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Biomedical subjects

M Takao

Publications and source records attributed to M Takao.

At least 19 recordsLinked to original sources
PubMed1995

A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light.

Many eukaryotic organisms, including humans, remove ultraviolet (UV) damage from their genomes by the nucleotide excision repair pathway, which requires more than 10 separate protein factors. However, no nucleotide excision repair pathway has been found in the filamentous fungus Neurospora crassa. We have isolated a new eukaryotic DNA repair gene from N.crassa by its ability to complement UV-sensitive Escherichia coli cells. The gene is altered in a N.crassa mus-18 mutant and responsible for the exclusive sensitivity to UV of the mutant. Introduction of the wild-type mus-18 gene complements not only the mus-18 DNA repair defect of N.crassa, but also confers UV-resistance on various DNA repair-deficient mutants of Saccharomyces cerevisiae and a human xeroderma pigmentosum cell line. The cDNA encodes a protein of 74 kDa with no sequence similarity to other known repair enzymes. Recombinant mus-18 protein was purified from E.coli and found to be an endonuclease for UV-irradiated DNA. Both cyclobutane pyrimidine dimers and (6-4)photoproducts are cleaved at the sites immediately 5' to the damaged dipyrimidines in a magnesium-dependent, ATP-independent reaction. This mechanism, requiring a single polypeptide designated UV-induced dimer endonuclease for incision, is a substitute for the role of nucleotide excision repair of UV damage in N.crassa.

Amino Acid Sequence↗
PubMed1995

Exhaled nitric oxide in isolated pig lungs.

Endothelium-derived nitric oxide (NO) is an important regulator of vascular resistance. Low concentrations of NO have been recorded in the exhaled breath of spontaneously breathing animals and humans. To determine whether NO synthesis in the lung contributes to the NO measured in the breath, we measured the concentration of NO in the exhaled air of isolated perfused and ventilated porcine lungs by using a chemiluminescence method. With NO-free normoxic ventilation (21% O2-5% CO2-74% N2) of eight porcine lungs perfused with a Krebs-dextran and albumin perfusate, baseline exhaled NO was 5.8 +/- 1.8 parts per billion (ppb) and pulmonary vascular resistance (PVR) was 8.9 +/- 1.8 mmHg.l-1.min. Hypoxic ventilation (5% O2-5% CO2-90% N2) caused a fall in NO to 3.6 +/- 1.8 ppb and a rise in PVR to 13.6 +/- 3.6 mmHg.l-1.min. Vasoconstriction with the thromboxane analogue U-46619 (10(-9) M) raised PVR to 31.7 +/- 6.8 mmHg.l-1.min but did not decrease NO levels from baseline. Subsequent addition of acetylcholine (10(-6)M) lowered PVR to 22.1 +/- 4.5 mmHg.l-1.min and increased exhaled NO to 7.0 +/- 2.0 ppb. Addition of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (10(-5) M), to four lungs caused a rise in PVR to 43.0 +/- 7.0 mmHg.l-1.min and a decrease in NO to 1.5 +/- 1.0 ppb. Addition of autologous blood to the perfusate of four lungs caused no change in PVR from baseline but decreased exhaled NO to 2.7 +/- 0.5 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Relationship of cigarette smoking to the severity of coronary and thoracic aortic atherosclerosis.

We studied the relationship of cigarette smoking to the severity of coronary and thoracic aortic atherosclerosis in 116 men who received coronary angiography and transesophageal echocardiography. Severity of coronary atherosclerosis was assessed in terms of Gensini's score (GS), and that of thoracic aortic atherosclerosis was assessed by the average sclerotic length (ASL) and average sclerotic area (ASA). The plasma fibrinogen levels were significantly positively correlated with smoking, and fasting blood sugar levels tended to be positively associated with smoking. GS was inversely associated with serum levels of high density lipoprotein (HDL) cholesterol. ASL and ASA were positively associated with age, fasting blood sugar levels and plasma fibrinogen levels, and these associations were statistically significant. Analysis of covariance was used to examine the net association between cigarette smoking and GS, ASL or ASA controlling for age, total cholesterol, HDL cholesterol, fasting blood sugar and plasma fibrinogen. We found that GS, ASL, and ASA were all significantly increased with increasing number of cigarette years. Additional adjustment for other risk factors (triglyceride, uric acid, body mass index, alcohol use and hypertension) also showed a strong independent contribution of smoking to GS, ASL and ASA. We concluded that the cumulative exposure to cigarette smoking was an independent indicator of the severity of coronary atherosclerosis as well as thoracic aortic atherosclerosis.

Adult↗
PubMed1994

A new class of DNA photolyases present in various organisms including aplacental mammals.

