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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 451 records · Page 25Linked to original sources
PubMed1993

Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome.

The clonal composition of EBV-infected cells was examined in three cases of EBV-associated hemophagocytic syndrome by analysis of the heterogeneity of terminal repetitive sequences in the EBV genome, indicating monoclonal expansion of EBV-infected cells in all cases. Involvement of T lymphoid cells was determined by in situ hybridization using 35S-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in combination with immunostaining for the TCR-beta chain, CD45RO, CD20, CD30 and CD68 antigens in these three cases. The majority of lymphoid cells showing EBER transcripts were stained by antibodies against CD45RO and T cell receptor-beta. In contrast, EBER-specific signals were not detectable on B cells or hemophagocytic cells. These data support the concept that EBV-associated T cell proliferation is a primary feature of EBV-AHS.

Adolescent↗
PubMed1993

Studies of HIV-1 protease inhibitors. I. Incorporation of a reduced peptide, simple aminoalcohol, and statine analog at the scissile site of substrate sequences.

Inhibitors of the protease of human immunodeficiency virus type-1 (HIV-1) were designed and synthesized. A reduced peptide, simple aminoalcohol, and statine analog, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), were inserted at the scissile site of substrate sequences of HIV-1 protease. While both reduced peptides and simple aminoalcohol derivatives were weak inhibitors, the peptides containing AHPPA demonstrated moderate inhibitory activity. The more potent alcohol configuration of AHPPA is (R), which is opposite to the configuration in potent inhibitors of other aspartic proteases. In particular, compound 28 ((3R,4S)-4-(N-tert-butoxycarbonyl- L-glutaminyl-L-asparaginyl)amino-3-hydroxy-5-phenylpentanoic acid 2'-methylbutylamide) had a Ki of 0.36 microM and exhibited excellent enzyme specificity.

Amino Acid Sequence↗
PubMed1993

Studies of HIV-1 protease inhibitors. II. Incorporation of four types of hydroxyethylene dipeptide isosteres at the scissile site of substrate sequences.

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors containing four types of hydroxyethylene dipeptide isosteres were designed and synthesized. These inhibitors consist of eight stereoisomers of phenylalanylproline (Phe-psi[H.E.]-Pro), four stereoisomers of phenylalanylalanine [Phe-psi[H.E.]-Ala), and one stereoisomer each of phenylalanylglycine (Phe-psi[H.E.]-Gly) and cyclohexylalanylalanine (Cha-psi[H.E.]-Ala) hydroxyethylene dipeptide isosteres. For the synthesis of the latter two isosteres, a newly developed synthetic method for gamma-lactone was applied. The inhibitory activities of these peptides were evaluated by cleavage assay of partially purified gag proteins or purified synthetic peptide. Of the inhibitors examined, compounds 2c (Z-Asn-(2S,3R,4S,5S)-Phe-psi[H.E.]-Pro-NHB(un); Bu(n) = n-butyl, Ki = 0.50 microM), 21a (Z-Asn-(2R,4S,5S)-Phe-psi[H.E.]-Ala- NHBu(n), Ki = 0.34 microM) and 23 (Z-Asn-(2R,4S,5S)-Cha-psi[H.E.]-Ala- NHBu(n), Ki = 0.46 microM) were moderately potent inhibitors. The results revealed that the alkyl substituent at C2 is essential, and the stereochemistry of the hydroxyethylene dipeptide isosteres greatly affected their inhibitory activities.

Amino Acid Sequence↗
PubMed1993

Method for detection of intracellular pH threshold; comparison between subjective observation and regression analysis.

