Search PubMed⌕ Search

Biomedical subjects

C Yamamoto

Publications and source records attributed to C Yamamoto.

At least 73 records · Page 4Linked to original sources

Evaluation of liver function by co-administration methodology using 13C-labelled benzoic acid and hippuric acid coupled with nuclear magnetic resonance spectroscopy.

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.

Animals↗

Increased production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells in undialyzed chronic renal failure.

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.

Adult↗

Genetic analysis of equine methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) was used to determine genetic relationships among 15 methicillin-resistant Staphylococcus aureus (MRSA) isolates from mares with metritis and from a stallion with dermatitis in Hokkaido. All the 15 isolates showed phage pattern 6/47/54/75, coagulase type IV, and enterotoxin type A. The restriction endonuclease SmaI cut their genomic DNAs into 15 or 16 fragments ranging in size from 8 to 630 kb. Fourteen of the 15 isolates showed the same PFGE pattern, whereas the remaining one appeared to be closely related. The 9 human MRSA isolates showing the same phenotypic characteristics as the horse isolates gave different PFGE patterns from those of the horse isolates.

Animals↗

Airway inflammation in COPD assessed by sputum levels of interleukin-8.

STUDY OBJECTIVE: To assess the characteristics of airway inflammation in patients with COPD. METHODS: We measured the sputum concentration of interleukin-8 (IL-8), a chemokine involved in the migration and activation of neutrophils and eosinophils. We also measured myeloperoxidase (MPO) as a parameter of neutrophil activity and eosinophil cationic protein (ECP) as a parameter of eosinophil activity. Spontaneous sputum samples were obtained from 33 patients with stable COPD and 30 patients with asthma. Induced sputum samples were obtained from 12 normal control subjects. RESULTS: The sputum concentration of IL-8 was significantly higher in the patients with COPD than in the patients with asthma or in the control subjects (p<0.0001). Concentrations of MPO and ECP were significantly higher in the patients with COPD than in the control subjects but did not differ significantly between the patients with COPD and those with asthma. In the patients with COPD, the sputum concentration of IL-8 was significantly correlated with the concentration of MPO (r=0.55, p<0.001) and of ECP (r=0.53, p<0.01). The sputum concentration of IL-8 was negatively correlated with FEV1/FVC (r=-0.78, p<0.0001) in the COPD group. CONCLUSIONS: Results suggest the activation of both neutrophils and eosinophils in the airways of patients with COPD. It appears that IL-8 plays a primary role in this activation. The sputum concentration of IL-8 appeared to be closely associated with the degree of airflow obstruction in patients with COPD and may serve as a marker in evaluating the severity of airway inflammation, which is a risk factor for COPD.

Adult↗

[CPE chemotherapy for tongue carcinoma--clinical effects and side effects].

UNLABELLED: Recent advances in chemotherapy have markedly improved the treatment results for oral cancer. Among many chemotherapeutic regimens, the usefulness of multiple combination chemotherapy with cisplatin as the primary drug has been frequently reported. During the past 6-year period, we have performed combination chemotherapy with cisplatin as the primary drug, peplomycin, and etoposide (CPE chemotherapy) as one of the chemotherapeutic regimens for oral cancer. The subjects were 11 patients (7 males and 4 females) with tongue cancer treated by CPE chemotherapy as neoadjuvant chemotherapy at our department between March, 1990 and April, 1995. RESULTS: PR in 8 (73%), and NC in 3 (27%). No patient showed CR and PD. The side effects observed were reversible findings such as transient myelosuppression, nausea-vomiting, and alopecia. No patient showed severe or persistent suppression of hematopoietic function.

Alopecia↗

[Exercise performance and body composition in patients with chronic obstructive pulmonary disease].

Malnutritions is one cause of exercise intolerance in patients with chronic obstructive pulmonary disease. We studied the relation between exercise limitation and body composition in 20 clinically stable patients with chronic obstructive pulmonary disease. Maximal work capacity was measured during incremental exercise on a cycle ergometer, along with maximal oxygen uptake. Anaerobic threshold was determined by the V-slope method. Bone mineral content, lean mass, and fat mass were assessed by dual-energy X-ray absorptiometry. Bone mineral content and lean mass were significantly lower in moderately malnourished patients (%IBW < 80) than in well-nourished patients (%IBW > or = 90). Fat mass was significantly lower in mildly malnourished patients than in well-nourished patients. Maximal work capacity, maximal oxygen uptake, and anaerobic threshold correlated significantly with lean mass, but not with fat mass. These data suggest that lean mass is one determinant of exercise capacity in patients with chronic obstructive pulmonary disease.

