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Z Ota

Publications and source records attributed to Z Ota.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antisense oligonucleotides to proliferating cell nuclear antigen and Ki-67 inhibit human mesangial cell proliferation.

Proliferating cell nuclear antigen (PCNA) and Ki-67 are cell cycle-associated nuclear proteins and are used as markers for proliferating cells. This study attempted to inhibit glomerular mesangial cell (MC) proliferation, which is the hallmark of many forms of glomerular disease, by inhibiting these nuclear proteins with antisense oligodeoxynucleotides. The antisense and sense phosphorothioate oligodeoxynucleotides complementary to PCNA and Ki-67 mRNA, including the initiation codon, were synthesized. Human MC were cultured in growth medium in the presence of sense or antisense oligodeoxynucleotides, and the effects of these oligodeoxynucleotides on mesangial cell proliferation were evaluated by direct cell count. Both PCNA and Ki-67 antisense oligodeoxynucleotides significantly inhibited mesangial cell proliferation as compared with sense oligodeoxynucleotides. Antisense oligodeoxynucleotides (10 microM) for PCNA and Ki-67 inhibited mesangial cell growth by greater than 50%. The effect of antisense oligodeoxynucleotides on target protein expression was examined by immunocytochemistry using specific monoclonal antibodies. Reverse transcription-polymerase chain reaction also was performed to evaluate the effect of antisense oligodeoxynucleotides on PCNA and Ki-67 mRNA expression. Studies of target protein and mRNA expression revealed that the inhibitory effects of the antisense oligonucleotides were mediated through decreases in the expression of both mRNA and protein. Sense oligodeoxynucleotides produced little effect. These results indicate that antisense oligodeoxynucleotides targeting PCNA and Ki-67 mRNA reduce the expression of these gene products and inhibit mesangial cell proliferation. Moreover, these results suggest the feasibility of antisense strategies designed to inhibit PCNA and Ki-67 expression for the inhibition of mesangial cell proliferation in vivo.

Cell Division↗
PubMed1996

Reactive oxygen species induce apoptosis in cultured human mesangial cells.

Apoptosis is a distinct form of cell death that is observed under various physiologic and pathologic conditions, and it is thought to be important in regulating the number of glomerular cells. This study investigated the possible role of reactive oxygen species in the induction of apoptosis in cultured human mesangial cells. Fragmented nuclei with condensed chromatin, a morphologic characteristic of apoptosis, were observed by electron microscopy in mesangial cells exposed to 0.02 mM hydrogen peroxide for 4 h. Nuclear DNA extracted from mesangial cells that had been incubated with hydrogen peroxide (2 to 20 mM) or with xanthine (0.05 mM) and xanthine oxidase (5 to 100 mU/mL) showed the ladder pattern on electrophoresis that is a biochemical marker for apoptosis. Hydrogen peroxide (0.02 to 20 mM) decreased the number of viable cells, as determined by trypan blue exclusion, in a dose-dependent manner. Hydrogen peroxide or xanthine and xanthine oxidase increased the lactate dehydrogenase release from mesangial cells in a dose- and time-dependent manners. The release of lactate dehydrogenase was prevented by treatment with a free radical scavenger, catalase. Hydrogen peroxide (2 mM) also significantly increased the number of mesangial cells with fragmented DNA as detected by in situ nick end-labeling Results indicate that reactive oxygen species induce apoptosis in cultured human mesangial cells. Furthermore, apoptosis of mesangial cells induced by reactive oxygen species may contribute to the loss of such cells observed in glomerular disease.

Apoptosis↗
PubMed1996

Syndrome of inappropriate secretion of antidiuretic hormone following intra-thoracic cisplatin.

A case of malignant thymoma with pure red cell aplasia (PRCA) complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following intrathoracic cisdichlorodiammine platinum (CDDP) administration is reported. A 59-year-old Japanese woman who presented with severe general fatigue was diagnosed with PRCA associated with a thymoma, based on the findings of a bone marrow biopsy, computed tomography of the chest, and the existence of anti-acetylcholine receptor antibodies. She underwent a thymectomy after frequent blood transfusions. This was followed by intrathoracic CDDP administration, because of pleural dissemination. Nine days following chemotherapy, her serum sodium concentration was found to be 104mM, while her consciousness was drowsy with severe fatigue and vomiting. This hyponatremic state was diagnosed as SIADH induced by CDDP infusion into the thoracic space, based on the hypo-osmolality of her serum, the hyper-osmolality of her urine, and an inappropriate level of plasma vasopressin.