The aim of this study is to examine the objectivity and reproducibility of intracellular pH threshold (pHT) detected by eye (E), and by regression analysis on linear (L), semilog (SL) and log-log (LL) models. Threshold for inorganic phosphate-to-phosphocreatine ratio (PT) was also examined by three regression analysis. Fifteen males volunteered as subjects. They performed wrist flexion in a ramp protocol of 0.14W/min till exhaustion. Throughout the exercise, 31P-MRS was obtained continuously from wrist flexors. Intracellular pH and phosphate compound in the muscle tissue were monitored as minute-by-minute data. In E, three observers determined pHT subjectively as a work rate just before pH decrement. In three regression analysis, pHT was detected as an intersection of a pair of linear regression lines which was selected statistically or subjectively. pHT detected by four methods showed significant reproducibility between each other, although PT did not. These results provide one of the evidences of threshold behavior of change in pH, and a question of existence of PT in contrast to pHT.

Exercise↗
PubMed1993

Influence of ramp slope on intracellular pH threshold during progressive exercise.

The purpose of this study was to examine the effect of ramp slope during progressive exercise test on the intracellular pH threshold (pHT) of working muscle. To attain the purpose, we measured intracellular pH of wrist flexor by 31P-MRS during four kinds of ramp wrist flexion. Five Japanese males participated as subjects. They performed wrist flexion in a bore of MRS system, with ramp increments of 0.14, 0.20, 0.26 and 0.31 W/min till exhaustion. Intracellular pH of wrist flexor muscle was estimated from a chemical shift between inorganic phosphate (Pi) and phosphocreatine (PCr) on a 31P-MR spectra. Pi-to-PCr ratio (Pi/PCr) as an index of oxidative phosphorylation potential was also calculated. pH and Pi/PCr were obtained as minute-by-minute data throughout the exercise. pHT was determined as a work rate (W) just before that at which the intracellular acidosis (acidemia) occurred. Although work endurance was shortened significantly, achieved maximal work rate (WRmax) was increased with an increase in ramp slope. pHT both in the unit of W and %WRmax was not affected significantly by the ramp slope. On the other hand, Pi/PCr at pHT decreased with an increase in ramp slope, significantly. These results suggested that intracellular homeostasis with reference to acid-base equilibrium was not dependent on oxidative phosphorylation status, but a work output of the muscle.

Exercise↗
PubMed1993

Effect of restricted blood flow on intracellular pH threshold of working muscle.

Threshold of decline in intracellular pH of muscle (pHT) during incremental wrist flexion was studied by 31P-MRS, under two levels of occlusions in which the cuff of the upper arm was inflated to systolic (ES) and diastolic blood pressure (ED), and no occlusion (E). To observe the effect of occlusion per se, intracellular pH at rest under the same two levels of occlusion was measured. Additionally, NIRS was applied to monitor the oxygenation and blood volume of the tissue during the same experimental protocol as the 31P-MRS study. Ten healthy Japanese males participated as subjects in the 31P-MRS study, and three of them in the NIRS study. They performed wrist flexion in incremental loads of 0.14 W/min ramp until voluntary exhaustion. 31P-MRS and NIRS were obtained from wrist flexor muscles. Change in intracellular pH (pH) during wrist flexion showed a threshold behavior even in ischemic conditions, although pH did not decrease at rest under the same two levels of occlusion. This finding indicated that decrease in pH under occlusion is also resulted from exercise induced lactic acidosis. Obtained pHT in ES was smaller than in ED and E significantly, and there was no significant difference between pHT in ED and that in E. From the results of NIRS study, it was confirmed that only venous outflow but not arterial inflow was restricted under an occlusion at a pressure of diastolic blood pressure, but both under an occlusion at a pressure of systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Effects of 5-fluorouracil and a combination of tegafur and uracil (UFT) on nucleotide metabolism in L1210 ascites tumor.

Changes in the deoxyribonucleotide pools following a single oral administration of 13 mg/kg of 5-fluorouracil (5-FU) or of 64.8 mg/kg of UFT (a mixed compound of tegafur and uracil) were investigated. We compared their pharmacodynamics and effects on nucleotide metabolism in L1210 ascites tumor on day 3 after intraperitoneal tumor inoculation. The intracellular dTTP pool decreased to half the control level 1-6 hr after the administration of 5-FU. The dTTP pools rapidly recovered after 6 hr. In contrast, UFT kept the intracellular dTTP level to 1/3 to 1/2 of the control level for 24 hr. Either drug elevated the intracellular dATP pools, but decreased dCTP pools. UFT influenced the intracellular dATP and dCTP levels longer than 5-FU. Orally administered UFT seemed to exert a longer and more potent inhibitory effect on thymidylate synthetase than equimolar 5-FU. In view of these results, we suggest that UFT could be a more potent chemotherapeutic drug than 5-FU in oral administration.

