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Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 217 records · Page 12Linked to original sources
PubMed1995

Inhibition of GM-CSF production by recombinant human interleukin-4: negative regulator of hematopoiesis.

Interleukin-4 (IL-4), also known as B-cell stimulatory factor-1 (BSF-1), was initially identified as a T-cell product that mediates anti-IgM-induced DNA synthesis in B-lymphocytes. Various aspects of this highly pleiotropic cytokine have been described, including those on hematopoietic progenitor cells. However, the role of IL-4 in the hematopoietic system has been given different interpretations. Normal human hematopoietic progenitor cells do not proliferate under control of the autocrine system and cytokines are needed for proliferation and differentiation. However, IL-4 in itself does not support proliferation of these cells and if this is the case, the effects of IL-4 on hematopoietic progenitor cells still need to be investigated from the point of view of synergism with other cytokines as well as the control of accessory cells in the production of cytokines. We describe here some properties of IL-4 in association with cytokine production, with special emphasis on granulocyte-macrophage colony-stimulating factor (GM-CSF) production.

Animals↗
PubMed1995

Vasorelaxant effect of isocarbacyclin methyl ester incorporated into lipid microspheres on isolated canine arteries.

TTC-909 is a preparation of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated into lipid microspheres. The characteristics of vasorelaxation induced by TTC-909 were investigated in isolated canine arteries. TTC-909 produced concentration-dependent relaxation of prostaglandin F2a(PGF2a)-induced and U-46619 (TXA2 receptor agonist)-induced contraction in basilar, coronary, renal, mesenteric, and femoral arteries. The vasorelaxant potency of TTC-909 was compared with the potencies of TEI-9090, TEI-7165 (CAS 88911-35-7, free acid of TEI-9090), prostaglandin I2 (PGI2), and prostaglandin E1 (PGE1) on PGF2a-induced contraction in basilar and femoral arteries. The relaxing potency of TTC-909 was similar to the values for TEI-9090, TEI-7165, and PGI2, and more potent than that of PGE1 in both of these arteries. An esterase inhibitor, diisopropyl fluorophosphate (DFP), reduced the vasorelaxant effect of TEI-9090, but not that of TEI-7165, on PGF2a-induced contraction in femoral arteries. These results suggest that TTC-909 has vasorelaxant potency similar to that of PGI2 and greater than that of PGE1. Further, it appears that TEI-9090 was converted to TEI-7165 by esterase and then produced its vasorelaxing effect.

Animals↗
PubMed1995

Effect of isocarbacyclin methyl ester incorporated into lipid microspheres on cutaneous blood flow in rat.

A new stable prostacyclin analogue, isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090), incorporated into lipid microspheres (TTC-909), was examined for its effects on cutaneous blood flow and mean blood pressure in rats in comparison with PGE1 (LM) (prostaglandin E1 in lipid microspheres). TTC-909 at 0.3 micrograms/kg i.v. significantly increased the sole cutaneous blood flow without changing blood pressure. A significant decrease in mean blood pressure was observed with TTC-909 above 1 microgram/kg i.v. PGE1 (LM) also showed a decrease in the blood pressure from 1 microgram/kg i.v., whereas the sole cutaneous blood flow was not affected even at 10 micrograms/kg i.v. These results suggest that TTC-909 dilates the skin vessels preferentially to other blood vessels in the rat and that effect is more potent than that of PGE1 (LM). TTC-909 may thus prove to be an effective agent for the treatment of peripheral vascular disease.

Animals↗
PubMed1995

Effect of isocarbacyclin methyl ester incorporated in lipid microspheres on experimental models of peripheral obstructive disease.

The effect of TTC-909 (isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated into lipid microspheres) on obstruction of the peripheral artery was studied in two different animal models. The first was a peripheral occlusion model induced by intra-arterial injection of sodium laurate in rats. The second was a tail gangrene model induced by subcutaneous injection of both ergotamine and epinephrine in rats. Intravenous bolus-administered TTC-909 at 1.0 microgram/kg resulted in the inhibition of both progression of lesions induced by sodium laurate and the extension of tail gangrene by ergotamine and epinephrine. Moreover, the inhibitory effect of TTC-909 was more potent than that of PGE1 (LM) (prostaglandin E1 incorporated into lipid microspheres). These findings suggested that TTC-909 may be clinically useful for the therapy of peripheral vascular disorders such as thromboangiitis obliterans (TAO) and atherosclerosis obliterans (ASO).