DNA photolyase specifically repairs UV light-induced cyclobutane-type pyrimidine dimers in DNA through a light-dependent reaction mechanism. We have obtained photolyase genes from Drosophila melanogaster (fruit fly), Oryzias latipes (killifish) and the marsupial Potorous tridactylis (rat kangaroo), the first photolyase gene cloned from a mammalian species. The deduced amino acid sequences of these higher eukaryote genes show only limited homology with microbial photolyase genes. Together with the previously cloned Carassius auratus (goldfish) gene they form a separate group of photolyase genes. A new classification for photolyases comprising two distantly related groups is proposed. For functional analysis P.tridactylis photolyase was expressed and purified as glutathione S-transferase fusion protein from Escherichia coli cells. The biologically active protein contained FAD as light-absorbing cofactor, a property in common with the microbial class photolyases. Furthermore, we found in the archaebacterium Methanobacterium thermoautotrophicum a gene similar to the higher eukaryote photolyase genes, but we could not obtain evidence for the presence of a homologous gene in the human genome. Our results suggest a divergence of photolyase genes in early evolution.

Amino Acid Sequence↗
PubMed1994

The pulmonary vascular response to acute hypoxia in chronic pulmonary disease: morphological assessment with magnified pulmonary wedge angiography.

To detect hypoxic pulmonary vasoconstriction (HPV) morphologically, we investigated the pulmonary vascular response to acute hypoxia in 27 patients with chronic pulmonary disease (CPD) and 8 healthy subjects. Pulmonary hemodynamic measurements and magnified pulmonary wedge angiography (MPWA) were carried out before and after inhalation of 13% oxygen in nitrogen for 15 min. The diameters of central arteries (A) and muscular arteries (B) were measured using a densitometric method. Vasoconstriction was detected in the muscular arteries than in the central arteries by MPWA. There was a significant correlation between delta P (changes of mean PA pressure) and delta B/A (changes in diameters of B/A) in the CPD group. A significant correlation was found between delta SvO2 and delta B/A in the control group. We conclude that MPWA was a very useful method for the simple detection of HPV in patients with CPDs and we detected one site of HPV on the ninth generation of the pulmonary arterial tree by MPWA.

Adult↗
PubMed1992

A case of asymptomatic cortisol producing adrenal adenoma.

We describe a man without the clinical findings of Cushing's syndrome, but who harbored an incidentally found cortisol-producing adrenal adenoma. On adrenal 131I-adsterol imaging, there was good uptake to the nodule, but no visualization of the contralateral adrenal. No abnormalities were found in the basal plasma cortisol, ACTH, urinary free cortisol and 17OHCS. However, dynamic hormone assessment revealed the existence of abnormal cortisol secretion: no suppression to dexamethasone, incomplete response to human corticotropin-releasing hormone, and lack of diurnal variation in plasma cortisol. Left adrenalectomy was performed with the diagnosis of cortisol-producing adrenal tumor. The pathological finding was an adrenal adenoma, and the perifusion of the excised tissues revealed a negligible response of the tumor tissue to ACTH though the residual normal cortex responded. Postoperative course was uneventful without replacement therapy with cortisol. It is suggested that the tumor autonomously produced a small amount of cortisol not only insufficient to provide clinical Cushing's syndrome, but also to provide typical suppression of hypothalamo-pituitary corticotroph-adrenal system.

Adenoma↗
PubMed1992

[Urodynamic studies before and after gradual urethral dilatation with metal sounds for female urethral stricture].

We evaluated the urodynamics in women with urethral stricture after urethral dilatation. A total of 16 patients underwent treatment with gradual urethral dilatation at increasing intervals (2 weeks, 1 month, 3 months and 6 months). Their urethra was dilated up to 30 F. with metal sounds. Urethral calibration with bougie à boule, uroflowmetry and urethral pressure profile were performed before urethral dilatation and 1 week after the last dilatation. The urethral caliber was increased from 18.1 +/- 0.6 F. to 23.5 +/- 1.0 F. (P less than 0.005), average flow rate from 9.4 +/- 0.8 ml/sec to 11.2 +/- 1.1 ml/sec (P less than 0.025) and maximum urethral pressure with a full bladder decreased from 105.4 +/- 9.4 cmH2O to 87.5 +/- 10.5 cmH2O (P less than 0.05). With gradual urethral dilatation with metal sounds, (1) the urethra was significantly dilated, (2) maximum urethral pressure was significantly decreased and (3) average flow rate was significantly increased.

Adult↗
PubMed1992

[Reconstructive surgery for mitral regurgitation caused by degenerative disease--indications for expansion and early clinical outcomes].

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Adolescent↗
PubMed1991

Unique characteristics of superoxide dismutase of a strictly anaerobic archaebacterium Methanobacterium thermoautotrophicum.

