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Biomedical subjects

K Mitsui

Publications and source records attributed to K Mitsui.

At least 19 recordsLinked to original sources

Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung.

We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.

Animals

Outbreaks of group A beta-hemolytic streptococcal pharyngitis in children: correlation of serotype T4 with scarlet fever.

We evaluated the clinical features of 121 children who had group A beta-hemolytic streptococcal (GABHS) pharyngitis during 2 outbreaks in the Chikuhou district, Fukuoka, Japan, with respect to T types. During the first outbreak (November 1989-February 1990), T12 (50%) and T22 (27%) were the dominant T types isolated. During the second outbreak (January-April 1991), 64% of the typable strains were T4. Pus on the tonsils was less common and strawberry tongue more common in patients with eruptions than in those without. Skin eruptions were much more common in the patients infected with T4 than with other T types (p < 0.001). Despite a 10-day regimen of amoxicillin, 12/69 patients (17.4%) had evidence of GABHS on repeat cultures. The results suggest that T4 may be associated with a high incidence of scarlet fever. Serotyping should be performed to identify disease carriers and patterns of GABHS infection.

Adolescent

[Gianturco expandable metallic stents in the treatment of superior vena cava syndrome caused by lung cancer].

Treatment of superior vena cava syndrome (SVCS) caused by advanced lung cancer is still controversial. We inserted Gianturco expandable metallic stents (GEMS) in 5 patients with SVCS due to the extension of lung cancer. GEMSs were introduced intravenously through the catheter after intraluminal balloon dilation of the stenotic sites. SVCS was successfully and easily relieved by this method without any significant complication. GEMS placement seems to be a useful alternative to bypass grafting procedure for the treatment of SVCS.

Adult

[Annual changes of bacteria isolated from urinary tract infections and their susceptibility to new quinolone agents].

Statistical analyses were conducted on bacterial strains isolated from the urine of patients with urinary tract infections (UTI) in the Department of Urology at Aichi Medical University from January 1988 through December 1991. The drug sensitivity of the bacterial strains isolated from patients with complicated UTI between 1988 and 1991 was analyzed and compared. Among the outpatients with uncomplicated UTI, a total of 352 strains were isolated. E. coli was isolated the most frequently (90.1%). Among the outpatients with complicated UTI, a total of 829 strains were isolated. Enterococcus sp. was isolated the most frequently (21.2%). P. aeruginosa and S. aureus showed a tendency to increase. Among the inpatients with complicated UTI, a total of 671 strains were isolated. Enterococcus sp. was isolated the most frequently (22.5%). P. aeruginosa and S. aureus showed a tendency to increase, while E. coli and Enterobacter sp. showed a tendency to decrease. E. coli was highly sensitive to all drugs except ampicillin (ABPC). Proteus sp. and Klebsiella sp. were highly sensitive to norfloxacin (NFLX). P. aeruginosa was highly sensitive to gentamicin (GM). The frequency of NFLX-sensitive P. aeruginosa significantly dropped from 84.6% to 40.9% among the outpatients (P < 0.01), and from 75.0% to 44.4% among inpatients (P < 0.05). S. aureus was highly sensitive only to minocycline (MINO). The frequency of NFLX-sensitive S. aureus significantly dropped from 66.6% to 23.3% among inpatients (P < 0.05). Enterococcus sp. was highly sensitive to ABPC and MINO. Of the new quinolones, tosufloxacin (TFLX) had the strongest antimicrobial activity followed by (ciprofloxacin) CPFX on all the bacterial strains tested.

Bacteria

Endothelin-1 mediates regional blood flow during and after pulmonary operations.

