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F Gejyo

Publications and source records attributed to F Gejyo.

230 records · Page 13Linked to original sources

Identification of beta-aspartylglycine in uremic serum and its toxicity.

An unidentified ninhydrin-positive substance of acidic nature was found in the serum of uremic patients. This substance was isolated from hemodialysate by the methods of ion-exchange chromatography, gel-filtration and paper electrophoresis, and identified as beta-aspartylglycine by amino acid analysis, N-terminal amino acid determination and comparison with authentic sample synthesized in this laboratory. The quantitative determination of beta-aspartylglycine in serum revealed that the serum concentrations of beta-aspartyl-glycine in uremic patients increased much higher than those in normal subjects. The toxicity of beta-aspartylglycine in mice with acute renal failure induced by uranyl acetate was investigated. The mice given more than 1,0 g/kg body weight of beta-aspartylglycine showed behavioral alterations: low response to the stimuli and low activity, and some mice died by the injection of 4.0 g/kg body weight of the peptide. These results suggested that beta-aspartyl-glycine might be a possible factor which influences the development of uremic toxaemia.

Acute Kidney Injury↗

Elevation of serum levels of beta-aminoisobutyric acid in uremic patients and the toxicity of the amino acid.

A reliable method for the determination of beta-aminoisobutyric acid in serum was developed utilizing an automated amino acid analyzer. The serum concentrations of beta-aminoisobutyric acid were determined in 20 normal subjects and in 71 uremic patients. The mean serum level of beta-aminoisobutyric acid was markedly increased in the uremic patients to 0.856 +/- 0.910 (mean +/- SD) mg/100 ml as compared with a normal value of 0.026 +/- 0.027 mg/100 ml. The distribution of serum beta-aminoisobutyric acid level in uremic patients was wide-spread, and there was no correlation between the serum levels of the amino acid and those of urea nitrogen, creatinine and uric acid. The toxicity of beta-aminoisobutyric acid on mice with acute renal failure induced by uranyl acetate was investigated and compared with that of alpha-amino-n-butyric acid and gamma-amino-n-butyric acid. All mice given more than 4 g/kg body wt of beta-aminoisobutyric acid showed twitching and cramps, and some of them died. However, the control mice given an equivalent dose of alpha-amino-n-butyric acid or gamma-amino-n-butyric acid showed no change. These results suggest that beta-aminoisobutyric acid might be a factor influencing the development and progression of uremic toxemia.

Acute Kidney Injury↗

Identification of beta-aminoisobutyric acid in uremic serum.

An unidentified ninhydrin-positive substance found in uremic sera but not found in normal sera was isolated by gel-filtration through Sephadex G-75 followed by high voltage paper electrophoresis (pH 3.5), and identified as beta-aminoisobutyric acid using paper chromatography and automated amino acid analyzer. The quantitative determination of beta-aminoisobutyric acid in serum revealed that the level of beta-aminoisobutyric acid in uremic sera was much higher than that of normal sera. Gas chromatographic determination of the enantiomorphs of beta-aminoisobutyric acid showed that uremic sera contain R- and S-isomers of the amino acid, but with the R-isomer as the dominating form.

Aminoisobutyric Acids↗

High-level expression of naked DNA delivered to rat liver via tail vein injection.

BACKGROUND: High levels of foreign gene expression in mouse hepatocytes can be achieved by rapid tail vein injection of a large volume of a naked DNA solution, the 'hydrodynamics-based procedure'. Rats are more tolerant of the frequent phlebotomies required for monitoring blood parameters than mice, and thus are better for some biomedical research. METHODS: We tested this technique for the delivery of a therapeutic protein in normal rats, using a rat erythropoietin (Epo) expression plasmid vector, pCAGGS-Epo. RESULTS: We obtained maximal Epo expression when the DNA solution was injected in a volume of 25 ml (approximately 100 ml/kg body weight) within 15 s. We observed a dose-response relationship between serum Epo levels and the amount of injected DNA up to 800 microg. Using quantitative real-time PCR, the vector-derived Epo mRNA expression was mainly detected in the liver. When a lacZ expression plasmid was injected similarly, beta-galactosidase was exclusively detected in the liver, mainly in hepatocytes. Toxicity attributable to the technique was mild and transient, as assessed by histochemical analysis. Epo gene expression and erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 12 weeks, the last time point examined. Repeated administration of the plasmid DNA also effectively led to erythropoiesis. CONCLUSIONS: These results demonstrate that gene transfer into the liver via rapid tail vein injection can easily be achieved in the rat, which is more than 10 times larger than the mouse, and has significant value for gene function analysis in rats.

