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S Asano

Publications and source records attributed to S Asano.

At least 199 records · Page 11Linked to original sources
PubMed1997

Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases.

Lymph node enlargement is common in active systemic lupus erythematosus (SLE), a disease characterized by well defined clinical criteria. Although numerous reports have described the characteristic histology of SLE lymphadenopathy to include necrotizing lesions and hematoxylin bodies, no detailed description has examined the histopathologic features that are similar to Castleman's disease (CD) in SLE patients. In this report, we describe the clinicopathologic findings of CD-like peripheral lymphadenopathy, which was identified in five (26%) of 19 SLE patients. These five patients were all female with an age range of 24 to 44 years, and four of them presented with multicentric lymphadenopathy. They also had systemic symptoms and abnormal laboratory findings, indicating active disease, although two patients had not fulfilled the diagnostic criteria of SLE at the initial disease. The size of the enlarged lymph nodes seldom exceeded 2.0 cm in diameter, and biopsies revealed histopathologic features similar to CD, of intermediate type in three patients and hyaline vascular type in two according to the classification of Flendrig [7]. Immunohistochemical studies demonstrated polyclonal plasma cell populations in all five cases. Epstein-Barr virus genomes were detected in the small lymphocytes of two of the three cases examined by in situ hybridization studies. Recently, the histopathologic findings of CD have been associated with a disrupted immune response, and the present data suggest that SLE should be listed as one of the diseases showing the histopathologic features similar to CD.

Adult↗
PubMed1997

Autologous bone marrow transplantation for patients with advanced chronic myelogenous leukemia.

We report on seven chronic myelogenous leukemia (CML) patients who received autologous bone marrow transplantation (ABMT) using bone marrow (BM) cells while at the chronic phase (CP) under the various treatments. Of the seven patients, four progressed to accelerated phase (AP) in 83-248 weeks after onset and three patients entered blastic crisis (BC) in 84-171 weeks after onset. All patients received high-dose chemoradiotherapy followed by infusion with 11.3 +/- 12.1 x 10(7) (average +/- S.D.) of bone marrow mononuclear cells (BM-MNCs)/kg IFN-alpha was resumed shortly after platelet recovery. Of the four patients in AP, one developed a recurrence of blastoma in 7 weeks, one progressed to second AP in 138 weeks after ABMT and two patients have survived the second CP for 159 and 330 weeks since ABMT, respectively. One of them achieved the complete disappearance of Ph1-positive metaphases for 33 weeks after ABMT. Of patients who received AMBT in BC, three relapsed within 8 weeks and died in 9, 17 and 58 weeks after ABMT, respectively. Hematological recovery was delayed in four patients. Therefore, we retrospectively re-evaluated the number of BM-MNCs collected through 50 procedures from 40 patients with CML-CP. The total MNCs obtained from 30 collections under IFN-alpha treatment was 27.4 +/- 30.9 x 10(8) cells (average +/- S.D.), being significantly lower than that obtained from 20 collections in pre-treatment state or with single chemotherapy other than IFN-alpha treatment (81.8 +/- 68.2 x 10(8) cells) (P < 0.005). The total number of MNCs correlated to white blood cell (WBC) count at BM collection (P < 0.01), which was also lower in the IFN-alpha(+) group than in the IFN-alpha(-) group (7.2 +/- 5.7 and 25.6 +/- 32.3 x 10(9)/l; P < 0.005). Our findings suggested that ABMT with the use of a sufficient number of progenitor cells might be helpful to CML patients in early AP and reach in extended periods of second CP. In addition, we suggest that BM collection is required before the start of IFN-alpha therapy because the total number of BM-MNCs correlated to the WBC count, which might be lower in IFN-alpha treatment.

Adolescent↗
PubMed1997

Pharmacokinetic studies of intravenous glycosylated recombinant human granulocyte colony-stimulating factor in various hematological disorders: inverse correlation between the half-life and bone marrow myeloid cell pool.

