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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 91 records · Page 5Linked to original sources

[Clinical analysis of 14 patients with anti-myeloperoxidase antibody positive rapid progressive glomerulonephritic syndrome].

We investigated the clinical features and outcome of 14 patients with anti-myeloperoxidase antibody (MPO-ANCA) positive rapidly progressive glomerulonephritic syndrome. Underlying diseases included microscopic polyarteritis in 6 patients, idiopathic crescentic glomerulonephritis with lung hemorrhage in 2 patients, idiopathic glomerulonephritis in 3 patients, rapidly progressive glomerulonephritic syndrome without renal biopsy in 1 patient, crescentic glomerulonephritis associated with Sjögren syndrome and progressive systemic sclerosis in 1 patient and crescentic glomerulonephritis associated with sarcoidosis in 1 patient. Five patients were male (mean age, 59.2 years) and 9 were female (mean age, 54.0 years). On admission, most patients had anemia, leukocytophilia, and marked elevation of C-reactive protein (CRP). Average hemoglobin, white blood cell count and CRP levels on admission were 8.1 mg/dl, 11,500/mm3 and 14.7 mg/dl, respectively. Average serum creatinine was 4.0 mg/dl. All patients were treated with steroids either with or without cyclophosphamide. As the patients recovered clinically, the MPO-ANCA titers declined. Although most patients responded well to immunosuppressive therapy, some died of serious complications (such as acute respiratory distress syndrome, fungal infection, and pneumocystis pneumonia). The prognosis of patients with severe renal failure was especially poor. We conclude that early diagnosis, treatment and intensive care during immunosuppressive therapy are very important in the management of MPO-ANCA-positive rapidly progressive glomerulonephritis.

Adolescent↗

Effects of posture on creatinine clearance and urinary protein excretion in patients with various renal diseases.

To investigate the effects of a change in posture on renal function, we measured Ccr and the urinary excretion of protein, albumin, immunoglobulin G (IgG) and transferrin in 80 patients with renal disease and in 9 healthy controls. Patients and controls were studied serially while supine for 60 min; then after standing upright for 60 min. Almost all subjects showed a drop in the Ccr with standing (p < 0.01). The percent change in Ccr after standing was more remarkable in patients with glomerulonephritis vs the healthy subjects (74.0 +/- 21.9% vs 89.9 +/- 12.3%, p < 0.01). The change in urinary excretion of protein and albumin after standing in patients with membranous nephropathy (MN-N) significantly exceeded that in patients with IgA nephropathy (IgA-N) (182.1 +/- 89.3% vs 108.1 +/- 59.2% in urinary protein and 181.7 +/- 98.7% vs 113.3 +/- 40.9% in urinary albumin, p < 0.01). Urinary excretion of IgG and transferrin tended to increase after standing in those two groups, but not significantly. Results indicate that posture affects urinary protein excretion, probably via an increase of glomerulocapillary hydrostatic pressure and/or change in the permeability of the glomerular capillary walls. We recommend that comparable postures should be used when protein excretion is used as a diagnostic tool and in monitoring structural damage to glomeruli, particularly in patients with membranous nephropathy.

Adult↗

[A consideration in regard to 16 patients died at home].

We had given the service to the patients who desired home care. And now we made inquiries about 16 cases died at home. They were satisfied with our service and death at home. But in regard to the question "If you die at home, Are you satisfied?¿, half the number answered "NO". We should recognize the present condition that we can not fulfill the needs of patients and their families.

Adult↗

Renal cell carcinoma producing alpha-fetoprotein (AFP) with a unique lectins-affinity profile.

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare entity and merely 7 cases have been reported so far. The present case, a 71-year-old woman, showed a high serum AFP level of 204 ng/ml. The RCC of the autopsied right kidney consisted mainly of spindle-shaped or bizarre sarcomatous tumor cells. AFP was immunolocalized only in the concomitant clear cell component. Concanavalin A (Con A)-nonadsorption rate of serum AFP was 42%, which was an intermediate value between those of yolk sac tumors and metastatic liver carcinomas. Lens culinalis agglutinin (LCA)-affinity study of the patient's AFP showed an unknown peak X, which was eluted between the known peaks 2 and 3. These results suggest a certain structural alteration in carbohydrate moieties of the AFP derived from this RCC. A review of the clinicopathologic features of 8 patients with AFP-producing RCC was made to understand the pathophysiology of AFP-producing neoplasms.

Aged↗

Molecular cloning and characterization of avian N-methyl-D-aspartate receptor type 1 (NMDA-R1) gene.