Cisplatin↗
PubMed1996

Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus with antiphospholipid antibody.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity characterized by the formation of fibrous tissue plugs within terminal bronchioles and alveolar ducts. Although BOOP has been associated with several connective tissue disorders, there are rare reports of BOOP in patients with systemic lupus erythematosus (SLE). We present a patient with SLE accompanying antiphospholipid antibody who developed recurrent respiratory symptoms and radiographic abnormalities. The diagnosis of BOOP was confirmed by transbronchial lung biopsy. This case suggests that not only SLE, but also the presence of antiphospholipid antibody, may be associated with the development of BOOP.

Adult↗
PubMed1996

Takayasu's arteritis associated with ulcerative colitis; genetic factors in this association.

Both ulcerative colitis and Takayasu's arteritis are though to be organ-specific immune-mediated inflammatory diseases. We present the rare case of a 23-year-old woman with a 4-year history of ulcerative colitis who developed Takayasu's arteritis one month after giving birth. She was found to carry the human leukocyte antigens (HLA)-B52 and DR2, which were previously noted to be associated with these inflammatory conditions in the Japanese population. The pathogenic relevance of this haplotype to the concomitant development of these two conditions is discussed.

Adult↗
PubMed1996

Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes.

The phenotypic change of the mesangial cell is considered to play a pivotal role in the accumulation of extracellular matrix in diabetic nephropathy. This investigation was undertaken to evaluate the expression of the various isoforms of contractile proteins in the streptozocin (STZ)-induced diabetic rat kidney and in renal biopsy specimens from patients with diabetic nephropathy. Specific antibodies to myosin heavy chain isoforms (SM1, SM2, SMemb), caldesmon, and alpha-smooth muscle actin and cDNAs for SMemb were used. Increased expression of SMemb at the mRNA and protein levels was demonstrated at 1 week after STZ administration in the rat. Both levels were increased at 4 weeks. Mesangial staining of caldesmon was observed at 4 weeks and that of alpha-smooth muscle actin at 24 weeks. Immunohistochemical mesangial staining of the contractile proteins was pronounced in patients with diabetic nephropathy in contrast to the trace mesangial staining in normal control subjects. These results indicate that the phenotypic change in mesangial cells occurs in the early stages of diabetes and that several stages in phenotypic changes may exist. Expression of the contractile protein isoforms, especially SMemb, should serve as a new marker for the subsequent glomerular hypertrophy and sclerosis.

Actins↗
PubMed1996

Myocardial troponin T levels in patients with diabetic nephropathy.

We investigated myocardial troponin T (TnT) level as a marker for myocardial injury at various stages of diabetic nephropathy, including end-stage renal failure. One hundred and four diabetic patients were included in this study. These patients were divided into 5 groups as follows: Group I, composed of 41 patients without nephropathy who served as controls; Group II, composed of 15 patients with micro-albuminuria; Group III, composed of 15 patients with macroalbuminuria; Group IV, composed of 8 patients with renal failure who were not receiving hemodialysis; and Group V, composed of 25 patients who were receiving hemodialysis for renal failure. The following markers of myocardial injury were measured in these patients: myocardial TnT, creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MCL-1). Our results showed that as the disease state of diabetic nephropathy advanced to renal failure, myocardial TnT levels became elevated. Group V showed significantly higher myocardial TnT levels than either Group I, Group II or Group III. Group IV showed significantly higher myocardial TnT levels than either Group II or Group III. The rate of ischemic changes on electrocardiograms also tended to increase with advance to renal failure in these patients. However, there was no correlation between myocardial TnT levels and serum Cr levels, used as an index for renal function. Myocardial TnT levels had a higher specificity for cardiac muscle than other markers for myocardial injury and are not significantly influenced by renal function. Myocardial TnT may be useful as a marker of myocardial injury for patients with chronic renal failure.

Adult↗
PubMed1996

A patient with sarcoidosis associated with recurrent urolithiasis and tubular injury caused by calcium deposition.

A 38-year-old woman was hospitalized in January 1994 with renal dysfunction and hypercalcemia. Before admission, she was diagnosed as having urolithiasis, and had been treated twice with extracorporeal shock wave lithotripsy (ESWL). Ophthalmologically, she exhibited iritis and secondary glaucoma. Hypercalcemia, an extremely low titer of parathyroid hormone (PTH), and elevation of angiotensin-converting enzyme (ACE) and lysozyme activity were noted. These findings suggested sarcoidosis, although the chest X-ray showed only fibrotic changes. Hypercalcemia was suspected of having been caused secondarily by sarcoidosis. Since her laboratory data also showed renal dysfunction and abnormal urinalysis, a renal biopsy was performed. The histological findings indicated a tubular and interstitial disorder without glomerular abnormality; calcium deposition, which was detected by X-ray energy dispersive analysis, was observed in the tubular cytoplasm. Administration of prednisolone alleviated the renal dysfunction and decreased the elevation of ACE activity and lysozyme level of the blood. Sarcoidosis is sometimes associated with hypercalcemia, but rarely with renal dysfunction. These findings suggested that sarcoidosis may be associated with renal dysfunction due to tubular injury caused by calcium deposition in the tubules, and that glucocorticoid therapy was effective for these disorders.