The pharmacokinetics of an intravenous bolus dose of glycosylated recombinant human G-CSF (rhG-CSF) was examined in 15 patients with various hematological disorders and 3 normal volunteers. The elimination half-life of rhG-CSF varied with the disorder. The half-life of an initial dose of rhG-CSF (2 micrograms/weight kg) was significantly prolonged in patients with aplastic anemia (2.7 +/- 0.3 h, n = 3) and myelodysplastic syndrome-refractory anemia (2.0 +/- 0.3 h, n = 3) when compared with those in normal controls (0.9 +/- 0.5 h, n = 3). In contrast, in patients with acute myelogenous leukemia which was overt leukemia from myelodysplastic syndrome-refractory anemia with excess of blasts in transformation, the half-life was shortened after chemotherapy (0.2 +/- 0.1 h, n = 3). The half-life of rhG-CSF in 2 patients with acute lymphoblastic leukemia in complete remission was prolonged (2.0 and 2.7 h) at the time of marrow-suppression after chemotherapy and then shortened (0.5, 1.0 h, respectively) in the recovery phase. The half-life of rhG-CSF was very weakly, inversely correlated with absolute neutrophil count in blood (n = 24, r2 = 0.32, P < 0.01), and was inversely correlated with the absolute count of bone-marrow myeloid cells (nucleated cell count in bone-marrow aspirates x the percentage of myeloid cells/100) of patients with aplastic anemia and myelodysplastic syndrome-refractory anemia (n = 12, r2 = 0.63, P = 0.002). These results suggest that the half-life of intravenously administered rhG-CSF (2 micrograms/kg) reflects the size of the myeloid cell compartment in vivo, and support the hypothesis that receptor-mediated consumption mainly accounts for the clearance of exogenous G-CSF.

Adolescent↗
PubMed1997

Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes.

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.

Adolescent↗
PubMed1997

Fatal GVHD demonstrating an involvement of respiratory muscle following donor leukocyte transfusion (DLT).

A 41-year-old female patient with AML, who relapsed after an allogeneic BMT from her HLA-identical sister, was treated by a donor leukocyte transfusion (DLT). Thereafter, bone marrow aplasia accompanied by the disappearance of leukemic blasts following the GVHD was observed. The patient died of chronic GVHD with respiratory muscle involvement 19 months after the DLT. Although the DLT was considered helpful in suppressing the proliferation of the leukemic cells, it might also have caused the severe GVHD observed in this case. Efforts to separate the lymphocyte clones responsible for GVL from those for the GVHD thus appear to be necessary for the further development of the therapeutic approach, so-called DLT.

Adult↗
PubMed1997

Isoform-specific up-regulation by ouabain of Na+,K+-ATPase in cultured rat astrocytes.

There are two alpha-subunit isoforms (alpha1 and alpha2) and two beta-subunit isoforms (beta1 and beta2) of Na+,K+-ATPase in astrocytes, but the functional heterodimer composition is not known. Ouabain (0.5-1.0 mM) increased the levels of alpha1 and beta1 mRNAs, whereas it decreased those of alpha2 and beta2 mRNAs in cultured rat astrocytes. The increases in alpha1 and beta1 mRNAs were observed at 6-48 h after addition of the inhibitor. Immunochemical analyses showed that ouabain increased alpha1 and beta1, but not alpha2 and beta2, proteins, and that the isoforms in control and ouabain-treated cultures were of glial origin. Low extracellular K+ and monensin (20 microM) mimicked the effect of ouabain on alpha1 mRNA. The ouabain-induced increase in alpha1 mRNA was blocked by the protein synthesis inhibitor cycloheximide (10 microM), the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (30 microM), and the calcineurin inhibitor FK506 (1 nM). These findings indicate that chronic inhibition of Na+,K+-ATPase up-regulates the alpha1 and beta1, but not alpha2 and beta2, isoforms in astrocytes, suggesting a functional coupling of alpha1beta1 complex. They also suggest that intracellular Na+, Ca2+, and calcineurin may be involved in ouabain-induced up-regulation of the enzyme in astrocytes.

Animals↗
PubMed1997

Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study. Multicenter Study Group.

A multicenter randomized controlled study was undertaken in order to determine whether epoetin beta (EPO) ameliorates the anemia in aplastic anemia (AA) patients treated with granulocyte colony-stimulating factor (G-CSF). Enrolled patients were randomized into 3 groups: group C receiving G-CSF alone as the control; group L receiving G-CSF and 200 IU/kg of EPO; group H receiving G-CSF and 400 IU/kg of EPO. Throughout the study, the dose and the administration interval of G-CSF were adjusted to maintain neutrophil counts between 1000 and 5000 microliters EPO was administered subcutaneously for 12 wk as the first step in treatment and when favorable effects were observed over this period, treatment was continued for another 12 wk as the second step in treatment. Significant erythroid responses were defined as increases in untransfused hemoglobin values > 1.0 g/dl or > 50% decreases in RBC transfusion requirements over the treatment period. Of 131 patients enrolled, 88 patients allocated to groups L and H were evaluated for toxicity to EPO and 110 were evaluated for erythroid responses. Four of the 31 patients (12.9%) in group C, 6 of the 41 patients (14.6%) of group L, and 14 of the 38 patients (36.8%) of group H showed erythroid responses in the first step in treatment. The erythroid responses of group H were significantly higher than those of the other 2 groups (p < 0.05). The significant effects of EPO were due to erythroid responses in non-severe AA. Responding patients were significantly different from non-responders with regard to disease severity, hemoglobin concentration, reticulocyte count, serum endogenous erythropoietin levels and serum transferrin receptors; non-severe AA patients were more likely to respond to EPO, and responding patients had lower serum EPO and higher hemoglobin concentration, reticulocyte count and serum transferrin receptors than non-responders. The response rate increased in the second step in treatment, suggesting that long-term treatment improved the efficacy of EPO. No serious side-effects were observed. From these results, we conclude that EPO given in combination with G-CSF is a safe and effective alternative for the treatment of anemia of a subset of AA patients.

