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Y Kurata

Publications and source records attributed to Y Kurata.

At least 19 recordsLinked to original sources
PubMed1992

Effects of splenectomy on immune thrombocytopenic purpura in (NZW x BXSB) F1 mice: analyses of platelet kinetics and anti-platelet antibody production.

Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham-operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy.

Animals↗
PubMed1992

The Arg-Gly-Asp (RGD) recognition site of platelet glycoprotein IIb-IIIa on nonactivated platelets is accessible to high-affinity macromolecules.

We have characterized a murine IgG monoclonal antibody, OP-G2, specific for platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3). OP-G2 Fab fragments inhibit fibrinogen-mediated platelet aggregation and competitively inhibit adenosine diphosphate-induced binding of 125I-fibrinogen to washed platelets. OP-G2 binding to GPIIb-IIIa is specifically inhibited by RGD-containing peptides but not the fibrinogen gamma-chain carboxy-terminal peptide, and OP-G2 Fab fragments, like RGD-containing peptides, alter the conformation of GPIIb-IIIa resulting in the expression of a ligand-induced binding site (LIBS) recognized by PMI-1. OP-G2 fails to bind to the recombinant Cam variant of GPIIb-IIIa (alpha III beta 3Cam) wherein an Asp119 to Tyr119 substitution in GPIIIa abrogates the ability to recognize RGD. These data indicate that OP-G2 recognizes an epitope at or in very close proximity to the RGD recognition site of GPIIb-IIIa and that, in every aspect tested, OP-G2 behaves like a macromolecular RGD ligand. Interestingly, two-color flow cytometry shows that OP-G2 IgG can bind to nonactivated platelets. Quantitative binding assays indicate that nonactivated platelets bind approximately 50,000 125I-OP-G2 molecules/platelet. Furthermore, the affinity of OP-G2 for platelets activated with thrombin is roughly fivefold higher (nonactivated, kd = 24.8 nmol/L; activated, kd = 4.9 nmol/L). These results suggest that the RGD recognition site of GPIIb-IIIa is available to macromolecules that contain RGD even on nonactivated platelets, provided that the affinity of the ligand is adequate.

Amino Acid Sequence↗
PubMed1992

Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1.

To determine the mechanism by which platelet counts increase after corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we studied the platelet kinetics using prednisolone (PDN)-treated ITP-prone mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40 days), but not in nontreated controls (0.60 +/- 0.24 days, P less than .01). No increase in platelet production (platelet turnover) was found in PDN-treated W/B F1 mice, but significant decreases in platelet-associated antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted. Studies on organ localization of radiolabeled platelets showed that hepatic uptake significantly decreased in the treated W/B F1 mice, but not in nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-endothelial phagocytic activity in W/B F1 mice, we studied in vivo clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. W/B F1 mice treated with PDN showed a marked impairment of their ability to clear these cells, although PDN had little effect on the number of splenic or hepatic macrophage Fc gamma receptors. These results and our previous findings of splenectomy suggest that PDN improves platelet counts not only by suppressing systemic reticulo-endothelial phagocytic function but also by reducing antibody production.

Animals↗
PubMed1992

Effect of a novel class I antiarrhythmic agent, TYB-3823, on the calcium current in single guinea pig ventricular myocytes.

The effect of TYB-3823 on Ca2+ current (ICa) of guinea pig ventricular myocytes was investigated by means of whole-cell patch-clamp technique. TYB-3823 (100-1,000 microM) caused a concentration-dependent decrease in ICa. Furthermore, a reduction of ICa induced by TYB-3823 (1,000 microM) was progressively accentuated by repetitive membrane depolarization, indicating a rate-dependent block of ICa. However, the inhibitory potency on ICa was approximately 1/1000 of a Ca2+ antagonistic agent, verapamil hydrochloride. Considering evidence that 3-30 microM TYB-3823 decreased the maximum upstroke velocity of the action potential of guinea pig ventricular muscles, it is indicated that the drug does not show its Ca2+ antagonistic property in the usual concentration range as a class I antiarrhythmic agent.

Animals↗
PubMed1992

Effects of aminoglycoside antibiotics on the auditory brainstem response and post rotatory nystagmus in rats.

Effects of three aminoglycoside antibiotics, amikacin (AMK), tobramycin (TOB), and gentamicin (GM), on the auditory and vestibular functions were assessed in rats, the most frequently used species in toxicity studies. Chronic electrodes for auditory brainstem response (ABR) recording were implanted on the epidural surface, and those for post rotatory nystagmus (PRN) were implanted at the nictitating membrane and the outer canthus. AMK, TOB, and GM were given intramuscularly twice daily for 3-4 weeks at a daily dose of 350, 150, and 100 mg/kg, respectively. The amplitude of each wave of the ABR was decreased or disappeared in the groups treated with AMK, TOB, and GM. In the PRN, the duration of the nystagmus was decreased in the TOB group and completely lost in the GM group. No abnormality was observed in the PRN in the AMK group. These results were similar to those reported in the ototoxicity studies of these drugs in guinea pigs and indicate that ototoxicity can be evaluated in rats as successfully as in guinea pigs by this procedure.

