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Biomedical subjects

J Kobayashi

Publications and source records attributed to J Kobayashi.

At least 379 records · Page 21Linked to original sources

[Studies on the chemical constituents of Rutaceae++ plants. LXVI. The chemical constituents of Toddalia asiatica (L.) Lam. (T. aculeata Pers.). (1). Chemical constituents of the root bark].

Chemical constituents of the root bark of Toddalia asiatica (L.) Lam. (T. aculeata Pers.), Rutaceae, were examined. In addition to twelve known coumarins [toddaculin (2), coumurrayin (5), toddanone (6), 8-(3,3-dimethylallyl)-6,7-dimethoxycoumarin (7), isopimpinellin (8), 6-(3-chloro-2-hydroxy-3-methylbutyl)-5,7-dimethoxycoumarin (9), 6-formyllimettin (10), 5,7,8-trimethoxycoumarin (12), toddasin (13), (+)-toddanol (14), 6-(2-hydroxy-3-methoxy-3-methylbutyl)-5,7-dimethoxycoumarin (18), and toddalolactone (21)] five new coumarins [toddalenol (17), toddalosin (19), 5-methoxysuberenon (23), toddalenone (24), and 8-formyllimettin (25)] were isolated. Furthermore seven known benzo[c]phenanthridine alkaloids [des-N-methylchelerythrine (4), oxychelerythrine (15), arnottianamide (16), oxyavicine (22), avicine (30), chelerythrine (31), and chelerythrine-psi-cyanide (34)] and four known quinoline alkaloids [N-methylflindersine (11), 4-methoxy-1-methyl-2-quinolone (20), skimmianine (35), integriquinolone (36)], one known triterpenoid [beta-amyrin (3)], and four unknown components [unknown I-IV (26)-(29)] were isolated.

Alkaloids↗

Serum-free cultivation of anchorage-dependent cells on microcarrier: effective production of human macrophage colony-stimulating factor.

For the purpose of establishing a large scale production process of biologically active substances by cultivation of anchorage-dependent mammalian cells, basic studies were carried out on the following items; establishment of a new cell line and derivation of high productivity; construction of optimal serum-free medium; optimization of cultivation method using microcarrier in serum-free medium; and establishment of purification process. The cell line, TRC-29SF, used in this study was newly established from human renal carcinoma with a function of producing macrophage colony-stimulating factor constitutively. Improvement of M-CSF productivity upon TRC-29SF cell line was performed by M-CSF gene amplification with dhfr-MTX system and by truncation of membrane-binding amino acid sequence by recombinant DNA technique. Two kinds of serum-free media, IPEG-85 and IREG-89, were formulated for the growth of TRC-29SF cell and its transformant, respectively. A new cell-adhesion method which permits homogeneous attachment to microcarrier in short term was developed by equalizing the sedimentation velocity between cells and microcarrier by addition of 7% Ficoll into the medium. High cell density perfusion culture of TRC-29SF cells was achieved by microcarrier method using IPEG-85 medium, and final cell density reached over 10(7) cells/ml. Based on the results obtained, long-term perfusion cultures were performed using Mn10-5 and Mn10-5/R600 cell lines, which were created by M-CSF gene transfection and amplification. We found that the productivity of M-CSF per cell began to decrease from the end of logarithmic growth phase. Long-term cultivation with high productivity was accomplished by perfusing medium containing 2 mM sodium butyrate. Purification process for M1-CSF from the culture supernatant of transformed cell line was also established.

Amino Acid Sequence↗

9-methyl-7-bromoeudistomin D, a powerful radio-labelable Ca++ releaser having caffeine-like properties, acts on Ca(++)-induced Ca++ release channels of sarcoplasmic reticulum.

