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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 577 records · Page 32Linked to original sources
PubMed1996

Recombinant feline herpesvirus type 1 expressing immunogenic proteins inducible virus neutralizing antibody against feline calicivirus in cats.

In this study, an entire open reading frame encoding the capsid protein of feline calicivirus (FCV) F4 strain was inserted into the deletion locus (SmaI site) of the thymidine kinase (TK) deficient mutant (C7301dlTK) of feline herpesvirus type 1 (FHV-1) and the resulting recombinant virus was designated as C7301dlTK-Cap. Expression of the FCV antigens by C7301dlTK-Cap was confirmed by indirect immunofluorescence assay and immunoblot analysis. To assess whether the recombinant virus can induce virus neutralizing (VN) antibody against FCV in the natural host, three cats were inoculated intranasally and orally with C7301dlTK-Cap (two cats) or C7301dlTK (one cat). As a result, sera collected from cats inoculated with the C7301dlTK-Cap possessed VN antibody against FCV. This recombinant virus is expected as a new polyvalent recombinant vaccine against FHV-1 and FCV infections.

Animals↗
PubMed1996

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma.

It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumors. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P < 0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumors. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

Adult↗
PubMed1996

Clinical significance of serum CYFRA 21-1 in gastric cancer.

We studied the clinical significance of the soluble cytokeratin 19 fragment detected with monoclonal antibody CYFRA 21-1 in the sera of patients with histologically proven gastric cancer. Sera of 110 patients with gastric cancer were analysed for CYFRA 21-1 levels by a two-step sandwich enzyme immunoassay. There were no significant differences between CYFRA 21-1 levels and the histotype, depth of invasion or vessel invasion. However, CYFRA 21-1 was significantly higher in the presence of peritoneal metastases, liver metastases and extensive nodal involvement. When the positive cut-off value was defined as 5 ng ml-1, the CYFRA 21-1 in the stage IV and recurrent cases was 55.6% and 66.7%, respectively, which was as high as carcinoembryonic antigen (CEA) and greater than carbohydrate antigen 19-9 (CA 19-9). The positivities in stage I/II and III were zero and 5.9%, respectively, and false-positive rate in 76 patients with benign gastrointestinal disorders was 2.6%. There appeared to be no correlation between CYFRA 21-1 and CEA or CA 19-9. The patients with above 5 n ml-1 of CYFRA 21-1 had a significantly poorer prognosis. Multivariate analysis indicated that CYFRA 21-1 was an independent prognostic factor, while CEA and CA 19-9 failed to be of prognostic value. In conclusion, CYFRA 21-1 is a reliable tumour marker for gastic cancer in predicting very advanced cases, recurrence of the disease and overall poor prognosis.

Antibodies, Monoclonal↗
PubMed1996

Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.

beta 2microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGEs). We demonstrated that AGE was localized to amyloid deposits in patients with DRA by immunohistochemistry using a monoclonal anti-AGE antibody. To clarify the mechanism of AGE modification of beta 2m-amyloid, we studied the effects of 3-deoxyglucosone (3-DG), a potent protein crosslinking the intermediate of the Maillard reaction, on the AGE modification of beta 2m, and quantified the serum levels of 3-DG in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and undialyzed patients. The serum levels of 3-DG were markedly increased in the dialyzed and undialyzed uremic patients. Although the serum level of 3-DG decreased after HD with a mean reduction rate of 67%, it was still significantly higher than in normal serum. Incubation of beta 2m with 3-DG at 37 degrees C emitted fluorescence characteristic for AGE, and caused AGE modification and dimer formation of beta 2m as demonstrated by Western blotting using the same monoclonal anti-AGE antibody used for immunohistochemical demonstration of AGE in DRA. The AGE-modified dimer of beta 2m could be extracted from the amyloid tissue of a patient with DRA. 3-DG showed more intense and faster reactivity with beta 2m to form AGE and dimer as compared with glucose, and aminoguanidine suppressed the AGE and dimer formation of beta 2m by 3-DG. In conclusion, 3-DG accumulating in uremic serum may be involved in the AGE modification of beta 2m-amyloid.

