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Biomedical subjects

T Sakuma

Publications and source records attributed to T Sakuma.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Transport of ions across alveolar epithelial cells in resected human lungs].

Little information is available regarding the effect of ion transport agonists and antagonists on ion transport in the human lung. Therefore, we studied ion transport in lungs resected from patients with lung cancer. A test solution of 45 ml of isosmotic albumin was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air space very slowly, the concentration of alveolar protein over 4 h was used to quantify the volume of alveolar fluid. Ion transport was measured from the changes in ion concentrations and the volume of alveolar fluid. In the basal condition, the net efflux of Na+ and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+ ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M) increased the efflux of Na+ and Cl-, but did not affect the influx of K+. Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely correlated with Na+ transport and with Cl- transport. However, the values of Na+ transport were greater than those of Cl- transport. These data suggest that Na+ transport is accompanied by Cl- transport and fluid movement out of the alveolar space in resected human lungs.

Adrenergic beta-Agonists↗
PubMed1995

[Daytime pulmonary hypertension in the obstructive sleep apnea syndrome].

Patients with obstructive sleep apnea syndrome (OSAS) may have daytime pulmonary hypertension (PH). Transient and sometimes severe elevations of pulmonary arterial pressure during sleep as a result of intermittent upper airway obstruction may lead to daytime PH. We sought to study the factors involved in the development of daytime PH. Right-heart catheterization, pulmonary function tests, and arterial blood gas measurements were done in 25 patients in whom OSAS was diagnosed by whole-night polysomnography. Eight of the patients (32%) had PH, defined by a mean pulmonary arterial (PA) pressure > or = 20 mmHg. For the group as a whole, mean PA pressure was positively and significantly correlated with daytime PaCO2 (r = 0.79), percent of ideal body weight (r = 0.45), and Hb (r = 0.40). Mean PA pressure was negatively and significantly correlated with PaO2 (r = -0.54), FEV 1% (r = -0.52), and %FVC (r = -0.68). In contrast, mean PA pressure was not significantly correlated with apnea index or with sleep desaturation. These data indicate that daytime PH was not directly related to sleep-disordered breathing, but was related to daytime hypoxemia, daytime hypercapnia, obesity, obstructive and restrictive respiratory impairments, and secondary polycythemia.

Adult↗
PubMed1995

[Contribution of oxidative stress to pulmonary hypertension induced by chronic hypoxia].

Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with media wall thickening of pulmonary arteries in rats. Platelet-activating factor plays an important role in the pulmonary vascular remodeling induced by chronic hypoxia, and reactive oxygen species are involved in tissue injury induced by platelet activating factor. We therefore hypothesized that reactive oxygen species contribute to the pulmonary hypertension induced by chronic hypoxia, and examined the effect of N-acetyl-L-cysteine (NAC), a free radical scavenger and the precursor of glutathione sulfhydryl (GSH), on hypoxia-induced pulmonary hypertension. We used a chemiluminescence-HPLC assay to measure the levels of phosphatidylcholine hydroperoxide (PCOOH) in the rat lungs exposed to hypoxia. Three weeks of normobaric hypoxia (FiO2 = 0.1) with NAC significantly reduced pulmonary hypertension, right ventricular hypertrophy, and media wall thickening of the pulmonary arteries. NAC had no effect on the hematocrit of normoxic or chronically normobaric hypoxic rats. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. These results indicate that hypoxia induces oxidative stress in the lung tissue, and that oxidative stress may have a role in the development of pulmonary hypertension induced by chronic hypoxia in rats.

Acetylcysteine↗
PubMed1994

Molecular cloning and sequence analysis of hamster CYP2E1.

Two cDNA clones, pHSj31 and pHSj3, coding for CYP2E1 were isolated from a hamster liver cDNA library. The sequence analyses revealed that they encoded the same polypeptide of 493 amino acid residues (M(r) = 56,616) and differed from the length of their 3'-untranslated region. The deduced amino acid sequence of hamster CYP2E1 showed approx. 90% identities with those of the rats and mice, and approx. 80% identities with those of the rabbits, monkeys and humans. The NH2-terminal 35 deduced amino acid sequences of hamster CYP2E1 were completely identical with purified protein, ha P-450j. The Northern blot analysis showed that CYP2E1 was expressed in livers and to lesser extents in kidneys and lungs.

Amino Acid Sequence↗
PubMed1994

The granulocyte colony-stimulating factor produced in the human lung and its effect on liquid movement in the rabbit lung.

