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F Gejyo

Publications and source records attributed to F Gejyo.

At least 109 records · Page 6Linked to original sources
PubMed1999

Modification of beta 2-microglobulin with D-glucose or 3-deoxyglucosone inhibits A beta 2M amyloid fibril extension in vitro.

beta 2-microglobulin (beta 2M) is a major constituent of amyloid fibrils (fA beta 2M) deposited in patients with A beta 2M amyloidosis. Recently, advanced glycation end products (AGE) of beta 2M and fA beta 2M have been suggested to play an important role in the pathogenesis of A beta 2M amyloidosis. We first characterized the states of AGE modification of fA beta 2M. Western blot analysis with a monoclonal anti-AGE antibody showed that purified fA beta 2M was naturally modified with AGE. Immunohistochemical studies of amyloid-deposited tissue have revealed a patchy distribution of the AGE-modified area in the amyloid deposits. Then we modified beta 2-m either with D-glucose or with 3-deoxyglucosone (3-DG) and investigated the effect of these modification on fA beta 2M extension in vitro, using the recently established first-order kinetic model of fA beta 2M extension in vitro. Western blot analysis and enzyme linked immunosorbent assay with a monoclonal anti-AGE antibody showed that these sugar-modified beta 2M contained AGE. During the incubation of fA beta 2M with native beta 2-m at 37 degrees C, the fluorescence of thioflavin T increased without a lag phase and proceeded to equilibrium. On the contrary, only a slight increase in fluorescence was observed during the incubation of fA beta 2M with sugar-modified beta 2M. Moreover, sugar-modified beta 2M exhibited a dose-dependent inhibitory effect on the extension reaction of fA beta 2M with native beta 2M. These results may suggest that in some in vivo situations, the modification of beta 2-m with AGE could play an inhibitory role for the formation of fA beta 2M.

Amyloid↗
PubMed1999

[Pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia].

A 48-year-old man was admitted to our hospital complaining of fever, dyspnea, and cough. He had been treated with pranoprofen and antibiotics by an outpatient clinic for the preceding 4 days. Chest X-ray films revealed Kerley B lines, perivascular cuffing, and hilar haze with pleural effusion in both lungs. Chest computed tomographic films showed non-segmental patchy infiltrates, and thickening of bronchovascular bundles and interlobular septa. Laboratory data showed eosinophilia in peripheral blood (28%) and severe hypoxemia (PaO2:60 torr). Bronchoalveolar lavage fluid disclosed an increased total cell count, eosinophils (39%), and CD 4/CD 8 ratio (2.1). Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils and mononuclear cells into alveolar wall's and spaces. Acute eosinophilic pneumonia was suspected on the basis of Allen's diagnostic criteria (N Engl J Med: 1989). After discontinuation of pranoprofen, the patient's clinical symptoms, laboratory data, and chest X-ray findings improved rapidly without steroid therapy. A leukocyte migration test (LMT) for pranoprofen was positive and a challenge test for smoking was negative. An environmental provocation test in the patient's home gave negative results. A challenge test for pranoprofen was not performed due to the lack of informed consent. Based on these findings, our diagnosis was pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia.

Acute Disease↗
PubMed1999

[The diagnostic role of the methacholine inhalation challenge in adult patients with chronic persistent cough].

Chronic persistent cough (CPC) is a common medical problem. We determined the value of the methacholine inhalation challenge (MIC) in the evaluation of CPC. We also sought other clinical factors that affect MIC. Patients were selected for the study if 1) CPC was the only presenting symptom, 2) a current roentgenogram did not contribute to the diagnosis, and 3) spirometry revealed a normal FEV1. We measured the minimum dose of methacholine (bronchial sensitivity, Dmin) by the "Asthograph" method. We determined the correlation between log Dmin and demographic and clinical variables, i.e. age, %FVC, %FEV1, FEV1%, %V50, %V25, eosinophil count in peripheral blood, and serum IgE level. The causes of CPC in 51 patients (20 men and 31 women, mean age 41 years) were cough-variant asthma in 29 patients, postinfectious persistent cough in 13 patients, atopic cough in 6 patients, and others in 3 patients. Log Dmin significantly but weakly correlated with %V25 (4 = 0.31, p = 0.02). The sensitivity and specificity of Dmin (< 10 units) in diagnosing cough-variant asthma was 93% and 87%, respectively. Demographic or clinical variables other than Dmin were not useful for the diagnosis of cough-variant asthma. We conclude that MIC is useful for the differential diagnosis of CPC while the usefulness is limited in some cases.