Amikacin↗
PubMed1992

Lack of renal tumour-initiating activity of a single dose of potassium bromate, a genotoxic renal carcinogen in male F344/NCr rats.

The renal tumour-initiating activity of potassium bromate (KBrO3), a known genotoxic rat renal carcinogen, was investigated in male F344/NCr rats. 6-wk-old rats were given KBrO3 intragastrically as a single dose of 300 mg/kg body weight, which was confirmed by our preliminary toxicity study as a maximum tolerated single dose for this strain of rat. Starting 2 wk after KBrO3 treatment, groups of 39 rats received either a basal diet or a diet containing 4000 ppm barbital sodium (BBNa) as a promoting regimen and were killed at 30, 52, or 104 wk. Control rats received either dietary BBNa (4000 ppm) or the basal diet alone from wk 2 to 52 or 104 wk. Nephropathy was observed in all rats treated with KBrO3 followed by BBNa at 30 wk and in rats receiving BBNa alone, but not in rats exposed to KBrO3 alone. Dysplastic renal tubular cell foci (DTF), putative preneoplastic renal tubular cell lesions were found associated with nephropathy in rats exposed to KBrO3 followed by BBNa from 47 wk. The incidences and multiplicities of DTF and renal tubular cell tumours observed from 31 to 104 wk revealed no initiating effect of KBrO3 treatment. These results indicate that the KBrO3 dose of 300 mg/kg did not initiate renal carcinogenesis.

Animals↗
PubMed1992

Synergism of environmental carcinogens and promoters on bladder cancer development initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine in F344 rats.

Synergistic or additive effects of combined treatments with carcinogens or promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated rat bladder carcinogenesis were examined. Male F344 rats were given BBN as an initiator followed by low doses of 3 sodium salts (sodium bicarbonate, sodium L-ascorbate and sodium citrate) and/or 3 antioxidants (butylated hydroxyanisole, butylated hydroxytoluene and tertiary butylhydroxyquinone). Combined treatments with 3 sodium salts or 3 antioxidants, and especially all 6 chemicals together promoted bladder carcinogenesis. In addition, these combined treatments were associated with increased DNA synthesis of the bladder epithelium. Combined administration of the carcinogens, o-anisidine, p-cresidine, and 4-chloro-o-phenylenediamine at low doses also enhanced BBN-initiated bladder carcinogenesis. These results indicate that environmental carcinogens or promoters can exert synergistic or additive actions on bladder cancer induction.

Animals↗
PubMed1992

Impaired suppressor function of T cells induced by autologous mixed lymphocyte reaction in patients with idiopathic thrombocytopenic purpura.

Autologous mixed lymphocyte reaction (AMLR)-induced suppressor function was studied in 12 patients with chronic idiopathic thrombocytopenic purpura (ITP). The function was found to be significantly impaired (20 +/- 55%; p less than 0.005) compared with normal subjects (69 +/- 25%). AMLRs in these patients were significantly decreased (p less than 0.05) compared with normal subjects. There was no significant correlation between AMLR-induced suppressor function and platelet counts. Nine patients were studied for AMLR-induced suppressor function before and after splenectomy. The platelet counts increased significantly as a result of splenectomy, but the AMLR-induced suppressor function showed no significant improvement. The results of this study suggest that suppressor dysfunction in ITP may be an immunologic defect irrespective of disease activity. We consider that this abnormality may reflect in vivo failure of the immunoregulatory (feedback) mechanism in ITP.

Adult↗
PubMed1992

Dose-dependent renal tubular toxicity of harman and norharman in male F344 rats.

The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 week to termination, no mortalities occurred. Marked elevation of water consumption was evident in rats given harman or norharman at 1,000 ppm, but not at 500 ppm, together with large increases in urine of low specific gravity. Urinary lysosomal enzymes (N-acetyl-beta-D-glucosaminidase, NAG, and lactate dehydrogenase, LDH) and sugar levels were increased, and the brush border enzymes (gamma-glutamyl transpeptidase, GGT, and alkaline phosphatase, ALP) decreased. Furthermore, serum biochemistry revealed clear elevation of parameters indicating renal toxicity in these rats. Histopathologically, rats fed 1,000 ppm harman or norharman, but not 500 ppm, demonstrated focal toxic renal degenerative/necrotic and regenerative lesions in proximal, distal, and collecting tubules. These changes were associated with a clearly increased labeling index (LI) of the nuclei of renal tubular epithelial cells on immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU). Chemical specific crystal formation within tubular lumina was evident in rats fed 1,000 ppm, but not 500 ppm, this being considered the cause of the renal tubular lesions. It was concluded that harman and norharman exert renal toxicity at the dietary level of 1,000 ppm, but not 500 ppm, in male F344 rats.