Levels of the granulocyte colony-stimulating factor (G-CSF) were determined in the plasma and resected lung tissue from patients who underwent pulmonary resection. Moreover, the effect of recombinant human (rh) G-CSF on the permeability of pulmonary endothelium and on liquid clearance from the alveolar spaces was investigated in rabbits. The plasma levels of G-CSF increased from 30 pg/ml preoperatively to 409 +/- 236 pg/ml 3 h postoperatively (P < 0.05), while the levels of G-CSF in the resected lung tissue were increased in the alveolar fluid, to 1,834 +/- 1,054 pg/ml, and in the pulmonary blood, to 5,466 +/- 2,019 pg/ml. It was found that rh G-CSF 25 micrograms administered into the subcutaneous tissue of rabbits increased extravascular lung water to 3.45 +/- 0.26 vs 2.98 +/- 0.20 in control experiments (P < 0.05); however, rhG-CSF 0.75 microgram/kg administered into the alveolar spaces did not affect liquid clearance from the alveolar spaces. The findings of this study led us to conclude that G-CSF is synthesized in the human lung and increases the permeability of pulmonary endothelium, but not liquid clearance across the alveolar epithelium.

Animals↗
PubMed1994

Pharmaceutical application of LC-MS. 1--Characterization of a famotidine degradate in a package screening study by LC-APCI MS.

The application of LC-MS to characterize low-level degradates in pharmaceutical dosage formulations is a new and challenging field. In a package screening study, a low-level degradate of famotidine (1, 3-[[[2-[[aminoiminomethyl]-amino]-4-thiazolyl]methyl] thio]-N-(aminosulphonyl)-propanimid-amide, an H2-receptor antagonist, molecular weight: 337) was detected by HPLC in film-coated tablets packaged in child-resistant (CR) foil pouches which were stressed at 40 degrees C/75% relative humidities (RH) for 4 months. LC-atmospheric pressure chemical ionization (APCI) mass spectrometry using positive ion mode yielded a molecular weight of 349 for the degradate, suggesting that it was formed by the addition of one carbon to the famotidine molecule. A detailed analysis of the positive product ion mass spectrum of the protonated degradate ion in a LC-MS-MS study indicated that the carbon was added to the side of N-(aminosulphonyl)-propanimid-amide of famotidine. The structure of the degradate was determined to be 2, which was confirmed by LC-APCI MS and HPLC study of the product formed from the reaction of famotidine with formaldehyde--a one-carbon reagent.

Chromatography, High Pressure Liquid↗
PubMed1994

Alveolar fluid clearance in the resected human lung.

Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not been any information regarding the effect of ion transport agonists or antagonists on alveolar liquid clearance in the human lung. Therefore, we studied alveolar liquid clearance in the recently resected human lung from patients who underwent surgery for lung cancer. A test solution of 40 ml of isosmolar albumin solution was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air spaces very slowly, the concentration of alveolar protein over 4 h was used to quantify alveolar liquid clearance. Basal alveolar liquid clearance was 12 +/- 2% over 4 h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, and ouabain (10(-3) M), an inhibitor of Na,K-ATPase activity, reduced alveolar liquid clearance by 40 and 49%, respectively (p < 0.005). Terbutaline (10(-3) or 10(-4) M) doubled alveolar liquid clearance to 28 +/- 9% over 4 h (p < 0.05). Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in alveolar liquid clearance. In conclusion, (1) alveolar liquid clearance in the human lung can be markedly reduced by inhibition of apical sodium channel uptake or Na,K-ATPase activity, and (2) beta-adrenergic stimulation markedly increases the rate of alveolar liquid clearance in the resected human lung without pulmonary perfusion.

Aged↗
PubMed1994

Adrenogenital syndrome caused by an androgen-producing adrenocortical tumor.

We describe here a typical case of virilizing adrenocortical tumor. A 23-year-old Japanese woman had her male-like musculature, hirsutism, the absence of breast development and marked clitoromegaly. Adrenal androgens were remarkably elevated, with plasma dehydroepiandrosterone sulfate 2,752 micrograms/dl, plasma testosterone 250 ng/dl and urinary 17-ketosteroids 203.4 mg/day. A well-encapsulated tumor approximately 7 cm in diameter was detected in the left adrenal gland by computed tomography, magnetic resonance imaging and arteriography. The tumor was surgically resected and histologically diagnosed as a benign adrenocortical adenoma. The elevated adrenal androgens returned to normal postoperatively with amelioration of her masculinized clinical features.

Adenoma↗
PubMed1994

[Reflux nephropathy within first year of life. Studies of its clinical features and kidney scar-formation according to treatment modalities].