Alprostadil↗
PubMed1995

Interferon-alpha-induced apoptosis in human erythroid progenitors.

Recombinant human interferon-alpha (rIFN-alpha) inhibits erythropoiesis, in vivo and in vitro. In an attempt to clarify mechanisms related to this inhibition, effects of rIFN-alpha on highly purified human peripheral blood burst-forming units-erythroid (BFU-E) (20-60% purity) were compared with effects on erythroid progenitors in various stages of development. Day-1 and -7 cultured cells were equivalent to primitive BFU-E and colony-forming units-erythroid (CFU-E), respectively. Day-1 BFU-E supported by recombinant human erythropoietin (rEpo) and interleukin-3 (rIL-3) was inhibited by rIFN-alpha in a dose-dependent manner, and a significant inhibition occurred at 2000 U/mL rIFN-alpha. Limiting dilution analysis demonstrated that rIFN-alpha directly inhibits BFU-E rIFN-alpha inhibited the proliferative capacity or the colony expression of erythroid progenitors, with no relation to the stage of development, but inhibition of differentiation was not apparent. This evidence suggested that apoptosis of erythroid progenitors was induced by IFN-alpha. When day-7 cells were incubated with IFN-alpha in the presence of rEpo, there was an increased breakdown of total cellular DNA into DNA fragments of less than 5 kb; hence, the inhibitory effect of IFN-alpha on erythroid progenitors may mediate apoptosis.

Adult↗
PubMed1995

Spatial ventricular gradient in patients with Wolff-Parkinson-White syndrome in comparison with normal subjects: vectorcardiographic evidence for significant repolarization changes due to preexcitation.

We investigated the use of the spatial ventricular gradient (VG) from vectorcardiogram (VCG) to determine whether significant repolarization differences were present in patients with WPW syndrome compared with normal subjects and also examined which VG parameter (i.e., elevation, azimuth, and magnitude) reflected the differences in repolarization properties during preexcitation. VG was calculated in 49 patients of Wolff-Parkinson-White (WPW) syndrome (group A: left-sided accessory pathway, n = 29; group B: right-sided, n = 20). Group N consisted of 607 normal subjects. In group A, the azimuth of VG was significantly (p < 0.01) greater than in groups B and N. In group B, the elevation of VG was significantly (p < 0.01) greater than in groups A and N. There were no significant differences in the magnitude of VG among groups. QRS duration was significantly (p < 0.01) related with the elevation of VG in group B. These findings suggested that VG is useful for spatial evaluation of repolarization abnormalities during preexcitation, which are related to the site of the accessory pathway.

Adolescent↗
PubMed1995

Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel disease.

Leukocytapheresis (LCAP) with a leukocyte removal filter was administered to 44 patients with inflammatory bowel disease (IBD), diagnosed as ulcerative colitis (UC) in 25 and Crohn's disease (CD) in 19. Clinical and blood examinations showed no side effects in any of the patients. During intensive therapy, clinical improvement was recognized in 21 of the 25 UC patients (84%), 8 of whom had an excellent response, and in 16 of the 19 CD patients (84.2%), 4 of whom had an excellent response. The clinical improvement continued throughout the maintenance therapy in 19 of the UC patients (76%) and in 12 of the CD patients (63.2%). In both the UC and the CD patients, flow cytometry study showed that those who had improved generally had high values for the percentages of HLADR+, HLADR+CD3+, HLADR+CD8+, and CD11a+CD8+ cells before the first LCAP, and that these values decreased to near the normal range after both intensive and maintenance therapy. In the patients who showed poor response, in contrast, the values had been at or near normal before the initial LCAP administration. The clinical improvement and the findings on flow cytometry suggest that LCAP exerts an immuno-modulatory effect and is an effective therapy for patients with IBD in whom conventional drug treatments have failed.

Case-Control Studies↗
PubMed1995

Ultrasonographic evaluation of the carpal tunnel syndrome in hemodialysis patients.