Aged↗

[Cytokine producing ability of peripheral blood mononuclear cells in the clinical course of pulmonary tuberculosis].

Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of peripheral blood plastic-dish adherent cells and non-adherent cells obtained from patients with active pulmonary tuberculosis (N = 17) and healthy controls (N = 14) upon stimulation with purified protein derivatives (PPD) were assessed. Adherent cells and non-adherent cells were obtained two times from each patient with active pulmonary tuberculosis without any underlying diseases, on admission before the initiation of administering anti-tuberculous drugs and 2 months later from the negative conversion of Mycobacterium tuberculosis in sputum culture. ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels produced by non-adherent cells on admission were significantly higher than that of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was reduced after treatment for tuberculosis (p < 0.03), but still remained higher than that in healthy controls. IL-10 levels of non-adherent cells of patients were lower than those of healthy controls, although the difference was not significant. IL-10 levels produced by non-adherent cells on admission correlated with the time needed for negative conversion of bacilli in sputum culture (p < 0.05). IL-10 level produced by adherent cells from nutritionally normal patients were significantly higher than that of healthy controls (p < 0.05), and elevated IL-10 level was significantly reduced after therapy (p < 0.05). In the normonourished patients, the time needed for negative conversion of the bacilli in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N = 5) was significantly longer than that of patients reduced IL-10 level after therapy. These results suggest that IL-10 produced by monocytes may diminish the TH1 responses of patients with pulmonary tuberculosis.

Acute Disease↗

[Expression of basic fibroblast growth factor and fibroblast growth factor receptor 1 in the experimental retinal vein occlusion model].

Retinal ischemia promotes retinal neovascularization. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are important growth factors for neovascularization. We did experimental retinal vein occlusion (RVO) and examined the expression of basic FGF and FGF receptor 1(one of the basic FGF receptors) by in situ hybridization. We used adult pigmented rats (Brown-Norway strain). Dye laser photocoagulation (577 nm) was applied to the retinal arteries and veins within two disc diameters of the optic nerve head to injure the retinal vessels. After one week, laser photocoagulation was applied to only the retinal veins to occlude them (RVO model). As a control, laser photocoagulation was applied to the posterior retina avoiding the retinal vessels. After treatment, the eyes were removed and 10 microns thick cryostat-cut chorioretinal section were used for in situ hybridization with probes as mentioned above. In the RVO model, expression of messenger RNA of basic FGF (b-FGF) and FGF receptor 1 increased in the inner nuclear layer and the inner segment of the photoreceptors, and appeared in the retinal vessel wall in the early stage. This shows that b-FGF and FGF receptor 1 increased in the ischemic retina, and were produced on the retinal vessel wall. This suggests that b-FGF may be involved in protection, regeneration, and proliferation of the retinal vascular endothelial cells in retinal circulatory disturbance.

Animals↗

Comparison of pulsed-field gel electrophoresis and phage typing for discriminating poultry strains of Staphylococcus aureus.

OBJECTIVE: To compare pulsed-field gel electrophoresis (PFGE) patterns of Staphylococcus aureus from chickens in England, Belgium, Bulgaria, Argentina, and Japan, to assess the value of PFGE for discriminating strains, and to compare results obtained by PFGE with those obtained by biotyping and phage typing. SAMPLE POPULATION: 78 S aureus isolates from diseased and healthy chickens. PROCEDURE: Chromosomal DNA of S aureus was digested with restriction endonuclease Sma I, and fragments were separated by PFGE in 1% agarose gel. RESULTS: All 78 strains from 5 countries were classified as poultry ecovar according to a previously established biotyping system. Chromosomal DNA was cut by Sma I into 18 to 23 fragments ranging from about 3 to 685 kb. Seventy-eight strains produced 15 types, arbitrarily designated A to O, and 45 subtypes. Some differences were observed in PFGE patterns among countries. However, 10 fragments (333, 190, 110, 63, 55, 42, 34, 19, 10, and 3 kb) were highly conserved and were shared by almost all (> 78%) of the strains examined. The PFGE patterns were compared with those obtained by phage typing. All 29 strains belonging to avian phage-group II produced type A and 19 subtypes. Of the 15 strains belonging to phage-group I, 11 produced 8 types (B to H, O) and 5 subtypes that were different from those of type A. CONCLUSIONS: Genomic DNA fingerprinting by PFGE is an effective technique for discriminating poultry S aureus strains and appears to be a useful method for subtyping strains of avian phage groups or the poultry-specific ecovar.