Adult↗
PubMed1999

[Apo-E phenotype].

Explore the source record for details and available documents.

Apolipoproteins E↗
PubMed1999

Accumulation of aberrant Y chromosomes in gamma-ray-induced thymic lymphomas lacking p53.

Male F(1) hybrids between MSM mice carrying a deficient p53 allele and BALB/c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtained, 46 of which developed in mice carrying the deficient p53 allele. Because the Y chromosome contributes little to cellular function, the stability of the Y chromosome in the tumors was assessed by polymerase chain reaction by examining three genes: Smcy and Sry on the short arm and Sts in the pseudoautosomal region of the long arm of the Y chromosome. Twenty-one lymphomas had lost one or two genes, probably as a result of mitotic recombination or interstitial deletion, whereas no lymphomas had lost all three genes. The p53 status of the lymphomas was determined by genotyping and allelic loss analysis; 34 had retained two wild-type p53 alleles, suggesting normal function; 34 had lost both alleles, indicating loss of function; and the other 12 had at least one wild-type p53 allele, so their p53 status was unclear. Compilation of these data revealed that changes in the Y chromosome were detected in only two of the 34 lymphomas retaining functional p53 but in 18 of the 34 lymphomas lacking p53 function, suggesting that p53 deficiency leads to an increase in the accumulation of radiation-induced aberrant chromosomes. This is consistent with our previous result from analysis of the inactive X chromosome. In contrast, a decrease in the fidelity of mitotic transmission in p53-deficient lymphomas was not noted for the Y chromosome.

Abnormalities, Radiation-Induced↗
PubMed1999

[Two cases of silicosis exhibiting MPO-ANCA associated disorder].

We reported two cases of silicosis exhibiting MPO-ANCA associated disorder. Case 1 was a 69 year-old man with silicosis and chronic interstitial pneumonia. He was admitted because of fever, dry cough, left chest pain, dyspnea and body weight loss. He was diagnosed as acute exacerbation of interstitial pneumonia, pericarditis and gastrointestinal bleeding. Case 2 was a 67 year-old man with silicosis. He repeated attack of fever, hoarseness, dysphagia and headache. The cell counts of cerebrospinal fluid increased and the thickness of cerebellar tent and left dura mater was observed in the brain MRI. Therefore, he was diagnosed as pachymeningitis and neuropathy of cranial nerves. Both cases were complicated by silicosis and the laboratory findings showed high serum levels of P-ANCA, ANA and rheumatoid factor and inflammatory responses, indicating they were suspected vasculitis. The two cases were treated by steroid and immunosuppressive therapy and had good clinical response. Silicosis may affect multiple organ involvement associated with P-ANCA.

Aged↗
PubMed1998

Apolipoprotein E and antioxidants have different mechanisms of inhibiting Alzheimer's beta-amyloid fibril formation in vitro.

We compared the mechanisms of apolipoprotein E- (apoE-) and antioxidant- (AO-) mediated inhibition of beta-amyloid fibril (fA beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. We first applied a kinetic plot to transform a sigmoidal time-course curve of fA beta formation from freshly prepared amyloid beta-peptides (A beta) into a straight line. Mathematical treatment of this plot demonstrated that the above-described sigmoidal curve is a logistic curve and provided us with a kinetic parameter t(1/2), the time when the rate of fA beta formation is maximum. t(1/2) of beta-amyloids (A beta) (1-42) and (1-40) were 18.7 +/- 1.7 min and 6.3 +/- 0.2 h, respectively (mean +/- SD, n = 3) and were independent of the initial A beta concentration examined. Although apoE extended t(1/2) of both A betas in a dose-dependent manner, AO did not. On the other hand, the final amount of fA beta formed was decreased by both apoE and AO dose-dependently. We then analyzed the effect of apoE and AO on the extension reaction of fA beta, based on a first-order kinetic model. Although apoE extended the time to proceed to equilibrium in a dose-dependent manner, AO did not. On the other hand, both apoE and AO dose-dependently decreased the final amount of fA beta formed. These results indicate that apoE and AO inhibit fA beta formation in vitro by different mechanisms and suggest the existence of multiple pharmacological targets for the prevention of fA beta formation.

