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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 505 records · Page 28Linked to original sources

[The pharmacokinetics of cisplatin and its influence on renal function according to different infusion methods (report II)--alleviation of renal impairment by bismuth subnitrate combined with ginseng and tang-koui ten].

In the previous report, we discussed in vivo dynamics and renal impairment resulting from the difference in cisplatin CDDP administration. In the present study, we investigated in vivo dynamics and renal impairment under 1 h of continuous drip infusion of CDDP. The free-type Pt concentration ratio, which is considered to indicate antitumor activity in the overall plasma Pt concentration at the end of the administration, was noted to be approximately 64%. This was significantly higher than other administration methods, making this an effective administration procedure. However, NAG, which is considered to be an index of renal impairment along with the amount of beta 2-microglobulin urine excretion, showed higher values than those by other administration methods. Thus, using the 1-hr continuous CDDP drip infusion, we attempted to alleviate the renal impairment, combining bismuth subnitrate with ginseng and Tang-koui ten. As a result, the amount of beta 2-microglobulin excretion in the urine was diminished as well as NAG, and a reduction of the renal impairment was noted. These alleviational effects of the renal impairment were attributed to the method of consistent oral administration by which alleviation could take place with little load on the patient.

Acetylglucosaminidase↗

[A cured case of adult respiratory distress syndrome caused by septicemia of Staphylococcus aureus].

A 33-year-old woman was admitted as an emergency case because of shock condition after delivery. Physical examination revealed fever, cyanosis and coarse crackles throughout the entire chest. Laboratory data showed leukocytosis and increase of CRP value. Adult respiratory distress syndrome (ARDS) was diagnosed based on progressive severe hypoxemia and bilateral diffuse alveolar shadows on chest X-ray film. The cause of ARDS was considered to be septicemia as staphylococcus aureus was cultured from lochia. The patient was intubated, then artificially ventilated employing PEEP. Chemotherapy using three different kinds of antibiotics was started, combined with the administration of corticosteroid and a protease inhibitor, Urinastatin. The patient finally recovered completely.

Adult↗

Effect of theophylline on improvement of the pulmonary function in the treatment of acute episodes of asthma: the influence of the severity of acute asthma.

The bronchodilating effect of theophylline was studied from the perspective of its influence on the severity of acute asthmatic attack and where its acting site is located on bronchi. Pulmonary function including maximal expiratory flow-volume curve breathing of room air and of a gas mixture containing 80% helium and 20% oxygen (He-O2) was measured at each incremental plasma theophylline concentration plateau (5, 10, and 15 micrograms/mL) in 12 acutely ill asthmatic patients. Before starting the administration of theophylline, clinical findings were used to classify the severity of the asthmatic attack into mild, moderate, or severe groups. Our data suggested that theophylline acts on both the central and peripheral airways and that theophylline improves the airway obstruction in a dose-dependent fashion when the severity of acute attack is mild.

Acute Disease↗

[Localization of spinal tumors by MRI].

Exact localization of the spinal tumors is particularly important for differential diagnosis and surgery. Therefore, it was attempted to evaluate the diagnostic accuracy of MRI in localizing the spinal tumors exactly. Nineteen cases of spinal cord tumors, being localized in the intradural extramedullary, extradural and both intradural and extradural spaces, were studied with MRI. Intradural extramedullary tumors showed small CSF spaces just below and above the tumor which were demonstrated as CSF intensity on T1 and T2 weighted images. Although extradural tumors did not show CSF spaces, there was extradural sign or dural density between the tumor and the spinal cord. Intradural and extradural tumors were outlined as having both characteristics. Signal intensities of the spinal tumors were not characteristic for specific histology. Gd-DTPA was quite useful for accurate localization of the tumors. In comparison with myelography, MRI was superior to myelography in extradural tumors and equally useful for intradural and extradural tumors, but it was less diagnostic in intradural extramedullary tumors. In general, MRI was quite useful in localizing the spinal tumors exactly and the accuracy of MRI was quite high. In the near future this technique will replace myelography and other radiologic methods.