The carpal tunnel syndrome (CTS) is the most frequent clinical symptom of dialysis-related amyloidosis. We examined CTS by ultrasound imaging and correlation between CTS and bone amyloidosis was sought. One hundred and forty-two wrists of 71 hemodialysis (HD) patients and 28 of 14 normal volunteers (group 1) were studied. Patients on HD were divided into 4 groups based on HD duration: Group 2, less than 5 years; group 3, 5-10 years; group 4, 10-15 years; and group 5, more than 15 years. The frequency of CTS increased gradually with HD duration: 0% in group 2, 35.3% in group 3, 36.4% in group 4 and 74.1% in group 5. The thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel was significantly greater in groups 4 (p < 0.05), and 5 (p < 0.05) than in group 1 (2.25 +/- 1.30 and 3.11 +/- 1.02 in group 4 and 5 vs 1.15 +/- 0.34 mm in group 1); and the width of the carpal tunnel (CT) was significantly larger in group 5 than in group 1 (6.92 +/- 1.78 in group 5 vs 5.53 +/- 1.48 mm in group 1, p < 0.05). Wrists operated on for CTS had significantly increased PRL and CT compared to the control group and patients without CTS. Patients with CTS had wider PRL than the control and HD patients without CTS. Cystic radiolucent lesions (CRL) of carpal bones characteristic of bone amyloidosis were noted in 15 of 71 HD patients. The thickness of PRL and width of CT in HD patients with CRL exceeded those in patients without CRL. These data indicated that ultrasonographic findings of wrists were closely correlated with the degree of CTS and CRL. The usefulness of ultrasonographic evaluation of PRL thickness and CT width in the evaluation of dialysis-related amyloidosis should be evaluated.

Amyloidosis↗
PubMed1994

Stable expression of the neuronal BI (class A) calcium channel in baby hamster kidney cells.

Plasmids containing the BI (alpha 1) cDNA with the dihydrofolate reductase (DHFR) gene, skeletal muscle alpha 2-subunit cDNA with the neo marker gene, and beta-subunit cDNA were co-transfected into baby hamster kidney (BHK) cells. BHK cells lack endogenous calcium channel activity. Twenty percent of the methotrexate (MTX) and G418 resistant clones were found to express calcium channel activity using the patch-clamp technique. A single clone, BHKBI147, demonstrated stable electrophysiological characteristics over 20 passages. Ca2+ currents of the BI channel in BHKBI147 cells were largely blocked by a specific P-type blocker, omega-AgaIVA, with an IC50 of 150 nM. Unlike the BI channel, Ca2+ currents of cardiac L-type channels expressed in BHK cells were completely blocked by the L-type antagonist, nifedipine, with an IC50 of 56 nM.

Animals↗
PubMed1994

Leukemic meningitis in a patient with splenic lymphoma with villous lymphocytes (SLVL). Meningitis as a possible initial manifestation of SLVL.

BACKGROUND: Splenic lymphoma with villous lymphocytes (SLVL) is a low grade, non-Hodgkin's lymphoma with a stable or slowly progressive clinical course. To the authors' knowledge, central nervous system involvement has not been described previously in patients with SLVL. METHODS: Morphologic, immunocytochemical, and immunohistochemical analyses were conducted to determine the nature of villous lymphocytes in the peripheral blood, spleen, and cerebrospinal fluid (CSF) of a patient with massive splenomegaly. RESULTS: A diagnosis of SLVL was made, based on tartrate-resistant acid phosphatase-negative peripheral villous lymphocytosis with CD19+, CD20+, HLA-DR+ phenotypes, and the involvement of spleen white pulp with these cells. Mononuclear cells in the CSF showed the same morphologic and immunocytochemical features seen in the villous lymphocytes in the peripheral blood and spleen. Splenectomy and intrathecal chemotherapy were successful in clearing leukemic cells from the CSF. CONCLUSION: In this patient with SLVL in whom leukemic meningitis developed, meningitis was found to be a possible initial manifestation of SLVL.

B-Lymphocytes↗
PubMed1994

Defective leukocyte function-related cryoprecipitable protein in cryoglobulinemia.