Amyloid beta-Peptides↗
PubMed1998

Polymorphisms of angiotensin converting enzyme and plasminogen activator inhibitor-1 genes in diabetes and macroangiopathy1.

BACKGROUND: An insertion or deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene and a 4/5-guanine tract polymorphism (4G/5G) in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene are associated with the plasma activities of these substances and with coronary heart disease. In smooth muscle cells and mesangial cells, the angiotensin II synthesized by ACE increases mRNA expression and the activity of PAI-1, which promotes antifibrinolysis and the accumulation of extracellular matrix. Therefore, ACE and PAI-1 polymorphisms may have a synergistic effect on diabetic nephropathy and macroangiopathy. METHODS: Using multivariate logistic regression analyses, we investigated the independent or synergistic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on the development of diabetic nephropathy and macroangiopathy in 208 patients with non-insulin dependent diabetes mellitus (NIDDM) over a 15 year period. RESULTS: Advanced diabetic nephropathy, defined as impaired renal function and diabetic retinopathy, was present in 98 patients. Manifest macrovascular diseases, confirmed by both clinical signs and physical and laboratory examinations, were present in 56 patients. There was no significant difference in the genotype distribution of ACE or PAI-1 polymorphisms between subjects with advanced nephropathy and those with normal renal function. There was no significant difference in the renal survival rate between patients with differing ACE or PAI-1 genotypes. Subjects with macroangiopathy had a higher frequency of the DD genotype than those without macroangiopathy. Subjects with both DD and 4G4G genotypes had a higher incidence of macroangiopathy than those with any other pair of genotypes. Multivariate logistic regression analysis showed that there was no association between ACE or PAI-1 polymorphisms and diabetic nephropathy. The ACE DD genotype and its interaction with the PAI-1 4G4G genotype and the presence of advanced diabetic nephropathy were positively associated with macrovascular disease. CONCLUSION: These results indicate that the ACE DD genotype and its interaction with the PAI-1 4G4G genotype are independent risk factors for macroangiopathy, but not for the progression of diabetic nephropathy in NIDDM patients, and that the genotyping of PAI-1 and ACE polymorphisms, especially in patients with advanced diabetic nephropathy, may be useful for predicting and preventing macroangiopathy-related events.

Adult↗
PubMed1998

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats.

ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24 hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6 days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase.

Animals↗
PubMed1998

Apolipoprotein E4 reduces risk of diabetic nephropathy in patients with NIDDM.

Hypercholesterolemia is a major determinant of the decline of renal function in patients with diabetes. Apolipoprotein E polymorphism may influence the metabolism of lipoprotein in diabetic patients. The purpose of this study was to investigate the association between genetic polymorphisms in apolipoprotein E and the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus over a 10-year period (13 to 37 years; median, 20 years). Subjects with a stable renal function without overt proteinuria had a higher cholesterol level, lower incidences of hypertension and proliferative diabetic retinopathy, and a higher frequency of the E4 allele than subjects with a decline in renal function (end-stage renal failure requiring dialysis treatment). In the diabetic patients, the apolipoprotein E4 carriers had a higher cholesterol level than did the noncarriers. The survival rate from renal disease in the apolipoprotein E4 carriers was higher than in the noncarriers among the diabetic patients. Apolipoprotein E polymorphism and hypertension were identified as independent risk factors for the progression to renal failure. Results indicate that apolipoprotein E polymorphism is associated with the progression of diabetic nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and other alleles are risk factors.

Adult↗
PubMed1998

Mitral valve prolapse and autonomic function in panic disorder.

