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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 325 records · Page 18Linked to original sources
PubMed1994

Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo.

Commercial aurintricarboxylic acid (ATA) was separated into molecular-weight (MW) fractions of < 210 to > 25,000, using gel permeation chromatography. Fractions with MW > 1,300 effectively inhibited both botrocetin-induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW > 17,000. Platelet retention for a human in vitro was reduced by ATA at 150 microM, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t-PA in electrically and copper coil-induced thrombosis models. These results suggest that specific inhibitors of the vWF-GPIb interaction such as ATA may prove useful as antithrombotic agents.

Animals↗
PubMed1994

Interleukin-10 is a potent inhibitor of tumor cytotoxicity by human monocytes and alveolar macrophages.

The effects of purified human interleukin-10 (IL-10) on the expression of antitumor activity of human monocytes and alveolar macrophages (AMs) obtained by centrifugal elutriation and bronchoalveolar lavage, respectively, from the same healthy donors were examined. Monocytes and AMs were incubated for 16 h in medium with lipopolysaccharide (LPS) in the presence or absence of IL-10 or IL-4, and then their tumoricidal activity was assayed by measuring 125I-IUdR release from human melanoma (A375) cells. Addition of IL-10 to cultures of monocytes or AMs with LPS resulted in dose-dependent suppression of their cytotoxicity against A375 cells, the suppression of the activity of monocytes being the higher. IL-10 also suppressed the synergistic effects of interferon-gamma and desmethyl muramyldipeptide in activation of monocytes. IL-10 inhibited the early induction phase of monocyte activation but not the effector phase (monocyte-mediated cytotoxicity). IL-10 plus IL-4 inhibited the antitumor activities of AMs and monocytes much more than either IL-10 or IL-4 alone. IL-10 and IL-4 at suboptimal concentrations also showed synergistic inhibitory effects. These findings suggest that IL-10 may be important in vivo in down-regulating the antitumor activities of monocytes and AMs in the lung by inhibiting their productions of antitumor effector molecules.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Measurement of temafloxacin in human scalp hair as an index of drug exposure.

Scalp hair samples were obtained at 1-month intervals up to 3 months from healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, temafloxacin. Hair was sectioned into 1-cm lengths from the scalp end. After corresponding portions from 10 pieces of hair were dissolved in 1 N NaOH, temafloxacin was extracted by chloroform and measured by HPLC equipped with fluorescence detection (excitation and detection wavelengths, 280 and 460 nm, respectively). In all subjects taking a single oral dose (600 mg; n = 6) or repeated oral doses (900 mg/day, b.i.d., for 6.5 days; total, 5850 mg; n = 6), the drug was detected in hair. The 1-cm length of hair, in which temafloxacin was peaked, was shown to move at the rate of 1 to 1.3 cm/month when the hair of growing stage was analyzed. The largest sum of the concentrations of temafloxacin found in any set of measurements in hair in each subject was 31.7 +/- 15.0 (mean +/- SD, n = 6) and 226.3 +/- 99.4 ng/mg hair (n = 6) for the single and repeated doses, respectively. The drug concentration in hair increased by a factor of 7.1, whereas the ratios between the single and repeated doses were 9.8, 1.3, and 10.7 for the total given dose, observed maximal plasma concentration (Cmax), and area under the plasma concentration curve, respectively. It was obvious that the Cmax was the least likely factor determining temafloxacin concentration in hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum and lipopolysaccharide.

We investigated the effect of the potent immunosuppressive agent, FK506, on experimental glomerular thrombosis in rats by combined injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was administered intramuscularly three hours prior to injection of NTS that was followed one hour later by LPS. Rats were killed five hours after the LPS injection. Compared with placebo, FK506 pretreatment significantly reduced thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria and the rise of serum creatinine level. Early infiltration of polymorphonuclear leukocytes into the glomeruli after LPS injection was significantly suppressed in the FK506 group compared with the placebo group. We also measured serum tumor necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay. Peak serum TNF activity was observed one hour after LPS injection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formation is T cell independent. These data suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an anti-inflammatory effect in vivo.