9-Methyl-7-bromoeudistomin D (MBED), a derivative of eudistomin D isolated from a marine tunicate, induced Ca++ release from the heavy fraction of fragmented sarcoplasmic reticulum (HSR) in the same way as that of caffeine, followed by spontaneous Ca++ reuptake in the Ca++ electrode experiment. The rate of 45Ca++ efflux from HSR vesicles was accelerated markedly by MBED or caffeine in a concentration-dependent manner. The 50% effective concentrations of MBED and caffeine were approximately 1 microM and 1 mM, respectively, indicating that MBED is 1000 times more potent than caffeine in HSR. Procaine, ruthenium red or Mg++ caused concentration-dependent inhibition of MBED-triggered Ca++ release from HSR. The bell-shaped profile of Ca++ dependence for MBED is very similar to that of caffeine. The caffeine-produced maximum response of 45Ca++ efflux was increased further by adenosine-5'-(beta, gamma-methyl-ene)triphosphate, whereas that was not changed by MBED. MBED also caused Ca++ release from sarcoplasmic reticulum (SR) of chemically skinned fibers. These stimulatory effects of MBED on the Ca++ release from skeletal muscle SR were almost indistinguishable from those of caffeine except the difference in potencies. The [3H]ryanodine binding to junctional terminal cisternae membranes was not inhibited by MBED or caffeine. MBED did not cause Ca++ release from the light fraction of fragmented SR and turbidity change of mitochondrial suspension. These observations suggest a most likely idea that MBED binds to the caffeine-binding site in the Ca channel protein and thus produces the potentiation of Ca(++)-induced Ca++ release from SR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Xestoquinone, a novel cardiotonic agent activates actomyosin ATPase to enhance contractility of skinned cardiac or skeletal muscle fibers.

Xestoquinone (XQN), a novel cardiotonic principle from the sea sponge Xestospongia sapra, enhanced Ca+(+)-induced tension development of chemically skinned fibers from guinea pig cardiac muscle, even at both free Ca++ concentrations as low as -log molar free Ca++ (pCa) 9 to 8. In skinned fibers from guinea pig skeletal muscle, XQN (10 microM) also increased developed tension with a similar Ca++ dependence to that for cardiac fibers. In contrast to the unique Ca+(+)-dependence of XQN effects, the reference drug sulmazole enhanced Ca+(+)-induced tension development of skinned cardiac fibers at pCa 6.6 but did not affect it at pCa 8. In natural actomyosin from canine cardiac muscle, as well as in that from rabbit skeletal muscle, XQN (1-30 microM) enhanced the rate and extent of superprecipitation. Moreover, XQN produced a concentration-dependent increase in the myofibrillar ATPase activity of canine cardiac muscle, even at very low free Ca++ concentrations below the normal threshold for ATPase activation (pCa 9-8). The natural actomyosin ATPase activity of chicken smooth muscle was not influenced by XQN (up to 30 microM). In cardiac myofibrils, no significant difference was observed between the bound 45Ca+(+)-pCa relationship curves in the presence and absence of XQN (10 microM). Furthermore, XQN (30 microM) did not cause or potentiate Ca+(+)-induced Ca++ release from cardiac sarcoplasmic reticulum vesicles. These observations suggest that XQN directly activates actomyosin ATPase activity of cardiac and skeletal myofibrils, thus producing an enhanced superprecipitation activity as well as an increase in skinned fiber contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanism of inotropic action of xestoquinone, a novel cardiotonic agent isolated from a sea sponge.

Xestoquinone (XQN) isolated from the sea sponge Xestospongia sapra produced dose-dependent cardiotonic effects on guinea pig left and right atria. A direct action of XQN (1-30 microM) on the contractile machinery of cardiac myofilaments was demonstrated in chemically skinned fiber preparations from guinea pig papillary muscles. In atrial preparations, the XQN-induced inotropic effect was markedly inhibited by verapamil or nifedipine, but was not affected by practolol, chlorpheniramine, cimetidine, tetrodotoxin or reserpine. The Ca++ dependence curve for the contractile response of the atria was substantially shifted to the left by XQN (10 microM), and this XQN-induced shift was reversed by verapamil. The time-to-peak tension and relaxation times of the atrial contractions were shortened by XQN, and the action potential duration was markedly prolonged. Whole-cell patch clamp recordings in left atrial strips confirmed that XQN (30 microM) increased the slow inward current. However, there was a temporal dissociation between altered tension development and prolongation of the action potential duration. Cyclic AMP phosphodiesterase activity was inhibited and tissue cyclic AMP content of guinea pig left atria was increased by XQN (0.3-10 microM) in a concentration-dependent manner, but increases in cyclic AMP content did not occur in parallel with increases in contractile response. These observations suggest that an enhancement of intracellular cyclic AMP content and Ca++ influx across the cell membrane contribute to the late phase of XQN-caused cardiotonic responses, whereas the early phase may largely be elicited through direct activation of contractile elements. XQN may provide a novel leading compound for valuable cardiotonic agents.

