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Biomedical subjects

K Yokota

Publications and source records attributed to K Yokota.

At least 127 records · Page 7Linked to original sources
PubMed1997

The mechanism of action of KBT-3022, a new antiplatelet agent.

1. The mechanism of action of a new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and its active main metabolite, desethyl KBT-3022, was investigated. 2. KBT-3022 and desethyl KBT-3022 inhibited cyclooxygenase from ovine seminal gland with IC50 values of 0.69 and 0.43 microM, respectively. 3. At concentrations higher than those required for cyclooxygenase inhibition, desethyl KBT-3022 inhibited cAMP-phosphodiesterase, specific binding of U46619, and release of phosphatidic acid from thrombin-stimulated platelets. 4. Oral administration of KBT-3022 inhibited the production of thromboxane B2 during blood coagulation more potently than the production of 6-keto-prostaglandin F1 alpha from aortic strips in guinea pigs. 5. These findings suggest that KBT-3022 may inhibit platelet activation principally via the inhibition of cyclooxygenase by desethyl KBT-3022.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Molecular properties of the proteasome activator PA28 family proteins and gamma-interferon regulation.

BACKGROUND: Recent cDNA cloning of two homologous proteasome activators, PA28 alpha and PA28 beta, indicated the presence of a structurally related third protein, Ki antigen, but a functional relationship between Ki antigen and the two PA28 proteins is unknown. Accumulating evidence has implicated an important role for PA28 in the major histocompatibility complex (MHC) class I-restricted antigen processing pathway. Recently, an immunomodulatory cytokine gamma-interferon (gamma-IFN) was found to increase greatly the messages for PA28 alpha and PA28 beta, but not Ki antigen, in human cells. RESULTS: Ki antigen was co-immunoprecipitated with the 20S proteasome by anti-proteasome antibody, and associated reversibly with the 20S proteasome, as observed for PA28 alpha and PA28 beta. Therefore, Ki antigen was renamed PA28 gamma. Anti-PA28 gamma antibody, however, did not immunoprecipitate PA28 alpha and PA28 beta. gamma-IFN caused an almost complete loss of the PA28 gamma protein in cells without affecting its mRNA level, whereas the levels of both mRNA and protein for PA28 alpha and PA28 beta were coordinately upregulated by gamma-IFN. Finally we showed that the human chromosomal genes of PA28 alpha and PA28 gamma were located on 14q11.2 and 17q21.32-21.33, respectively. CONCLUSION: PA28 gamma (equivalent to Ki antigen) is a new member of the PA28 family proteins. It exists as a unique homopolymer under non-denaturing conditions. gamma-IFN was found to induce the expression of PA28 alpha and PA28 beta, whereas it caused almost complete loss of the PA28 gamma protein in cells. The reciprocal expression of the PA28 family proteins may imply their involvement in distinct biological processes.

Amino Acid Sequence↗
PubMed1997

IgA protease produced by Streptococcus sanguis and antibody production against IgA protease in patients with Behçet's disease.

The production of IgA protease in twelve strains of Streptococcus sanguis isolated from patients with Behcet's disease (BD) was examined. Protease activity was detected in 10 out of 12 strains. The protease was purified from one representative strain, S. sanguis 113-20, by employing Rotofor and DEAE-Sephacel chromatography. The molecular mass of the purified protease was approximately 100 kDa, and it cleaved the proline-threonine site of the IgA. Both IgG and IgA titers against the cells (113-20) and the purified IgA protease in the sera of BD patients and healthy controls, 36 each, were assayed. The IgG titers against the cells and protease were not significant in the BD patients or controls, but the IgA titers against the cells and protease in the BD patients were significantly higher than those of the controls. These data indicate that the BD patients are infected with IgA protease-producing S. sanguis strains, which cause an increase of IgA titer against these organisms and IgA protease antigen. Since the organisms can proliferate in BD patients for a long period of time (years), it seems that IgA antibodies cannot effectively eliminate the organisms.

Amino Acid Sequence↗
PubMed1997

A rapid and simple method to quantify Helicobacter pylori adhesion to human gastric MKN-28 cells.

A rapid and simple method to quantitatively analyse Helicobacter pylori adhesion to human gastric epithelial cells was developed by using an enzyme-linked immunosorbent assay. This method made it possible to quantitatively evaluate the adhesion activities of many different H. pylori strains at a time. Our studies indicate that this method is well suited for the quantitative analysis of H. pylori adhesion to gastric epithelial cells.

Bacterial Adhesion↗
PubMed1997

Risk factors for sensitisation to methyltetrahydrophthalic anhydride.