Animals↗

Magnetic resonance T1 gradient-echo imaging in hepatolithiasis.

BACKGROUND: We examined the role of magnetic resonance T1-weighted gradient-echo (MRT1-GE) imaging in hepatolithiasis. METHODS: MRT1-GE, precontrast computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) of 10 patients with hepatolithiasis were compared for their diagnostic accuracies in the detection and localization of intrahepatic calculi. The diagnosis of hepatolithiasis was confirmed by surgery. For localization of the stone, we divided the bile ducts into six areas: right and left hepatic ducts and bile ducts of the lateral, medial, right anterior, and right posterior segments of the liver. Chemical analysis of the stones was performed in eight patients. RESULTS: The total number of segments proved by surgery to contain stones was 18. Although not significantly different, the sensitivity of MRT1-GE was 77.8% (14 of 18 segments), higher than that of MRCP (66.7%, 12 of 18 segments) and that of CT (50%, nine of 18 segments). The sensitivity of magnetic resonance imaging (MRCP + MRT1) was significantly higher than that of CT (p < 0.01). Multiple logistic regression analysis showed that the result of surgery was significantly affected only by the result of magnetic resonance imaging. On MRT1-GE, all the depicted stones appeared as high-intensity signal areas within the low-intensity bile duct irrespective of their chemical composition. CONCLUSION: MRT1-GE imaging provides complementary information concerning hepatolithiasis.

Adult↗

Application of confocal laser scanning microscopy to the observation of bone biopsy specimens.

Iliac bone biopsy specimens from five patients with endstage renal disease were observed by confocal laser scanning microscopy. Images of affected bone specimens were accurately focused, whereas images viewed with conventional light microscopy from thick ground sections were obscure. Especially at high magnifications, fine structures of bone cells, otherwise blurred, were clearly observed with confocal scanning microscopy. From thin-cut sections, images satisfactory for pathological diagnosis were viewed with light microscopy even at high magnification. However, the sections tended to shrink vertically compared with the cross-sectional images of the blocks observed directly by confocal laser scanning microscopy. A three-dimensional image of bone tissue was also constructed from serial optical sections. Confocal laser scanning microscopy is a useful technique for observing bone tissues, and may become essential for the evaluation of bone biopsy specimens.

Adult↗

Significance of glomerular deposition of C3c and C3d in IgA nephropathy.

BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy. The clinico-pathological significance of the glomerular deposition of complement breakdown products, C3c and C3d in IgA nephropathy remains to be clarified. METHODS: We examined the relationship between glomerular staining patterns of C3c and C3d and clinico-pathological findings with 163 patients with IgA nephropathy. Renal biopsy specimens were stained with C3c and C3d by immunofluorescence, and patients were divided into the following two groups: the intensity of C3c deposition stronger than C3d deposition, or equal to it (group A); the intensity of C3d deposition stronger than C3c deposition (group B). RESULTS: In group A, the incidence of severe hematuria (over 20 urinary red blood cells in high-power field microscope (x400)) or of higher urinary fibrinogen degenerated products (over 0.1 microg/ml) was significantly higher than that in group B. In addition, group A showed a significant decrease in the glomerular filtration rate. Group A also showed a significantly higher incidence of glomerular endocapillary proliferation than in group B. CONCLUSION: These findings suggest that the glomerular deposition of C3c is associated with the inflammatory active phase of glomeruli in IgA nephropathy.

Adolescent↗

Thoracic aortic dissection in a patient with autosomal dominant polycystic kidney disease treated with maintenance hemodialysis.

A patient with autosomal dominant polycystic kidney disease (ADPKD) on maintenance hemodialysis (HD) experienced spreading back pain with a sudden onset, and was diagnosed with thoracic aortic dissection. Reports of ADPKD with aortic dissection are rare. Hypertension, which is essentially universal both among ADPKD and hemodialysis patients, is a known risk factor for aortic dissection. Additionally, some reports have indicated that patients with ADPKD have aortic fragility. We suspect that aortic dissection may be less rare than presently apparent among HD patients with ADPKD.