We investigated the significance of mitral valve prolapse (MVP) and autonomic function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP was higher in these patients (32.2%) than in the healthy controls (16.7%), but the difference was not significant. In the group with PD accompanied by depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. The severity of MVP was mild; nearly all of the cases were silent, without cardiac murmur, and there was no problem with the left ventricular function. The coefficient of variation for R-R intervals on electrocardiograms (CV R-R) was smaller in patients with PD than in healthy controls. The CV R-R of PD patients was significantly lower in the group with MVP than in the group without MVP, suggesting a strong association with the parasympathetic nervous system. Since the CV R-R tended to decrease in the presence of depression, involvement of the parasympathetic nervous system was inferred.

Adolescent↗
PubMed1998

Decreased serum apolipoprotein AII/AI ratio in systemic amyloidosis.

OBJECTIVE: To investigate if serum apolipoprotein A-I and A-II (apoAI and apAII) concentrations change in subjects with systemic amyloidosis secondary to underlying disorders. METHODS: Serum concentrations of apoAI and apoAII were measured in 21 multiple myeloma patients, including eight with amyloidosis; 95 rheumatoid arthritis patients, including 45 with amyloidosis; and 73 haemodialysis patients, including 32 with amyloidosis. RESULTS: ApoAII values tended to be reduced in subjects with amyloidosis in each group, but could not effectively distinguish amyloidosis. However, apoAII/AI ratios were significantly lower in subjects with amyloidosis in all groups. The ratio of 0.2 had diagnostic sensitivity and specificity for amyloidosis; 50% and 100%, respectively, in multiple myeloma; 80% and 78%, respectively, in rheumatoid arthritis; and 46% and 90%, respectively, in patients requiring long term haemodialysis. CONCLUSION: The apoAII/AI ratio can be a useful biochemical marker of suspect amyloidosis in patients with underlying diseases, especially those with rheumatoid arthritis.

Amyloidosis↗
PubMed1998

Significance of glomerular deposition of protein S in various glomerulopathies.

To elucidate the relationship between glomerular deposition of protein S (PS) and renal lesions or dysfunction, 30 patients with various glomerulopathies were examined. Glomerular PS deposition was found in 20 patients (group A), and other 10 patients showed no deposition (group B). PS was found mainly along the capillary loops and segmentally in the mesangium. Group A showed significantly more severe proteinuria than group B (p < 0.05). Group A patients showed significant decreases in glomerular filtration rate (p < 0.01). Patients in group A had significantly lower plasma levels of plasmin-alpha2-plasmin inhibitor complexes (p < 0.05) and thrombin-antithrombin III complexes (p < 0.01) than those in group B. Group A showed significant decreases in the mean values of plasma total PS (p < 0.01) and protein C (PC) antigens (p < 0.01) and C4b-binding protein (C4bp; p < 0.05) as compared with group B patients. There was a positive correlation between plasma PS and C4bp (p < 0.02). Histologically, group A showed a significantly higher incidence of glomerular deposition of factor XIII (subunit a), alpha2-plasmin inhibitor, PC (p < 0.05), and C4bp (p < 0.01). The present study demonstrates that glomerular PS deposition indicates the existence of PC and C4bp in the glomeruli and suggests that the glomerular PS deposition may modify the activation of fibrinolytic and coagulation systems within the glomeruli in various glomerulopathies.

Adult↗
PubMed1998

Serum levels of soluble interleukin-2 receptor in patients with various renal diseases.

To clarify the serum levels of soluble interleukin-2 receptor (sIL-2R) in patients with renal diseases, we examined 281 patients without various renal diseases with or without systemic disease (including 197 patients without systemic diseases and 84 patients with systemic diseases). The sIL-2R level was significantly higher in patients with renal diseases, than in healthy volunteers. In the group of renal diseases, the sIL-2R level in patients with rapidly progressive nephritic syndrome was especially higher than in patients with other renal diseases. In patients without systemic diseases, the serum level of sIL-2R was significantly and positively correlated with the urinary excretion of protein, and the serum levels of creatinine and uric acid, and was negatively correlated with the glomerular filtration rate (GFR). In the patients with systemic diseases, the correlation between the serum levels of sIL-2R and the serum levels of creatinine or GFR were not as strong as observed in the patients without systemic diseases. The serum level of sIL-2R was outside the normal range in patients with systemic diseases with a serum level of creatinine above 2.0 mg/100 ml. These findings suggest that the serum levels of sIL-2R in patients with renal disease may increase and correlate with the impaired renal function, that he increased sIL-2R levels in patients with systemic diseases may be dependent on the activity of systemic disease, and that it may be not useful indicator of diseases activity in patients with systemic diseases when the serum level of creatinine was above 2.0 mg/100 ml.