OBJECTIVES: To examine an association between specific IgE to methyltetrahydrophthalic anhydride (MTHPA) and exposure time, atopic history, smoking habits, and total IgE concentrations. METHODS: A cross sectional survey was carried out on a population of 148 workers from two condenser plants using epoxy resin with MTHPA, an acid anhydride curing agent known to cause allergy. RESULTS: Using a Pharmacia CAP system with a MTHPA human serum albumin conjugate, specific IgE antibody was detected in serum from 97 (66%) out of the 148 workers exposed to MTHPA. Stepwise multiple linear regression analysis showed a striking relation between log concentrations of specific and total IgE (P < 0.0001). Furthermore, when the workers were divided into two groups according to a cut-off point (100 IU/ml) between low and high total IgE, current smoking was significantly (P = 0.025) associated with specific IgE production only in the group with low total IgE (< 100 IU/ml). CONCLUSIONS: Smoking is the most significant risk factor for raising specific IgE to MTHPA in the group with low total IgE concentrations.

Adult↗
PubMed1997

Inhibitory effects of insulin on intracellular calcium and aggregatory response of platelets are impaired in hypertensive subjects with insulin resistance.

To determine the effects of insulin on intracellular calcium and platelet aggregatory responses in hypertensive subjects with insulin resistance, we measured insulin sensitivity in terms of glucose disposal rate (GDR) by the hyperinsulinemic euglycemic clamp technique (GC) in 14 non-diabetic untreated hypertensive subjects, and determined basal ([Ca2+]i) and thrombin-stimulated (T-[Ca2+]i) platelet-free calcium concentrations and thrombin-stimulated platelet aggregatory response (AG) before (PRE[Ca2+]i, T-PRE[Ca2+]i, and PRE AG, respectively) and during (POST[Ca2+]i, T-POST[Ca2+]i, and POST AG, respectively) GC. As a control for GC, vehicle (normal saline) was infused on another day. No significant difference was observed between PRE[Ca2+]i and POST[Ca2+]i, T-PRE[Ca2+]i and T-POST[Ca2+]i, or PRE AG and POST AG, GDR inversely correlated with delta[Ca2+]i (POST [Ca2+]i-PRE[Ca2+]i, r = -0.75, p < 0.02), delta T-[Ca2+]i, (T-POST[Ca2+]i-T-PRE[Ca2+]i, r = -0.63, p < 0.02) and delta AG (POST AG-PRE AG, r = -0.67, p < 0.01). No significant changes were observed in these variables during vehicle infusion. [Ca2+]i, T-[Ca2+]i, and AG decreased during GC as compared with baseline in hypertensive subjects with normal insulin sensitivity, but were unchanged in those with insulin resistance, suggesting that the vasodilatory and anti-platelet aggregatory effects of insulin are impaired in patients with insulin-resistant hypertension.

Adult↗
PubMed1997

Specific antibodies against methyltetrahydrophthalic anhydride and risk factors for sensitization in occupationally exposed subjects.

OBJECTIVES: Occupational exposure to methyltetrahydrophthalic anhydride (MTHPA) from an epoxy resin was studied to evaluate the nature of reported ocular and nasal complaints and some risk factors for sensitization. METHODS: Seventy-three current and 22 former workers underwent a questionnaire survey and serologic investigations. Total and MTHPA-specific immunoglobulin (Ig)E levels were measured by means of a Pharmacia CAP system, and MTHPA-specific immunoglobulin (Ig)E levels were measured by enzyme immunoassay. RESULTS: Forty-six (63%) of the currently exposed workers has positive MTHPA-specific IgE, and no significant difference was found between those continuously or intermittently exposed (58% and 71%, respectively). Work-related ocular or nasal symptoms were significantly associated with specific IgE but not with specific IgG4. This finding indicates that there is an IgE-mediated mechanism in most cases of work-related symptoms associated with MTHPA exposure. The total IgE levels were significantly (P < 0.005) higher in the specific IgE-positive workers than in the specific IgE-negative workers (geometric mean 101 IU/ml and 44.8 IU/ml, respectively). Multiple logistic regression analysis also revealed that the group with high total IgE levels (> or = 80 IU/ml) had a significant relative risk (RR 4.7) of producing MTHPA-specific IgE as compared with the group with low total IgE levels (< 80 IU/ml). CONCLUSIONS: These results show that MTHPA has a high sensitizing ability and that a high total IgE level is the most significant risk factor for workers exposed to MTHPA. However, to evaluate conclusively the effect of high total IgE levels on sensitization, further prospective studies are necessary.

Adult↗
PubMed1997

[The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients with renal cell carcinoma].