Birds have several advantages in the study of memory formation, as imprinting and passive avoidance behaviors in chick are often used as model systems. However, the primary structure of the bird N-methyl-D-aspartate (NMDA) responsive glutamate receptor, which is assumed to play a critical role in memory formation, has not been determined. In this report we describe the cDNA cloning of a subunit of NMDA receptors (NMDA-R1) from duck and analysis of its structure and distribution in the brain. The N-terminal 898 amino acids of the NMDA-R1 were well conserved between duck and mammals, but the homology was completely lost in the C-terminus. In situ hybridization showed that the duck NMDA-R1 gene was expressed throughout the brain as it is in mammals.

Amino Acid Sequence↗

Measurement of amino acid metabolism derived from [1-13C]glucose in the rat brain using 13C magnetic resonance spectroscopy.

To clarify the unique characteristics of amino acid metabolism derived from glucose in the central nervous system (CNS), we injected [1-13C]glucose intraperitoneally to the rat, and extracted the free amino acids from several kinds of tissues and measured the amount of incorporation of 13C derived from [1-13C]glucose into each amino acid using 13C-magnetic resonance spectroscopy (NMR). In the adult rat brain, the intensities of resonances from 13C-amino acids were observed in the following order: glutamate, glutamine, aspartate, gamma-aminobutyrate (GABA) and alanine. There seemed no regional difference on this labeling pattern in the brain. However, only in the striatum and thalamus, the intensities of resonances from [2-13C]GABA were larger than that from [2,3-13C]aspartate. In the other tissues, such as heart, kidney, liver, spleen, muscle, lung and small intestine, the resonances from GABA were not detected and every intensity of resonances from 13C-amino acids, except 13C-alanine, was much smaller than those in the brain and spinal cord. In the serum, 13C-amino acid was not detected at all. When the rats were decapitated, in the brain, the resonances from [1-13C]glucose greatly reduced and the intensities of resonances from [3-13C]lactate, [3-13C]alanine, [2, 3, 4-13C]GABA and [2-13C]glutamine became larger as compared with those in the case that the rats were sacrificed with microwave. In other tissues, the resonances from [1-13C]glucose were clearly detected even after the decapitation. In the glioma induced by nitrosoethylurea in the spinal cord, the large resonances from glutamine and alanine were observed; however, the intensities of resonances from glutamate were considerably reduced and the resonances from GABA and aspartate were not detected. These results show that the pattern of 13C label incorporation into amino acids is unique in the central nervous tissues and also suggest that the metabolic compartmentalization could exist in the CNS through the metabolic trafficking between neurons and astroglia.

Amino Acids↗

Evaluation of tumor-associated antigen (2H6 antigen) in detecting early stages of gastric cancer.

A sandwich enzymed-linked immunosorbent assay (ELISA) was developed by using monoclonal antibody 2H6 (2H6 MoAb). MoAb 2H6 could be used to detect the 2H6 antigen in the sera of several cancers, showing positive rates of 65.4%, 66.7%, 47.4%, 80.0%, 45.2% and 16.7% in gastric cancer, hepatocellular carcinoma, cancers of the colon, esophagus, breast and pancreas, respectively. On the other hand, the positive rates in benign diseases or healthy donors were 3.4%, 3.4%, 4.2%, 8.3%, 6.9%, and 1.2% in myasthenia gravis, polymyositis, gastritis, gastric ulcer, other benign diseases and normal healthy donors, respectively. Fifty-two patients with gastric cancer were investigated in detail. The positive rates of serum 2H6 antigen, CEA, AFP, CA19-9 and CA125 in patients with gastric cancer were 65.4%, 9.6%, 2.3%, 25.0% and 8.1%, respectively. Among these tumor markers, serum 2H6 antigen levels alone were significantly elevated in patients with early stage (I and II) gastric cancer. Furthermore, combining the measurement for serum 2H6 with CA19-9 increased the percentage of gastric cancer slightly. No correlation between 2H6 antigen and these other tumor markers was observed. The serum levels of 2H6 antigen were monitored post-surgically in 11 patients for 12 weeks and they were found to diminish gradually. The findings suggest that the measurement of serum 2H6 antigen may be a useful marker for an early stage of gastric cancer.

Adolescent↗

FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum and lipopolysaccharide.

We investigated the effect of the potent immunosuppressive agent, FK506, on experimental glomerular thrombosis in rats by combined injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was administered intramuscularly three hours prior to injection of NTS that was followed one hour later by LPS. Rats were killed five hours after the LPS injection. Compared with placebo, FK506 pretreatment significantly reduced thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria and the rise of serum creatinine level. Early infiltration of polymorphonuclear leukocytes into the glomeruli after LPS injection was significantly suppressed in the FK506 group compared with the placebo group. We also measured serum tumor necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay. Peak serum TNF activity was observed one hour after LPS injection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formation is T cell independent. These data suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an anti-inflammatory effect in vivo.