Adult↗

[Clinical assessment of pulmonary hypertension in collagen diseases].

The occurrence of pulmonary hypertension (PH) has been reported in association with collagen diseases. Because of its grave consequences it is of greatest importance to make an early diagnosis of PH and initiate adequate treatment. For this purpose we have carried out right heart catheterization study to determine pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR), and cardiac index in thirty-four consecutive patients with collagen diseases including cases of mixed connective tissue disease (MCTD). We also compared the hemodynamic data with clinical pictures and the results of non-invasive cardiopulmonary tests which were done before catheterization study. Pulmonary hypertension as defined by the mean PAP of greater than 20 mmHg was observed in 11 of the 34 cases. PH was observed in five of 6 cases with MCTD and six of 17 cases with PSS including 2 cases with overlapping SLE and PM. The frequencies of positive anti-nRNP antibody, serositis, Raynaud's phenomenon and muscle involvement were significantly higher in cases with PH than in cases without PH. Catheterization study was most useful for diagnosis of cases with mean PAP of less than 25 mmHg, whereas echocardiographic study identified all cases with mean PAP of greater than 25 mmHg. No significant correlation was observed between mean PAP and vital capacity, total lung capacity or diffusion capacity measured as the percent of predicted normal values, which suggests that vascular abnormalities play a more significant role in the pathogenesis of PH than pulmonary fibrosis in collagen diseases.

Adult↗

[The pathogenesis of trehalose dimycolate-induced hemorrhagic pneumonia induced in mice as animal model of human alveolar hemorrhagic syndrome].

Trehalose dimycolate (TDM) is a glycolipid contained in the cell walls of Mycobacteria, Nocardia and Corynebacteria. An intraperitoneal injection of TDM into mice has been known to produce hemorrhagic pneumonia without affecting any other organs. Thus, it provides a unique experimental model for studies of the mechanisms of alveolar hemorrhagic syndrome, including idiopathic pulmonary hemosiderosis. It has been reported that T lymphocytes are essential for the production of TDM-induced hemorrhagic pneumonia, however, the overall cellular mechanism is not yet clear. The purpose of this study is to re-examine and clarify the role of T lymphocytes in the pathogenesis of TDM-induced hemorrhagic pneumonia. To achieve it we considered 1) the dynamics of infiltrating lymphocytes to find out if there is a certain T lymphocyte subpopulation infiltrating predominantly into the lung, 2) the effect of in vivo depletion of T lymphocyte subpopulation by monoclonal antibodies, and 3) the effect of transfer of T lymphocytes into nude mice. The analysis of the dynamic change of the number of lymphocytes showed that the number of L3T4+ cells as well as Lyt2+ cells decreased on day 2 or 3 after TDM injection, thereafter increased, however, neither subpopulation infiltrated predominantly into the lung. Alveolar hemorrhages occurred in L3T4+ cell-depleted and/or Lyt2+ cell-depleted mice, and hemorrhages were enhanced in Lyt2+ cell-deplete mice. Alveolar hemorrhages occurred even in nude mice, and the intensity of hemorrhages or the cell numbers in the lung did not differ from those in T lymphocyte-reconstituted nude mice, however, hemorrhages were enhanced in L3T4+ cell-reconstituted nude mice. These results suggested that T lymphocytes are not primarily involved in the cellular mechanisms of the pathogenesis of TDM-induced hemorrhagic pneumonia, however, L3T4+ cells modify the process of the production of hemorrhagic pneumonia secondarily and enhance it.

Animals↗

[Aortic and tricuspid valve replacement in a case of corrected transposition of the great arteries].

It is well known that corrected transposition of the great arteries (C-TGA) is accompanied with tricuspid valve regurgitation, but very few reports have described complication of this anomaly with aortic valve regurgitation (AR). We have performed aortic valve replacement (AVR) in a case of C-TGA associated with AR which had been evaluated the grade of 3/4 according to Sellers' classification, simultaneously done the valve replacement for the dysplastic tricuspid valve and annuloplasty for the right-side atrioventricular valve (mitral valve). The patient has a favorable postoperative course.

Aortic Valve Insufficiency↗

[The mechanism of ergonovine-induced airway smooth muscle contraction].

There have been three articles in the clinical literature concerning ergonovine maleate-induced bronchospasm. The effect of this alkaloid on isolated canine tracheobronchial smooth muscle was analyzed to investigate the mechanism of ergonovine-induced airway smooth muscle contraction. Both ergonovine and serotonin (5-hydroxytryptamine, 5HT) contracted canine tracheal smooth muscle with EC50 1.4 X 10(-8) M and 5.1 X 10(-7) M, respectively. The maximal contractile response observed with ergonovine was approximately 30% less than that observed with 5HT. In diverse blockers such as methysergide, atropine, prazosin, propranolol, pyrilamine and cimetidine, only methysergide competitively blocked both ergonovine and 5HT responses with a similar calculated dissociation constant (pKB); 8.3 +/- 0.2 against ergonovine and 8.5 +/- 0.2 against 5HT (n = 6, p = 0.9). The relative affinity and efficacy of ergonovine and 5HT were determined by use of a partial irreversible antagonist, phenoxybenzamine. The calculated affinity of ergonovine was about 16 times higher than that of 5HT. The relative efficacy of EC100 for ergonovine was 0.2 but at EC10 it was 41.9 (5HT efficacy = 1). Ergonovine 10(-9) M or 10(-8) M shifted the 5HT dose-response curve to the right without reducing the maximal response, but the shift was nonparallel. Ergonovine and 5HT also contracted canine bronchial smooth muscle in a dose dependent manner with EC50 6.4 X 10(-8) M and 1.8 X 10(-7) M, respectively. The dose-responses curve of these two agonists were competitively blocked by methysergide 10(-6) M. These data indicate that ergonovine directly contracts canine tracheobronchial smooth muscle as a result of its combination with 5HT receptors. This effect may result in the precipitation of an asthmatic attack in susceptible individuals.

Animals↗

[Evaluation of predictability of in vitro SDI assay in comparison with in vivo nude mouse assay].

Twenty lines of human gastro intestinal and breast cancer xenografts, in which chemosensitivity spectra by the in vivo nude mouse assay had been clarified. were subjected to the in vitro SDI (succinate dehydrogenase inhibition) assay using MTT dye to assess the accuracy of this drug sensitivity test against 4 drugs i.e., mitomycin C (MMC), adriamycin (ADM) 5 fluorouracil (5-FU), and cisplatin (CDDP). After 3 days incubation, the suspension of every tumor cells including small fragments showed a marked decrease of SD activity even when no anticancer drug was added to the assay medium. Among these 4 drugs evaluated MMC exhibited a statistically significant correlation between chemosensitivity values of the in vitro SDI assay and those of the nude mouse assay. However, the other 3 drugs demonstrated no correlation between the values of these two methods. Since the primary cultured fibroblasts revealed, in general, lower sensitivity to these drugs, contamination of fibroblast may decrease the SDI values when materials from solid tumors with rich stroma such as a type of stomach cancer were subjected. It is considered that the prediction of chemosensitivity to every drug will be impossible by a in vitro SDI assay.

Animals↗

[Cataract epidemiological study in west Sumatra].

A cataract epidemiology survey using a photo-documentation system was performed for people over age 40 who live in West Sumatra Island. The percent prevalence of cataracts, including early senile changes, were 28.7% in the 50 year-old population, 64.7% in the 60, 83.8% the 70 and 95.8% for people over 80. Prominent cataractous opacification was recognized in 8.8% the 50-59 year old population, 21.1% for those in their 60s, 38.7% for those in their 70s and 83.3% in people over 80. The most frequently observed cataract types were cortical and nuclear, followed by mixed types which had almost the same ratio. The incidence of nuclear cataracts was 3.5% and 8.5% in the 40-49 and 50-59 year-old population, respectively. The percent of nuclear cataracts seen in the 60 and 70 year-old population were 22.7% and 32.4%, respectively. Cataract incidence in 50-59 year-old diabetic subjects was significantly higher than that in non-diabetic subjects. Cataract incidence in 50-59 year-old subjects with high myopia was significantly higher than in cares of other types of refractive error. The main type of lens opacification seen in the high myopia cases was nuclear. Cataract prevalence in the 50 year-old age group who had received a high level of education was significantly lower than that of others.

Adult↗

Gene cloning and sequence determination of leucine dehydrogenase from Bacillus stearothermophilus and structural comparison with other NAD(P)+-dependent dehydrogenases.

The gene for leucine dehydrogenase (EC 1.4.1.9) from Bacillus stearothermophilus was cloned and expressed in Escherichia coli. The selection for the cloned gene was based upon activity staining of the replica printed E. coli cells. A transformant showing high leucine dehydrogenase activity was found to carry an about 9 kilobase pair plasmid, which contained 4.6 kilobase pairs of B. stearothermophilus DNA. The nucleotide sequence including the 1287 base pair coding region of the leucine dehydrogenase gene was determined by the dideoxy chain termination method. The translated amino acid sequence was confirmed by automated Edman degradation of several peptide fragments produced from the purified enzyme by trypsin digestion. The polypeptide contained 429 amino acid residues corresponding to the subunit (Mr 49,000) of the hexameric enzyme. Comparison of the amino acid sequence of leucine dehydrogenase with those of other pyridine nucleotide dependent oxidoreductases registered in a protein data bank revealed significant sequence similarity, particularly between leucine and glutamate dehydrogenases, in the regions containing the coenzyme binding domain and certain specific residues with catalytic importance.

Amino Acid Oxidoreductases↗

Binding of nucleotides to an extramitochondrial acetyl-CoA hydrolase from rat liver.

Cold labile extramitochondrial acetyl-CoA hydrolase (dimeric form) purified from rat liver was activated by various nucleoside triphosphates and inhibited by various nucleoside diphosphates. Activation of acetyl-CoA hydrolase by ATP was inhibited by a low concentration of ADP (Ki congruent to 6.8 microM) or a high concentration of AMP (Ki congruent to 2.3 mM). ADP and AMP were competitive inhibitors of ATP. A Scatchard plot of the binding of ATP to acetyl-CoA hydrolase (dimer) at room temperature gave a value of 25 microM for the dissociation constant with at least 2 binding sites/mol of dimer. Cold-treated monomeric enzyme also associated with ATP-agarose, suggesting that the monomeric form of the enzyme also has a nucleotide binding site(s), probably at least 1 binding site/mol of monomer. Phenylglyoxal or 2,3-butanedione, both of which modify arginyl residues of protein, inactivated acetyl-CoA hydrolase. ATP (an activator) greatly protected acetyl-CoA hydrolase from inactivation by these reagents, while ADP (an inhibitor) greatly (a substratelike, competitive inhibitor), and CoASH (a product) were less effective. However, addition of ADP plus valeryl-CoA (or CoASH) effectively prevented the inactivation by 2,3-butanedione, but that is not the case for phenylglyoxal. These results suggest that one or more arginyl residues are involved in the nucleotide binding site of extramitochondrial acetyl-CoA hydrolase and that their nucleotide binding sites locate near the substrate binding site.

Acetyl-CoA Hydrolase↗

Prediction of peptide retention times.

A new approach for predicting the retention times of peptides, either with isocratic or gradient elution is described. The isocratic capacity factors of peptides are correlated with their molecular weights and with their hydrophobicities. Given the experimental conditions, and the amino acid composition, it is possible to calculate the retention time of a peptide eluted by a gradient, for any slope of gradient, flow-rate and column length.

Animals↗

Arylamine N-acetyltransferase from chicken liver. I. Monoclonal antibodies, immunoaffinity purification, and amino acid sequences.

Five monoclonal antibodies against arylamine acetyltransferase (EC 2.3.1.5) from the chicken liver were established by immunizing a mouse with a partially purified enzyme preparation. None of the antibodies cross-reacted with arylamine N-acetyltransferase from the livers of cow, rabbit, and rat, nor with arylalkylamine N-acetyltransferase from the chicken pineal gland, indicating a high specificity of the antibodies. By using the antibodies, two immunoaffinity purification procedures were elaborated: A partially purified enzyme preparation was incubated with the monoclonal antibody, and the resulting enzyme-IgG complex was separated by a protein A-Sepharose column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single protein band with a molecular mass of 34 kDa in addition to the heavy and light chains of IgG. Secondly, an immunoaffinity column was prepared by immobilizing a monoclonal antibody to Sepharose 4B. After a partially purified enzyme preparation was absorbed on the column, N-acetyltransferase activity was eluted with 1 M NaCl and 1 M urea. The eluted sample contained a single 34-kDa protein. The purified enzyme preferred arylamines to arylalkylamines as substrates, indicating that it was arylamine N-acetyltransferase. The purified protein was subjected to digestion by lysylendopeptidase and separated by high performance liquid chromatography. Partial amino acid sequences of three peptides were determined by a gas-phase sequence analyzer.

Acetyl-CoA C-Acetyltransferase↗

Arylamine N-acetyltransferase from chicken liver II. Cloning of cDNA and expression in Chinese hamster ovary cells.

A cDNA clone encoding the full coding region of chicken liver arylamine acetyltransferase (EC 2.3.1.5) was isolated from lambda gt10 cDNA library by screening with the 32P-labeled oligonucleotide deduced from the amino acid sequence reported in the preceding paper. The complete nucleotide sequence of the cDNA was determined, from which the amino acid sequence of N-acetyltransferase was deduced. It consisted of 1,302 nucleotides including a 861-nucleotide region coding for 287 amino acids with a molecular weight of 32,914. Two methods were applied to confirm that the cDNA encoded arylamine N-acetyltransferase. First, mRNA was synthesized in vitro by Bluescript and subsequently translated in vitro. The molecular mass of the translation product was 34 kDa consistent with that of the enzyme purified from the chicken liver. The translated protein was immunoprecipitated by a monoclonal antibody to N-acetyltransferase. Second, the cDNA was inserted into an expression vector pcDL1 and introduced into Chinese hamster ovary cells. The supernatant of the homogenate of transfected cells showed a high level of N-acetyltransferase activity with a substrate specificity comparable to that of the liver enzyme. Northern blot analysis revealed three mRNAs corresponding to 4.7, 2.0, and 1.4 kilobases. The levels of N-acetyltransferase mRNAs were relatively high in the liver and distributed in various tissues. Genomic Southern blot analysis indicated the presence of only one gene in the chicken haploid genome.

Acetyl-CoA C-Acetyltransferase↗

Tight binding of glucocorticoid-receptor complexes to histone-agarose.

"Activated" glucocorticoid-receptor complexes purified about 3,000-fold from rat liver were found to bind to histone-agarose. Because of their tight binding, they could not be eluted from the column by high salt solution (3 M KCl) or low salt plus polyol buffer (50% ethylene glycol), but their binding could be disrupted by pyridoxal 5'-phosphate; more than 70% recovery of the "activated" receptor complexes was achieved with buffer containing 20 mM pyridoxal 5'-phosphate. This interaction of "activated" glucocorticoid-receptor complexes of rat liver with histone-agarose suggests a role of histones in the mechanism of action of steroid hormone.

Animals↗