Acute Disease↗
PubMed1994

Epitopes and biological activities of two monoclonal antibodies to platelet integrin alpha IIb beta 3.

We have developed two monoclonal antibodies (MAbs), B6A3 and C4G1. The whole molecules of the two MAbs inhibited in vitro human platelet aggregation induced by either ADP, collagen or thrombin, and their F(ab')2 fragments inhibited ex vivo platelet aggregation induced by ADP in monkey. The concentrations necessary for complete inhibition were 5 and 1 microgram/ml for B6A3 and C4G1, respectively. The Fab fragment of C4G1 but not B6A3 inhibited platelet aggregation. B6A3 and C4G1 bound to activated platelets with dissociation constants of 0.25 and 0.82 nM, respectively. B6A3 recognized an epitope on beta 3, which was sensitive to reduction and alkylation of cystine residues, and C4G1 recognized a conformational epitope on the alpha IIb beta 3 complex, which was sensitive to EDTA. The binding of fibrinogen to activated platelets was inhibited by both MAbs. However, the binding of fibrinogen to isolated alpha IIb beta 3 was inhibited by the whole molecule of C4G1 but not B6A3, although both MAbs bound to the isolated alpha IIb beta 3. The binding of these MAbs to the isolated alpha IIb beta 3 was not inhibited by either Arg Gly Asp Ser (RGDS) or fibrinogen gamma-peptide. In addition, B6A3 but not C4G1 bound to human endothelial cells. These MAbs should contribute to the elucidation of the mechanism of platelet aggregation.

Amino Acid Sequence↗
PubMed1994

Increased vascular endothelial cell markers in patients with chronic renal failure on maintenance haemodialysis.

Plasma levels of the vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (t-PA), and von Willebrand factor (vWF) were measured in 55 patients on maintenance haemodialysis (HD). TM, PAI-1 and vWF antigen levels were significantly increased in patients before HD, but t-PA antigen was not Compared with levels before HD, t-PA and vWF antigens were significantly increased 1 h after HD and at the end of HD. TM antigen was significantly increased 1 h after HD, and plasma PAI-1 antigen was decreased at the end of HD. TM and vWF antigen levels were negatively correlated with the time (years) on HD. It is concluded that HD may cause endothelial cell damage and that the increases in plasma TM, PAI-1 and vWF levels before HD, and the decrease in the release of TM and vWF antigens from vascular endothelial cells, might be caused by vascular endothelial cell damage from long-term HD.

Adult↗
PubMed1994

Cyclosporin A enhances susceptibility of multi-drug resistant human cancer cells to anti-P-glycoprotein antibody-dependent cytotoxicity of monocytes, but not of lymphocytes.

Cyclosporin A (CsA) was previously found to bind to P-glycoprotein expressed on multidrug-resistant (MDR) cancer cells. In the present study, the effect of CsA on anti-P-glycoprotein monoclonal antibody (mAb)-dependent cell-mediated cytotoxicity (ADCC) against human MDR cells was examined. The ADCC reaction was assessed by 4-h 51Cr-release assay. Highly purified lymphocytes (> 99%) and monocytes (> 99%) obtained from blood mononuclear cells (MNC) of healthy donors were used as effector cells. CsA decreased the cytotoxic activity of MNC against MDR cells, but enhanced their ADCC activity in the presence of anti-P-glycoprotein mAb MRK16. Lymphocyte-mediated ADCC and natural killer activity against MDR cells were also suppressed by addition of CsA. CsA induced a significant dose-dependent increase in monocyte-mediated ADCC activity. Interestingly, pretreatment of MDR cancer cells, but not of monocytes, with CsA significantly enhanced ADCC activity mediated by monocytes, but not by lymphocytes. A CsA analog (PSC833) and FK-506, but not verapamil also increased the sensitivity of MDR cells to ADCC by monocytes. CsA did not affect the binding of monocytes to MDR cells in the presence of MRK16 mAb. These results indicate that CsA may directly enhance the susceptibility of MDR cancer cells to the monocyte-mediated ADCC reaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

A major pathogenic antigen of Heymann nephritis is present exclusively in the renal proximal tubule brush border--studies with a monoclonal antibody against pronase-digested tubular antigen.