Clinical data of 106 patients (177 renal units) with vesicoureteral reflux diagnosed within first year of life were reviewed to clarify its clinical feature and reflux nephropathy. 1) 82.1% (87/106) of them were boy, 83.1% (147/177) of renal units had high grade reflux (VUR grade III or more). These findings suggested that some of them were Fetal Vesicoureteral Reflux. 2) At presentation, 57.1% (101/177) of renal units showed renal parenchymal scars and 18.9% (20/106) of cases had renal dysfunction (s-Cr > or = 0.6 mg/dl). Renal dysplasia or hypoplasia was found in rather high incidence of 8.5% (15/177) suggested that normal fetal nephrogenesis is also disturbed in early infants having VUR. 3) The patients having multiple renal scarring bilaterally had significant impaired both tubular and glomerular function, showing reflux nephropathy. 4) During more than 2 years follow-up on 102 renal units, totally 29 of them (28.4%) showed new scar-formation and/or scar-advancement. Among the kidneys more than grade III reflux and undergone antireflux surgery, those with delayed surgery had the incidence of new scar-formation and/or scar-progression as high as 48.6% (18/37). On the other hand, in those with immediate surgery, the incidence was much lower of 14.3% (5/35). In addition, the incidence in case of non-surgery was 38.5% (5/13). Indication or timing of antireflux surgery for infants is still controversial however, the above results suggest that early antireflux surgery which aimed to eliminate reflux and risk of upper urinary tract deterioration from infantile immatured kidney is more beneficial in order to prevent progression of renal scarring and attain normal renal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Cicatrix↗
PubMed1994

[Effects of Pseudomonas aeruginosa on transport of protein and liquid from alveolar spaces in anesthetized rabbits].

We determined the effects of Pseudomonas aeruginosa on transport of protein and liquid across the alveolar epithelium in anesthetized rabbits. Following the injection of 3 microCi of 131I-albumin in anesthetized rabbits as a vascular marker, we instilled 3 ml/kg of 5% albumin solution with 10(7) or 10(9) CFU P. aeruginosa, 3 microCi of 125I-albumin and 3 mg of Evans blue into the alveolar spaces of the right lung. The rabbits were ventilated with 60-100% oxygen and 1-2% halothane over 8 h. We removed the lungs and aspirated the alveolar fluid 8 h after instillation. We measured protein concentration in instilled and aspirated alveolar fluid, and radioisotope counts in alveolar fluid, homogenized lung and plasma. Then we calculated the influx and efflux of radioisotope across the alveolar epithelium. Liquid clearance from the alveolar spaces and the lungs was calculated using protein concentration of alveolar fluid and extravascular lung water. In the experiments with 10(9) CFU P. aeruginosa, we found that 125I-albumin remaining in the lungs decreased and 125I-albumin in plasma increased. Lung liquid clearance decreased by 15%. However, protein and liquid clearance in the experiments with 10(7) CFU P. aeruginosa or autologous serum were not different from those in the control experiments. P. aeruginosa was cultural from blood, right pleural effusion, and liver in the experiments with 10(9) CFU P. aeruginosa, but not in the experiments with the alveolar epithelium, but decreases clearance of liquid from the alveolar spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1994

[Effect of amurinone on human pulmonary artery in vitro].

We studied the effect of amurinone, a phosphodiesterase inhibitor, on human pulmonary arterial smooth muscle in vitro. Amurinone caused dose-dependent relaxation of pulmonary arterial strips precontracted with 60 mM KCl. Preincubation with either meclofenamate (31 microM), a cyclooxygenase inhibitor, or L-NG-nitroarginine (100 microM), an endothelium-derived relaxing factor (EDRF) production inhibitor, failed to inhibit amurinone-induced pulmonary vasodilation. The cyclic AMP (cAMP) levels in the supernatant of the lung vessel homogenates significantly increased after incubation with amurinone. These results indicate that amurinone causes relaxation of human pulmonary artery in vitro, and suggest a role for cAMP in the mechanisms of amurinone-induced pulmonary vasodilation.

Adult↗
PubMed1994

Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs.

Sex-related differences in the expression of cytochrome P450 isozymes in hamsters were investigated. Three distinct cDNA clones (assigned as CYP2C25, CYP2C26, and CYP2C27) were isolated from liver cDNA libraries from male and female hamsters, using rat CYP2C11 cDNA as a probe. Sequence analysis revealed that these three forms were very similar to each other (> 90% identity of nucleotide sequences) and belong to the CYP2C gene subfamily. The CYP2C25, CYP2C26, and CYP2C27 cDNA clones consisted of an open reading frame encoding 490 amino acids. CYP2C25, CYP2C26, and CYP2C27 proteins expressed in Saccharomyces cerevisiae catalyzed the hydroxylation of tolbutamide and the N-demethylation of aminopyrine and benzphetamine. Only CYP2C25 showed testosterone hydroxylase (16 beta) activity. Northern blot analyses with specific oligonucleotide probes demonstrated that expression of CYP2C27 was male specific and male predominant in kidneys and livers, respectively. No sex-related difference was observed in the expression of CYP2C25 and CYP2C26. These results support our previous findings that sex-related differences in the expression of liver microsomal cytochromes P450 occur in hamsters.

