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Biomedical subjects

H Matsuo

Publications and source records attributed to H Matsuo.

At least 19 recordsLinked to original sources

Prednisolone inhibits hyperosmolarity-induced expression of MCP-1 via NF-kappaB in peritoneal mesothelial cells.

The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis (CAPD) is poorly elucidated. We investigated the cellular mechanism of high-glucose-induced expression of monocyte chemoattractant protein-1 (MCP-1), which is important in recruiting monocytes into the peritoneum and progression of peritoneal fibrosis, and examined the inhibitory mechanism of glucocorticoids. Rat peritoneal mesothelial cells were cultured in high-glucose-containing medium and then analyzed for phosphorylation levels of p42/44 and p38 mitogen-activated protein (MAP) kinases (MAPK), MAPK or extracellular signal-regulated kinase kinase (MEK)1/2, c-Jun N-terminal kinase (JNK)1/2, and protein kinase C (PKC) by Western blotting. Expression of MCP-1 was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. DNA-binding activity of nuclear factor (NF)-kappaB was measured by electrophoretic mobility shift assay. High glucose increased MCP-1 mRNA and MCP-1 protein expression. Although glucose increased phosphorylation of MEK1/2, p42/44 MAPK, p38 MAPK, JNK1/2, and PKC, and DNA-binding activity of NF-kappaB, its effect on MCP-1 expression was suppressed only by PKC and NF-kappaB inhibitors. Mannitol caused a similar increase in PKC and NF-kappaB activation and MCP-1 synthesis. Prednisolone increased I-kappaB-alpha expression and inhibited glucose/mannitol-induced NF-kappaB DNA binding and MCP-1 expression without affecting PKC phosphorylation. The inhibitory effects of prednisolone on MCP-1 expression were reversed by mifepristone, a glucocorticoid receptor antagonist. Our results indicate that glucose induces MCP-1 mainly through hyperosmolarity by activating PKC and its downstream NF-kappaB, and that such effect was inhibited by prednisolone, suggesting the efficacy of prednisolone in preventing peritoneal fibrosis in patients on CAPD.

Animals↗

A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter.

Cystinuria is caused by the inherited defect of apical membrane transport systems for cystine and dibasic amino acids in renal proximal tubules. Mutations in either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene have been identified mainly from Italian, Libyan Jewish, North American, and Spanish patients. In the present study, we have analyzed cystinuria cases from oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1 genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine in COS-7 cells was measured to determine the functional properties of mutants. The protein expression and localization were examined by Western blot and confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to possess mutations in SLC7A9. The most frequent one was a novel missense mutation P482L that affects a residue near the C-terminus end of the protein and causes severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein was expressed and sorted to the plasma membrane as well as wild type. The alteration of Pro482 with amino acids with bulky side chains reduced the transport function of b(0,+)AT/BAT1. Interestingly, the mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. The results of the present study contribute toward understanding the distribution and frequency of cystinuria-related mutations of SLC7A9.

Amino Acid Substitution↗

Clinical characteristics of vaginal discharge in bacterial vaginosis diagnosed by Nugent's criteria.

PURPOSE OF INVESTIGATION: To determine which clinical signs have an important contribution in bacterial vaginosis (BV) diagnosed by Nugent's criteria. METHODS: This was a cross-sectional study of 58 women undergoing vaginal examination at Hayashi women's clinic, Hyogo Prefecture. Characteristics of vaginal discharge (color, amount, odor, and pH level) and the number of clue cells were compared among normal, intermediate, and BV groups. BV was diagnosed by using Nugent's criteria. RESULTS: The incidence of BV in our study population was 25.9%. Compared to the non-BV group, women in the BV group were found more often to have yellowish color and a moderate amount of discharge (66.67% vs 33.33%, NS; 55.56% vs 44.44%, NS), odorous discharge (100% vs 0%, p < 0.05) and furthermore, pH level and the number of clue cells were significantly higher. CONCLUSION: Odor, pH level and the number of clue cells in the vaginal discharge were helpful clinical signs for early detection of BV diagnosed by Nugent's criteria.