Animals↗

[The relation between diabetes mellitus and IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and monocytes in patients with pulmonary tuberculosis].

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Adult↗

[Validation of three limulus tests for the determination of endotoxin in dialysate/substitute used in on-line hemodiafiltration].

The on-line hemodiafiltration, a newly developed technic of artificial kidney, requires a large mount of dialysate as a substitute for filtered plasma. The dialysate is prepared in the hospital, and is liable to be contaminated. To avoid adverse effects from contaminants, the dialysate needs to be checked at least for endotoxin (ET) with a highly sensitive, accurate and precise method. Three commercial kits, Endospecy (Seikagaku, Tokyo), ES-single (Wako, Osaka) and QCL (BioWhittacker, Maryland), were tested to see if they receive any interference from dialysate. The recoveries of Escherichia coli and Salmonella ET spiked in dialysate at final concentrations of 50, 100 and 150 EU/l were evaluated against those spiked in distilled water using simple linear regression analysis. The validation criteria was that the coefficient of a regression line which was forced to pass through the origin should fall between 0.75 and 1.25. No interference was observed with Endospecy. The QCL showed no interference with E. coli ET but enhancement with Salmonella ET. The ES-single was least sensitive for either ET. Dilution of dialysate affected the recoveries by QCL and ES-single but not those by Endospecy. The Endospecy was thus the only reagent that could detect ET level as low as 1.0 EU/l without interference from dialysate. The rise in body temperature after 4-hour on-line hemodiafiltration was correlated with ET level in the substitution fluid (r = 0.48, p < 0.05), and was significant when the level was 1.0 EU/l or more. These results suggest that the ET level of substitution fluid should be monitored with Endospecy and that the level should be kept below 1.0 EU/l.

Dialysis Solutions↗

[The relationship between a decrease in fat mass and serum levels of TNF-alpha in patients with chronic obstructive pulmonary disease].

To investigate the relationship between malnutrition and TNF-alpha levels in patients with chronic obstructive pulmonary disease (COPD), we measured concentrations of TNF-alpha in serum from fifty four patients with stable COPD. The patients were divided into three groups, according to ideal body weight (IBW): group A, %IBW > or = 90; group B, 90 > %IBW > or = 80; group C, %IBW < 80. Serum TNF-alpha levels in group C were significantly higher than in group A (mean +/- SD; 3.00 +/- 0.43 pg/ml and 2.25 +/- 0.29 pg/ml, respectively, p < 0.0001), group B (2.41 +/- 0.47 pg/ml, p < 0.001), and healthy controls (2.33 +/- 0.30 pg/ml, p < 0.001) who were age- and %IBW-matched with patients in group C. Sixteen patients with COPD underwent body composition analysis by dual energy X-ray absorptiometry. Serum TNF-alpha levels in patients with COPD significantly correlated with fat mass (r = -0.67, p < 0.001). No association was observed between lean mass and serum TNF-alpha levels. These data suggest that TNF-alpha is involved with malnutrition in patients with COPD, and that TNF-alpha may cause a decrease in fat mass in patients with COPD.

Absorptiometry, Photon↗

[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

Aged↗

Sensitive response of cultured vascular smooth-muscle cells to cadmium cytotoxicity: comparison with cultured vascular endothelial cells and kidney epithelial LLC-PK1 cells.

Response to cadmium cytotoxicity of cultured bovine aortic smooth-muscle cells was compared with that of cultured bovine aortic endothelial cells and porcine kidney epithelial LLC-PK1 cells. The cell damage was evaluated by morphology and the lactate dehydrogenase leakage assay. It was found that vascular smooth-muscle cells are markedly sensitive to cadmium cytotoxicity. The accumulation of intracellular cadmium was much higher but that of metallothionein was much less in vascular smooth-muscle cells than in LLC-PK1 cells; vascular endothelial cells were in between vascular smooth-muscle cells and LLC-PK1 cells. The content of reduced glutathione was slightly increased by cadmium in all three cell types. The present data suggest that a much lower inducibility of metallothionein with a high accumulation of intracellular cadmium in vascular smooth-muscle cells resulted in a marked sensitivity of the cells to cadmium cytotoxicity. Vascular smooth-muscle cells may be one of the critical target of cadmium toxicity.

