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Biomedical subjects

M Kido

Publications and source records attributed to M Kido.

At least 19 recordsLinked to original sources

RNase E polypeptides lacking a carboxyl-terminal half suppress a mukB mutation in Escherichia coli.

We have isolated suppressor mutants that suppress temperature-sensitive colony formation and anucleate cell production of a mukB mutation. A linkage group (smbB) of the suppressor mutations is located in the rne/ams/hmp gene encoding the processing endoribonuclease RNase E. All of the rne (smbB) mutants code for truncated RNase E polypeptides lacking a carboxyl-terminal half. The amount of MukB protein was higher in these rne mutants than that in the rne+ strain. These rne mutants grew nearly normally in the mukB+ genetic background. The copy number of plasmid pBR322 in these rne mutants was lower than that in the rne+ isogenic strain. The results suggest that these rne mutations increase the half-lives of mukB mRNA and RNAI of pBR322, the antisense RNA regulating ColE1-type plasmid replication. We have demonstrated that the wild-type RNase E protein bound to polynucleotide phosphorylase (PNPase) but a truncated RNase E polypeptide lacking the C-terminal half did not. We conclude that the C-terminal half of RNase E is not essential for viability but plays an important role for binding with PNPase. RNase E and PNPase of the multiprotein complex presumably cooperate for effective processing and turnover of specific substrates, such as mRNAs and other RNAs in vivo.

Bacterial Proteins

[Superior septal approach for mitral valve surgery].

The superior septal approach (SSA) for mitral valve surgery is a useful approach, but it may bring about demage to sinus node function or an atrial electrical vulnerable condition because the sinus node artery is divided and a large portion of both atria is incised. From April 1992 to December 1994, we used this approach in 17 patients. There was no hospital death and none had perioperative complications associated with the approach. All nine patients in sinus rhythm preoperatively returned to sinus rhythm before discharge from the hospital and remained so at late follow-up. Five of 9 patients with sinus rhythm had electrophysiological examination preoperatively and all 9 patients had the examination postoperatively. Atrial vulnerability was not deteriorated after the operation in all cases. Under pharmacologic autonomic blockade, sinoatrial conduction time (SACT), sinus node recovery time (SNRT) after overdrive atrial pacing, and corrected SNRT were 73 +/- 35 msec, 1142 +/- 168 msec, and 365 +/- 122 msec, respectively. All these values were with in normal range and these were no significant differences between before and after the operation. All patients with sinus rhythm had 3 minutes of Bruce stage 1 exercise 9 months after the operation. The heart rate response to the exercise was as good as in healthy control people. In conclusion, as far as the midterm postoperative period, the effect of SSA on sinus node function and atrial vulnerability was acceptable.

Adult

[Significance of hot shot in patients with unstable angina undergoing emergency coronary artery bypass graft surgery].

We investigated the efficacy of terminal warm blood cardioplegia (hot shot) in patients with cardioplegic techniques. From January 1991 through April 1993, 68 patients recieved hypothermic cardioplegia induced by cold modified St. Thomas' Hospital solution containing 10mg/L of diltiazem hydrochloride followed by intermittent infusion of the cold crystalloid solution or cold blood cardioplegia without hot shot. From May 1993 through December 1994, 65 patients recieved hot shot before removal of aortic cross-clamp following the hypothermic cardioplegia. The earlier group consisted of 51 patients with stable angina undergoing elective CABG and 17 patients with unstable angina undergoing emergency of urgent CABG. The later group consisted of 44 patients with stable angina and 21 patients with unstable angina. The unstable angina undergoing coronary artery bypass graft surgery (CABG) using antegrade incidence of perioperative myocardial infarction was significantly higher in patients with unstable angina without hot shot (35%) compared to those with stable angina with and without hot shot (2% and 4%, respectively) and those with unstable angina with hot shot (5%). The level of maximum creatine kinase-MB (IU/L) was significantly greater in patients with unstable angina without hot shot (134 +/- 26) compared to those with stable angina with and without hot shot (57 +/- 7 and 65 +/- 4, respectively) and those with unstable angina with hot shot (57 +/- 8). The doses of dopamine and dobutamine (mg/kg) administered during 48 hours after CABG was not different between patients with stable angina with and without hot shot (13.9 +/- 0.9 vs 13.9 +/- 0.9), but tended to be lower in patients with unstable angina with hot shot (13.7 +/- 1.3) compared to those without hot shot (18.6 +/- 2.1). Left ventricular stroke work index (g.m/m2/b) immediately after CABG was comparable between patients with stable angina with and without hot shot (40 +/- 2.0 vs 36 +/- 1.5), but significantly greater in patients with unstable angina with hot shot (39 +/- 2.3) compared to those without hot shot (29 +/- 2.2). These results suggest that hot shot may provide a significant benefit in myocardial preservation during CABG especially in patients with unstable angina.