Cross-Sectional Studies↗

Topical application of autologous serum for the treatment of late-onset aqueous oozing or point-leak through filtering bleb.

PURPOSE: To evaluate the efficacy of topical autologous serum application to stop aqueous oozing or point-leak through filtering bleb after trabeculectomy. PATIENTS AND METHODS: A total of 21 consecutive eyes with oozing and 21 eyes with a point-leak through a functional bleb after trabeculectomy with 5-fluorouracil or mitomycin C were enrolled in this randomized, case-control study. In eyes randomly assigned to the serum group, an antibiotic and the autologous serum, which was sterilely diluted to 20% with physiological saline, were topically applied four times a day for up to 12 weeks. In eyes assigned to the control group, the antibiotic alone was applied according to the same protocol. Intraocular pressure (IOP) and the presence of oozing or a point-leak were tested before and every 2 weeks after starting the treatments. RESULTS: In the serum and control groups, oozing stopped in 62.5 and 0% of eyes, respectively (P=0.003), and point-leaks stopped in 27.3 and 18.2%, respectively (P>0.9). IOP significantly increased from 10.0+/-3.2 (mean+/-standard deviation) to 11.8+/-3.3 mmHg in eyes in which oozing stopped (P=0.066), and from 11.4+/-2.7 to 15.4+/-2.3 mmHg in eyes in which a point-leak stopped (P=0.042). CONCLUSIONS: Autologous serum application was significantly effective to stop aqueous oozing but not point-leaks. Stopping oozing or point-leaks was significantly associated with an increase in IOP.

Administration, Topical↗

Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is an allergic reaction characteristically induced by intense exercise combined with the ingestion of causative food. Recent reports have shown that aspirin intake is a contributing factor in some patients with FDEIA. Wheat is known to be the most frequent causative food, and the IgE-binding epitopes of a major wheat allergen (omega-5 gliadin) in wheat-dependent exercise induced anaphylaxis (WDEIA) have already been clarified. However, the mechanism of eliciting the symptom in WDEIA remains not fully understood. OBJECTIVES: The aim of this study was to examine the relationship of serum gliadin levels and allergic symptoms induced by exercise or aspirin in patients with WDEIA. METHODS: Six patients with a history of recurrent anaphylaxis associated with wheat ingestion were diagnosed as having WDEIA by the provocation test, which included wheat ingestion, exercise, aspirin intake and a combination of these challenges. During the tests, serum levels of gliadins were monitored by gliadin-specific sandwich ELISA. The effects of exercise and aspirin on serum gliadin levels were also investigated in four healthy subjects. RESULTS: Immunoreactive gliadins appeared in the sera of patients during the provocation test with both wheat-exercise and wheat-aspirin challenges in parallel with allergic symptoms. Serum gliadin levels also increased under the two same challenge conditions in the healthy subjects, although they exhibited no allergic symptoms. However, low levels of gliadin were detected in the sera of both patients and healthy subjects when challenged with wheat alone. CONCLUSION: We demonstrated for the first time that blood gliadin levels correlate with clinical symptoms induced by exercise and aspirin in patients with WDEIA. These findings suggest that exercise and aspirin facilitate allergen absorption from the gastrointestinal tract.

Adolescent↗

Adrenomedullin contributes to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide.

