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Biomedical subjects

H Sato

Publications and source records attributed to H Sato.

At least 541 records · Page 30Linked to original sources

Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease.

BACKGROUND: It has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease. OBJECTIVE: We aimed to assess whether there is a genetic difference between these two groups of AE patients. METHOD: We determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients. RESULTS: MCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL. CONCLUSION: These results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.

Adolescent↗

Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases.

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.

Acute Disease↗

Echinococcus granulosus human infection stimulates low avidity anticarbohydrate IgG2 and high avidity antipeptide IgG4 antibodies.

Total IgG and IgG subclasses recognizing carbohydrate and peptidic epitopes from native and periodate treated partially purified hydatid cyst fluid (ppHCFA) and protoscolex somatic antigens (PSA) were tested by ELISA in hydatid patients sera. Binding of the major cross-reactive antiphosphorylcholine antibodies was inhibited with free reagent. A predominant anticarbohydrate antibody response against ppHCFA and PSA is shown. Although the main contributing IgG subclass to the antipeptide response against both antigens was IgG4, IgG1 also significantly contributed to the anti-PSA peptidic epitopes response. Western blot showed that IgG1 antibodies strongly recognized in ppHCFA a periodate susceptible 38 kDa antigen. The IgG4 antibodies mainly recognized the periodate-resistant 12, 16 and 24 kDa antigens. In addition, IgG2 antibodies recognized three strongly periodate-susceptible broad bands (116, 55 and 24 kDa antigens). PSA-specific IgG1 and IgG4 antibodies showed similar patterns of antigen recognition as well as no significant reduction of reactivity after periodate treatment while the IgG2 antibody recognition was strongly affected by this treatment. Furthermore, IgG2 showed significantly lower avidities than IgG1 and IgG4 antibodies recognizing both antigens. In conclusion, hydatid patients showed an enhanced production of low avidity anticarbohydrate IgG2 as well as high avidity antipeptide IgG4 antibodies.

Animals↗

Characterization of a truncated recombinant form of human membrane type 3 matrix metalloproteinase.

Membrane type 3 matrix metalloproteinase (MT3-MMP), an activator for the zymogen of MMP-2 (proMMP-2, or progelatinase A), is known to be expressed in human placenta, brain, lung and rat vascular smooth muscle cells, but information about its biochemical properties is limited. In the present study, we expressed and purified a truncated form of MT3-MMP lacking the transmembrane and intracytoplasmic domain (DeltaMT3) and characterized the enzyme biochemically. DeltaMT3 digested type III collagen into characteristic 3/4- and 1/4-fragments by cleaving the Gly781-Ile782 and Gly784-Ile785 bonds of alpha1(III) chains. Although DeltaMT3 did not have such an activity against type I collagen, it attacked the Gly4-Ile5 bond of the triple helical portion of alpha2(I) chains, leading to removal of the crosslink containing N-terminal telopeptides. By quantitative analyses of the activities of DeltaMT3 and a similar deletion mutant of MT1-MMP (DeltaMT1), DeltaMT3 was approximately fivefold more efficient at cleaving type III collagen. DeltaMT3 also digested cartilage proteoglycan, gelatin, fibronectin, vitronectin, laminin-1, alpha1-proteinase inhibitor and alpha2-macroglobulin into almost identical fragments to those given by DeltaMT1, although carboxymethylated transferrin digestion by DeltaMT3 generated some extra fragments. The activity of DeltaMT3 was inhibited by tissue inhibitor of metalloproteinases-2 (TIMP-2) and TIMP-3 in a 1 : 1 stoichiometry, but not by TIMP-1. ProMMP-2 was partially activated by DeltaMT3 to give the intermediate form. These results indicate that, like MT1-MMP, MT3-MMP exhibits proteolytic activities against a wide range of extracellular matrix molecules. However, differences in the proMMP-2 activation and tissue distribution suggest that MT3-MMP and MT1-MMP play different roles in the pathophysiological digestion of extracellular matrix.

Collagen↗

Protective activity of the purified protein antigen of Erysipelothrix rhusiopathiae in pigs.