Aged

Hypoglycemia associated with localized fibrous mesothelioma of the pleura.

Hypoglycemia is known to be a rare consequence of non-islet cell tumors. A patient having severe, episodic hypoglycemia was found to have a large mass occupying the right hemithorax. The hypoglycemia resolved immediately after surgical removal of the tumor. Histologic examination of the tumor revealed localized fibrous mesothelioma.

Female

[A case of pulmonary hyalinizing granuloma with its occupational history of dust exposure].

Multiple pulmonary nodules were found in a patient who had an occupational history of coal mining for eleven years and road construction for fifteen years. An open lung biopsy was performed, because nodules had increased in size compared to previous ones and a trasbronchial biopsy was not diagnostic. The nodules were composed of dense concentric lamellar collagenous structures with a serpentine pattern surrounded by an infiltration of histiocytes, lymphocytes and plasma cells with Russel bodies. These findings are compatible with pulmonary hyalinizing granuloma (PHG) named by Liebow A. A. The etiopathogenetic mechanism and the difference between PHG and silicotic nodule is discussed.

Aged

Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets.

A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o-tolylimidazol-2-yl)sulfinylpropoxy]-2( 1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

[A case of sarcoidosis with advanced cystic and fibrotic changes in a young patient].

A 29-year-old man was referred to our hospital because of exertional dyspnea and progressive eruption on the buttocks and the lower extremities. Chest roentgenograms and computed tomograms taken at that time revealed diffuse fibrotic changes accompanied by multiple cavities and bullae in the lungs. There were no signs of mediastinal or hilar lymphadenopathy. A chest roentgenogram taken 7 years before admission showed no abnormalities. Serum ACE and lysozyme levels were high: 29.9 IU/l and 14.1 micrograms/ml, respectively. 67Ga scintigraphy showed diffuse uptake in both lung fields. The PPD skin test was negative, and repeated sputum smears and cultures were negative for pyogenic bacteria and acid-fast bacilli. Examination of transbronchial lung biopsy and skin biopsy specimens confirmed the diagnosis--they showed noncaseating epithelioid granulomas with giant cells and a negative reaction of the stain to acid-fast bacilli, which are compatible with sarcoidosis. The patient was given 30 mg/d of prednisone orally. The dyspnea and eruption were clearly alleviated, although there was little roentgenographic regression of cystic or fibrotic changes. There have been only a few reports of cystic and fibrotic changes early in the course of sarcoidosis. The cystic lesions in this case were probably secondary pulmonary cavities caused by the contracting and obstructive changes related to pulmonary fibrosis.

Adult

Reduction of bicyclo[3.3.1]nonane-2,8-diones with baker's yeast.

Reduction of bicyclo[3.3.1]nonane-2,8-dione (1) and its homologues 2 and 3 with baker's yeast affords (1R,5S,8S)-8-hydroxybicyclo[3.3.1]nonan-2-one (4) and its higher homologues 5 and 6 with ca 97% e.e. in 72-86% yields. The absolute configuration of 5 was confirmed by the X-ray crystallographic analysis of its camphanic ester 22.