PURPOSE: The correlation between the serum soluble interleukin-2 receptor (SIL-2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin lymphomas. The prognostic significance of sIL-2R levels in the serum of patients with renal cell carcinoma (RCC) was investigated. METHOD: sIL-2R were measured in patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay technique. Cases of RCC were classified according to the clinical stage, pathological grade and growth type. The IL-2R expression of RCC was evaluated by RT-PCR. RESULT: The serum sIL-2R levels of patients with RCC showed significantly higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC were closely associated with the stage, grade and growth type of disease. The patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of IL-R was detected only by using the template from the mRNA extracted from a resected tumor tissue of the RCC but not from the RCC cell lines. CONCLUSION: It was suggested that the measurement of serum sIL-2R levels is useful for predicting the prognosis.

Adult↗
PubMed1997

[The combination of amoxicillin-clavulanic acid and ofloxacin in the treatment of multidrug-resistant Mycobacterium tuberculosis].

A 67-year-old [correction of 53] man with multidrug resistant tuberculosis (MDR-TB) had been persistently positive for acid-fast bacilli (AFB) both on sputum smear and also on culture with the Ogawa egg medium for 30 years since 1951. The case had been treated previously with isoniazid, rifampin, streptomycin, ethambutol, kanamycin, ethionamide, paraaminosalicylate and cycloserine; however, M. tuberculosis strains isolated from this patient acquired a high resistance to all of these agents. Then, a new regimen of chemotherapy, INH combined with ofloxacin (OFLX) and amoxicillin-clavulanic acid (AMPC/ CVA), was applied to the case. He was successfully treated with this regimen, and a marked decrease in the amount of AFB on smear as well as on culture was observed during the course of chemotherapy. No adverse effects were seen meanwhile. These data suggest that it is worth while to try a regimen containing AMPC/CVA and OFLX in the treatment of MDR-TB.

Aged↗
PubMed1997

[Effectiveness of a health education class to increase fish intake evaluated by serum fatty acid compositions].

For prevention of cardiovascular disease, we recommended increased fish intake for 50 middle-aged women and men of 40-83 years old at a three-month community-based health education program in an inland farming community. The effectiveness of the education program was evaluated by examining changes in serum lipids and serum fatty acid compositions. For comparison, we selected 48 men and women of 38-82 years old did not participated in the program. Before education, there was no significant difference in the dietary frequency of fish, meat, egg and dishes prepared with oil, mean values of serum lipids or serum fatty acid compositions except for saturated fatty acid, gamma-linolenic acid, dihomo-gamma-linolenic acid and alpha-linolenic acid. After three months, the frequency of fish intake of one or more times per day increased from 33% to 43% in the education group while the frequency of fish intake did not change in the control group. In the education group, serum n3 polyunsaturated fatty acid composition increased from 8.8% to 10.6%. This fatty acid increase was primarily observed in eicosapentaenoic acid and docosahexaenoic acid. The n3/n6 ratio increased from 0.21 to 0.31. In the control group, no change was observed in n3 polyunsaturated fatty acids. This study suggests that the community-based dietary education increased fish intake and serum n3 polyunsaturated fatty acids in women and men of 40 years old or older.

Adult↗
PubMed1996

Cytokine-mediated communication between dendritic epidermal T cells and Langerhans cells. In vitro studies using cell lines.

Murine epidermis contains two leukocyte populations: Langerhans cells (LC), which are APC of dendritic cell (DC) lineage, and dendritic epidermal T cells (DETC), which are members of the tissue-type gamma delta T cell family. Despite close physical approximation in vivo, the extent to which LC and DETC affect each other's function has remained unknown. We addressed this question using the long term DC line XS52 and the gamma delta T cell line 7-17, both of which were established from mouse epidermis, and both of which retain important features of the resident populations from which they were derived. XS52 DC proliferated maximally when cocultured with gamma-irradiated 7-17 DETC. They also proliferated in response to culture supernatants collected from anti-CD3- or Con A-activated 7-17 DETC, but not from nonstimulated DETC. In both systems, DETC-induced XS52 DC growth was inhibited partially (up to 70%) by Abs against granulocyte/macrophage CSF (GM-CSF) or CD115 (CSF-1 receptor) and nearly completely (up to 90%) by both together. Among 28 tested cytokines, only GM-CSF, CSF-1, IL-4, and IL-13 promoted XS52 DC growth significantly. Anti-IL-4 failed to inhibit DETC-induced XS52 cell growth, and IL-4 was not detectable in DETC supernatants. Thus, we conclude that GM-CSF and CSF-1 (and perhaps IL-13) account for the DC growth-promoting activity secreted by DETC. These results suggest that during coculture, XS52 DC activate 7-17 DETC to secrete both GM-CSF and CSF-1. In fact, when cultured with XS52 DC, 7-17 DETC also elevated their expression of the gamma c receptor and acquired proliferative responsiveness to their own growth factor IL-15. We propose that LC and DETC in situ may interact with each other in a similar manner, thereby regulating their residence and function.