Aminopyrine↗
PubMed1993

Folding topology and DNA binding of the N-terminal fragment of Ada protein.

Three amino terminal fragments of Escherichia coli Ada protein (39 kDa) with different molecular masses (14 kDa, 16 kDa and 20 kDa) were prepared in large quantities from an E. coli strain harboring plasmids constructed for the overproduction of the truncated proteins. The three fragments can be methylated to an extent similar to that of the intact molecule. The methylated 16 kDa fragment specifically binds to the ada box on a DNA duplex. NMR analyses revealed that the 14 kDa fragment comprises two alpha-helices and a beta-sheet with parallel and anti-parallel mixed strands. A comparison of the 15N-1H HMQC spectra of the fragments has led to the conclusion that this tertiary structure within the 14 kDa fragment is retained in the larger 16 kDa and 20 kDa fragments.

Amino Acid Sequence↗
PubMed1993

Electrospray ionization mass spectrometry as a mechanistic tool: mass of human leucocyte elastase and a beta-lactam-derived E-I complex.

We have utilized liquid chromatography electrospray ionization mass spectrometry (ESI-MS) to probe the nature of the covalent E-I complex of human leucocyte elastase (HLE) and a beta-lactam. The mass spectrum of HLE isozyme 4 displayed one major and two minor components with masses of 25,202, 25,043, and 24,522 Da, respectively. Isozyme 3 displayed three components, with masses of 25,180, 24,030, and 24,523 Da. These data suggest that the isozymes differ in the type and not the content of carbohydrate. The minor components represent decreases in carbohydrate content. Inactivation of isozyme 4 with trans-4-(ethoxycarbonyl)-3-ethyl-1-[(4-nitrophenyl)sulfonyl]-azetidin -3-one increased the mass of the three components by that of the parent compound. Similar results were obtained with the mixture of HLE isozymes. These observations demonstrate that HLE does not catalyze the beta-elimination of p-nitrophenylsulfinate as Firestone et al. [(1990) Tetrahedron 46, 2255) suggested. In addition, it suggests that a "double hit" of both the active-site serine and histidine is not required to form a stable acyl-enzyme. Noncovalent complexes between HLE and either the tight-binding secretory leucoprotease inhibitor (SLPI) or a slow tight-binding peptide difluoroketone inhibitor were not observed by ESI-MS. SLPI displayed a mass of 11,710 Da in the absence and presence of HLE. These data demonstrate the utility of ESI-MS to probe the mechanism of inhibition of enzymes by mechanism-based inhibitors.

Anti-Bacterial Agents↗
PubMed1993

Adult T-cell leukemia with leukemic cell infiltration in the conjunctiva. A case report.

A 77-year-old Japanese woman who had suffered from skin eruptions since 1986 was admitted in January, 1990. A diagnosis of adult T-cell leukemia/lymphoma (ATL) was made on the basis of clinical and laboratory data. On admission, erythematous lesions were present in both eyelids. Yellowish-white elevated lesions were found along the limbal conjunctiva, and extended segmentally into the cornea of both eyes. Microscopically, leukemic infiltration into the subepithelial layer of the conjunctiva was observed. Ophthalmic manifestations in ATL have not been well described, because of a little attention paid to them.

Aged↗
PubMed1993

Effects of percutaneous transluminal mitral valvuloplasty on plasma catecholamine levels during exercise.

Elevation of plasma catecholamine levels during exercise in patients with mitral stenosis correlated with the severity of the disease. We investigated the plasma norepinephrine changes in six patients before and after percutaneous transluminal mitral valvuloplasty (PTMV) during continuously graded ergometer exercise. Peak exercise intensity was increased from 65.8 W to 87.5 W after PTMV. Plasma norepinephrine level at 60 W workload intensity was decreased from 2308 +/- 864 pg/ml to 841 +/- 233 pg/ml after PTMV (p < 0.05). We concluded that PTMV decreased the plasma norepinephrine level during exercise in the patients with mitral stenosis. Percutaneous transluminal mitral valvuloplasty is a novel procedure for the improvement of symptoms in patients with mitral stenosis.

Adult↗