Acetylglucosamine↗
PubMed1992

[Anti-platelet antibody and platelet function].

The effect of anti-platelet antibodies, including murine monoclonal antibodies, autoantibodies and alloantibodies, on platelet function was analyzed. The target antigen of these antiplatelet antibodies, investigated in the present study, was a glycoprotein IIb/IIIa, which is a receptor of fibrinogen and plays an important role in platelet aggregation. Some of these antibodies inhibited agonist-induced platelet aggregation. The target antigen of one murine monoclonal antibodies, designated OP-G2, was a glycoprotein IIb/IIIa and interestingly, this antibody induced platelet aggregation, which required divalent cation and fibrinogen. We compared the epitope of these antibodies by inhibition assay and found the epitope of these antibodies to be very close. The binding of OP-G2 to the platelets required Ca2+. These data suggest that OP-G2 recognizes an epitope at or in very close proximity to the fibrinogen binding site of GPIIb/IIIa, as compared with other antibodies.

Antigens, Human Platelet↗
PubMed1992

Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans.

Vimentin expression was studied immunohistochemically in renal cortical tubules of untreated male rats of various ages, rats exposed to toxins (barbital sodium, folic acid) and carcinogens (streptozotocin, N-bis(2-hydroxypropyl)nitrosamine, barbital sodium, and in humans of various ages with or without renal epithelial tumors. Fetal, neonatal, and young adult rats did not express vimentin in renal cortical tubules. Regenerative renal tubular lesions from rats with aging nephropathy and from rats with toxic nephropathy both expressed vimentin. Mitogenic lesions induced by folic acid at 24 hours, however, were not immunoreactive for vimentin. Carcinogen-induced preneoplastic renal cortical tubular lesions in rats were most often focally immunoreactive whereas strong vimentin expression was found in almost all induced renal tumors. In kidneys of three children (younger than 2 years of age), vimentin was not found in renal cortical tubular cells except in rare individual cells in one case. Vimentin was abundant in basophilic regenerative tubules in kidneys of aged individuals, however. Most (7/10) human renal carcinomas and latent preneoplastic or neoplastic renal tubular lesions found incidentally at autopsy (2/4) showed vimentin expression. The authors suggest that the switching to vimentin expression in phenotypically normal renal cortical tubular cells in rats and humans, which do not usually express the intermediate filament protein vimentin, should be considered vimentin metaplasia. Vimentin expression is dissociated from increased cell proliferation in hyperplastic and neoplastic lesions, however. Instead the degree of dedifferentiation of the tubule cells and changes in phenotype were associated with vimentin expression.

Age Factors↗
PubMed1992

[Clinical significance of antinuclear antibody in patients with idiopathic thrombocytopenic purpura].

The clinical significance of antinuclear antibodies (ANA) in patients with chronic idiopathic thrombocytopenic purpura (ITP) was evaluated. Serum samples of 55 patients with ITP without clinical features of systemic lupus erythematosus (SLE) were examined. The average follow-up period was 5.5 years. Positive ANA was found in 23 of the 55 patients. Twelve of these 23 showed a high-titer of ANA. There was no difference in platelet counts between ANA positive patients and negative patients, and there was no correlation between platelet counts and antibody titers. Ten of the 23 positive sera had precipitating antibodies to nuclear antigens; 7 SS-A and 3 RNP antibodies. The platelet counts of the 7 cases with anti-SS-A antibody positive were slightly low compared with those of the anti-SS-A antibody negative patients. None of the 10 patients developed SLE during the average follow-up period of 8.1 years. These results suggest that ITP patients who have a high-titer of ANA or antibody against SS-A do not always develop SLE. It was concluded that ANA with a high titer or precipitin to nuclear antigens, particularly SS-A, dose not predict a high risk of developing SLE in the future.

Adult↗
PubMed1992

Expression of the differentiated phenotype of chondrocyte in adjuvant induced arthritis of rat.