Adult↗
PubMed1996

Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis.

Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are major mediators for the differentiation, proliferation, and activation of the macrophage. Recently, M-CSF was documented to play a pivotal role in the development of nephritis via macrophage activation in MRL-lpr mice. The macrophage is also considered to be an important component in the development of human glomerulonephritis. The expression and function of colony-stimulating factors (CSF) in the human kidney have not yet been defined. This study was undertaken to elucidate the various roles of CSF in the development of glomerulonephritis in humans. We examined the glomerular expression of M-CSF and GM-CSF in patients with various forms of glomerulonephritis and in normal subjects using immunohistochemical methods and nonradioisotopic in situ hybridization. The expression of CSF at both the protein and mRNA level in the glomeruli was compared with the degree of mesangial proliferation; the number of macrophages, Ki67-positive cells, and HLA-DR-positive cells; and the degree of alpha-smooth muscle actin-positive area in the glomerulus and clinical data. M-CSF and GM-CSF were expressed mainly on the mesangial cells in the glomerulus. Intraglomerular expressions of CSF at the protein level were increased in cases of IgA nephropathy and lupus nephritis. There was a positive correlation among the M-CSF protein expression and glomerular proliferation, macrophage infiltration, and the degree of proteinuria. M-CSF mRNA expression also was increased in the cases of IgA nephropathy and lupus nephritis. The number of Ki67-positive cells and HLA-DR-positive cells and alpha-smooth muscle actin-positive area in the glomerulus were increased in the cases with enhanced M-CSF expression. These results suggest that the glomerular secretion of M-CSF promotes macrophage infiltration into the glomerulus and activates resident and extraneous macrophages in the mesangial proliferative glomerulonephritis. M-CSF is considered to be a major mediator in the development of mesangial proliferative glomerulonephritis in humans.

Adult↗
PubMed1996

Changes in urinary enzyme activity and histochemical findings in experimental tubular injury induced by gold sodium thiomalate.

To elucidate the renal injury induced by gold treatment, we administered various doses of gold sodium thiomalate (GST) to Wistar rats and investigated alterations in the urinary enzyme activity, gamma-glutamyl transpeptidase (gamma GTP) and N-acetyl-beta-glucosaminidase (NAG) activity, and histochemical change of enzymes, gamma GTP, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in the renal tissue. The single administration of a large dose of gold salts induced acute tubular necrosis and enzyme leakage was detected histochemically without damage to the glomerulus. After chronic administration of small doses of gold salts, the urinary gamma GTP activities gradually increased, but urinary NAG activities did not. These findings suggested that the change in urinary enzyme activities, which leaked from inside of brushborder or lysosome, indicated the degree or localization of tubular damage, because renal tubules were selectively injured by gold salts.

Acetylglucosaminidase↗
PubMed1995

Immunohistological localization of the novel epitope related to type IV collagen in normal and diseased renal tissues.

Type IV collagen is a major component of the renal glomerular extracellular matrix. A recently characterized monoclonal antibody, JK132, which was originally produced by immunization with human placental type IV collagen, recognizes a new epitope which is different from alpha 1-alpha 6 chains of type IV collagen. Using immunofluorescence and immunogold electron microscopy, the distribution of the epitope of JK132 has been compared with the distribution of alpha 1, alpha 2, alpha 3 and alpha 4 chains of type IV collagen in normal human kidney and in the renal tissues of patients with various types of glomerulonephritis. In normal human kidney, JK132 reacted with mesangial matrix, Bowman's capsular basement membrane (BCBM), tubular basement membrane, and vessel walls, but did not react with glomerular basement membrane (GBM). This distribution is different from the distribution of alpha 1-alpha 4(IV) chains. In IgA nephropathy and membranoproliferative glomerulonephritis, the staining intensity for JK132 was increased in expanded mesangial matrix. In glomeruli with severe mesangial proliferation, the epitope of JK132 extended to the endothelial side of the GBM. In membranous nephropathy, staining for JK132 was virtually unchanged from normal. This study suggests that the epitope of JK132 increases in amount during the process of mesangial proliferation and could serve as a marker for mesangial matrix expansion in glomerulonephritis.