Animals↗
PubMed1993

Enhanced incorporation of 1-beta-D-arabinofuranosylcytosine by pretreatment with etoposide.

We examined the effects of timing of administration of etoposide on cytosine arabinoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.

Animals↗
PubMed1993

Contralateral external carotid-to-middle cerebral artery graft using the saphenous vein. Case report.

A variation of the extracranial-intracranial arterial bypass, using a long saphenous vein graft, is presented. The saphenous vein graft was inserted from the contralateral external carotid artery to the distal middle cerebral artery to replace the common and internal carotid arteries in a patient with a large neck tumor that invaded the common and internal carotid arteries, the esophagus, and the trachea. The patient had a positive balloon Matas' test. The saphenous vein was covered with an artificial vascular graft so that turning of the head or movement of the mandible did not displace or compress the graft. A large volume of flow began immediately after anastomosis. A description of the case and the operative technique is presented herein.

Aged↗
PubMed1993

Superficial temporal artery interposition graft after resection of bilateral anterior cerebral arteries. Case report.

A patient with an olfactory neuroblastoma in the frontal skull base was treated with primary tumor excision and partial resection of the A2 segment of both anterior cerebral arteries (ACA's). Revascularization was carried out using a superficial temporal artery (STA) interposition graft between the proximal and distal stumps with A3 segment-to-A3 segment end-to-side anastomosis. This technique established flow to the peripheral territories of the ACA's through the interposed STA graft. The technical aspects and possible role of this procedure are presented.

Adult↗
PubMed1993

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 1. Effectiveness on neutropenia by various causes and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia in children was studied in 23 cases of aplastic anemia, 13 cases of chronic benign neutropenia, 6 cases of congenital neutropenia (Kostmann type), 2 cases of cyclic neutropenia, 2 cases associated with glycogenosis type Ib and 1 cases associated with immune deficiency. KW-2228 was administered at 1-8 micrograms/kg subcutaneously and at 2-16 micrograms/kg intravenously. As a principle, the administration was started at low doses and continued for 7-28 days increasing the doses in the cases who didn't respond to the treatment well. The response rate of all the cases by the physicians in charge was 81. 8% (36/44). The mean absolute neutrophil count was increased from 304 to 1,300/microliters in aplastic anemia, from 204 to 3,027/microliters in chronic benign type, from 125 to 2,193/microliters in Kostmann type, and from 360 to 2,007 microliters in others. KW-2228 did not induce any noteworthy serious side effects. These results indicated that KW-2228 is a useful drug to treat neutropenia in children.

Adolescent↗
PubMed1993

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 2. Effectiveness on neutropenia associated with administration of anticancer agent and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia associated with chemotherapy was studied in pediatric patients with malignant tumor. To patients repeatedly treated with the same chemotherapy, KW-2228 was administered subcutaneously at 1 microgram/kg or intravenously at 2 micrograms/kg once a day in the 2nd course of the chemotherapy. During the administration term of KW-2228, the nadir of neutrophils went up, and the duration of neutrophil count under 500/microliters as well as the interval for recovery of the count to 500/microliters were remarkably shortened, compared with those during the observation term. Further, the duration of fever in patients and the administration days of antibacterial agent were also reduced. The effective rate judged by attending doctors was as high as 78.9%, consisting of 83.3% in 42 cases of subcutaneous administration and 73.5% in 34 cases of intravenous administration. Side effects such as slight skeletal pain and slight fever in one case each (2.3% in total) were improved without treatment. It is concluded that KW-2228 may be a useful drug for treatment of neutropenia associated with chemotherapy in pediatric patients with malignant tumor.

