 +/- 304/microliters), and B cells (1,947 +/- 402/microliters), Th/i/Ts/c ratio (2.04 +/- 0.34), serum IgG level (3,414 +/- 1,326mg/l), and natural killer activity (25.7 +/- 4.7%). However, splenic lymphocyte subsets and mitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982 +/- 1,496mg/l) but did not affect other immunological parameters. These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function.

Animals↗

Definition of total biosynthesis pathway of taurolipids in Tetrahymena cells.

Taurine-combined fatty acids were found in the lipotaurine fraction of cells of Tetrahymena thermophila. Taurine and fatty acid moieties of the compounds were identified by nuclear magnetic resonance and gas chromatography-mass spectrometry, respectively. The molar ratio of fatty acid methyl esters and taurine in the hydrolysate of the lipotaurine fraction by methanolic hydrochloric acid hydrolysis, was 1.06:1.00. From the results, the structures of six taurine-combined fatty acids including lipotaurine in the fraction were identified. These structures suggest that the compounds are precursors of lipotaurine as an intermediate of taurolipids biosynthesis, and lipotaurine is biosynthesized via 2-(octadecanoylamino)ethanesulfonic acid and 2-(7-hydroxy-13-octadecenoylamino)ethanesulfonic acid. From the results of the present study and our previous studies, the total biosynthesis pathway of taurolipids is defined.

Animals↗

Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas.

Recently, loss or inactivation of genes at specific chromosomal loci has been considered to be one of the important mechanisms during the development of human tumors. In order to identify tumor suppressor genes for gastric carcinoma, we performed restriction fragment length polymorphism analysis on 48 human gastric carcinomas. Allele losses were investigated for 14 specific loci on chromosomes 1, 5, 6, 7, 10, 11, 12, and 17. Loss of heterozygosity on chromosome 17p13.1 (p53 locus) was detected in 13 (68%) of 19 informative cases. Well-differentiated adenocarcinoma showed high frequencies of allele losses on chromosomes 5q (60%) and 17p (67%) in early cancers and on chromosomes 1q (67%), 5q (36%), 7p (33%), 7q (39%), and 17p (73%) in advanced cancers. In poorly differentiated adenocarcinomas, loss of heterozygosity was detected on chromosomes 1p (38%), 12q (31%), and 17p (60%). Allele losses on chromosomes 1q, 5q, and 7p were not detected in poorly differentiated adenocarcinoma, their frequencies being significantly different between the two histological types. These results suggest that allele loss on chromosome 17p is a common event in gastric carcinoma, regardless of histological type, and that allele loss on chromosome 5q may play a role in the carcinogenesis of well-differentiated adenocarcinoma. Additionally, allele losses on chromosomes 1q and 7p may be involved in the progression of well-differentiated adenocarcinoma.

Adenocarcinoma↗

Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor.

During the search for ANP receptor ligands of microbial origin, we isolated a novel polysaccharide, HS-142-1, from culture broth of Aureobasidium sp. HS-142-1 inhibited [125I]-rANP binding to ANP receptor in rabbit kidney cortex membranes with an IC50 of 0.3 mu g/ml, but gave no effects on specific binding of [125I]-Endothelin nor [125I]-Angiotensin II to their respective receptors in bovine lung membranes. HS-142-1 competitively and selectively inhibited ANP binding to its guanylyl cyclase-containing receptor purified from solubilized bovine adrenocortical membranes and blocked cGMP production elicited by ANP. HS-142-1 is the first non-peptide antagonist selective for ANP functional receptor and will be a powerful tool to elucidate the physiological functions of ANP.

Adrenal Cortex↗

Expression vectors for streptavidin-containing chimeric proteins.

We have constructed expression vectors for streptavidin-containing chimeric proteins. These vectors carry the DNA sequence corresponding to the core region of the streptavidin molecule, and have several unique cloning sites which facilitate construction of gene fusions of streptavidin with a target protein. A chimeric protein of streptavidin and the target protein should be expressible in Escherichia coli by using the T7 expression system. Because of the strong and specific biotin-binding affinity of the streptavidin moiety, such streptavidin-containing chimeric proteins should extensively expand the applications of the streptavidin-biotin system, and offer a variety of applications as new biological tools.

Amino Acid Sequence↗

Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's disease.

The total sequence data for mitochondrial DNA (mtDNA) revealed distinct clustering of point mutations (pms) in mtDNA among one patient with myoclonus epilepsy with ragged-red fibers (MERRF), two patients with Parkinson's disease (PD), two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and one patient with fatal infantile cardiomyopathy (FICM). Among 33 to 62 pms found in each patients, sequentially diverged five clusters of pms were detected and designated as C-1 to C-5. C-1, consisted of fourteen pms, existed in the MERRF patient, C-1 and C-2 (nine pms) in one PD patient, C-1 to C-3 (seven pms) in another PD patient, C-1 to C-4 (one pm) in one MELAS patient and C-1 to C-5 (three pms) in another MELAS patient and the FICM patient. From these clustering of pms, a phylogenetic tree of mitochondrial encephalomyopathies (ME) was constructed. This tree clearly indicated that the ME and PD patients are members of the same gene family, and the MELAS and FICM patients are each others' closest relative. Each patient's unique pms (14 to 28 pms) were detected and, from their characteristic features, the types of the mutations specific for the disease were classified as mit- + syn- for MERRF, mit- + p- for PD, and syn- + mit- for MELAS. An inverse relation was found between the total number of pms and life span of the MELAS and FICM patients.

Adolescent↗

Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

The total sequences of mitochondrial DNA were determined in two patients with juvenile-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to Complex I deficiency. Patients 1 and 2 had three and two unique point mutations, respectively, causing replacement of phylogenically conserved amino acids. A transition from G to A was found at nucleotide position 5601 in the alanine tRNA gene of Patient 2, and a transition from A to G was found at 3243 in the leucine (UUR) tRNA gene of both patients. The latter mutation located at the phylogenically conserved 5' end of the dihydrouridine loop of the tRNA molecule, and was present in two patients with adult-onset MELAS and absent in controls. These results indicate that a mass of mtDNA mutations including the A-to-G transition in the tRNA(Leu) gene is a genetic cause of MELAS.

Adolescent↗