Collagen↗
PubMed1995

Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis.

The pathologic feature of acute interstitial nephritis is the infiltration of mononuclear cells, predominantly lymphocytes and monocytes, into the interstitium. We present an unusual case of a 49-year-old man with drug-induced acute interstitial nephritis whose renal biopsy specimen showed a massive infiltration of eosinophils into the interstitium and eosinophils infiltrating into the glomerulus through a gap in Bowman's capsule and the juxtaglomerular zone. The patient initially was referred to us with a recurrence of the nephrotic syndrome. Deterioration of renal function and an increase in proteinuria was noted at that time. Triazolam, a sleep inducer, was the suspected cause of the acute interstitial nephritis. Renal biopsy revealed sclerotic glomeruli containing eosinophils among massive infiltrated eosinophils and a loss of endothelial cells and mesangial cells in contrast to a preservation of epithelial cells. Infiltrating eosinophils were directly attached to the glomerular basement membrane, and free granules from the eosinophils were observed in the capillary lumen. In addition to chronic sclerotic change, eosinophils may have further damaged the glomerular capillary wall, leading to an increased severity of proteinuria in this case.

Eosinophilia↗
PubMed1995

Distribution of extracellular matrix receptors in various forms of glomerulonephritis.

Integrins are heterodimeric transmembrane receptor glycoproteins consisting of alpha and beta subunits that mediate adhesion and interactions between cells and extracellular matrix. Such interactions may be perturbed in various pathologic states, resulting in the altered phenotypic expressions of the integrins in affected tissues. To ascertain the alterations in integrins in various renal diseases, their distribution was investigated in different forms of glomerulonephritis by indirect immunofluorescence and immunoelectron microscopy using specific antibodies directed against beta 1 integrins and integrin alpha v beta 3 (vitronectin receptor). In addition, the distribution of certain extracellular matrix components (ie, fibronectin, vitronectin, and type IV collagen) was examined. Integrin beta 1 and alpha v beta 3 were highly expressed in proliferating mesangial cells in immunoglobulin A nephropathy, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. Their putative ligands (ie, fibronectin, vitronectin, and type IV collagen) also were increased in the expanded mesangial regions. In immunoglobulin A nephropathy, integrin beta 1 and alpha v beta 3 were seen by immunoelectron microscopy to be localized to the mesangial cell membranes in close proximity to the immune complex deposits; however, fibronectin and vitronectin immunoreactivities were observed in the mesangial immune complex deposits. Similarly, vitronectin also was detected in the immune complex deposits of other forms of proliferative nephritis, ie, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. In diffuse proliferative lupus nephritis, the cellular crescents displayed immunoreactivity toward integrin alpha v beta 3 and vitronectin. In nonimmune complex glomerular disease associated with nephrotic syndrome (ie, minimal change nephrotic syndrome), integrin alpha 3 beta 1, which normally has a linear capillary distribution, was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen↗
PubMed1995

Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain.

With use of iron histochemistry and immunohistochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein-positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin-eosin staining only in pyramidal cells of the hippocampal CA1 region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3'-diaminobenzidine intensification revealed iron deposits in the CA1 region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin-immunopositive microglia paralleled the iron accumulation in the hippocampal CA1 region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron-catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia.

Animals↗
PubMed1995

Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephropathy.

Advanced protein glycation has been proposed as a major factor in the development of diabetic nephropathy. Advanced glycation end products (AGEs) have altered the structure of extracellular matrix component and impaired self association in vitro. To elucidate the role of AGEs in the progression of diabetic nephropathy, the present study was undertaken to localize glomerular AGEs immunohistochemically. Ultrastructural changes of the mesangial matrix were analyzed with high resolution scanning electron microscopy. No glomerular AGEs staining was noted in normal control kidney specimens, or in tissue from glomerulonephritis patients without diabetes mellitus. The mesangium showed a positive AGEs staining in advanced stages of diabetic nephropathy, and the most characteristic finding was the strong AGEs staining in nodular lesions. By high resolution scanning electron microscopy, control and diabetic mesangial matrices revealed a meshwork structure composed of fine fibrils (10 nm in width) and numerous pores (12 to 13 nm in diameter). In the nodular lesions, however, loosening of the meshwork was significant, and the diameter of the pores was enlarged (approximately 24 nm). This study provides the first immunohistochemical evidence that AGEs are localized in diabetic glomeruli, most notably to nodular lesions. Advanced glycation might play a role in the progression of diabetic nephropathy through impairment of the assembly of matrix proteins in vivo.

Adult↗