Adolescent↗
PubMed1993

[Sideroblastic anemia preceded by essential thrombocythemia with 20q- chromosome abnormality].

A 78-year-old man presented with marked thrombocytosis (126.4 x 10(4)/microliters), low neutrophil alkaline phosphatase (NAP) score and an abnormal karyotype of 46, XY, del(20) (q11q13) (18 of 20 cells), without obvious anemia or ringed sideroblasts in bone marrow. He received ranimustine (MCNU) with a diagnosis of essential thrombocythemia. After 2 years, he was admitted because of macrocytic anemia. The peripheral blood smear showed anisopoikilocytosis with a few nucleated red blood cells. Moderate thrombocytosis (71.7 x 10(4)/microliters) and a low NAP score were also observed. Bone marrow aspiration revealed erythroid hyperplasia with a significant increase in ringed sideroblasts (85% of erythroblasts). Cytogenetic studies showed the same abnormal karyotype 46, XY, del(20) (q11q13) in 100% of metaphase cells as those at initial diagnosis. A diagnosis of sideroblastic anemia preceded by essential thrombocythemia was made. No rearrangement or amplification of c-src was revealed. The observation of the same chromosome abnormality (20q-) in different phases of this patient's disease indicates that chronic myeloproliferative disorders and myelodysplastic syndrome may share some borderline or transitional cases with a similar pathogenesis.

Aged↗
PubMed1993

[A case of operated invasive thymoma accompanied with the thrombocytopenia].

Thymoma with thrombocytopenia has rarely been reported. We recently encountered a case of operated invasive thymoma with thrombocytopenia. A 74-year-old woman was admitted to our hospital with the chief complaint of 'shortness of breath' and general fatigue. Chest X-ray, CT and MRI showed a mass 5 x 5 cm in size at the anterior mediastinum. In hematological test, a significant decrease in platelets count (1.6 x 10(4)/mm3) and a increase in PA-IgG (134.5 ng/10 cells) were found. This finding suggests that thrombocytopenia is due to immunological abnormality. Steroid therapy (prednisolone 60 mg) was begun but was not effective and then, extended thymectomy was performed. After operation, prednisolone (30 mg) therapy was continued. Although prednisolone therapy was gradually decreased and stopped, platelets count was gradually increased 10.8 x 10(4)/mm3. Extended thymectomy and steroid therapy were effective.

Aged↗
PubMed1993

Effects of topical application of UF-021, a novel prostaglandin-related compound, on aqueous humor dynamics in rabbit.

The mechanism underlying the intraocular pressure (IOP) lowering effect of a novel prostaglandin-related compound, (+)-isopropyl Z-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)-cyclopentyl]hept-5 -enoate (UF-021), and the influence of this new hypotensive agent on the permeability of the blood-aqueous barrier (BAB) were studied in albino rabbits. A single instillation of 0.06% UF-021 significantly lowered the IOP with a peak reduction of 5.2 mmHg without changing the aqueous flow rate. Uveoscleral outflow and outflow facility to general blood circulation were both increased. The BAB permeability evaluated with fluorescein isothiocyanate-labeled rabbit albumin (FITC-RA) showed approximately sixfold increase after a single instillation of 0.06% UF-021, which suggested a drug-induced compromise of the rabbit BAB.

Administration, Topical↗
PubMed1993

[Clinical evaluation of S-1108 in children].

We administered S-1108 to 16 children with ages ranging from 7 month to 15 years at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3 urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was 100% and bacteriological eradication rate was 83.3%. No adverse effects were observed. These results suggested that S-1108 could be used safely in children.

Adolescent↗
PubMed1993

Angiomyolipoma of the liver. Ultrasound, CT, MR imaging and angiography.

Angiomyolipoma, a rare benign liver tumor, was observed in a 50-year-old woman examined with US, CT, MR imaging and angiography. Dynamic studies using CT and MR imaging were valuable in differentiating the disease from hepatocellular carcinoma with fat deposits.

Angiography, Digital Subtraction↗