We have isolated a nephritogenic 120-kD antigen from rat renal tubule brush border that induces rat Heymann nephritis. A MoAb that recognized this antigen reacted exclusively with the brush border on indirect immunofluorescence and immunoelectron microscopy. Rabbit antiserum against this antigen also reacted exclusively with the brush border. With the injection of this antiserum, rabbit IgG became detectable along the glomerular basement membrane (GBM) after 3 days. Our 120-kD antigen was shown to have a close relationship with gp330 based on the following: (i) this antigen can induce active Heymann nephritis as gp330; (ii) our MoAb reacted with the immune deposits of nephritic kidneys induced not only by the 120-kD antigen but also by gp330, and conversely, rabbit antiserum against gp330 reacted with those induced by the 120-kD antigen as well as gp330; and (iii) by immunoblotting, polyclonal antibodies against the 120-kD antigen reacted with gp330 and polyclonal antibodies against gp330 reacted with the 120-kD antigen. These observations indicate that antigen present exclusively in the brush border can induce active Heymann nephritis, and the common antigenic determinants shared by brush border and the coated pits of glomerular epithelium may not be a prerequisite to induce nephritis. A more precise relationship between the 120-kD antigen and reported C14 fusion protein or 40-kD alpha 2MRAP remains to be established.

Animals↗
PubMed1994

Differential effects of Na+, K(+)-ATPase inhibition by ouabain on acid secretory responses to histamine and bethanechol in the mouse isolated stomach.

1. The effect of Na+,K(+)-ATPase inhibition by ouabain on gastric acid secretion was studied in the mouse isolated whole stomach preparation. 2. Ouabain caused a transient enhancement of histamine-induced gastric acid secretion followed by an inhibitory phase. On the other hand, ouabain caused a rapid reduction of bethanechol-stimulated acid secretion without an enhancement phase. 3. In dibutyryl cyclic AMP-induced acid secretion, ouabain led to a transient increase in acid secretion followed by a fall, as was seen with the histamine stimulation. Ouabain caused a rapid reduction of A23187-induced acid secretion. 4. Ouabain by itself increased basal acid secretion, and thereafter slowly suppressed the acid secretion. 5. Atropine inhibited both the ouabain-induced enhancement of the stimulated gastric acid secretion and the ouabain-induced stimulation of basal acid secretion. 6. The present study showed that Na+,K(+)-ATPase inhibition by ouabain caused a phasic enhancement of the stimulated gastric acid secretion through release of endogenous acetylcholine when the secretagogues act via an intracellular cyclic AMP pathway. It also inhibited the stimulated acid secretion irrespective of secretagogues, probably through its inhibitory effect on Na+,K(+)-ATPase in the gastric parietal cell.

Animals↗
PubMed1994

Increased excretion of urinary transforming growth factor beta in patients with focal glomerular sclerosis.

The urinary transforming growth factor beta (TGF-beta) excretion was measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN), and 6 with membranous nephropathy (MN), and in 7 healthy subjects by enzyme-linked immunosorbent assay using a monoclonal antibody specific for TGF-beta 1 + 2 + 3. A significantly increased urinary TGF-beta excretion was observed in FGS patients (555.5 +/- 458.4 ng/mg Cr) as compared with normal controls (46.9 +/- 43.9 ng/mg Cr) (p < 0.05) and a relative increase in SLE patients (96.4 +/- 58.2 ng/mg Cr) and a decrease in MN patients (24.8 +/- 13.3 ng/mg Cr). In contrast, there was no difference in TGF-beta excretion between IgAN patients (54.1 +/- 37.4 ng/mg Cr) and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found. As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. The results obtained in this study raised the possibility that extracellular matrix might be produced by glomerular cells in vivo under the control of TGF-beta and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.

Adolescent↗
PubMed1994

Ileal lymphoma in swine.