Amyloidosis↗
PubMed1996

Alternate repetition of short fore- and backfiltrations reduces convective albumin loss.

An effective therapeutic means to remove relatively large polypeptide uremic toxins seems to be a hemofiltration (HF) or hemodiafiltration (HDF) employing a larger-pore membrane, that is, a protein-permeable membrane. With either method, however, a significant amount of albumin will be lost into the ultrafiltrate or dialysate. Now, repetition of alternate short fore- and backfiltrations may prevent the development of the ultrafiltration-induced higher albumin concentration on the membrane surface (protein concentration polarization), where a single forefiltration time is shorter than the time needed for completion of protein concentration polarization. Since the albumin concentration on the protein-permeable membrane surface will be one of the determinants of albumin loss by convection, such HDF treatment may reduce protein loss into the dialysate. To examine this assumption, we alternately repeated short and rapid fore- and backfiltrations (push/pull HDF) through a protein-permeable membrane, each less than 1 second in duration and at each filtration volume of 15 ml, where a pyrogen-free dialysate was supplied. The present results indicated that the albumin amount lost by push/pull HDF was approximately one-third of that by conventional HDF. Nevertheless, the reduction rates of beta 2-microglobulin and myoglobin were significantly greater by push/pull HDF than by conventional HDF.

Blood Proteins↗
PubMed1996

Monocyte/macrophage response to beta 2-microglobulin modified with advanced glycation end products.

We recently found that acidic beta 2-microglobulin (beta 2m), a major isoform of beta 2m in amyloid fibrils of patients with dialysis-related amyloidosis (DRA), contained early Amadori products and advanced glycation end products (AGEs) formed nonenzymatically between sugar and protein. Further analysis revealed that acidic beta 2m induces monocyte chemotaxis and macrophage secretion of bone-resorbing cytokines, suggesting the involvement of acidic beta 2m in the pathogenesis of DRA. Acidic beta 2m, however, is a mixture of heterogeneous molecular adducts due to various types of modification. In the present study, we investigated the modification responsible for the biological activity of acidic beta 2m toward monocytes/macrophages. The presence of a fair amount of beta 2m species with deamidation was detected in acidic beta 2m isolated from urine of non-diabetic long-term hemodialysis patients, but deamidated beta 2m had no biological activity. In contrast, normal beta 2m acquired the activity upon incubation with glucose in vitro. Among the glycated beta 2m, the pigmented and fluorescent beta 2m that formed after a long incubation period, that is, AGE-modified beta 2m, exhibited biological activity, whereas beta 2m modified with Amadori products, major Maillard products in acidic beta 2m, had no such activity. These findings suggest that AGEs, although only a minor constituent of acidic beta 2m, are responsible for monocyte chemotaxis and macrophage secretion of cytokines, implicating the contribution of AGEs to bone and joint destruction in DRA.

Adult↗
PubMed1996

Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity.

The presence of obesity increases the risk of thrombotic vascular diseases. The role of fat accumulation and its effect on plasminogen activator inhibitor-1 (PAI-1) levels was investigated in humans and animals. Plasma PAI-1 levels were closely correlated with visceral fat area but not with subcutaneous fat area in human subjects. PAI-1 mRNA was detected in both types of fat tissue in obese rats but increased only in visceral fat during the development of obesity. These data suggest that an enhanced expression of the PAI-1 gene in visceral fat may increase plasma levels and may have a role in the development of vascular disease in visceral obesity.

3T3 Cells↗
PubMed1996

Clinical significance of CD45RO expression on peripheral blood mononuclear cells in HTLV-I-infected individuals.