To investigate the role of endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, in the physiologic response to surgical stress, we measured plasma endothelin-1 concentrations by a sandwich-enzyme immunoassay in patients with lung cancer undergoing pulmonary operations (n = 12). In the first group (n = 6), we measured plasma endothelin-1 concentrations at multiple sampling sites (median cubital vein, pulmonary artery, and left atrium). Plasma endothelin-1 levels were significantly increased at all sampling sites at the end of the operation. Although there was no difference between the increased plasma levels of endothelin-1 in the pulmonary artery and in the left atrium, the increased level in the median cubital vein (peripheral venous blood) was significantly higher than that in the pulmonary artery (mixed venous blood). This result suggests that the production of endothelin-1 might differ between various organs under surgical stress. In the second group (n = 6), we measured plasma endothelin-1 concentrations both in the median cubital vein and in the ipsilateral radial artery, and also measured cardiac output and forearm blood flow. The increase in endothelin-1 levels in the median cubital vein was significantly higher than that in the radial artery after the operation. The endothelin-1 output from the forearm, calculated by the forearm blood flow and the arteriovenous difference of endothelin-1 concentrations, significantly increased after the operation. Although the cardiac output significantly increased after the operation, the forearm blood flow significantly decreased. The present findings provide a novel hypothesis that the preferential release of endothelin-1 from the peripheral vasculature of the forearm may partly contribute to a compensatory response to surgical stress, for example, the reduction of local blood flow in nonvital organs so as to increase the blood flow in vital organs.

Adult

[Evaluation of postoperative pulmonary complications and remaining pulmonary arterial flow of lobectomized lung cancer patients using pulmonary digital subtraction angiography].

Postoperative pulmonary complications cause the decrease of the flow of remaining pulmonary circulation. We examined the effects of the difference of resected lobes on the postoperative course and remaining pulmonary circulation of the lobectomized lung cancer patients using a pulmonary digital subtraction angiography. In all cases with preoperative pulmonary complications, circulatory flow of the remaining lung on the operated side significantly decreased. In the cases without preoperative pulmonary complications, only the cases performed left upper lobectomy developed the decrease of the circulatory flow on the operated side. This seemed to be chiefly caused by a postoperative continual atelectasis of the remaining lower lobe due to kinking of the bronchus. On the other hand, the postoperative decrease of the residual pulmonary circulatory flow on the operated side was not developed in the cases undergoing a segmentectomy, even with pulmonary complications. Therefore, for any case requiring a left upper lobectomy or the case with an impaired lung requiring any type of lobectomy, contralateral pulmonary function should be exactly evaluated preoperatively.

Aged

[MRSA pyothorax due to bronchopleural fistula after grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta--a successful treatment by open drainage and omentopexy].

Treatment of postpneumonectomy pyothorax due to bronchopleural fistula (BPF) is troublesome, especially with methicillin-resistant staphylococcus aureus (MRSA) infection. Moreover, in a bypass-grafting case, the management becomes more complicated. We reported a successful treated case of MRSA pyothorax due to BPF after grafting and pneumonectomy. In a 48-year-old woman performed grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta, MRSA pyothorax due to BPF occurred. BPF was successfully closed by fibrin-glueing under bronchofiberscopy. However pyothorax was not improved by thoracic irrigation for a month. Therefore, open pleural drainage underwent. At the same time, bronchial stump and graft surface was covered with the omental pedicle flap. The open wound had become sterile in two months, and the thoracic window was closed three months after the open drainage.

Aorta, Thoracic

[A resected case of thymolipoma].

We reported a resected case of thymolipoma, which has been hardly experienced. The patient was 21-year-old female and consulted a doctor for general fatigue. Chest roentgenogram revealed a mass-like shadow at the right lower mediastinum, which was suspected mediastinal tumor. The mass of right anteroinferior mediastinum, which was clearly shown by chest CT scan and MRI, was continued to the right lobe of the thymus. Under a diagnosis of anterior mediastinal tumor, operation was carried out. The tumor, which was 10 x 8 x 7 cm in diameter and 160 g in weight, was removed together with right lobe of the thymus. Histological diagnosis of thymolipoma was obtained from the resected specimen.

Adult

[Use of airway stent subsequent to endoscopic Nd-YAG laser treatment in central airway obstruction].

Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state.

Adult

Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.

Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. We identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate factor X in the presence of factor VIII, phospholipids, and Ca2+, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311----Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

Amino Acid Sequence

Bilateral hydrophobic zipper as a hypothetical structure which binds acidic ribosomal protein family together on ribosomes in yeast Saccharomyces cerevisiae.