Eleven cases of alimentary lymphoma affecting the ileum were observed among 26 cases of swine lymphoma detected by meat inspection in Kochi, Japan. The ileal lymphomas were located in the Peyer's patches, along with early involvement of regional lymph nodes, and showed a characteristic pattern of follicular invasion leading to diffuse growth. Following the National Cancer Institute Working Formulation, 10 neoplasms were classified as diffuse, large, noncleaved cell lymphomas and one neoplasm was a diffuse, mixed, small to large cell lymphoma. Both types of lymphoma featured numerous intermingled "starry sky" histiocytes. The lymphoma cells tended to infiltrate into the muscular layer of the ileum in an "Indian file" pattern. Two cases also showed transserosal metastasis into the abdomen and leukemic change. The lymphoma cells showed membrane positivity for alkaline phosphatase and diffuse cytoplasmic staining for acid phosphatase and non-specific esterase. Monoclonal intracytoplasmic immunoglobulins were demonstrated in nine neoplasms (IgM-lambda in seven, IgG-lambda in one, and IgG-kappa in one). In the areas of follicular invasion, an attenuated network of follicular dendritic cells was visualized via an antiserum against the beta subunit of S-100 protein. Ultrastructurally, strands of dilatated rough endoplasmic reticulum and scattered or clustered dense bodies were noted. When compared with feline and human alimentary lymphoma, including Burkitt's lymphoma, the present neoplasms possessed distinctive features, such as originating in Peyer's patches, transserosal metastasis, and predominantly large B cell type with IgM-lambda type immunoglobulin expression, although some features were similar.

Animals↗
PubMed1994

Production of IL-1 and its receptor antagonist is regulated differently by IFN-gamma and IL-4 in human monocytes and alveolar macrophages.

Interleukin-4 (IL-4) has previously been found to downregulate interleukin-1 (IL-1) production, but to upregulate the production of IL-1 receptor antagonist (IL-1ra) in human monocytes stimulated with lipopolysaccharide (LPS). In the present study we wanted to determine whether the production of IL-1ra in human monocytes and alveolar macrophages (AMs) is regulated differently at the protein and messenger ribonucleic acid (mRNA) levels by IL-4 and interferon-gamma (IFN-gamma). AMs and monocytes obtained from healthy donors by bronchoalveolar lavage and centrifugal elutriation were stimulated with LPS in the presence or absence of IL-4 or IFN-gamma, and the expression of mRNA for IL-1 and IL-1ra was measured by Northern blot analysis. The production of IL-1 and IL-1ra was quantitated by enzyme immunoassays (EIAs). Spontaneous IL-1ra production was seen in AMs after incubation for 4 h in medium alone, but not in blood monocytes, at both the protein and mRNA levels. The spontaneous expression of the IL-1ra gene in AMs was augmented by incubation with IL-4. Interleukin-1 beta (IL-1 beta) production by LPS-stimulated AMs and monocytes was upregulated by IFN-gamma, but downregulated by IL-4. Interestingly, when stimulated with LPS, IFN-gamma inhibited IL-1ra production by monocytes, but up-regulated its production in human AMs at the protein and mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Structural components of beta-eudesmol essential for its potentiating effect on succinylcholine-induced neuromuscular blockade in mice.

beta-Eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizoma, potentiates the neuromuscular blocking effect of succinylcholine (SuCh). The potentiating effect is greater in diabetic muscles than in normal ones. To identify the structural components of beta-eudesmol contributing to this action, we examined the potentiating effect of newly synthesized tertiary alcohols related to beta-eudesmol in phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. Potentiating effects were exhibited by cyclohexylidene derivatives but not by cyclohexanone or cyclohexanol derivatives. The compound 2-(3-hydroxy-3-methylbutyl)cyclohexylidene exhibited a potentiating effect, but 3-(3-hydroxy-3-methylbutyl)cyclohexylidene did not. These results indicate that both the presence of an exo-methylene attached to a cyclohexane ring and the distance between the exo-methylene and the hydroxy group in beta-eudesmol are involved in the potentiating effect on SuCh-induced neuromuscular blockade.