Cryoprecipitable proteins (CPP), purified from plasmas removed during plasmapheresis treatment of patients with type II and type III cryoglobulinemia (CG), were evaluated in vitro for their effect on normal leukocyte function. CPP reduced normal mononuclear cell blastogenesis and polymorphonuclear cell phagocytosis responses in a dose-dependent fashion. At the maximum concentration studied, 5,000 micrograms/ml, CPP were shown to suppress normal blastogenesis and phagocytosis 30-60% and 50-80% below the albumin control, respectively. A 50% suppression of normal blastogenesis and phagocytosis was observed at 500 micrograms/ml for type III CPP. Leukocyte functions in CG patients were evaluated and compared to those of healthy controls. Blastogenesis and phagocytosis were significantly inhibited in CG patients. These studies suggest that CG patients have defective leukocyte function and that CPP have suppressive effects on normal leukocyte function. Our studies suggest that removal of CPP in CG patients may prove beneficial not only in reducing typical symptoms of CG but also in reducing the potential inhibitory effects of CPP on leukocyte function.

Adult↗
PubMed1994

Synthesis of a phosphatidyl derivative of vitamin E and its antioxidant activity in phospholipid bilayers.

A novel phospholipid containing a chromanol structure at its polar head group was synthesized from egg yolk phosphatidylcholine and 2,5,7,8-tetramethyl-6-hydroxy-2-(hydroxyethyl)chroman by transphosphatidylation catalyzed by phospholipase D from Streptomyces lydicus. The structure of the product synthesized was shown by spectral analysis to be 1,2-diacyl-sn-glycero-3-phospho-2'-hydroxyethyl- 2',5',7',8'-tetramethyl-6'-hydroxychroman. The phosphatidylchromanol (PCh) showed antioxidant activity against radical chain oxidation of methyl linoleate in solution in a manner similar to that of d-alpha-tocopherol (alpha-Toc) and 2,2,5,7,8-pentamethyl-6-chromanol. However, PCh was less effective as a chain-breaking antioxidant than was alpha-Toc when unilamellar egg yolk phosphatidylcholine liposomes were exposed to either a water-soluble or a lipid-soluble radical initiator. It is likely that the phospholipid nature of PCh affects the location and the mobility of the chromanol moiety in the membrane bilayer resulting in a decrease in antioxidant activity. On the other hand, the antioxidant activity of PCh was little different from that of alpha-Toc in unilamellar liposomes when exposed to a lipid-soluble radical initiator in the presence of ascorbic acid. It appears that PCh in phospholipid bilayers can be regenerated by ascorbic acid in aqueous phase as can be alpha-Toc. The new phospholipid, phosphatidylchromanol, should prove useful as a chain-breaking antioxidant in phospholipid membranes.

Antioxidants↗
PubMed1994

Recombinant human interleukin-4 inhibits the production of granulocyte-macrophage colony stimulating factor by blood mononuclear cells.

The effect of recombinant human (rh) interleukin-4 (rIL-4) on human blood BFU-E was investigated using two populations of cells: platelet-depleted low-density mononuclear cells (FH,Pl- cells), as unpurified cells, and highly purified BFU-E. When FH,Pl- cells were cultured with rh-erythropoietin (rEp), rIL-4 inhibited BFU-E growth in a dose-dependent manner. However, the addition of rIL-4 did not affect rh-interleukin-3 (rIL-3) supported BFU-E growth. Limiting dilution analysis (LDA) of FH,Pl- cells showed that rIL-4 suppressed endogenous production of burst-promoting activity (BPA) by accessory cells. Highly purified BFU-E were used as target cells to measure BPA in the conditioned medium (CM) that was prepared by FH,Pl- cells. When 100 purified BFU-E were cultured in 0.5 ml clots with 20% (vol/vol) of the CM, the number of BFU-E colonies was increased by the CM. The increase was significantly reduced by the addition of the CM prepared in the presence of rIL-4, but anti-IL-4 blocked the effect of rIL-4. The concentration of IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CM was determined by an enzyme-linked immunoadsorbent assay (ELISA). The spontaneous production of GM-CSF but not IL-3 was detected, and this was significantly decreased in the presence of rIL-4. Anti-GM-CSF but not anti-IL-3 inhibited CM supported BFU-E growth, indicating that the main BPA in the CM is GM-CSF and that rIL-4 suppresses the spontaneous production of GM-CSF by accessory cells. From these studies, we conclude that rIL-4 has a unique mechanism as a negative regulator on erythropoiesis through the inhibition of BPA production by blood mononuclear accessory cells.