Acidic ribosomal protein family of yeast Saccharomyces cerevisiae consists of four species of 13-kDa proteins and one species of 38-kDa protein. These proteins are thought to form a complex on ribosomes functioning in the translational elongation reaction, but the structural basis how to associate with one another is not known. In this communication, we show for the first time the presence of a structure equivalent to the leucine zipper on a putative alpha-helix in the 38-kDa acidic ribosomal protein, A0. Then, all the 13-kDa acidic ribosomal proteins are shown to have two periodic arrays of hydrophobic amino acid residues arranged on the opposite sides of a putative alpha-helix, which is referred to as the "bilateral hydrophobic zipper". Therefore, it is proposed that one of the 13-kDa acidic ribosomal proteins associates with 38-kDa protein A0 via the hydrophobic zipper and then the other 13-kDa proteins associate side by side via the bilateral hydrophobic zippers.

Amino Acid Sequence

A cytolysin, theta-toxin, preferentially binds to membrane cholesterol surrounded by phospholipids with 18-carbon hydrocarbon chains in cholesterol-rich region.

We have previously suggested the existence of two distinctive states of cholesterol in erythrocyte and lymphoma cell membranes as revealed by high- and low-affinity binding sites for theta-toxin of Clostridium perfringens [Ohno-Iwashita, Y., Iwamoto, M., Mitsui, K., Ando, S., & Nagai, Y. (1988) Eur. J. Biochem. 176, 95-101; Ohno-Iwashita, Y., Iwamoto, M., Ando, S., Mitsui, K., & Iwashita, S. (1990) Biochim. Biophys. Acta 1023, 441-448]. To understand factor(s) which determine membrane cholesterol heterogeneity, we analyzed toxin binding to large unilamellar liposomes composed of cholesterol and phospholipids (phosphatidylcholine/phosphatidylglycerol = 82:18, mol/mol). Liposomes containing phospholipids with 18-carbon hydrocarbon chains at both positions 1 and 2 of the glycerol have both high- and low-affinity toxin-binding sites with Kd values similar to those of intact erythrocytes, whereas liposomes with hydrocarbon chains containing 16 or fewer carbons at either position 1 or 2 have only low-affinity toxin-binding sites. The cholesterol/phospholipid ratio, in addition to the length of phospholipid hydrocarbon chain, also determines the number of toxin-binding sites, indicating that at least these two factors determine the topology of membrane cholesterol by creating distinctively different affinity sites for the toxin. Since theta-toxin binding detects specific populations of membrane cholesterol that are not detectable by the measurements of susceptibility to cholesterol oxidase and cholesterol desorption from membranes, the toxin could provide a unique probe for studying the organization of cholesterol in membranes.

Bacterial Toxins

Increased plasma concentrations of endothelin-1 during and after pulmonary surgery.

We studied the involvement of endothelin-1 (ET-1) in the physiological response to surgical stress. Plasma concentrations of ET-1 were measured by a sandwich-type enzyme immunoassay. The blood samples were collected from the pulmonary artery (PA), the left atrium (LA), and the median cubital vein (MCV) in four patients who had undergone pulmonary lobectomy. The samples were collected before, during, and after surgery. Plasma ET-1 concentrations increased in the blood from all sampling sites. The highest concentration of plasma ET-1 was observed at 6 h after surgery in MCV (3.97 +/- 1.47 pg/ml, mean +/- SD) and at the end of surgery in PA (1.79 +/- 0.48 pg/ml) and in LA (1.93 +/- 0.43 pg/ml). These values returned to the baseline value within 72 h after surgery [1.21 +/- 0.19 (MCV), 1.00 +/- 0.18 (PA)]. Although the lung has a large capacity to remove ET-1 from the circulating blood, ET-1 concentrations measured in plasma samples obtained from the LA were not different from those obtained from the PA. This may suggest that the lungs have the ability to absorb and release ET-1 simultaneously during pulmonary surgery. The increase of ET-1 in MCV was greater than that in PA or in LA. This suggests the possibility of ET-1 release from the forearm.

Endothelins

Multiple neurite formation in neuroblastoma cell lines by griseolic acid, a potent inhibitor of cyclic nucleotide phosphodiesterases.