Animals↗
PubMed1996

Effect of KBT-3022, a new cyclooxygenase inhibitor, on experimental brain edema in vitro and in vivo.

The effect of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, on experimental brain edema was studied. In vitro, KBT-3022 (100 microM) and its metabolite desethyl KBT-3022 (10 and 100 microM), but neither acetylsalicylic acid nor indomethacin, inhibited arachidonic acid-induced swelling of guinea pig cortical slices. KBT-3022 (3-100 microM) and desethyl KBT-3022 (3-30 microM), but neither acetylsalicylic acid nor indomethacin, inhibited lipid peroxidation in guinea pig brain homogenate. In vivo, oral administration of KBT-3022 (1, 3 and 10 mg/kg) and indomethacin (10 and 30 mg/kg), but not acetylsalicylic acid, prevented brain edema induced by bilateral carotid occlusion and recirculation in gerbils. Indomethacin then prevented postischemic hyperthermia, but not KBT-3022. KBT-3022 (10 mg/kg) and indomethacin (30 mg/kg) inhibited lactate accumulation in gerbil brain after ischemia and recirculation. These results suggest that KBT-3022 prevents development of both cytotoxic edema in vitro and vasogenic edema in vivo.

Animals↗
PubMed1996

Quantitative detection of secretory immunoglobulin A to Helicobacter pylori in gastric juice: antibody capture enzyme-linked immunosorbent assay.

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori were estimated in serum and gastric juice specimens from patients with gastritis and peptic ulcers using antibody capture enzyme-linked immunosorbent assays (ACELISAs). The antibody titers of the ACELISAs are independent of the antibody concentration and reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. Using the ACELISAs it was possible to evaluate quantitatively not only serum IgA (SR-IgA) antibodies but also secretory IgA (SC-IgA) antibodies in gastric juice. There were significant differences between the patients and control group in the SR-IgA and SC-IgA ACELISAs. Furthermore, the ACELISAs made it possible to compare between SR-IgA antibodies in serum and SC-IgA antibodies in gastric juice. In all patients, the ratios of H. pylori-specific IgA were higher in gastric juice than in serum. These results suggest that H. pylori SC-IgA antibodies are mainly produced by the local immune response in the gastric mucosa. Our studies indicate that ACELISA is well suited for the analysis of local immune response in mucosa.

Adult↗
PubMed1996

Lymphocyte activation effect of (1-->6)-2,5-anhydro-D-glucitol and it derivatives with 3,4-di-O-methyl and sulfate groups.

(1-->6)-2,5-Anhydro-3,4-di-O-methyl-D-glucitol (2a) and (1-->6)-2,5-anhydro-D-glucitol (2c) and its sulfated derivative (2d) were synthesized and their biological activities were evaluated in regards to the effects on murine lymphocytes. The polymers showed different effects on the lymphocytes depending on the substituent groups. The sulfated polymer (2d) induced mitogenic activities, and specifically activated the CD4(-)CD8(-) subset of lymphocytes.

Animals↗
PubMed1996

Electrocardiographic abnormalities in patients receiving hemodialysis.

We assessed standard 12-lead and Holter electrocardiographic (ECG) abnormalities in maintenance hemodialysis (HD) patients. Of 221 outpatients receiving HD, 143 (65%) had ECG abnormalities. Rates were higher in male, elderly, hypertensive, and diabetic patients than in female, younger, normotensive, and nondiabetic patients. The prevalence of ECG changes correlated inversely with HD duration. Serial ECGs were compared in 87 patients whose average HD duration was 7.5 +/- 2.5 years. Thirty-four patients (39%) showed normal ECGs throughout, 27 (31%) relatively stable abnormalities, 22 (25%) worsening, and 4 (5%) reversion to normal. Age, hypertension, and diabetes are factors related to abnormal ECG findings. Among the 142 Holter recordings from 72 patients, 70 (97%) were basically in sinus rhythm, and 2 (3%) were in atrial fibrillation. The average frequency of supraventricular premature contractions (SVPCs) was 1597 +/- 9725 per 24 hours, and that of ventricular premature contractions (VPCs), 556 +/- 1415. VPCs were multifocal in 9%, in runs in 25%, and early in 1%. In 29 (40%) of recordings, VPCs appeared mainly during and for several hours after HD. ST-T changes were seen in 43 (60%). In 11, ST depression occurred during and a few hours after HD. Patients receiving HD showed diverse ECG abnormalities. Holter ECGs revealed a high incidence of arrhythmias and ST-T changes, which frequently appeared in relation to HD timing.

Adolescent↗