Animals↗
PubMed1994

[Cholecystokinin receptors involved in the central and peripheral nervous control mechanisms in gastric acid secretion].

Cholecystokinin (CCK) has a unique pharmacological profile as a "brain-gut peptide hormone", and recent development of specific non-peptide antagonists prompted us to investigate the role of the receptors of this peptide in nervous control mechanisms of gastric acid secretion. CCK-8 induced a distinctive acid secretory response after intracerebroventricular (i.c.v.) administration, as well as after intravenous infusion in the perfused stomach preparation in rats. L364718, a CCKB-receptor antagonist, had an inhibitory effect against CCK-8 when applied i.c.v., while L365260, a CCKB-receptor antagonist, had no influence, suggesting the apparent dominant control of CCKA receptors in the central nervous system on gastric acid secretion. However, L364718 caused remarkable potentiation in the acid secretory response to the intravenous CCK-8 infusion, and L365260 significantly inhibited the CCK-8-stimulated acid secretion. The potentiation of the acid secretory response to CCK-8 by the CCKA antagonist was completely blocked by vagotomy or atropine, as well as hexamethonium. Thus it was suggested that a vagal control mechanism was involved in the potentiation. Denervation of capsaicin-sensitive primary afferent nerve by repeated capsaicin injection also decreased the potentiated response to CCKA antagonist. This seems to suggest the involvement of the vago-vagal reflex in the control of gastric acid secretion by endogenous CCK. Ketanserin, a serotonin 5-HT2/1C-receptor antagonist, showed a distinctive inhibition of acid secretion induced by CCK-8 (i.c.v.), suggesting the involvement of serotonergic control of acid secretion in the CCK-8 action. Current developments in the research in this field were briefly reviewed in relation to our findings.

Animals↗
PubMed1994

Effect of eicosapentaenoic acid ethyl ester on albuminuria in streptozotocin-induced diabetic rats.

Wistar rats (4-week-old) were administered with streptozotocin (45 mg/kg) through tail veins. After 3 months, diabetic rats were divided into 2 groups. One group (EPA group, n = 16) was fed a lipid-free diet (90%, w/w) plus lard (8%) and 90% pure eicosapentaenoic acid ethyl ester (2%) for 6 months. The other group (control group, n = 16) was fed in the same way except that eicosapentaenoic acid ethyl ester was replaced by safflower oil. Twenty-four-hour urine was collected just before starting the experimental diets and during the 6-month experimental period at monthly intervals. There were no differences in food intake and body weight between the two groups throughout the experiment. The mean microalbuminuria of the EPA group became significantly lower than that of the control group after 4 months on the diets through the end of the study (6 months). The mean microalbuminuria levels at the end of the study were 1.38 mg/day in the EPA group (n = 9) and 5.19 mg/day in the control group (n = 6) (p < 0.01). Eicosapentaenoic acid administration might retard the progression of diabetic nephropathy by reducing microalbuminuria.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Combined treatment with cyclophosphamide and prednisolone can induce remission of nephrotic syndrome in a patient with renal amyloidosis, associated with rheumatoid arthritis.

A 67-year-old woman, who had been diagnosed with classical rheumatoid arthritis (RA), was admitted to our hospital because of massive proteinuria. Biopsy of the kidney revealed deposition of amyloid fibrils in the subepithelial and subendothelial spaces of the glomerular capillary walls. Though the treatment with prednisolone and dipyridamole against nephrotic syndrome and amyloidosis due to RA was not effective, cyclophosphamide, which was added after tapering of prednisolone, was able to induce remission of nephrotic syndrome after two years. The levels of CRP and serum amyloid A protein (SAA) returned to within the normal limits. As the impairment of renal function is thought to be due to deposition of amyloid supplied from the precursors of amyloid fibrils filtered from the general circulation in RA patients, remission of nephrotic syndrome might result from the suppression of production of SAA or removal of amyloid fibrils. Cyclophosphamide, which has the potential both to suppress disease activity in RA and to produce degradation of amyloid fibrils in glomeruli, may be useful against renal or systemic amyloidosis complicated by RA.

Aged↗