The morphological change of several neuroblastoma cell lines induced by griseolic acid, a novel and potent inhibitor of cyclic nucleotide phosphodiesterase (PDE), was examined. In the cell lines tested, Neuro-2a (a murine neuroblastoma cell line) showed dose-dependent (1 microM-1 mM) neurite extension. Griseolic acid markedly increased the intracellular cyclic AMP level of Neuro-2a cells, suppressed DNA synthesis (82% at 1 mM), and induced multipolar (multiple-neurite-bearing)-type neuritogenesis. A similar type of neurite outgrowth was induced by 8-bromo-cyclic AMP, which also elevated the intracellular cyclic AMP concentration. In contrast, when Neuro-2a cells were treated with retinoic acid, neurite formation was of the monopolar (single-neurite-bearing) type. Papaverine and theophylline, which have been frequently used as PDE inhibitors, failed to induce these morphological changes up to 1 mM, probably owing to the lesser potency of these compounds as compared with griseolic acid on the inhibition of PDE. Retinoic acid, theophylline, and papaverine were ineffective at elevating the intracellular cyclic AMP level. These results suggest that multipolar-type cell shape change in Neuro-2a cells is correlated with the accumulation of intracellular cyclic AMP and that griseolic acid is a useful compound to induce neuroblastoma cells into terminal differentiation.

2',3'-Cyclic-Nucleotide Phosphodiesterases

A case of renin producing leiomyosarcoma originating in the lung.

A 54-year-old woman was referred to our hospital for the treatment of a tumor of the right chest wall. Clinical examination revealed hypertension, hypokalemia, metabolic alkalosis, hyperaldosteronism and hyperreninemia. Computed tomography and an abdominal echogram indicated a tumor in the right phrenic area and two tumors in the retroperitoneum near the pancreas head. After the surgical resection of these tumors, the primary reninism was diminished. The pathological diagnosis of these tumors was leiomyosarcoma. Plasma active and inactive (trypsin-activated) renin activities (PRA) were 85.7 and 38.9 ng angiotensin I/ml/h, respectively. These PRA did not respond to either postural stimulation or suppression by the volume expansion. Active and inactive renin activities in a right phrenic area tumor were 208 and 32 ng angiotensin I/mg protein /h, respectively. Those of an abdominal tumor were 196 and 30 ng angiotensin I/mg protein/h, respectively. Renin mRNA identical in molecular size to that of the human kidney was identified by northern blot analysis. This is the first case report of renin producing leiomyosarcoma derived from the lung, which is characterized by relatively lower plasma prorenin concentrations.

Abdomen

[Recurrent herpetic keratitis in mice].

In order to investigate the mechanism of recurrence in herpes simplex keratitis, it is very important to establish an animal model. As a first step, mice were examined with the slit-lamp biomicroscope to determine whether they spontaneously showed recurrent epithelial keratitis after healing of primary herpetic keratitis. Among 90 eyes of 45 inbred C57BL/6 mice, recurrent epithelial keratitis stained with fluorescein was observed in 10 eyes of 9 mice during the observation period up to 50 days after the primary corneal infection with herpes simplex virus (HSV) type I Amakata strain (virulent strain). Recurrent epithelial keratitis was observed in 17 eyes of 15 mice among 116 eyes of 58 ddy mice infected with HSV-I Ska strain (avirulent strain). The epithelial lesions showed punctate or dendritic patterns and continued for one to 7 days. HSV antigen was detected by the fluorescent antibody technique in the cornea of 5 out of 8 eyes which showed recurrent epithelial keratitis using another ddy mice group tested. It was limited in the epithelium of the cornea. These results show that mice herpetic keratitis recurs spontaneously.

Animals

Examination of the role of serine phosphorylation in phospholipase C-gamma and its related P47 in cAMP-mediated depression of epidermal growth factor signal transduction.

Forskolin-pretreatment of A431 cells reduced both intrinsic and epidermal growth factor (EGF)-induced EGF receptor phosphorylation, however, phosphorylation of phospholipase C-gamma (PLC-gamma) was stimulated under the same conditions. No significant difference was detected in the amount of phosphotyrosine of PLC-gamma between two cultures with or without forskolin treatment followed by EGF. On the other hand, phosphorylation of a 47 kDa protein (P47) which cross-reacted with an anti-PLC-gamma monoclonal antibody, was stimulated by both forskolin and EGF. Phosphorylation was exclusively on serine residues in this case. These results indicate that both PLC-gamma and P47 are phosphorylated by a cAMP-dependent protein kinase and the EGF-stimulated serine kinase, and suggest that serine phosphorylation of PLC-gamma has no effect on ligand-dependent coupling with the EGF receptor.

Colforsin