BACKGROUND: Plasma levels of adrenomedullin, a potent vasodilator peptide, are increased in cirrhotic patients, whereas its role in vascular hyporeactivity in cirrhosis has not been clarified. METHODS: Adrenomedullin expression was evaluated by radioimmunoassay and reverse-transcription polymerase chain reaction. Vascular reactivity to phenylephrine, alpha-adrenoceptor agonist, was investigated in the aortic rings from control rats and CCl-induced cirrhotic rats with ascites in the presence of the neutralizing antibody against adrenomedullin, human adrenomedullin and/or N-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor. RESULTS: Plasma adrenomedullin levels were significantly higher in cirrhotic rats than in controls (16.3 +/- 2.9 versus 7.4 +/- 1.7 fmol/mL, P < 0.05) and correlated negatively with systemic arterial pressure (r = -0.62, P < 0.05). Gene expression of adrenomedullin in various organs (liver, kidney, lung) and vessels (portal vein, aorta) was enhanced in cirrhotic rats compared with controls. Neutralizing antibody against adrenomedullin ameliorated the blunted contractile response to phenylephrine in cirrhotic aorta (Rmax: 1.5 +/- 0.1 versus 1.0 +/- 0.1 g/mg tissue, P < 0.05), whereas contraction remained unchanged in control aorta (Rmax: 1.9 +/- 0.2 versus 1.9 +/- 0.2 g/mg tissue). Intravenous infusion of human adrenomedullin induced a reduction of mean arterial pressure together with an increase of serum nitrate levels, which was abolished by neutralizing antibody against adrenomedullin. Human adrenomedullin caused a blunted contractile response to phenylephrine in both control and cirrhotic aortas, which was not observed in the presence of N-nitro-L-arginine methyl ester. CONCLUSIONS: These findings indicate that the overproduction of adrenomedullin may contribute to vascular hyporeactivity in cirrhosis via a release of nitric oxide.

Adrenergic alpha-Agonists↗

Fast omega-gliadin is a major allergen in wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis is an anaphylaxy induced by physical exercise after ingestion of wheat. An immediate-type hypersensitivity to water/salt-insoluble fraction of wheat proteins (gluten) has been considered to underlie in this disease. OBJECTIVE: The aim of the study is to determine the major allergen in Japanese patients with wheat-dependent exercise-induced anaphylaxis by using a panel of purified wheat gliadins and glutenins. METHODS: Water/salt-insoluble wheat proteins, alpha-gliadin, beta-gliadin, gamma-gliadin, fast omega-gliadin, slow omega-gliadin, high molecular weight glutenin and low molecular weight glutenin, were purified, and five patients with wheat-dependent exercise-induced anaphylaxis, whose diagnose had been determined by positive-challenge test, were evaluated for skin prick test, dot-blotting test and CAP-RAST inhibition test by using these purified wheat proteins. RESULTS: The fast omega-gliadin was the most potent allergen among these water/salt-insoluble proteins when evaluated by skin prick test and dot-blotting test. Fast and slow omega-gliadin, and gamma-gliadin caused dose-dependent inhibition of the serum IgE-binding to solid-phase gluten in the patients. The incubation with fast omega-gliadin of the patient's serum caused dose-dependent inhibition in the IgE-binding to gamma-gliadin as well as slow omega-gliadin, indicating a cross-reactivity of these proteins in IgE-binding. CONCLUSION: We concluded that fast omega-gliadin is a major allergen among these water/salt-insoluble proteins for wheat-dependent exercise-induced anaphylaxis in Japanese patients, and IgE against fast omega-gliadin cross-reacts to gamma-gliadin and slow omega-gliadin.

Adolescent↗

Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.

Aged↗

Effects of estriol on cell viability and 1,25-dihydroxyvitamin D3 receptor mRNA expression in cultured human osteoblast-like cells.