Adult↗
PubMed1997

[Structure-function study on gastric proton pump].

H+, K(+)-ATPase is a proton pump responsible for gastric acid secretion. It actively transport proton and K+ coupled with the hydrolysis of ATP, resulting in the formulation of a 10(6) fold proton gradient across the plasma membrane of parietal cells. The pump belongs to a family of P-type ATPases which include the Na+ pump (Na+, K(+)-ATPase) and the Ca2+ pump (Ca(2+)-ATPase). This review focuses on the structure-function relationship of this proton pump by using functional antibodies, specific inhibitor(s), a fluorescent reagent and site-directed mutants. First we prepared monoclonal antibodies which modified the functions of the H+, K(+)-ATPase . One of the antibodies, HK2032 inhibited the H+, K(+)-ATPase activity and the chloride conductance in gastric vesicles opened by S-S cross-linking, suggesting that the chloride pathway is in the H+, K(+)-ATPase molecule, and that the H+, K(+)-ATPase is a multi-functional molecule. Other antibody, HK4001 inhibited the H+, K(+)-ATPase activity by inhibiting its phosphorylation step. By using this antibody we found an H+, K(+)-ATPase isoform in the rabbit distal colon. Second we found that scopadulcic acid B, a main ingredient of Paraguayan traditional herb, is an inhibitor specific for the H+, K(+)-ATPase. This compound inhibited the H+, K(+)-ATPase activity by stabilizing the K(+)-form of the enzyme. Third we studied the conformational changes of the H+, K(+)-ATPase by observing the fluorescence of FITC-labeled enzyme. H+, K(+)-ATPase did not utilize acetylphosphate instead the ATP as an energy source of active transport, suggesting that the energy transduction system is not common among P-type ATPases. Finally we constructed a functional expression system of the H+, K(+)-ATPase in human kidney cells. By using this functional expression system in combination with site-directed mutagenesis, we studied the significance of amino acid residues in the catalytic centers (a phosphorylation site and an ATP binding site) and the putative cation binding sites. We newly found the sites determining the affinity for cations.

Adenosine Triphosphate↗
PubMed1997

Prevention of gastric ulcer relapse induced by indomethacin in rats by a mutein of basic fibroblast growth factor.

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H2-receptor antagonists (H2-RAs) on ulcer relapse in this model. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starting 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

Acetic Acid↗
PubMed1997

Role of endogenous basic fibroblast growth factor in the healing of gastric ulcers in rats.

Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580) may be involved in its effect on ulcer healing.

Animals↗
PubMed1997

Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain.

The present study was carried out to clarify whether orally administered 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a serotonin1A (5-HT1A)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg) caused a significant decrease in 3[H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect [3H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT1A receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.

5,7-Dihydroxytryptamine↗
PubMed1997

Inhibition by nitric oxide of the uptake of [3H]serotonin into rat brain synaptosomes.

[3H]Serotonin (5-HT) uptake by synaptosomes of rat brain was dose-dependently inhibited by nitric oxide (NO) donors such as sodium nitroprusside (SNP), 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e, 3-morpholinosydnonimine and S-nitroso-L-cysteine (NO-CYS). The inhibitory effect was blocked by reduced hemoglobin. The effect was not mimicked by ferrocyanide and ferricyanide. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-bromo cGMP) did not affect [3H]5-HT uptake into rat cortical synaptosomes. The reduced activity of [3H]5-HT uptake into the cortical synaptosomes pretreated with NO-CYS was partially reversed by washing the preparation after the treatment. Kinetic analysis showed that NO-CYS (100 microM) decreased the Vmax value without any change in the Km value. NO-CYS did not affect the specific binding of [3H]paroxetine, a ligand that binds to the 5-HT transporter, in membranes. NO-CYS and SNP, like iodoacetic acid and sodium cyanide, decreased the ATP content in cortical synaptosomes, but the effect on ATP content was not related to that on [3H]5-HT uptake. These findings suggest that NO inhibits reversibly [3H]5-HT uptake into rat brain synaptosomes without affecting the recognition site of the 5-HT transporter in a cGMP-independent manner, and the observed effect is not due to its metabolic effect.

Adenosine Triphosphate↗
PubMed1997

Potency of truncated secretory leukoprotease inhibitor assessed in acute lung injury models in hamsters.