Bridged Bicyclo Compounds

Pharmacokinetic analysis of in vivo metabolism of amino acid or dipeptide conjugates of salicylic acid in rabbit intestinal microorganisms.

We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine, and tyrosine) or SA-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by intestinal microorganisms and, also, by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behavior was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.

Administration, Oral

Effects of inhaled ceramic fibres on macrophage function of rat lungs.

To evaluate the biological effect of ceramic fibres on the clearance function of alveolar macrophages (AMs) morphological changes and phagocytic activity of AMs were assessed. Rats were exposed to respirable ceramic fibres with a mass median aerodynamic diameter of 4.4 microns and a concentration of 20.1 mg/m3 in an exposure chamber. They were killed after one week (group A) and two weeks (group B) of exposure, and four weeks (group C) and 12 weeks (group D) after exposure for two weeks. The AMs recovered by bronchoalveolar lavage (BAL) from each test group were incubated with yeast and phagocytic activity was determined by counting the number of yeast cells in AMs. Morphological features of AMs were assessed by scanning electron microscopy and quantified according to morphological changes. Total cell counts in BAL fluid from exposed rats in group A were higher than in control rats. Phagocytic activity of exposed AMs in group B and C exceeded that of control AMs. Morphological changes of the exposed AMs in groups A, B, and C were greater than those of control AMs. These findings suggest that ceramic fibres induced the phagocytic activity and morphological changes in AMs, and that the clearance function of AMs was stimulated by the inhaled ceramic fibres.

Animals

Retention and clearance of inhaled ceramic fibres in rat lungs and development of a dissolution model.

Male Wistar rats were exposed to aluminium silicate ceramic fibres by inhalation to study pulmonary deposition, clearance, and dissolution of the fibres. Rats were killed at one day, one month, three months, and six months after the termination of exposure. After exposure, fibres greater than 50 microns in length were seen with a scanning electron microscope in the alveolar region of the lung. Fibres were recovered from the lungs with a low temperature ashing technique and their number, diameter, and length were measured by scanning electron microscopy. The number of fibres remaining in the lungs declined exponentially with time after exposure and their silicon content also fell. The geometric median diameter of fibres decreased linearly with time. By six months after exposure, the surface of fibres recovered from the lungs had an eroded appearance. The results suggest that ceramic fibres are physically cleared from the lung and that they show signs of dissolution. Finally, the results were used to develop a theoretical model of fibre dissolution that gives a satisfactory fit to the experimental data.

Aluminum Silicates

Guinea pig asthma induced by red soft coral (Dendronephthya nipponica) inhalation.

Spiny lobster fishermen on the Pacific coast of Miyazaki Prefecture in Japan develop bronchial asthma due to occupational sensitization to red soft coral (Dendronephthya nipponica). To assess the role of sensitization in the development of bronchial hyperresponsiveness and the relationship between bronchial responsiveness and bronchial inflammation, we established a guinea pig model of red soft coral induced asthma. Twenty-four guinea pigs were intramuscularly immunized with a priming dose of red soft coral, 5 OD280 (15 mg protein) per 0.5 ml, and 0.5 ml complete Freund's adjuvant on day 1. Booster doses were repeated on day 15. By day 43 all sensitized animals showed high hemagglutination titers against red soft coral conjugated sheep erythrocytes and high IgG1 titers by passive cutaneous anaphylaxis. On day 43, the animals were challenged by inhalation of red soft coral extracts, 20 OD280 for 30 min. The respiratory resistance was monitored by the oscillation method. The respiratory resistance increased immediately upon inhalation in all sensitized animals and returned to baseline within 4 h. The bronchial reactivity to acetylcholine, measured 6 h after red soft coral inhalation in the sensitized animals when the respiratory resistance was returned to baseline, increased significantly (p < 0.05) as compared with the values measured 24 h before inhalation. The acetylcholine response measured 30 h later did not differ from preinhalation levels. There was a significant difference in the number of eosinophils (p < 0.001) in lamina propria and epithelium and of lymphocytes (p < 0.05) in the lamina propria 6 h after inhalation in the sensitized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance