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Biomedical subjects

Y Tsuda

Publications and source records attributed to Y Tsuda.

At least 19 recordsLinked to original sources

Liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric analysis of synthetic elastase inhibitor peptide.

A liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric method for the determination of tert-butyloxycarbonyl-Tyr-Leu-Val-CH2Cl (Boc-YLV-CH2Cl) was investigated. Boc-YLV-CH2Cl was eluted from a Cosmosil 5C8 column in a solvent system of 0.1% acetic acid-methanol (30: 70, v/v). The positive ion spectrum of Boc-YLV-CH2Cl showed a quasi-molecular ion at m/z 526 with fragment ions which provided structural information. Boc-YLV-CH2Cl was purified from blood and tissue samples with Sep-Pak C18 cartridges. The analysis in biological samples was performed by focusing the characteristic ion at m/z 526. The calibration graphs were linear over the concentration range studied (injected amounts of 9.5-190 pmol). The method was applied to the determination of Boc-YLV-CH2Cl in biological samples.

Amino Acid Sequence

Case report: nifedipine-rifampicin interaction attenuates the effect on blood pressure in a patient with essential hypertension.

A 72-year-old woman with 5-year history of essential hypertension developed peritoneal tuberculosis. The patient's hypertension, which had been well-controlled by long-acting nifedipine, deteriorated after the administration of rifampicin, an antitubercular agent. During use of nifedipine and rifampicin, both the peak plasma concentration and the area under the curve of nifedipine decreased markedly to about 40% of those without rifampicin. The findings suggest that rifampicin may increase the elimination of nifedipine, presumably by induction of its hepatic metabolism. Nisoldipine, another calcium antagonist, also failed to lower the patient's blood pressure, when given in combination with rifampicin. Taken together, these findings indicate that more caution should be urged when calcium antagonist is prescribed along with rifampicin.

Adrenergic alpha-Antagonists

Rapid myocardial perfusion imaging with 99Tcm-teboroxime and a three-headed SPECT system: a comparative study with 201Tl.

99Tcm-teboroxime is a new myocardial perfusion agent with a high first pass extraction and rapid myocardial washout. The usefulness of 99Tcm-teboroxime was evaluated for detection of myocardial ischaemia using a three-headed single photon emission tomography (SPECT) system which allows for rapid data acquisition. The subjects consisted of 14 patients, including seven with ischaemic heart disease, four with cardiomyopathy and three others. After the 99Tcm-teboroxime injection, dynamic data was collected every minute for 15 min with continuous rotation. High-quality SPECT images could be obtained by reconstructing the serial scans from 2 to 8 min. The sensitivity, specificity and accuracy of the 99Tcm-teboroxime study for the detection of the ischaemic region were not significantly different from those of the 201Tl study. Myocardial clearance was slow in the ischaemic lesion and in the myocardium of cardiomyopathy patients, while the coronary angiograms did not show any abnormality. These results therefore indicate that the rapid SPECT imaging and myocardial clearance of 99Tcm-teboroxime obtained with a three-headed SPECT system were useful for the detection of myocardial ischaemia.

Adolescent

Establishment of a novel granulocytic sarcoma cell line which can adhere to dermal fibroblasts from a patient with granulocytic sarcoma in dermal tissues and myelofibrosis.

A novel human myeloid cell line, designated HSM-1, has been established from the pleural effusion of a patient with granulocytic sarcoma (GS) who had been followed as having primary myelofibrosis for 10 years. When he was diagnosed as having granulocytic sarcoma in dermal tissues, no evidence of malignant transformation into leukaemia was found in both the peripheral blood and bone marrow. The established cell line was positive for myeloperoxidase, Sudan black B, Naphthol AS-D chloroacetate esterase. Surface marker analysis revealed that HSM-1 expressed CD4, CD13, CD11a, CD11b, Leu8, CD49b, CD49d, CD49e, CD29 and HLA-DR. To clarify why the unusual myeloid tumours developed in non-haematopoietic tissues, we examined the capability of HSM-1 to bind to skin fibroblast layers. The HSM-1 cells were found to bind to both bone marrow stromal layers and skin fibroblast layers. Among the other myeloid cell lines tested, none was found to bind to skin fibroblast layers. These findings suggest that the GS cell line may be derived from a haematopoietic precursor cell which can bind to skin fibroblasts and is localized in non-haematopoietic tissues resulting in the formation of extramedullary myeloid metaplasia. HSM-1 is a useful tool for analysing the characteristics of granulocytic sarcoma and homing receptors for haematopoietic stem cells.

Antigens, Surface

Isolation and structure elucidation of gymnemic acids, antisweet principles of Gymnema sylvestre.

The structure of gymnemagenin (3 beta,16 beta,21 beta,22 alpha,23,28-hexahydroxy-olean-12-ene), the sapogenin of the antisweet principles of Gymnema sylvestre, was established by X-ray analysis of the 3 beta,23;21 beta,22 alpha-di-O-isopropylidene derivative. On the basis of this result, the structure of deacylgymnemic acid was elucidated as the 3-O-beta-glucuronide from the carbon-13 nuclear magnetic resonance spectra. Five antisweet principles, gymnemic acid-III, -IV, -V, -VIII, and -IX, were isolated in pure states from the hot water extract of leaves of Gymnema sylvestre. Of these, three (GA-III, -IV, and -V) were known, while two (GA-VIII and -IX) were new compounds. The structures of GA-VIII and -IX were elucidated as 3'-O-beta-D-arabino-2-hexulopyranosyl gymnemic acid-III and -IV, respectively.

Carbon Isotopes

Application of poly-L-lysine to purification of leukocyte cathepsin G by affinity chromatography.

Poly-L-lysine with molecular masses of 3.3-290 kDa increased the amidolytic activities of leukocyte elastase and cathepsin G at low concentration, but had little effect on the activities of pancreatic elastase, alpha-chymotrypsin, plasmin and thrombin. Highly purified cathepsin G was obtained from column of EAH Sepharose 4B or Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose (affinity chromatography) by elution with poly-L-lysine solution (0.4 mg/ml, molecular weight (MW.) 290000 or 2.2 mg/ml, MW. 3300). Leukocyte elastase, adsorbed to Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose, was not eluted with poly-L-lysine solution. The amino acid composition of purified cathepsin G has been determined.

Amino Acid Sequence

Synthesis of trans-4-aminomethylcyclohexanecarbonyl-L- and -D-phenylalanine-4-carboxymethylanilide and examination of their inhibitory activity against plasma kallikrein.

Based on studies of structure-activity relationship, trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanine-4-carbox ymethylanilide (Tra-Phe-APAA) was designed as a selective plasma kallikrein inhibitor and synthesized. Tra-Phe-APAA inhibited plasma kallikrein with a Ki value of 0.81 microM, while it inhibited glandular kallikrein, plasmin, urokinase, factor Xa and thrombin with Ki values of greater than 500, 390, 200, greater than 500, and greater than 500 microM, respectively. However, its stereoisomer, Tra-D-Phe-APPA did not exhibit any detectable inhibitory activity against the above enzymes.

Animals

Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.

Amides

Successful treatment of primary amyloidosis with dimethylsulfoxide and cytoreductive chemotherapy.

A 42-year-old Japanese male was admitted to our hospital because of congestive heart failure (CHF). A diagnosis of primary amyloidosis was made on the basis of a heavy deposition of amyloid in the gastric submucosal tissue in addition to the hematological and immunological findings. Intermittent chemotherapy in combination with daily oral dimethylsulfoxide (DMSO) resulted in a dramatic decrease of plasma cells in the marrow as well as a gradual improvement of CHF. With this therapy, the cardiac ejection fraction was markedly improved. This case indicates that the long-standing administration of DMSO combined with cytoreductive chemotherapy is therefore effective in treating some cases with primary amyloidosis.

Adult

Analysis of growth failure in children treated for acute lymphoblastic leukemia.

Growth patterns were surveyed in 303 children with acute lymphoblastic leukemia who had remained in continuous first complete remission for a minimum of 1 year (median 3 years). Chemotherapy was given for 3 years, and central nervous system prophylaxis consisted of cranial irradiation at a total dose of 18 Gy or intravenous high-dose methotrexate (1.5-6 g/m2 for three to six doses). Intensive chemotherapy, including cyclophosphamide, doxorubicin, and cytosine arabinoside was given to children with high-risk features. Two of 205 children with low- or intermediate-risk features and 13 of 98 children with high-risk features showed a decrease in the growth rate of less than -2 SD. In 14 of these 15 patients, the age at onset was over 9 years and growth failure became most predominant in the prepubertal period: ten of these children showed a tendency toward delayed pubertal development, but eight showed later catch-up growth with pubertal maturation after completion of chemotherapy. Thus, chemotherapy appeared to contribute temporarily to the growth failure and gonadal impairment that occurred in the prepubertal period. No obvious correlation between the administered cranial irradiation and growth failure was found, but further study with a longer follow-up will be necessary to determine the long-term effects of irradiation on subsequent growth patterns in children.

Adolescent

[Fluorescence polarization immunoassay of isepamicin in blood spotted on filter paper].

A simple method has been developed for the determination of the aminoglycoside antibiotic isepamicin (ISP) in whole blood, using dried blood spots (DBSs) on filter-paper. ISP in the DBSs were recovered most effectively in 0.5 M Na2HPO4-NaH2PO4 buffer (pH 7) by incubation for 30 minutes at 35 degrees C in an ultrafiltration tube. The eluates from the DBS papers were centrifuged at 3,000 x g for 10 minutes. The clear, colorless filtrates were transferred to an Abbott TDx cartridge for measurement by the fluorescence polarization immunoassay. The lower limit for the quantitative determination of ISP in the DBS was 2.5 micrograms per ml of whole blood. The method permits a simple collection of blood at a microliter level and should prove particularly useful for therapeutic drug monitoring of ISP in blood at effective levels in pediatric and geriatric patients.

Animals

Correlation of regional cerebral blood flow and blood flow velocity in normal volunteers and patients with cerebro-vascular disease.

Transcranial Doppler sonography and measurement of regional cerebral blood flow using the Xenon133-inhalation technique have been used simultaneously in 10 normal volunteers and 13 patients with acute-onset cerebrovascular disorders during normocapnia and during hyperventilatory hypocapnia. Hypocapnia led to a reduction of both blood flow and blood velocity in the territory of the middle cerebral artery. However, correlation was poor in most cases with respect: 1) to hemispheric blood flow and flow velocity over the middle cerebral artery (BFV), 2) cerebral blood flow (CBF) over the middle cerebral artery (MCA) and BFV and 3) percentage changes of CBF over the MCA and BFV during hypocapnia. In normals correlation usually was better than in patients with cerebrovascular disorders. It was concluded that measurement of BFV over the MCA using transcranial Doppler sonography does not reflect either cerebral tissue perfusion or changes of tissue perfusion induced by alteration of CO2-content in the arterial blood.

Adult

Strategy changes in human contingency judgments as a function of contingency tables.

Judgment strategies of 169 undergraduate students on problems to judge the contingency between two binary events were identified by the method of rule-based analysis to clarify whether or not the strategies the subjects used would be affected by the concrete nature of the contingency table. Problems were constructed along two factors: total cell frequency and width of range of objective contingencies. Although the factor of total cell frequency had no effect on subjects' strategies, the number of subjects who changed strategies corresponding with problem instances increased when the objective contingencies were set closer to zero or when problems became more difficult. These results are discussed in the context of previous studies of this issue in the literature.

Adolescent

Semiquantitative regional cerebral blood flow evaluation using 123I-IMP SPECT in a case showing transient ischemic attack caused by putaminal hemorrhage.

A 69-year-old woman presented a transient cerebral ischemic attack, showing left arm weakness and slurred speech which recovered within 4 h of onset, while computed tomography indicated a putaminal hemorrhage. The regional cerebral blood flow distribution, measured semiquantitatively by use of 123I amphetamine emission tomography, was disturbed, which persisted more than one month up to a maximum of 4.5 months from the onset of symptoms. This case illustrates a variety of putaminal hemorrhage of good functional and vital prognosis, and provides an example in which the regional cerebral blood flow disturbances might persist for more than one month up to 4.5 months after the occurrence of a transient ischemic attack caused by a putaminal hemorrhage.

Aged

Endometrial cysts: diagnosis with MR imaging.

The value of 1.5-T magnetic resonance (MR) imaging in diagnosing endometrial cysts and differentiating them from other gynecologic masses was prospectively evaluated in 374 female patients with clinically suspected adnexal masses. A suggestive diagnosis of endometrial cyst was made when a cyst that was hyperintense on T1-weighted images exhibited homogeneous hyperintensity on T2-weighted images. A definitive diagnosis was made when a cyst that was hyperintense on T1-weighted images exhibited hypointense signal on T2-weighted images (shading) or when the lesion consisted of multiple hyperintense cysts on T1-weighted images (multiplicity) regardless of the signal intensity on T2-weighted images. Surgery was performed in 293 patients, and confirmation was obtained in 354 lesions. MR imaging enabled accurate diagnosis of 77 of 86 endometrial cysts and exclusion of the diagnosis of endometrial cyst in 263 of 268 other gynecologic masses with or without internal hemorrhage. The overall diagnostic sensitivity, specificity, and accuracy were 90%, 98%, 96%, respectively. MR imaging seems to be an acceptable diagnostic test on which clinical decisions can be based in selecting treatment.

Adnexal Diseases

Determination of leukocyte elastase concentration in plasma and serum by a simple method using a specific synthetic substrate.

The concentration of leukocyte elastase (ELP) in plasma and serum was determined by an amidolysis method using a specific synthetic substrate for ELP, Suc-Ala-Tyr-Leu-Val-pNA. Results were compared with those using ELISA. ELP levels in plasma from healthy donors were similar to those determined by ELISA; however, the levels in serum were lower than those determined by ELISA. Correlation coefficients of ELP levels in plasma and serum as measured by the two methods were 0.75 (amidolysis) and 0.90 (ELISA). On the other hand, the correlation coefficient between serum ELP by the two methods was 0.83. Half of the ELP levels in plasma from 150 patients and serum from 400 patients were significantly elevated when compared with those from healthy donors, and the ELP elevation determined by amidolytic assay correlated with some variables in blood, namely fibrin(ogen)-degraded products, fibrinogen, GOT, GPT, gamma-GTP, LDH and leucine aminopeptidase. Despite the fact that the amidolysis method detects the alpha 2-macroglobulin-ELP complex while ELISA detects the alpha 1-antitrypsin-ELP complex, a comparative study showed amidolysis to provide sufficiently sensitive measurement of both plasma and serum ELP.

Adult

Nematocidal principles in "oakmoss absolute" and nematocidal activity of 2,4-dihydroxybenzoates.

Nematocidal principles obtained from oakmoss absolute were identified as methyl 2,4-dihydroxy-3,6-di-methylbenzoate (2), ethyl 3-formyl-2,4-dihydroxy-6-methylbenzoate (4), and ethyl 5-chloro-3-formyl-2,4-dihydroxy-6-methylbenzoate (7). In relation to their structures, the nematocidal activity of 2,4-dihydroxybenzoates of methyl to tetradecyl was tested and the strongest activity was found in the octyl ester (minimal lethal concentration = 13 microM).

Animals