We evaluated the potency of truncated secretory leukoprotease inhibitor (truncated SLPI) in a human sputum elastase (HSE)-induced lung injury model and in a specific neutrophil-mediated acute lung injury model in hamsters. Intratracheal administration of HSE induced acute lung hemorrhage that could be measured by determination of the hemoglobin content in the bronchoalveolar lavage fluid. Intratracheal administration of truncated SLPI 1 hr before HSE administration inhibited acute lung hemorrhage in a dose-dependent manner (ED50 = 46.8 microg/kg), as did i.v. injection of the inhibitor given 2 min before HSE administration (ED50 = 14.7 mg/kg). Intratracheal administration of endotoxin (lipopolysaccharide) induced pulmonary neutrophilia. Twenty-four hours after lipopolysaccharide administration, the addition of formyl-methionyl-leucyl-phenylalanine resulted in a neutrophil-dependent acute lung injury that expressed an increase in hemoglobin content and in elastase-like activity in bronchoalveolar lavage fluids. In this model, lung injury was significantly attenuated by i.v. and intratracheal administration of truncated SLPI. These results suggest that truncated SLPI appears to be a good candidate inhibitor for the treatment of destructive lung diseases due to neutrophils.

Animals↗
PubMed1997

[A nonparametric estimation of survival curve with interval censored data].

Although survival analysis dealing with right-censored data has enjoyed wide use, analysis of data with left-censored and interval censored cases is available only to a very limited number of clinical researchers because of the difficulty in understanding the concepts and performing the calculations. This paper applies Turnbull's self-consistency algorithm, which he applied in his paper on survival data with only left-censored cases, for nonparametric estimation of survival curve including both left and interval censored data. A difference in the estimates of survival rate among different modes of calculation was demonstrated using the data from the Hematopoietic Cell Transplantation Registry of the Japan Society for Hematopoietic Cell Transplantation, which illustrated the necessity of a correct analysis.

Algorithms↗
PubMed1997

[A case report of thoracic aortic aneurysm associated with tubular hypoplasia].

A 55-year-old female was diagnosed as thoracic aortic aneurysm associated with tubular hypoplasia. A saccular aneurysm occupied the aortic arch between left common carotid and left subclavian arteries, arising from the cranial wall of the tubular hypoplasia. The aneurysmectomy was performed under cardiopulmonary bypass with selective cerebral perfusion and woven Dacron graft was implanted. The post-operative course was uneventful and she was discharged 32 days after the operation. Aneurysm associated with coarctation usually is thin walled, therefore an early surgical treatment should be urged.

Aortic Aneurysm, Thoracic↗
PubMed1997

Kinetic assay of serum and urine for urea with use of urease and leucine dehydrogenase.

We describe a new kinetic assay for determining urea in serum or urine with use of urease (EC 3.5.1.5) and leucine dehydrogenase (EC 1.4.1.9). The latter enzyme is suitable for the kinetic assay of NH4+ because its Km value for NH4+ at pH 8.75 is large (approximately 500 mmol/L). Interference from endogenous NH4+ in serum or urine is obviated by subtraction of the assayed endogenous NH4+ value in a sample blank. For serum, within-assay CVs (n = 10) were 0.39-0.58%; day-to-day CVs (n = 10) were 1.56-2.30%. In urine, within-assay CVs (n = 10) were 0.86-1.15%. Analytical recovery of urea (0.893-71.4 mmol/L) added to patients' sera (urea 6.14 mmol/L) was 99.2-105.2%. The calibration curve for serum was linear through zero for urea concentrations up to 142.9 mmol/L and for urine up to 714.3 mmol/L. No influences of added ammonium ion, bilirubin, hemoglobin, ascorbic acid, or Intralipid were observed. The regression equations for this method (y) and conventional methods (x = Determiner-LUN for serum assays, Serotec UUR-R for urine) were: y = 1.016x - 0.12 mmol/L (r = 0.999, S(y/x) = 0.34 mmol/L, n = 100) for sera, and y = 1.070x - 12.6 mmol/L (r = 0.998, S(y/x) = 7.41 mmol/L, n = 100) for urine.

Amino Acid Oxidoreductases↗
PubMed1997

[A case of thymic carcinoma with brain metastasis].

A 43-year-old female with a thymic carcinoma spreading to the extrathorac region is reported. She had received radiation and chemotherapy, after that thymic carcinoma was extirpated. Five months later, the patient was noticed to have a right side hemiparesis, following consciousness disturbance. CT and MRI revealed a left thalamic mass with a heterogenous enhancement effect. The tumor was diminished dramatically due to radiation. Metastasis of thymic carcinoma to the central nervous system is discussed.

Adult↗