We purified the protein antigen (P64), which contains 66 and 64 kDa proteins, from the alkaline extract (AE) of whole cells of Erysipelothrix rhusiopathiae strain Agata (serovar 5) to determine the protective activity of the antigen against E. rhusiopathiae infection in pigs. The serum titre of antibody against P64 rapidly increased in pigs immunized with 500 and 100 micrograms of P64 and reached maximum values at 3 weeks after the first immunization (1 week after the second immunization). However, the serum antibody titres were not increased in pigs immunized with 20 micrograms of P64 and in nonimmunized pigs. In the pigs immunized with live cell vaccine (acriflavin-fast attenuated strain Koganei 65-0.15), the serum titres of antibody against P64 also increased at 1-2 weeks after immunization. In a pig challenge test performed on immunized and nonimmunized pigs, all nonimmunized pigs showed typical clinical signs of swine erysipelas (fever, erysipeloid, arthritis), while all pigs immunized with 500 and 100 micrograms of P64 and live cell vaccine showed no clinical signs of this disease. In Western blot analysis, sera from pigs immunized with P64 and live cell vaccine strongly reacted with the 64 kDa protein. In contrast, the serum from nonimmunized pigs did not react with any proteins. From these results, it was suggested that a specific antibody against the 64 kDa protein could be increased in pigs immunized with P64 or live cell vaccine and that this anti-P64 antibody has a strong protective effect against E. rhusiopathiae infection in pigs.

Animals↗

Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosal carcinomas.

Although numerous studies have assessed the biologic parameters of tumors, measurement of these parameters has had, to date, little impact on histologic diagnosis. Furthermore, analysis of a single parameter is insufficient to evaluate tumor malignant potential. In the present study, cell proliferation, DNA ploidy and p53 product were analyzed to objectify the tumor malignant potential in colorectal adenomas and intramucosal carcinomas. Sixty-one adenomas and 49 intramucosal carcinomas were studied using immunohistochemical analysis of Ki-67 and p53, silver-staining nucleolar organizer region (AgNOR) stain and DNA ploidy in fresh samples. Intramucosal carcinoma exhibited a greater Ki-67-positive rate and AgNOR count than the adenomas, although these parameters varied widely among samples. The incidence of aneuploidy and p53 over-expression in colorectal intramucosal carcinomas was significantly higher than in colorectal adenomas. These results indicate that DNA aneuploidy and p53 accumulation are the most reliable parameters for distinguishing benign and malignant lesions.

Adenocarcinoma↗

Results of conservative treatment of upper urinary tract transitional cell carcinoma.

BACKGROUND: The treatment preserving the kidney for upper urinary tract tumor is still controversial. The indications and results of conservative treatment remain to be elucidated. Experiences of this type of treatment are reported. METHODS: Between April 1981 and March 1998, 14 patients with upper urinary tract transitional cell carcinoma were treated with renal preserving methods. Five were elective and nine were imperative cases. Treatments performed were partial nephrectomy, partial ureterctomy with or without adjuvant chemotherapy, endoscopic tumor resection and topical bacillus Calmette-Guerin instillation in one, 10, two and one patient, respectively. RESULTS: Crude and cause-specific 5 year-survival rates were 91.7 and 100%, respectively. Of 14 patients, five had bladder recurrences, but ipsilateral local recurrence developed in only one patient. Two patients died from metastasis of transitional cell carcinoma 61 and 89 months after initial treatment. The lesions of carcinoma in situ were well controlled with topical bacillus Calmette-Guerin therapy. CONCLUSION: The results of conservative treatment for upper urinary tract tumor were satisfactory and local excision can be indicated for low grade, solitary tumors located in the distal ureter.