Adult↗
PubMed1998

Echocardiographic evaluation of cardiac valvular abnormalities in adults with Down's syndrome.

It is well known that congenital heart abnormalities are common in children with Down's syndrome. However there are few studies on cardiac abnormalities in adults with Down's syndrome. Therefore, we estimated cardiac abnormalities by means of echocardiography in 30 institutionalized Japanese adults with Down's syndrome, but without cardiac symptoms. Two-dimensional echocardiography showed an incidence of 26.7% in mitral valve prolapse and 20% increase of echo brightness in the mitral valve. Doppler echocardiography revealed an incidence of 16.7% in mitral valve regurgitation, and 13.3% in aortic valve regurgitation. Thus, even adults with Down's syndrome who are apparently free of cardiac symptoms may be at risk for valvular disease.

Adult↗
PubMed1998

Synovial inflammatory cells captured 131I-beta 2-microglobulin in patients with dialysis related amyloidosis.

Dialysis related amyloidosis (DRA) is a major complication of long term hemodialysis therapy. It is well recognized that scintigraphic study using radioisotope-labeled beta 2-microglobulin (beta 2M) as a tracer is a sensitive and specific technique to diagnose DRA non-invasively. The aim of this study is to clarify the mechanism of 131I-beta 2M accumulation around the amyloid tissue. Three dialysis patients with carpal tunnel syndromes were examined for consecutive 131I-beta 2M scintigraphies every 24 hours for 3 days till the carpal tunnel synovectomy. Removed synovial tissues were processed for histological study. The scintigraphic study demonstrated tracer accumulations in the joints involved with DRA and the intensity increased in a time dependent fashion. Microscopic observations revealed many inflammatory cells presenting CD68-monocytes/macrophages antigen infiltrated into the synovial tissues. 131I-beta 2M was evident in the cytoplasm of the infiltrating cells, while no radioactivity was detected above background in the amyloid tissues. In conclusion, the tracer accumulations observed in the 131I-beta 2M scintigraphic studies were the consequence of circulating beta 2M assimilated by the infiltrating monocytes/macrophages. Thus, the undetermined elimination pathway of circulating beta 2M in the dialysis patients was identified as the storage pool in those inflammatory cells. The inflammatory change may play a crucial role in the local progression of DRA through the accumulation of circulating beta 2M around the established amyloid tissues.

Adult↗
PubMed1998

[Haemophilus parainfluenzae antigens in IgA nephropathy].

IgA nephropathy (IgAN), a common glomerular disease, is characterized by the presence of IgA deposits, predominantly in the glomerular mesangium, and by mesangial proliferative glomerulonephritis (GN). Concerning its pathogenesis, several investigators suggest that the deposited IgA is an antibody to viral, bacterial, or dietary antigens. Thus the antibody is probably produced as part of the specific host immune response to various environmental antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgAN. Nevertheless, attempts to isolate a specific IgA-circulating immune complex associated antigen in patients with IgAN have been unsuccessful. We have showed that such mucosal infections as pharyngitis are often associated with the acute onset of IgAN. Then IgAN is an immune complex disease that is caused by a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We observed that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgAN than from those with other diseases. We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and an increased serum concentration of IgA antibodies against OMHP in patients with IgAN. Further studies will be necessary to determine whether the association of OMHP antigens in the glomeruli and IgA antibody against OMHP antigens in the sera of patients with IgAN can be confirmed in other parts of the world and whether this association is important in the pathogenesis of IgAN. Nevertheless, the demonstration of glomerular deposition of OMHP antigens and of IgA antibody against OMHP in sera indicates a potential new avenue of investigation into the elusive cause of IgAN.

Antigen-Antibody Complex↗