Animals↗

Phorbol 12-myristate 13-acetate stimulates the release of glycosaminoglycans from cultured vascular endothelial cells: possible involvement of protein kinase C activation.

We investigated the release of glycosaminoglycans (GAGs) labeled with [3H]glucosamine and [35S]sulfate into the medium from cultured bovine aortic endothelial cells stimulated by phorbol 12-myristate 13-acetate (PMA) which is an activator of protein kinase C (PKC). The GAG release was significantly accelerated by PMA without an increase in the leakage of lactate dehydrogenase but was unchanged by 4 alpha-phorbol 12,13-didecanoate which lacks the ability of PKC activation. The acceleration of GAG release by PMA was strongly suppressed by a PKC inhibitor H-7 but not by HA 1004 which is an inactive analogue of H-7. Characterization of GAGs released into the medium revealed that PMA increased both heparan sulfate and the other GAGs in a similar degree. Although the release of GAGs stimulated by thrombin was also suppressed by another PKC inhibitor staurosporine, stimulation by plasmin was unaffected by the inhibitor. The present data suggest that protein kinase C mediates the release of endothelial cell GAGs including anticoagulant heparan sulfate and the stimulation of the release by thrombin includes this mechanism.

Animals↗

Cyclic AMP-dependent pathway that mediates suppressive regulation of glycosaminoglycan production in cultured vascular endothelial cells.

We investigated the effect of agents which increase the intracellular level of cyclic AMP (cAMP) on the production of glycosaminoglycans (GAGs) by cultured bovine aortic endothelial cells. It was found that the incorporation of [3H] glucosamine into GAGs was significantly decreased by forskolin, 8-bromo cAMP, 3-isobutyl-1- methylxanthine and prostaglandin E1. The leakage of lactate dehydrogenase into the medium, a marker of nonspecific cell damage, were not changed by forskolin. Forskolin-induced decrease in the [3H]glucosamine incorporation occurred in both heparan sulfate and the other GAGs. The [3H]glucosamine incorporation into GAGs was suppressed by forskolin also in human aortic and human umbilical vein endothelial cells, bovine aortic smooth muscle cells, porcine kidney epithelial LLC-PK1 cells and human fetal lung fibroblastic IMR-90 cells. In conclusion, it was suggested that intracellular cAMP mediates the suppressive regulation of GAG production in vascular endothelial cells; as a result, the cell surface heparan sulfate was reduced. The cAMP-dependent pathway appears to be important as an intracellular mechanism by which endothelial production of anticoagulant heparan sulfate is regulated.

1-Methyl-3-isobutylxanthine↗

Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses.

1. The effects of metabotropic glutamate receptor (mGluR) agonists on excitatory transmission at mossy fibre-CA3 synapses were studied in rat hippocampal slice preparations using both extracellular and whole-cell clamp recording techniques. 2. Application of a novel and potent mGluR2/mGluR3-specific agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 0.1 microM) reversibly suppressed field excitatory postsynaptic potentials evoked by mossy fibre stimulation. DCG-IV at the same concentration did not affect other glutamatergic excitatory transmissions at the commissural/associational input to CA3 or at the Schaffer collateral/commissural input to CA1 regions. 3. This suppressing effect of DCG-IV on mossy fibre transmission was dose dependent and partly antagonized by a competitive mGluR antagonist (+)-methyl-4-carboxylphenylglycine (1 mM). 4. The field potential changes induced by pressure application of glutamate (0.1 mM) to the stratum lucidum of the CA3 region was unaffected by 0.1 microM DCG-IV. 5. In whole-cell clamp experiments, 0.1 microM DCG-IV suppressed excitatory postsynaptic currents evoked by mossy fibre stimulation without inducing detectable inward current in CA3 neurons, and paired-pulse facilitation was enhanced by DCG-IV application. 6. These results suggest that mGluR2/mGluR3 are specifically expressed at mossy fibre synapses in the hippocampal CA3 region, and activation of the receptor suppresses synaptic transmission by an action on a presynaptic site.

Animals↗