Aged↗

Lipoprotein glomerulopathy: significance of lipoprotein and ultrastructural features.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a unique disease characterized by intraglomerular lipoprotein thrombi and type III hyperlipoproteinemia. Recently, we have demonstrated that LPG is associated with inherited apolipoprotein E (apoE) variants including apoE Sendai. On the other hand electron microscopy shows that intraglomerular lipoprotein thrombi consist of lipid granules of various sizes. To elucidate the relationship between the peculiar histology and abnormal lipid metabolism related to apoE Sendai, we studied lipoprotein profiles and ultrastructural features. METHODS: The subjects were 11 patients with LPG. Four patients were nephrotic, and two others became nephrotic within six months following the biopsy. Eight patients underwent apoE gene analysis and showed apoE Sendai. The other three were presumed to have apoE Sendai because this mutation was demonstrated in their kindreds. Under electron microscopy, diameters of more than 1000 lipid granules were measured in several glomeruli, and a mean value was calculated in each case. Lipoprotein profiles were analyzed by the ultracentrifugation methods. RESULTS: The mean diameter of intraglomerular lipid granules correlated inversely with the levels of plasma triglyceride (TG; rs = -0.73, P < 0.05), TG (rs = -0.77, P < 0.01) and cholesterol (Chol; rs = -0.75, P < 0.05) in very low-density lipoprotein (VLDL) fraction and TG in high-density lipoprotein (HDL) fraction (rs = -0.75, P < 0.05). The inverse correlation was also seen between the mean lipid diameter and TG/Chol ratios in whole plasma (rs = -0.80, P < 0.01) and in HDL (rs = -0.80, P < 0.01). In addition, the cases showing smaller lipid granules and higher TG/Chol ratios in plasma and in HDL were nephrotic or became nephrotic within six months. CONCLUSION: These results suggest that the size of lipid granules in LPG may become smaller under the influence of hypertriglyceridemia and particularly elevated plasma VLDL and HDL-TG, which may lead to heavy proteinuria.

Adolescent↗

Clinicopathological characteristics of interstitial foam cells in membranous nephropathy.

BACKGROUND: Interstitial foam cells are occasionally observed in various renal diseases, and they have been reported to belong to the monocyte/macrophage (M phi) lineage and to be associated with heavy proteinuria and hyperlipidemia. We investigated the characteristics of interstitial foam cells and their association with proteinuria and hyperlipidemia in idiopathic membranous nephropathy (MN). METHODS: Patients with MN (N = 320) were divided into two groups: group I consisted of 51 patients with interstitial foam cells, and group II consisted of the other 269 without foam cells. We compared clinical parameters and the findings of an immunohistochemical study using monoclonal antibodies to various types of leukocytes and adhesion molecules. RESULTS: The age at renal biopsy, the degree of proteinuria, serum levels of lipids, and other clinical parameters except for sex ratio were not different between the two groups. The ratio of nephrotic patients was compatible between groups I (56.9%) and II (52.8%). All interstitial foam cells were positive for CD68 and 25F9, which are markers for M phi and mature M phi, respectively, but were negative for CD3 or cytokeratin. Interstitial infiltrating cells were positive for CD68 and CD3 but were negative for 25F9. Furthermore, most of interstitial foam cells were positive for both leukocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), but not for ICAM-3 (the third ligand for LFA-1). By contrast, most of infiltrating nonfoamy M phi s were positive for ICAM-3 and LFA-1, however, ICAM-1 was observed on only some of them. CONCLUSION: These results suggest that interstitial foam cells in MN may not depend on proteinuria nor hyperlipidemia directly. The accumulation of foam cells, which have characteristics of mature M phi, may be related to ICAM-1 as a ligand of LFA-1, whereas infiltration of nonfoamy M phi s has a close relationship with ICAM-3. Thus, the formation of interstitial foam cells may be related to the phenotypical transformation of M phi s.

Adult↗

Efficacy of donor screening for HTLV-I and the natural history of transfusion-transmitted infection.