Rat cartilage tissue was found to produce two types of proteoglycan monomers distinguished by density gradient centrifugation under dissociative condition and with different molecular size (PG I and PG II) as observed in cultured rabbit costal chondrocyte and human cartilaginous tissues. The incorporation of 35S-sulfate and distribution of the molecular size of proteoglycan (PG) were studied to determine the differentiated phenotypes of chondrocyte in adjuvant induced arthritis of rats. The cartilaginous tissue from the acute inflammatory phase shows a low incorporation of 35S-sulfate into PGs but produce the same hydrodynamic size as that of the control. After that acute phase the incorporation recovered suggesting of a repair phase. But in the chronic phase both the incorporation and the produced hydrodynamic size of PGs were severely alternated. With our method this paper shows the drastic alternation about the cartilaginous properties of rat chondrocytes under these circumstances.

Animals↗
PubMed1992

[Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA-alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter].

A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte-depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions.

Adolescent↗
PubMed1991

13-Week oral toxicity study of captafol in F344/DuCrj rats.

Captafol fed at concentrations of 0, 0.075, 0.15, 0.3, and 0.6% to both sexes of F344 rats for 13 weeks produced dose-related decreases in body weight in males and females given 0.15% or higher concentrations. A dose-dependent decrease in urinary pH was observed in males receiving 0.3 or 0.6% and in females given 0.15% or higher concentrations of captafol. The 0.3 and 0.6% doses produced slight increases in leukocyte count and glutamic-pyruvic transaminase activity in females, along with a mild increase in alkaline phosphatase activity in the 0.6% case. The liver- and kidney-to-body weight ratios were increased in both male and female rats. Histopathological changes were observed in the forestomach, liver, and kidney. Squamous cell hyperplasia and edema accompanied by polynuclear leukocyte infiltration and dilation of vessels in the lamina propria were observed in the forestomach of both sexes given 0.15% or higher concentrations. Oval cell proliferation was apparent around Glisson's sheath in the livers of females given 0.3 and 0.6% captafol. Multifocal appearance of karyocytomegaly and tubular cell atypia in the proximal tubules of the kidney was found in the 0.3 and 0.6% groups of both sexes.

Alanine Transaminase↗
PubMed1991

B cells expressing CD5 antigen are markedly increased in peripheral blood and spleen lymphocytes from patients with immune thrombocytopenic purpura.

By two-colour flow cytometric analysis, we examined the proportion of B lymphocytes bearing CD5 cell surface antigen (CD 5+ B cells), which are capable of producing autoantibodies, both in peripheral blood and spleen from patients with chronic immune thrombocytopenic purpura (ITP). The percentage of CD5+ B cells in peripheral blood lymphocytes (PBLs) was significantly increased (P less than 0.005) in patients with ITP (3.7 +/- 2.2%, n = 30) as compared with normal controls (1.7 +/- 0.7%, n = 28). However, there was no correlation between the percentages of circulating CD5+ B cells and platelet counts. The percentage of splenic CD5+ B cells in ITP patients was much more increased (9.0 +/- 4.5%, n = 9), P less than 0.005) compared with that of other disorders (3.2 +/- 0.5%, n = 5). Furthermore, isolated splenic CD5+ B cells from two out of five ITP patients produced high levels of IgM-type, platelet-bindable antibodies (PBIgM) after stimulation with Staphylococcus aureus Cowan I (SAC), while CD5- B cells isolated from the same spleen or splenic CD5+ B cells from other non-autoimmune disorders failed to produce significant amount of PBIgM. In three ITP patients, no increase in PBIgM was detected despite SAC stimulation. The increased proportion of CD5+ B cells in peripheral blood and spleen, and their ability to produce anti-platelet antibodies indicate that they are directly involved in the autoimmune pathogenesis in ITP.

Adult↗
PubMed1991

The effect of TYB-3823, a new antiarrhythmic drug, on sodium current in isolated cardiac cells.

1. Sodium current (INa) blockade by TYB-3823, a newly synthesized antiarrhythmic agent, was investigated in isolated single ventricular myocytes by use of the whole cell patch-clamp technique. 2. TYB-3823 blocked INa under steady-state conditions (Kd,rest = 500 microM, Kd,i = 4.9 microM), findings consistent with a shift in the steady state INa availability curve to more negative potentials. 3. TYB-3823 produced use-dependent block at 2 Hz in conjunction with increase in pulse duration (5-300 ms), that was markedly enhanced at less negative holding potentials. 4. The time course of the onset of block was accelerated and the degree of use-dependent block was decreased at more negative holding potential. The time course of the onset of block was accentuated with enhancing block at more positive holding potentials. 5. The time course of recovery from use-dependent block was accelerated at more negative holding potentials but was accentuated at more positive holding potentials. 6. These results suggest that both tonic block and use-dependent block of sodium channels in cardiac tissue might result from an interaction of TYB-3832 with sodium channels mainly in the inactivated channel states and the kinetics of the interaction between drug and receptor may be modulated by the inactivation gate.

Animals↗