Acute Disease↗

Heat shock protein produced by Helicobacter pylori.

The cells of Helicobacter pylori were suspended in the medium containing 35S-methionine. After a heat shock of the cells at 42 C for 5, 10, and 30 min, the production of proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Out of many proteins produced by the cells, only 66 kDa protein production was dramatically increased by heat treatment. The N-terminal amino acid sequence of 66 kDa protein was quite similar to that of 62 kDa and 54 kDa proteins previously suggested as heat shock protein (HSP) of H. pylori based on the reaction with polyclonal and monoclonal antibodies against HSP 60 family proteins produced by other bacteria. Therefore, it was concluded that H. pylori produces the 66 kDa protein as its major heat shock protein which belongs to HSP 60 family.

Amino Acid Sequence↗

A major pathogenic antigen of Heymann nephritis is present exclusively in the renal proximal tubule brush border--studies with a monoclonal antibody against pronase-digested tubular antigen.

We have isolated a nephritogenic 120-kD antigen from rat renal tubule brush border that induces rat Heymann nephritis. A MoAb that recognized this antigen reacted exclusively with the brush border on indirect immunofluorescence and immunoelectron microscopy. Rabbit antiserum against this antigen also reacted exclusively with the brush border. With the injection of this antiserum, rabbit IgG became detectable along the glomerular basement membrane (GBM) after 3 days. Our 120-kD antigen was shown to have a close relationship with gp330 based on the following: (i) this antigen can induce active Heymann nephritis as gp330; (ii) our MoAb reacted with the immune deposits of nephritic kidneys induced not only by the 120-kD antigen but also by gp330, and conversely, rabbit antiserum against gp330 reacted with those induced by the 120-kD antigen as well as gp330; and (iii) by immunoblotting, polyclonal antibodies against the 120-kD antigen reacted with gp330 and polyclonal antibodies against gp330 reacted with the 120-kD antigen. These observations indicate that antigen present exclusively in the brush border can induce active Heymann nephritis, and the common antigenic determinants shared by brush border and the coated pits of glomerular epithelium may not be a prerequisite to induce nephritis. A more precise relationship between the 120-kD antigen and reported C14 fusion protein or 40-kD alpha 2MRAP remains to be established.

Animals↗

Inhibition of the nerve growth factor-induced neurite outgrowth by specific tyrosine kinase and phospholipase inhibitors.

The effects of nerve growth factor (NGF) on PC12h cells have been studied with reference to the relationship between neurite outgrowth and the activities of the enzymes involved in signal transduction in the early stage of NGF action. Pretreatment of cells with selective inhibitors of tyrosine kinase (ST638 and genistein) and phospholipases C (neomycin B) and A2 (p-Bromophenacyl bromide; BPB and indomethacin) depress neurite outgrowth following 60 min treatment with NGF (0.1 microgram/ml). The inhibitor of intracellular calcium mobilization, TMB-8, also significantly depresses the NGF-induced neurite outgrowth. Arachidonic acid release, induced by NGF, from the cell lipids is reduced following previous inhibition of above mentioned enzymes. Based on these results, it is suggested that NGF requires tyrosine kinase in its early stage of action (within 60 min) in PC12h cells, phospholipases C and A2 to release Ca2+ from intracellular stores and arachidonate from cellular phospholipids, in order to induce neurite outgrowth.

Animals↗

Purification and properties of bile acid sulfate sulfatase from Pseudomonas testosteroni.

The bile acid sulfate sulfatase (BSS) produced by Pseudomonas testosteroni was purified and characterized. Chromatofocusing behavior and amino acid sequence over twelve amino acid residues from N-terminus of the enzyme indicated that BSS was composed of two isoforms of which molecular weights were 125,000 and 103,000. Each isoform was a homodimer of a subunit of which molecular weight was 53,000 or 51,000, respectively. The optimum pH was 8.5 and BSS was stable at pH 5.8-8.0. The thermostability above 32 degrees C was improved by the addition of polyols, such as sorbitol, sucrose, and glycerol. BSS was a Mn(2+)-dependent enzyme and contained 1-2 atoms of manganese in its own protein molecule. All 3 alpha-sulfate esters of the bile acids routinely appearing in human serum were hydrolyzed by BSS to 3 beta-hydroxyl iso-compounds corresponding to each bile acid and sulfuric acid. We tentatively named this novel enzyme BSS (bile acid 3 alpha-sulfate sulfohydrolase).

Amino Acid Sequence↗