3',5'-Cyclic-AMP Phosphodiesterases↗

[A case report of atypical coarctation of the aorta with coarctation and left subclavian arterial aplasia].

A 18 year-old female was admitted to our hospital with hypertension of 190/100 mmHg in her right arm and 140/110 mmHg in the left arm. Femoral arterial pulsation was not palpable. Her physical status and growth of the lower limbs were normal. Aortography demonstrated slight coarctation with a pressure gradient of 10 mmHg and descending aortic stenosis with a pressure gradient of 80 mmHg. Main three branches from aortic arch were anatomically normal. However, the left subclavian artery distal to the origin of the left vertebral artery was not visualized and the axillary artery was perfused by collaterals. Atypical coarctation was replaced using a woven Dacron graft of 14 x 40 mm. Postoperatively proximal pressure decreased from 180/113 to 156/98 mmHg and there was no pressure gradient between proximal and distal of the graft. After six months blood pressure in the right arm gradually decreased to 120/78 mmHg.

Adolescent↗

[The metabolism of peptide leukotrienes in the lung may affect their coronary vasoconstrictive effect in anesthetized dogs].

The deteriorative effect of peptide leukotrienes (LTs) on the coronary circulation are well known. On the other hand, it has been recognized that some of these prostanoids are metabolized in the pulmonary vascular bed. To clarify the influence of the metabolism of LTs in the lung on their effects to the coronary circulation, we compared the changes of coronary circulation parameters by leukotriene D4 (LTD4) and C4 (LTC4) administered (5 mcg/kg) into the right atrium (RA) and the left atrium (LA) in 8 mongrel dogs. After the administration of LTD4 and LTC4, significant reduction of coronary blood flow (LTD4-RA 65.8 +/- 3.4%, LTD4-LA 54.8 +/- 2.3%, LTC4-RA 64.3 +/- 3.9%, LTC4-LA 66.9 +/- 3.7%) and elevation of coronary vascular resistance (LTD4-RA 130.5 +/- 8.2%, LTD4-LA 157.3 +/- 6.1%, LTC4-RA 138.7 +/- 8.0%, LTC4-LA 129.5 +/- 10.1%) were recognized. The effect of LTD4, administered into the left atrium was significantly greater than that administered into the right atrium (p less than 0.05). The difference between right and left atrial administration was not statistically significant, although a tendency for the effect to be greater with right atrial administration than left was recognized. The LTC4 concentration in aortic blood measured by radioimmunoassay was significantly lower in right atrial administration than left (p less than 0.05). These results suggested that LTD4 was metabolized and inactivated in the lung during its passage through the pulmonary circulation, and LTC4 was not only inactivated but also converted to LTD4 and activated in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevalence and risk factors of tricuspid regurgitation after correction of tetralogy of Fallot.

Tricuspid regurgitation was evaluated in 133 patients with tetralogy of Fallot after corrective operations for a real-time Doppler flow imaging system. Moderate or severe tricuspid regurgitation was found in 15% (10/66) of patients in whom the ventricular septal defect was closed through the right atrium and tricuspid valve, 13% (2/15) through the pulmonary artery, and 25% (13/52) through the right ventricle. These differences were not significant. Right ventricular systolic pressure was significantly higher (66 +/- 27 mm Hg) in patients with moderate or severe tricuspid regurgitation (group A) than in patients with mild or no tricuspid regurgitation (group B) (41 +/- 13 mm Hg) (p less than 0.01). Right ventricular end-diastolic pressure was significantly higher in group A (7.7 +/- 2.2 mm Hg) than in group B (6.1 +/- 2.9 mm Hg) (p less than 0.01). Significant pulmonary regurgitation (angiographic grades 3/4 to 4/4) was more frequent in group A (8/18; 44%) than in group B (14/64; 22%) (p less than 0.05). Residual ventricular septal defect (pulmonary/systemic flow ratio greater than 1.3) was also more frequent in group A (5/18; 28%) than in group B (0/64; 0%) (p less than 0.01). Right ventricular end-diastolic volume was significantly higher in group A (202% +/- 79% of the normal right ventricle) than in group B (158% +/- 38% of normal) (p less than 0.01). Thus significant tricuspid regurgitation was associated with high right ventricular systolic pressure, high right ventricular end-diastolic pressure, and significant pulmonary regurgitation and residual ventricular septal defect, which increased the right ventricular end-diastolic volume. Operative procedure for closing the ventricular septal defect was not related to the development of significant tricuspid regurgitation.