BACKGROUND: It has been 10 years since the implementation in Japan of donor blood screening for human T-cell lymphotropic virus type I (HTLV-I). This report reviews the effectiveness of screening in preventing transmission of HTLV-I through blood transfusion and the current status of patients with confirmed seroconversion due to transfusions given before the implementation of screening. STUDY DESIGN AND METHODS: Patients who received blood at Kyushu University Hospital from 1990 to 1997 were followed. Serum samples were collected before transfusion and 60 days or more after transfusion. Seroconversion was determined by a second-generation particle agglutination test. Confirmation tests were an immunofluorescence assay, enzyme-linked immunosorbent assay, and immunoblotting. Confirmed seroconverted patients were followed by a search of hospital records. RESULTS: Seroconversion was found in one of 4672 transfused patients, but the donor was identified and confirmed to be negative for anti-HTLV-I and virus genome by nested polymerase chain reaction. A total of 23,323 red cell concentrates and 17,237 platelet concentrates were transfused to these 4672 patients. Therefore, the anti-HTLV-I prevalence in blood for transfusion after screening was estimated at 1 in 45,560 (0.0022%; the upper 95% CI was 0.0080%). One hundred two seroconverted patients who were transfused before donor screening for HTLV-I were followed. One patient developed HTLV-I-associated myelopathy, diagnosed 18 weeks after seroconversion, and another patient developed uveitis 1 month after seroconversion. No patients developed adult T-cell lymphoma, and the survival rate of seroconverted patients was 92.5 percent 15 years after transfusion. CONCLUSION: This study confirmed that the present donor screening program for HTLV-I by the new particle agglutination test can almost completely prevent virus transmission by transfusion. Complications of HTLV-I transmission were at lower rates than expected.

Adolescent↗

The role of codeine phosphate premedication in fibre-optic bronchoscopy under insufficient local anaesthesia and midazolam sedation.

Midazolam is widely used as a sedative agent to produce amnesia in patients undergoing fibre-optic bronchoscopy. However, if a patient does not receive sufficient local anaesthesia, continuous severe cough and physical movement may interrupt the procedure and reduce its safety. We therefore examined whether codeine phosphate is a useful premedication for bronchoscopy. The study design was a randomized comparison between codeine phosphate and a placebo in patients undergoing light local anaesthesia and midazolam sedation. We used low dose local anaesthesia (5 ml of nebulized 2% xylocaine) on the assumption of insufficient local anaesthesia. Patients were allocated to receive codeine phosphate 0.4 mg kg-1 or a saline placebo 60 min before they were sedated with i.v. midazolam. If the patients exhibited severe cough during bronchoscopy, intrabronchial supplemental local anaesthesia (2% xylocaine solution in 1 ml increments) was instilled via a bronchoscope to the trachea and segmental bronchi to suppress the cough. The dose of supplemental xylocaine was assessed and the requirements were significantly lower in the codeine group compared to the placebo group: 36.4 +/- 10.2 mg vs. 95.1 +/- 24.6 mg, respectively. After bronchoscopy, patients were interviewed by a doctor to assess their willingness to undergo a repeat procedure if one was clinically indicated, but no significant difference was observed between the two groups. If local anaesthesia is insufficient, midazolam together with codeine phosphate premedication is useful for both the patient and the bronchoscopist.

Aged↗

Induction of antioxidant stress proteins in vascular endothelial and smooth muscle cells: protective action of vitamin C against atherogenic lipoproteins.

Elevated levels of lipid peroxidation and increased formation of reactive oxygen species within the vascular wall in atherosclerosis can overwhelm cellular antioxidant defence mechanisms. Accumulating evidence implicates oxidatively modified low density lipoproteins (LDL) in vascular dysfunction in atherosclerosis and oxidized LDL have been localized with in atherosclerotic lesions. We here report that human oxidatively modified LDL induce expression of 'antioxidant-like' stress proteins in vascular cells, involving increases in the activity of L-cystine transport, glutathione synthesis, heme oxygenase-1 and the murine stress protein MSP23. Moreover, treatment of human arterial smooth muscle cells with the dietary antioxidant vitamin C markedly attenuates adaptive increases in endogenous antioxidant gene expression and affords protection against smooth muscle cell apoptosis induced by moderately oxidized LDL. As vascular cell death is a key feature of atherosclerotic lesions and may contribute to the plaque 'necrotic' core, cap rupture and thrombosis, our findings suggest that the cytoprotective actions of vitamin C could limit plaque instability in advanced atherosclerosis.

Animals↗

Oxidative stress-inducible proteins in macrophages.