Aortic Dissection↗

Autoantibody against ribosomal protein L14 in patients with systemic lupus erythematosus.

OBJECTIVE: To isolate a specific antibody against ribosomal protein L14 and to assess the relationship of this antibody with some of the clinicalfeatures in patients with systemic lupus erythematosus (SLE). METHODS: We screened the sera of SLE patients by immunoblotting analysis using rat total ribosomal proteins as antigen to determine whether sera had antibody activity against ribosomal proteins other than the P S10, and L12 proteins. The sera from 2 patients had antibody activity against a 30-kDa ribosomal protein. This antigenic protein was identified to be ribosomal protein L14 by two-dimensional gel electrophoresis and immunoblotting, so the antibody against L14 was tested by immunoblotting analysis using glutathione-S-transferase fusion human-L14 protein (GST-L14) as the antigen. We examined sera from 126 patients with SLE, and as controls sera from 67 patients with dermatomyositis and polymyositis (DM/PM), 71 patients with systemic sclerosis (SSc), and 74 healthy donors. RESULTS: Antibody activity against GST-L14 was detected in 7 out of 126 SLE, but not in any of the DM/PM, PSS, or healthy controls. CONCLUSION: Antibody against ribosomal protein L14 was specifically detected in sera from patients with SLE. Although this antibody activity was not so prevalent in the patients with SLE, it might be one of the useful tools for diagnosis of SLE.

Adolescent↗

Autoantibodies against oxidized low-density lipoprotein (LDL) and carotid atherosclerosis in patients with rheumatoid arthritis.

OBJECTIVES: To examine the relationship between autoantibodies against oxidized low-density lipoprotein (oxLDL-Abs) and the progression of carotid atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients without evidence of risk factors for atherosclerosis (RA group) and 30 healthy volunteers (normal group) were investigated. The mean intima-media thickness of the common carotid artery (mean CCA-IMT) was measured by high-resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT, IgG oxLDL-Ab titer and patient factors such as body mass index, systolic blood pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum lipid levels were examined. RESULTS: Mean CCA-IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA group than in the normal group. Although mean CCA-IMT showed a positive correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA group were positively associated with mean CCA-IMT and independently with age and sex by multiple regression analysis. CONCLUSIONS: IgG oxLDL-Abs appear to be associated with the degree of carotid atherosclerosis in patients with RA, and are independent of traditional risk factors for atherosclerotic diseases. These results suggest a possible link between autoimmune mechanisms and accelerated atherosclerosis in RA.

Arthritis, Rheumatoid↗

A monoclonal antibody recognizing apolipoprotein E peptides in systemic amyloid deposits.

A monoclonal antibody was produced by immunization of mice with a crude amyloid A (AA) fibril preparation. This antibody (YK-2), when used in immunohistochemical studies, showed positive staining of amyloid deposits in tissues from patients with systemic amyloidosis (three idiopathic, three myeloma-associated, five reactive, one familial amyloid polyneuropathy, and three dialysis-associated). Immunoblotting revealed that YK-2 reacted with 14,000 and 7,000 dalton components of AA fibrils and a 36,000 dalton component of normal human serum. Absorption with purified human apolipoprotein E abolished staining. This suggests that fragments of apolipoprotein E are a common constituent of amyloid fibril of diverse origins, and it can be a new marker for immunohistochemical studies of systemic amyloidosis.

Amyloidosis↗

Further characterization of a monoclonal antibody recognizing apolipoprotein E peptides in amyloid deposits.

A monoclonal antibody (YK-2), which was previously established to react with apolipoprotein E (apoE) peptides in systemic amyloid deposits, was further characterized. Epitope of this antibody was determined to be the residue 221 to 230 of apoE. In comparison with polyclonal anti-apoE antibodies, this antibody showed strong reactivity with apoE peptides in amyloid fibril preparation but poor reactivity with native apoE protein or apoE in serum, indicating its usefulness for probing degraded apoE in amyloid deposits. Immunohistochemical studies resulted in strong reactivity for amyloid A and immunoglobulin light-chain deposits but weak for beta 2-microglobulin and beta amyloid (senile plaque) deposits. Although the association of apoE with amyloid is non-specific to the component peptide of amyloid fibrils, present findings suggest that the amount or degradation manner of apoE or the environment around the antibody epitope vary among types of amyloidosis.

Alzheimer Disease↗