Adolescent↗

Hemodynamic effects of bidirectional cavopulmonary shunt with pulsatile pulmonary flow.

The effects of "pulsatile" bidirectional cavopulmonary shunt (BCPS) produced by the flow from the ventricle or Blalock-Taussig (B-T) shunt on ventricular function and pulmonary circulation were evaluated in 10 patients with univentricular heart from 3 to 37 months (mean, 16.6 +/- 9.5 months) after surgery. Age at operation ranged from 7 months to 15 years (mean, 5.5 +/- 4.5 years). In addition to the BCPS, pulmonary flow was supplied from a B-T shunt on the contralateral side of the BCPS in five patients, from the ventricle through the stenotic pulmonary valve in four patients, and from both the ventricle and a B-T shunt in one patient. There were no operative deaths; however, there were two late deaths from acute respiratory infection 10 and 13 months after operation. Mean pulmonary arterial pressure measured the first day after operation ranged from 10 to 19 mm Hg (mean, 14 +/- 3 mm Hg). Mean pulmonary arterial pressure at postoperative cardiac catheterization was less than 15 mm Hg (mean, 12 +/- 4 mm Hg). Pulse pressure ranged from 3 to 12 mm Hg (mean, 7 +/- 4 mm Hg). Arterial oxygen saturation increased significantly from 77 +/- 5% before BCPS to 86 +/- 4% immediately after discharge from the intensive care unit (p less than 0.005) and 85 +/- 3% (p less than 0.025) at late cardiac catheterization. Pulmonary arteriovenous fistula was not detected in contrast echocardiography and pulmonary arteriography. Systemic ventricular end-diastolic volume index decreased significantly (p less than 0.01) from 141 +/- 54 ml/m2 before BCPS to 98 +/- 35 ml/m2 1 month after BCPS by echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

[Preservation and improvement of chest wall function].

Anterolateral multiple rib fractures near xiphoid process impaired mechanical linkage which resists distortion between pulmonary (upper) and abdominal (lower) rib cage resulting in flail chest. Repair of fractured ribs with ceramic pins improved phase shift between the diaphragm and the rib cage and the amplitude of the injured rib cage motion, and decreased rib cage distortion. Asymmetrical motion of lower rib and upper abdomen which suggested impairment of the diaphragm action on the abdominal rib cage was found in three patients whose emphysematous bullae were located in the middle and lower lung fields, and disappeared after bullectomy. To control the pressure in the pleural cavity after pneumonectomy from excessive negative pressure to atmospheric pressure with SF6 improved pulmonary function. Chest wall function can be preserved on the basis of functional anatomy and physiology of the chest wall.

Humans↗

[A successful surgical treatment of cor triatriatum with VSD, PDA and CoA].

A successful repair of cor triatriatum with VSD, PDA and CoA is reported. A two-month-old boy was admitted for evaluation of growth failure and cyanosis. Physical examination on admission revealed systolic murmurs at left sternal border. Chest X-ray showed increased pulmonary vascularities without cardiomegaly. Echocardiography showed abnormal wall in left atrium with VSD, PDA and CoA. An emergency operation consisting of patch closure of VSD, ligation of PDA and resection of the anomalous left atrial membrane were performed. At postoperative course, an episode of pulmonary hypertension crisis happened. But the patient tolerated this episode and survived.

Aortic Coarctation↗

[Successful surgical treatment of total anomalous pulmonary venous connection (supracardiac Ib type) showing an unusual shape of the pulmonary veins in an infant].

An experience of a 9-month-old infant with Darling's type Ib of total anomalous pulmonary venous connection is presented. In this case, the left pulmonary vein traveled horizontally behind the atrium, entered the right thoracic cavity and drained into the SVC together with the right lower, middle and upper pulmonary veins. The patient was treated with repair using Gersony-Malm's method and plasty of SVC because of the stenosis of the common pulmonary vein's entrance to the SVC. Her postoperative course was uneventful, and the result was satisfactory. To our knowledge, our case is the first successful correction not associated with other complex cardiac anomalies in the world.

