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Biomedical subjects

F Gejyo

Publications and source records attributed to F Gejyo.

At least 127 records · Page 7Linked to original sources

[Detection of apolipoproteins E5 and E7 by a widely used commercial ApoE IFE kit--evidence provided by genotyping].

The purpose of this study is to examine a possibility to detect apolipoprotein (apo) E5 and E7 isoproteins with a commercial kit widely used (Phenotyping Apo E IFE System, Jokoh Co. LTD., Tokyo) and to clarify the frequency of the rare alleles in Central Japan. A total of 1,445 subjects living in Central Japan (1,030 hemodialysis patients and 415 apparently healthy individuals) was phenotyped for apo E isoproteins with the kit using isoelectric focusing with immunoblotting. In 23 subjects, unique apo E4 isoproteins, which migrate more basically than apo E4 isoprotein, were found. These unique isoproteins were proved to be apo E5 or E7 isoproteins by PCR with restriction fragment length polymorphism and with amplification refractory mutation systems, respectively. No significant differences in the frequencies of apo E5 or apo E7 alleles were observed between healthy individuals and hemodialysis patients (0.011 vs. 0.018, NS). The frequencies of apo E5 and E7 alleles were 0.001 and 0.005, respectively, in healthy individuals, and 0.003 and 0.005, respectively, in hemodialysis patients. These data in Central Japan were consistent with those in Western Japan (Matsunaga, et al, Clin Genet, 1995). These results indicate that the commercial kit is applicable to detect the rare alleles, apo E5 and E7 alleles and that the frequencies of the rare alleles in Central Japan are similar to those in Western Japan.

Adult↗

Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimer's beta-amyloid fibril formation in vitro.

Recently, many research groups have examined the effect of apolipoprotein E (apoE) on beta-amyloid fibril (betaAf) formation in vitro. However, their data were somewhat controversial and no exact kinetic assessment of the role of apoE has thus far been available. We examined the effect of human apoE on betaAf formation in vitro, starting with various concentrations of freshly prepared beta-amyloid(1-40) (beta1-40) and using fluorescence spectroscopy with thioflavine T. When 50 microM of beta1-40 was incubated with a 1:1000 to 1:100 molar ratio of apoE, a dose-dependent inhibitory effect of apoE was observed. Both the nucleation and extension phases of betaAf formation in vitro were inhibited by apoE. On the other hand, when 300 microM of beta1-40 was incubated with a 1:100 molar ratio of apoE, the inhibitory effect of apoE was completely abolished. We then focused our study on the kinetics of the inhibitory effect of apoE on the extension phase of betaAf formation in vitro, utilizing the recently established first-order kinetic model of betaAf extension in vitro [Naiki, H., & Nakakuki, K. (1996) Lab. Invest. 74, 374-383]. The mathematical treatment of the data suggests that apoE inhibits the extension of betaAf in vitro, by making a complex with beta1-40, thus eliminating free beta1-40 from the reaction mixture. The equilibrium association constant with beta1-40 was practically the same among the three major recombinant apoE isoforms. These results indicate that the effects of apoE on betaAf formation in vitro is differential and could settle some of the controversy about beta-amyloid-apoE interaction in vitro.

Alzheimer Disease↗

Dialysis-related amyloidosis and clinical significance of extracorporeal removal of beta2-microglobulin.

Dialysis amyloidosis is a frequent complication encountered in patients receiving chronic hemodialysis. beta2-Microglobulin (beta2M) is a causative protein of amyloidosis, and its deposition in the tissues has been proven to be a primary cause of the onset. As a therapeutic approach to dialysis-related amyloidosis, high flux dialysis membranes permitting the elimination of beta2M with satisfactory biocompatibility have been developed, and the resultant high flux membranes have been clinically introduced. Positive clinical effects have been observed both in retrospective and prospective studies of the use of high flux membranes, together with a decrease in serum beta2M level. However, it cannot be concluded that amyloid deposits are decreased when the elimination of beta2M is maintained by a dialysis technique with a high flux membrane for some period of time. In the present paper, we review the recent clinical studies on extracorporeal removal of beta2M as a therapeutic approach to amyloidosis.

Adsorption↗

Genetic analysis of Pseudomonas aeruginosa by pulsed field gel electrophoresis.

We identified the serotypes and genomes patterns of 100 strains of Pseudomonas aeruginosa (P. aeruginosa) that had been isolated from patients who were admitted to the hospital of the Fukui Medical School between 1992 and 1995. A monoclonal diagnostic kit was used to identify the serotypes. Genome patterns were determined by pulsed field gel electrophoresis (PFGE). Serotypes A, B, C, D, E, F, G and I exhibited distinct genome patterns. Differences in genome patterns were also observed in strains of serotypes E and G, depending on the types of clinical samples collected and/or the area of the hospital from which they were isolated. Many of the multiple antibiotic-resistant strains of P. aeruginosa exhibited serotype E. The genome pattern differed between strains that were susceptible vs. resistant to multiple antibiotics. The latter strains exhibited similar genome patterns regardless of their origin. These findings suggest that analysis of genome patterns is important for identifying the origin of nosocomial infection caused by P. aeruginosa, serotype E.