The superoxide dismutase (SOD) gene of Methanobacterium thermoautotrophicum (Takao, M., Oikawa, A., and Yasui, A. (1990) Arch. Biochem. Biophys. 283, 210-216), a strictly anaerobic archaebacterium, was expressed in Escherichia coli. The gene product accounted for more than 30% of the host's soluble protein. The purified protein was an active iron-containing tetrameric SOD with specific activity similar to known manganese-containing SODs (MnSODs) of aerobic archaebacteria. Although M. thermoautotrophicum SOD is an iron-containing SOD (FeSOD), it resembles MnSODs in amino acid sequence as judged by criteria distinguishing FeSODs from MnSODs. Moreover, M. thermoautotrophicum SOD is resistant to azide and hydrogen peroxide as MnSODs are, suggesting that its evolution is distinct from known eubacterial FeSODs.

Amino Acid Sequence↗
PubMed1991

The enhancement of myocardial protection through an acalcemic storage solution containing nicardipine, a potent calcium channel blocker. A basic study using rat ventricular myocytes.

Adult rat ventricular myocytes were used as a model system for investigating the direct effects of nicardipine, a potent calcium-channel blocker, on preservation of the heart during periods of simple cold storage. Cells were stored at 4 degrees C for 24 hr with an acalcemic storage solution. The superfusate then was exchanged with hypoxic Tyrode solution (1.8 mmol/L CaCl2). After 2 hr of hypoxia at 20 degrees C, cells were reoxygenated and simultaneously warmed to 37 degrees C. The addition of nicardipine to both the storage solution and Tyrode solution resulted in the highest percentage of viable cells (70.5%). Using either the storage solution or Tyrode solution containing the compound, the percentages of viable myocytes were 51.9% and 52.2%, respectively. In the absence of the drug in either solution, the percentage was 38.0%. The effect of diltiazem, another potent calcium-channel blocker, was examined using the same experimental procedure. The addition of diltiazem to Tyrode solution elevated the viability of ventricular myocytes, but addition to the storage solution showed no cardioprotective effect. Moreover, the addition of 8-bromo cyclic GMP to the storage solution resulted in a cardioprotective effect. These results suggested that nicardipine exerts a direct effect on myocardial protection in hypothermic and acalcemic storage solution and that the pharmacological effect of nicardipine depends on a mechanism other than its calcium-channel blocking action.

Animals↗
PubMed1991

[The effects of gravity load on the canine kidney].

In Self-defense Force Hospitals we often treat pilots with renal stones who will be exposed to high gravity (G) load after the treatment. Because the regulation prohibits the flight of a pilot with urolithiasis, the stone must be removed completely by noninvasive procedure. Percutaneous nephrolithotomy, therefore, is one of the treatment of choice in such patients. The effect of G load on the kidney, in particular, on the renin-angiotensin-aldosterone (R-A-A) system and the safety of percutaneous nephrolithotomy in a pilot who is exposed to high G load have not been adequately investigated. In this study, I examined the effect of G load in canine kidney model. The effect of G load on R-A-A system: Twenty-two adult mongrel dogs of a mean weight of 10.9 kg. maintained on a normal Na+ intake were studied. To dogs in the sitting position, high G load was given. The exposure to G load consisted of maximum load of 8 G for 45 seconds with the onset ratio of 0.1 G/sec. for group 1, and 5 courses of maximum G load of 8 G for 10 seconds with the onset ratio of 2.5 G/sec., followed by 1.5 G for 60 seconds for group 2. Plasma renin activity was unchanged in group 1, but it increased in group 2. Plasma aldosterone increased from 68.6 +/- 17.9 to 252.0 +/- 56.4 pg/ml (p less than 0.005) in group 1. and from 191.8 +/- 40.6 to 479.2 +/- 76.0 pg/ml (p less than 0.005) in group 2 after G load. Angiotensin II decreased from 129.0 +/- 19.4 to 84.7 +/- 19.1 pg/ml (p less than 0.05) after G load in group 2. These data suggest that the increase in plasma aldosterone after G load in independent of the renin-angiotensin system. It is considered that the alteration of R-A-A system was caused by the change of blood flow distribution due to the effect of G load. The tolerance to G load on the kidney following subcutaneous nephrostomy: Unilateral subcutaneous nephrostomies were carried out under pentobarbital anesthesia in 15 adult female mongrel dogs. Each experimental dog was exposed to high G load 2 or 4 weeks after removal of the nephrostomy tube. Excretory urography, renal angiography and renal function tests were performed before and after G load. Excretory urograms demonstrated no remarkable changes at all after G load in all dogs. Renal angiograms revealed small renal infarction along the nephrostomy tract in almost all dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

Aerospace Medicine↗