Macrophages produce reactive oxygen species such as O2-, H2O2 and *OH that contribute to the pathogenesis of diseases such as inflammation and atherosclerosis. The cells have multiple defense systems against those reactive oxygen species, and we describe here such an oxidative stress-inducible defense system. Upon exposure to reactive oxygen species and electrophilic agents, murine peritoneal macrophages induce stress proteins to protect themselves. Using differential screening, we cloned two novel proteins designated MSP23 and A170 that are induced in the cells by low levels of reactive oxygen species, electrophilic agents and other oxidative stress agents. MSP23 is murine peroxiredoxin I having a thioredoxin peroxidase activity and A170 is known as an ubiquitin- and PKC xi-binding protein. In addition to these two proteins, heme oxygenase-1 (HO-1) and cystine transport activity are also induced in the cells under oxidative stress conditions. Using nrf2-deficient macrophages, we found that transcription factor Nrf2, which is known to interact with antioxidant responsive elements (AREs) in the regulatory sequences of the genes, plays an important role in the oxidative stress-inducible response in the cells.

Animals↗

In vivo performance of wax matrix granules prepared by a twin-screw compounding extruder.

The in vivo performance of wax matrix granules (WMGs) prepared by a twin-screw compounding extruder was evaluated in fasted beagle dogs. In vitro dissolution behavior of the model drug, diclofenac sodium (DS), from WMGs was strongly influenced by pH in a dissolution medium due to its solubility (DS is soluble in pH 6.8 and insoluble in pH 1.2 and 4.0) and was independent of paddle rotation rate (50, 100, and 200 rpm) of the dissolution apparatus. Pharmacokinetics parameters such as mean residence time (MRT) showed a sustained action of WMGs in beagle dogs; however, the transit time of WMGs in the small intestine is found to control total drug absorption. Furthermore, the values of the area under the curve (AUC) of the plasma concentration-time curve and the maximum concentration Cmax significantly decreased with decreases in hydroxypropylcellulose (HPC) content in WMGs. Good correlation between one in vitro dissolution parameter (mean dissolution time, MDT) and two in vivo parameters (AUC12 and MRT) suggested that it would be possible to design WMGs with a desired in vivo performance by controlling HPC content.

Animals↗

Experience with diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine in Japan.

In Japan, the morbidity rate for pertussis per 100,000 population was 147.6 in 1950 when whole cell pertussis vaccine was introduced but dropped to 0.2 in 1972 when routine immunization with a combined vaccine consisting of diphtheria toxoid, tetanus toxoid, and whole cell pertussis had been widely accepted. Thereafter, adverse reactions to the whole cell pertussis vaccine became a social problem and lowered the acceptance of the vaccine. As a result, the morbidity rate increased to 11.3 in 1979. Introduction of the safer yet efficacious acellular pertussis vaccine, consisting of mainly pertussis toxoid and filamentous hemagglutinin, into the routine childhood vaccination in combination with diphtheria and tetanus toxoids in 1981 increased the acceptance rate. The lowest morbidity rate, 0.1, was achieved in 1993. During the next 16 years, almost all cases were in unvaccinated or incompletely vaccinated persons. Regardless of whether whole cell or acellular pertussis vaccine was used, > 90% of the reported pertussis cases were in children < 10 years of age until 1990. However, since 1991, the rate of pertussis in young adults 20-44 years of age has been clearly increasing. To control pertussis, booster vaccination with diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine in adults should be considered.

Adult↗

A novel recognition motif of human NKT antigen receptor for a glycolipid ligand.

Murine NKT cells can recognize alpha-galactosylceramide (alpha-GalCer) in the context of a class Ib CD1d molecule. Here we show that alpha-GalCer can selectively activate freshly isolated human Valpha24(+)Vbeta11(+) cells, functionally defining the human NKT cells. The naive human NKT cell repertoire consisted of cells expressing an invariant Valpha24JalphaQ chain and a diverse array of beta chains derived from a single Vbeta11 gene segment. Stimulation with alpha-GalCer expanded a polyclonal subset of the human NKT cell repertoire carrying a novel complementarity-determining region (CDR) 3beta consensus motif that may directly interact with the sugar moiety of alpha-GalCer. Our data suggest that certain redundancy is allowed for CDR3beta of NKT antigen receptor to interact with the ligand and provide a first clue to understand the novel protein-carbohydrate interaction mechanisms.

Adult↗