It is clinically evident that administration of estriol (E3) increases the bone mass density of the lumbar vertebrae in postmenopausal women, and that combined treatment with estrogen and 1,25-dihydroxyvitamin D3 (VD3) increases femoral neck bone mass density compared with treatment with estrogen alone in postmenopausal osteoporotic women. However, the molecular mechanism whereby treatment with E3 affects osteoblast cell function is still unknown. This study was conducted first to examine the comparative effects of E3 and VD3 on the cell viability of cultured human osteoblast-like cells (HOS) and second to determine whether E3 affects VD3 receptor mRNA expression in HOS. The cell viability and VD3 receptor mRNA expression of cultured HOS were assessed by MTT assay and semi-quantitative reverse transcriptase-polymerase chain reaction with Southern blot analysis, respectively. The treatment with E3 increased the cell viability of cultured HOS compared with untreated control cultures. The increase in cell viability caused by the treatment with E3 was further augmented by the combined treatment with VD3. The addition of either E3 (3.52 x 10(-8) mol/l) or E3 (3.52 x 10(-7) mol/l) to cultured HOS for 24 h resulted in a fourfold and eightfold increase, respectively, in VD3 receptor mRNA expression in HOS, compared with that in untreated control cultures. These results suggest that E3 may up-regulate the cell viability of osteoblast cells, and that the concomitant treatment with E3 and VD3 further augments the cell viability being associated with an E3-induced increase in VD3 receptor mRNA expression in those cells.

Calcitriol↗

Cough receptor sensitivity to capsaicin does not change after allergen bronchoprovocation in allergic asthma.

BACKGROUND: The relationship between cough receptor sensitivity and eosinophilic inflammation of the airway in patients with asthma remains unclear. METHODS: Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled in a randomised parallel group study. Patients with asthma whose main symptom was cough were not enrolled in the study. Half the patients were randomly assigned to inhale saline and the other half to inhale HDM allergen. Cough receptor sensitivity to capsaicin, airway responsiveness to histamine, and sputum eosinophils analysed with hypertonic saline inhalation were investigated before and 24 hours after saline or HDM allergen bronchoprovocation. RESULTS: Patients inhaling saline showed no significant changes in sputum eosinophils (from 7.87% (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18); p=0.97), airway responsiveness to histamine (from 726.68 micro g/ml (95% CI 251.90 to 2096.36) to 773.01 micro g/ml (95% CI 251.36 to 2377.23); p=0.96), or capsaicin sensitivity (from 7.23 micro M (95% CI 2.45 to 21.31) to 7.24 micro M (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all patients, and late asthmatic response was observed in six of nine patients inhaling HDM allergen. Although there were significant increases in sputum eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15); p<0.01) and airway responsiveness to histamine (from 784.16 micro g/ml (95% CI 318.24 to 1932.24) to 377.81 micro g/ml (95% CI 118.43 to 1205.24); p<0.05) 24 hours after HDM allergen inhalation compared with baseline levels, capsaicin sensitivity did not change significantly (from 5.75 micro M (95% CI 1.91 to 17.30) to 6.20 micro M (95% CI 2.21 to 17.38); p=0.77). CONCLUSIONS: These findings suggest that cough receptor sensitivity to capsaicin is not associated with eosinophilic inflammation of the airway in patients with allergic asthma whose main symptoms are wheezing and dyspnoea but not cough.

Adult↗

Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms.

Nasu-Hakola disease (NHD) is an autosomal recessive disorder characterized by presenile dementia and bone cysts. Finnish patients revealed a large deletion in DAP12 gene encoding a key element for transducing activation signal. The authors examined six Japanese cases for DAP12 alleles. Five of the six had loss-of-function mutation, either a single-base deletion or a novel point mutation. The single patient without mutation normally expressed DAP12 protein. Japanese NHD has at least three genetic forms regarding DAP12.

Adaptor Proteins, Signal Transducing↗

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗

Agranulocytosis possibly caused by ranitidine in a patient with renal failure.