Adult↗
PubMed1994

Switching of mouse spermatogonial proliferation from the c-kit receptor-independent type to the receptor-dependent type during differentiation.

Testicular cells composed mostly of germ cells and immature Sertoli cells from neonatal mice 2 and 5 days old were cultured to investigate germ-cell proliferation mediated by the c-kit receptor. The addition of antibody to block the interaction of the c-kit receptor with its ligand inhibited the proliferation of cultured spermatogonia from 5-day-old mice in a dose-dependent manner, but not from that of 2-day-old mice. The addition of anti-c-kit ACK2 monoclonal antibody also inhibited the proliferation of spermatogonia from 5-day-old mutant Sld/Sld mice but not of 5-day-old mutant Wv/Wv mice. The results indicate that c-kit-positive type A spermatogonia in the testes of 5-day-old mice require steel factor (kit ligand) for their proliferation, whereas self-renewal and differentiation of c-kit-negative primitive type A spermatogonia in the testes of 2-day-old mice do not.

Animals↗
PubMed1994

Impaired proliferation and differentiation of myelodysplastic CD34+ cells.

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of hematopoiesis entailing hyperproliferative and ineffective hematopoiesis resulting in refractory cytopenia(s), and increased risk of transformation into acute myeloblastic leukemia (AML). The widely used classification defined by the French-American-British group (FAB) recognizes 5 cytological subtypes of different prognosis, based essentially on the presence and the frequency of marrow blasts. The percentage of marrow blasts does not exceed 30%, hence, direct investigations of biological and biochemical events of MDS blast cells have been hampered. The CD34 antigen is currently unique in its narrow specificity of expression on human lymphohematopoietic progenitor cells. This cell membrane phosphoglycoprotein has been used for immunologic blast cell purification, notwithstanding the frequency of marrow blasts, and has provided a set of tools for investigations of MDS i.e. a direct comparison of the nature of blast cells in each of the MDS subtypes, using immunologic, biologic, biochemical and molecular biological methodology. A combination of serum-free medium and a purification method for blast cells provided evidence that the progenitor cell growth abnormalities in these disorders involve a defect in the capacity of progenitor cells to respond to stimulation with growth factor(s), and has presented direct evidence for the manner in which myelodysplastic CD34+ cells are impaired.

Antigens, CD↗
PubMed1994

A time course study for optimal harvest of peripheral blood progenitor cells by granulocyte colony-stimulating factor in healthy volunteers.

In a search for the optimal method to harvest peripheral blood progenitor cells (PBPC) without myeloablative chemotherapy, we administered recombinant human granulocyte colony-stimulating factor (G-CSF) to adult, healthy volunteers and investigated the mobilization rate of the PBPC. The consecutive subcutaneous administration of G-CSF in a dose of 2 micrograms/kg/d for 5 days significantly increased colony-forming units-granulocyte/macrophage (CFU-GM) up to 2340 +/- 980 per mL whole blood with a 30 +/- 21-fold mobilization of PBPC, range 11- to 76-fold. Burst-forming units-erythroid (BFU-E) and mixed erythroid progenitors (CFU-Mix) were also increased, and the mobilization rate was 8.4 +/- 4.5-fold and 7.6 +/- 4.7-fold, respectively. A time course study of PBPC after final G-CSF injection was done for 0 to 30 hours on days 1, 3, and 5. After a single administration of G-CSF (day 1), there was no increment of PBPC during the subsequent 30 hours, but the white blood cell count (WBC) markedly increased. Three days after the injection of G-CSF, no increase of CFU-GM was seen during the first 2 hours, then a significant, time-dependent increase occurred for up to 30 hours. Five days after the injection of G-CSF, there was no increase of CFU-GM during the first 2 hours, and the significant increase at 24 hours was maintained for up to 30 hours. BFU-E and CFU-Mix showed the same pattern of expansion as seen with CFU-GM. Thus, subcutaneous administration of 2 micrograms/kg/d G-CSF for 5 days will lead to a successful PBPC harvest for transplantation, and the most suitable period for this is 24 to 30 hours after the final G-CSF administration.

Adult↗