Adult↗

Significance of glomerular deposition of apolipoprotein (a) in various glomerulopathies.

Apolipoprotein (a) [apo(a)] may interfere with the fibrinolytic system because of its structural similarity to plasminogen. In the present study, we evaluated the effect of glomerular deposition of apo(a) on coagulation and fibrinolysis in patients with glomerular diseases. Twenty-four patients (13 males and 11 females) with various glomerulopathies were studied. We examined renal biopsy specimens for the presence of apo(a), and investigated the relationship between the glomerular deposition of apo(a) and coagulation and fibrinolysis within the glomeruli. The patients who exhibited the deposition of apo(a) (group A) had a significantly higher incidence of deposition of apo B-100 and low-density lipoprotein (LDL) receptor, and a significantly lower incidence of deposition of plasmin-alpha 2-plasmin inhibitor complexes (PIC) and tissue-type plasminogen activator than did patients without apo(a) deposition (group B). Patients in group A had a significantly higher level of serum total cholesterol and lipoprotein (a) than did patients in group B. Plasma levels of PIC and D-dimer in group A were significantly lower than those in group B. The plasma level of thrombin-antithrombin III complexes in group A was significantly higher than that in group B. These findings suggest that glomerular apo(a) deposition plays a part in coagulation and fibrinolysis within the glomeruli in patients with glomerular diseases.

Adolescent↗

Histological localization of advanced glycosylation end products in the progression of diabetic nephropathy.

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Adult↗

Chronic erythropoietin treatment enhances endogenous nitric oxide production in rats.

To examine the effect of chronic administration of recombinant human erythropoietin (rHuEPO) on endogenous nitric oxide (NO) activity, we treated Sprague-Dawley rats with rHuEPO (100 IU kg-1 or 300 IU kg-1) or a corresponding vehicle for 2 weeks, administered subcutaneously on alternate days. Treatment elicited increases in haematocrit and systolic blood pressure in a dose-dependent fashion. Simultaneous administration of NG-nitro-L-arginine methyl ester (L-NAME, 20 mg dl-1 of drinking water), but not aminoguanidine (400 mg dl-1), induced a further significant rise in blood pressure. The effect of L-NAME was inhibited by a large dose of L-arginine (2.0 g dl-1). Polycythaemia and hypertension induced by chronic rHuEPO therapy were associated with increased urinary NO2- and NO3- (NOx-) excretion, while co-administration of L-NAME, but not aminoguanidine, reduced NOx- excretion. Our results indicate that chronic rHuEPO treatment has a significant pressor effect, but induces a compensatory increase in the steady-state release of NO by constitutive NO synthase in normal rats. Such enhanced NO synthesis may act as a protective mechanism against the hypertensive effect of rHuEPO.

Animals↗

[Pathogenesis of IgA nephropathy: role of outer membranes of Haemophilus parainfluenzae antigens].

IgA nephropathy is characterized by IgA deposits, predominantly in the glomerular mesangium and mesangial proliferative glomerulonephritis. Concerning its pathogenesis, several investigators suggest that the deposited IgA is an antibody to viral, bacterial, or dietary antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgA nephropathy. We previously observed that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgA nephropathy than from those with other diseases. We have also identified the glomerular deposition of the outer membranes of HP antigens (OMHP) and an increased serum concentration of IgA antibodies against OMHP in patients with IgA nephropathy. These findings suggest that HP has a role in the etiology of IgA nephropathy.

Antibodies, Bacterial↗

Apolipoprotein E and alpha 1-antichymotrypsin in dialysis-related amyloidosis.

Dialysis-related amyloidosis as represented by carpal tunnel syndrome is a serious complication of long-term dialysis treatment of patients with chronic renal failure. beta 2-microglobulin has been identified as a structural component of the amyloid deposits, but other factors also are associated with amyloid formation. We recently demonstrated the presence of apolipoprotein E and alpha 1-antichymotrypsin in the amyloid deposits. We therefore analyzed how polymorphic variants of both genes were related to the onset of amyloidosis. Among the apolipoprotein E genotypes, allele epsilon 2 represented a protective factor that delayed the onset of disease. In contrast, polymorphic alpha 1-antichymotrypsin alleles had no effect on the onset of amyloidosis. Thus, the apolipoprotein E epsilon 2 allele can be added to the list of factors that determine the onset of dialysis-related amyloidosis, which include patient age at initiation of dialysis therapy, dialysis duration, and the dialysis membrane used.

Amyloidosis↗