A 70-year-old Japanese woman with renal dysfunction under hemodialysis presented with vomiting and chill with fever. Over the previous 24 weeks she had been taking 75 mg of ranitidine after hemodialysis. Other medications taken were prednisolone, furosemide, alpha-calcidol, amlodipine and calcium carbonate. Before starting ranitidine, she had been treated with famotidine for about 2 years without complication. Hematological inspection on admission revealed agranulocytosis with WBC of 400/mm3. Ranitidine was discontinued and granulocyte colony-stimulating factor (G-CSF) was started. On Day 3, laboratory data showed slight improvement of cytopenia with WBC of 1,000/mm3. On Day 6, her hemogram showed marked improvement with WBC of 11,700/mm3 and G-CSF was discontinued. She was discharged on Day 10. Several cases describing ranitidine-induced cytopenia are associated with the use of ranitidine at a dose of 150 mg/day or higher, and adverse reactions were found within 2-35 days after beginning ranitidine treatment. In the case described here, however, the adverse reaction occurred after a longer treatment period with ranitidine at a lower dose. In conclusion, ranitidine should be administered with great caution to patients with severe renal dysfunction.

Aged↗

Effect of artificial carbon dioxide foot bathing on critical limb ischemia (Fontaine IV) in peripheral arterial disease patients.

BACKGROUND: It has been reported that artificial carbon dioxide (CO(2)) foot bathing improves subcutaneous microcirculation in peripheral arterial disease (PAD) patients. However, the effect for critical limb ischemia (CLI) with ulceration or gangrene (Fontaine stage IV) is not identified. The physiological effects of CO(2) bathing and the outcome of limb salvage in such patients were studied. METHODS: In 18 healthy volunteers (Study I), the dorsal pedis peripheral blood flow was measured by a laser Doppler flow-meter during CO(2) foot bathing (1000 ppm, 37 degrees C) for 10 min. A Holter electrocardiogram was also recording in the same period. Blood flow and cell volume significantly increased during bathing. Eighty-three CLI limbs (Fontaine IV) in 68 PAD patients (Study II) underwent artificial CO(2) foot bathing (for 10 minutes twice daily >2 months) were followed up >6 months. RESULTS: In Study I, analysis of heart rate variability showed that high frequency amplitude (HFA) considerably increased and the ratio of low frequency amplitude to HFA (LF/HF) noticeably decreased during bathing. In Study II, 69 limbs (83.1%) could be salvaged. Twenty-seven of 28 limbs (96.4%) which have ulcer and gangrene in only one toe, 13/16 limbs (81.2%) in multiple toes and 29/39 limbs (74.4%) in all toes and/or heel respectively were saved. CONCLUSIONS: The effect of CO(2) enriched water on the subcutaneous microcirculation might be brought about by peripheral vasodilation reflected by increased parasympathetic and decreased sympathetic activity, and the artificial CO(2) foot bathing is clinically effective on salvage of CLI (Fontaine stage IV) limbs.

Adult↗

Possibility of the reversal of multidrug resistance and the avoidance of side effects by liposomes modified with MRK-16, a monoclonal antibody to P-glycoprotein.

For cancer chemotherapy, avoiding the side effects of chemotherapeutic agents is difficult. Multidrug resistance is one of the major obstacles to successful cancer chemotherapy. P-Glycoprotein (P-gp) serves as an efflux pump and plays a key role in the multidrug resistance. We examined the effect of MRK-16, a monoclonal antibody against P-gp, modified liposomes (MRK-Lip) on the human myelogenous leukemia K-562 cells and its adriamycin resistance cell line K-562/ADM cells to avoid the side effects and to reverse the multidrug resistance. The uptake of vincristine (VCR) by K-562/ADM cells was lower than that by K-562 cells. This low uptake was increased in the presence of verapamil and MRK-16, however, it was not increased in the presence of control antibody, IgG2A. The binding of MRK-Lip to K-562/ADM cells was higher than that of IgG2A-modified liposome (IgG-Lip) and liposome without modification (Cont-Lip). Moreover, the cytotoxicity of VCR-encapsulated MRK-Lip to K-562/ADM cells was higher than that of VCR-encapsulated IgG-Lip and Cont-Lip. These results suggest that the interaction between liposomes and multidrug resistance cells was increased by the modification of liposomes with MRK-16. Consequently, the usefulness of MRK-Lip in cancer chemotherapy as a potent carrier was suggested.

ATP Binding Cassette Transporter, Subfamily B, Mem↗