The phenotype of peripheral blood mononuclear cells (PBMC) was examined in 13 healthy volunteers, 26 HTLV-I carriers, and 58 ATL patients (22 smouldering, five chronic, 24 acute, and seven lymphoma type). The percentage of CD4+, CD25+, CD28+ and CD45RO+ cells in the PBMC of the chronic and acute type patients was significantly higher than that of the volunteers, whereas the percentage of CD8+ and CD45RA+ cells in these patients was significantly low. The histogram for CD45RO fluorescence intensity (FI) revealed two patterns: pattern A consisted of CD45RO+ cells with high FI (CD45ROhigh) and intermediate FI (CD45ROint). Pattern B consisted exclusively of CD45ROhigh. Pattern A was evident in all volunteers. The percentage of subjects showing pattern B was increased in an order that reflected disease progression. In the patients with pattern A, the CD45ROint cells were CD4+ and CD8-, and the FI of CD2, CD3, and Fas within the CD45ROint cells appeared to be lower than that within the CD45ROhigh cells. The acute type patients with pattern A had a significantly longer survival curve than that of these patients with pattern B. These results suggest that the presence of CD45ROint cells may be related to protection against disease progression in HTLV-I-infected individuals.

Acute Disease↗
PubMed1996

Molecular cloning of the feline CD8 beta-chain.

Human mouse and rat CD8 have been described as being disulphide-linked heterodimers of alpha and beta chains. More recently the chicken alpha and beta chains were described. In the bovine and feline immune system only the z-chain was reported. In this study we have cloned and determined the nucleotide sequence of a cDNA encoding the beta-chain of the feline T-cell surface antigen CD8. Using a nested polymerase chain reaction- (PCR) and two primer pairs designed from the human CD8 beta cDNA nucleotide sequence, we amplified a 430 base pair fragment from a feline thymus cDNA library which was used as a probe for screening the feline library at high stringency. After three rounds of screening, five clones were isolated. A clone, named FTb-6, containing a 3.8 kilobase pair insert was mapped, sequenced and compared with the published sequences of the genes encoding the human, mouse, rat and avian CD8 beta. We have determined the primary structure of the feline CD8 beta. The feline CD8 beta has an open reading frame, 630 nucleotides in length encoding a protein with 210 amino acid residues and its composition showed that the feline molecule is a member of the immunoglobulin gene super family.

Amino Acid Sequence↗
PubMed1996

Character of a wheat amylase inhibitor preparation and effects on fasting human pancreaticobiliary secretions and hormones.

BACKGROUND & AIMS: Amylase inhibition induces carbohydrate tolerance, satiety, and weight loss and prolongs gastric emptying, effects that may be useful in the treatment of obesity and non-insulin-dependent diabetes mellitus. The aim of this study was to determine (1) purity of a wheat amylase inhibitor preparation, (2) intraduodenal concentration of the wheat amylase inhibitor preparation that inhibits > 90% amylase activity (which causes carbohydrate malabsorption), and (3) if the inhibitor alters pancreaticobiliary secretions or intraluminal pH. METHODS: High-performance liquid chromatography followed by electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used for characterization. Groups of 3 subjects received intraduodenal infusions of 3.0, 4.5, or 6.0 mg/mL of the inhibitor for 90 minutes during the middle of a 270-minute essential amino acid solution infusion (which stimulates 50% maximal pancreatic enzyme secretion). Pancreatic enzyme and bile acid delivery to the duodenum were measured for a 270-minute period. RESULTS: The inhibitor is 96% protein, 59% containing 0.19, 0.28, 0.38, and 0.53 inhibitors. The 0.38 inhibitor has the most antipancreatic alpha-amylase activity. The inhibitor reduced amylase activity in the duodenum dose dependently (r = 0.7; P = 0.04); > 4 mg/mL inhibited > 90% amylase activity but did not affect delivery of other enzymes or bile acids to the duodenum or gastric or duodenal pH. CONCLUSIONS: The preparation has a high protein purity and a high specific activity against alpha-amylase activity and effectively inhibits human pancreatic amylase activity secreted into the duodenum.

Adult↗
PubMed1996

Pathophysiology of advanced glycation end-products in renal failure.

beta 2-Microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis, a serious complication leading to bone and joint destruction in long-term haemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Intact beta 2-microglobulin per se seems an unlikely contributor to the pathogenesis, because no difference in the plasma levels of intact beta 2-microglobulin has yet been found between haemodialysis patients with and without this complication. Some investigators have therefore focused on the modification of this molecule. Recent studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils-the advanced glycation end-products (AGEs) formed by a non-enzymatic reaction between sugar aldose and protein. Further studies have suggested that the interaction of AGE-modified beta 2-microglobulin with monocyte/macrophage and osteoclast/osteoblast gives a plausible albeit partial explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This article discusses the pathophysiology of AGEs in renal failure and the modification of beta 2-microglobulin with AGEs, especially focusing on their structure and pathological role in dialysis-related amyloidosis.

Amyloid↗
PubMed1996

Advanced glycation end-products in diabetic nephropathy.

Advanced glycation end-products (AGEs) are the pigmented and fluorescent adduct formed by a non-enzymatic reaction between sugar and protein. Since AGEs are generated in high glucose milieu, then induce the structural and functional alteration of matnx proteins, and have biological effects on various kinds of cells including mesangial cells, AGEs have been implicated in tissue damage of diabetic nephropathy. To elucidate the factor(s) that determine the AGEs level in diabetic nephropathy, we quantitated the plasma pentosidine level of different status of diabetic nephropathy by HPLC assay. The plasma pentosidine level in diabetic nephropathy was found to be determined by factors such as renal function control of glucose and the patient's age; of these, renal function was the most critical factor. For a better understanding of the pathological role of AGEs in diabetic nephropathy, we then examined renal tissues of diabetic nephropathy immunohistochemically using antibodies specific for AGE proteins. Immunohistochemistry revealed the positive immunostaining for AGEs in the expanded mesangial area of diffuse diabetic glomerulosclerosis. The degree of staining was stronger than that in patients of IgA nephropathy with a similar degree of mesangial expansion. The nodular lesions, characteristic of diabetic nephropathy, were also stained positive for AGEs. These findings suggests a potential link of AGEs accumulation, which may be determined by renal function, control of glucose and age, to renal tissue damage in diabetic nephropathy.

Animals↗
PubMed1996

Immunoglobulins and their receptors on epidermal Langerhans cells in atopic dermatitis.

To elucidate the etiological role of immunoglobulin molecules on Langerhans cells (LCs) in atopic dermatitis, we conducted immuno-histochemical studies on the localization of immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA and IgM on epidermal LCs from 30 patients with atopic dermatitis (AD) and five non-atopic healthy volunteers. We also investigated the types of receptors for the immunoglobulins (Fc epsilon RI, Fc epsilon RII, Fc gamma RI, Fc gamma RII, and Fc gamma RIII) on epidermal LCs in the patients. IgE positive epidermal LCs were observed in 28 of 30 AD patients, and 46.7% of the epidermal LCs were positive for IgE. Both IgG1- and IgG2-positive epidermal LCs were observed in 70% of AD patients, and 21.8% and 28.7% of the total epidermal LCs were positive for IgG1 and IgG2, respectively. IgG3- or IgG4-positive LCs were present in only small proportions of AD patients. IgA-positive LCs were observed in 8 AD patients; our study suggested that the IgA bound on LCs was secretory IgA (S-IgA). These surface immunoglobulins were observed significantly more frequently on epidermal LCs in the involved skin of AD than in clinically uninvolved skin. No IgM-positive epidermal LCs were observed in the AD patients or healthy volunteers. In non-atopic healthy controls, no immunoglobulin-binding LCs were observed. In receptors for immunoglobulins, Fc epsilon RI and Fc gamma RII were exclusively expressed on nearly all epidermal LCs from all AD patients and all non-atopic controls. These results suggested that not only IgE but also IgG and IgA may play some etiological role in the pathogenesis of AD.

Adolescent↗