Female↗

[Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. II. In vitro combined effects of sulbactam/cefoperazone with imipenem/cilastatin, cefuzonam, flomoxef, amikacin or tobramycin].

We evaluated combined effects of sulbactam/cefoperazone (SBT/CPZ) with each of imipenem/cilastatin (IPM), cefuzonam, flomoxef, amikacin (AMK) and tobramycin (TOB) against 324 clinical strains. Through this study, we obtained the following results. 1. Against Serratia marcescens and Enterobacter cloacae, good synergism was obtained by combining SBT/CPZ with IPM, AMK, or TOB. 2. Against Pseudomonas aeruginosa, good synergism was obtained by combining SBT/CPZ with AMK or TOB. 3. When SBT/CPZ was used in combination with IPM, antagonism was observed among about 45% of strains of P. aeruginosa.

Amikacin↗

[Surgical treatment of tetralogy of Fallot with pulmonary atresia: early and late results].

From 1968 to 1987, 45 consecutive patients with tetralogy of Fallot and pulmonary atresia underwent corrective surgery. In the former 10 years, there were 8 operative deaths (40%) in the 20 patients and no late death. In the recent 10 years, there were 4 operative deaths and 4 late deaths in the 25 patients. In the 17 patients associated with large aorto pulmonary collateral artery (LAPCA) which was ligated in the most patients, there were 5 operative deaths (29%) and 3 late deaths. Nine patients (53%) survived long-term. There were 7 operative deaths (25%), one late death and 20 patients (71%) being long-term survivors in the 28 patients without LAPCA. Pulmonary hemodynamics were investigated in 10 patients without LAPCA and 11 with LAPCA after corrective surgery. Pulmonary arterial mean pressure (PAm) ranged from 9-24 (17 +/- 6) mmHg in patients without LAPCA and 15-92 (37 +/- 23) mmHg in those with LAPCA. Pulmonary arteriography showed arborization abnormality in 7 of the 11 patients with LAPCA. PAm inversely correlated well with number of pulmonary artery segments connected to the central pulmonary arteries. Postoperative pulmonary hypertension was found in patients with less than 16 bronchopulmonary segments connected to the central pulmonary arteries, and two of them died of pulmonary hypertension late after surgery. These results suggested that unifocalization to connect the central pulmonary artery more than 15 bronchopulmonary segments may be an important strategy for correction of this anomaly with LAPCA.

Child↗

Disulfide pairings in geographutoxin I, a peptide neurotoxin from Conus geographus.

The three intramolecular disulfide linkages of geographutoxin I, a peptide neurotoxin isolated from the venom of the marine snail Conus geographus, were examined by a novel method for determination of the positions of disulfide linkages in peptides [(1989) Bull. Chem. Soc. Jp. 62, 1986-1994]. The disulfide bridges were found to be between Cys3 and Cys15, Cys4 and Cys20, and Cys21, indicating that geographutoxin I has a rigid conformation consisting of three loops stabilized by these three disulfide linkages.

Amino Acid Sequence↗

Immunological quantitation and immunohistochemical localization of leukotriene A4 hydrolase in guinea pig tissues.

We prepared a highly specific polyclonal antibody against leukotriene (LT) A4 hydrolase using a recombinant human enzyme. Using this antibody, we quantified LTA4 hydrolase protein content in the cytosols of guinea pig tissues. The enzyme protein content correlated well with the enzyme activity with a correlation coefficient of 0.87. However, the enzyme activity per mg of the enzyme in the cytosols was low, particularly in the liver and adrenal gland, compared with the specific activity of the purified enzyme. These observations suggest the presence of inhibitory substances and/or inactive enzymes in the cytosols of these tissues. To determine the cellular localization of LTA4 hydrolase in tissues other than blood cells, we carried out immunohistochemical examinations of guinea pig tissues. We identified epithelial cells in the tracheobronchial system and gastrointestinal tract, smooth muscle cells in the bronchi and aorta, vascular endothelial cells, and the intestinal plexus as novel cellular sources of the enzyme in the parenchyme of the tissue. Thus, LTA4 hydrolase was widely distributed in various types of parenchymal cells in the tissues, and this observation warrants further investigations on the biological activities of LTB4 in these cells and tissues.

Animals↗