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N Yusa

Publications and source records attributed to N Yusa.

18 recordsLinked to original sources
PubMed2000

Urinary macrophages as activity markers of renal injury.

The presence of macrophages (Mφ) in the urine of patients with glomerulonephritis (GN) reflects the pathological events in the kidney, and we have discovered the following correlations between the Mφ phenotype and the pattern of renal injury. (1) Urinary macrophage (Mφ) counts increase in patients with proliferative GN, especially in the presence of active glomerular lesions (glomerular tuft necrosis, crescent, and endocapillary proliferation). In patients with hematuria, a combination of urinary Mφ and T-lymphocyte counts can be used to differentiate proliferative GN from non-proliferative renal disease (hereditary nephropathy and idiopathic renal hematuria). (2) The urinary Mφ of patients with active proliferative GN express FcgammaRIII (CD16) regardless of the type of GN. (3) There are two types of urinary CD68(+) cells, CD68(+)25F9(-) cells (infiltrating Mφ) and CD68(+)25F9(+) cells (mature Mφ). The CD68(+)25F9(-) cell counts in the urine correlate well with the activity of proliferative GN, and the CD68(+)25F9(+) cell counts in the urine correlate with the magnitude of non-selective proteinuria and with the subsequent decline of renal function. The CD68(+)25F9(+) cell count increases in the urine of patients with focal segmental glomerular sclerosis, but their numbers are negligible in minimal change nephrotic syndrome. These findings indicate that the analysis of the urinary Mφ phenotype is a useful strategy for evaluating renal injury as a 'risk-free renal biopsy'.

Antigens, CD↗
PubMed2000

Transcription factor Sp3 activates the liver/bone/kidney-type alkaline phosphatase promoter in hematopoietic cells.

The promoter region of the liver/bone/ kidney-type alkaline phosphatase gene was examined to define the cis-acting regulatory sequences and transcription factors responsible for its expression in hematopoietic cells. Transient transfection experiments revealed that regions deleted up to -154 base pairs upstream from the transcription initiation site had significant activities to induce bacterial chloramphenicol acetyltransferase gene. The shortest DNA fragment was found to contain three GC boxes in addition to a TATA box. Electrophoretic mobility shift assay and Southwestern analysis showed that Sp3 could bind to the fragment. Western blot analysis also detected Sp3 protein in eluate from the DNA probe mixed with the nuclear extracts. Through the use of Drosophila Schneider cells that lack the Sp1 family of transcription factors, Sp3 was shown to activate the basal promoter in a dose-dependent manner. When the amount of Sp3 was limited, the most proximal GC box was found to be critical for the basal promoter activity.

Alkaline Phosphatase↗
PubMed1999

Immunosuppressive effect of deoxyspergualin in proliferative glomerulonephritis.

A clinical trial of the immunosuppressive drug deoxyspergualin (DSG) was conducted in five patients with various forms of proliferative glomerulonephritis (immunoglobulin A nephropathy in two patients, purpura nephritis in one patient, membranoproliferative glomerulonephritis in one patient, and rapidly progressive glomerulonephritis in one patient). DSG was intravenously administered at 0.25 or 0.5 mg/kg/d for 4 weeks. A marked decrease in proteinuria (to <50% of baseline) was observed in four patients, and the other patient showed a 38% reduction in proteinuria, but the proteinuria was exacerbated again after discontinuation of DSG in three patients during a 4-week follow-up period. Proinflammatory CD16(+) (FcgammaRIII) monocytes disappeared from the peripheral blood during the administration of DSG but reappeared after DSG treatment was discontinued. A significant decrease in urinary macrophage counts that was far more marked than the decrease in peripheral blood monocyte counts was observed after administration of DSG. Interestingly, we also observed that the CD16 marker on the CD14(+) macrophage population in the urine disappeared in response to DSG treatment. These findings suggest that DSG may have a unique effect of suppression of FcgammaRIII expression on monocytes and/or macrophages that may result in amelioration of activated macrophage-mediated glomerulonephritis.

Adult↗
PubMed1999

Detection of urinary macrophages expressing the CD16 (Fc gamma RIII) molecule: a novel marker of acute inflammatory glomerular injury.

BACKGROUND: The CD16 antigen is the Fc gamma receptor III. CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi) that constitute a minor population in the peripheral blood of healthy individuals. Little is known about the expression of CD16 antigen on Mo/M phi in glomerulonephritis. METHODS: Flow cytometric analyses were performed on urine and blood samples obtained from 209 patients with various renal diseases. Patients variously suffered from rapidly progressive crescentic glomerulonephritis (RPGN), membranoproliferative glomerulonephritis (MPGN), postinfectious acute glomerulonephritis (AGN), Henoch-Schönlein purpura nephritis (HSPN), IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), lupus nephritis (LN), acute interstitial nephritis, hereditary nephropathy, idiopathic renal hematuria (IRH), and renal stone. RESULTS: The CD16+ M phi population of cells was present in the urine of hematuria-positive patients with proliferative glomerulonephritis, including AGN, IgAN, RPGN, MPGN, and LN with acute inflammatory lesions, such as endocapillary proliferation, tuft necrosis, and cellular crescents. In contrast, the urinary CD16+ M phi population was negligible in hematuria-positive patients with nonproliferative renal disease, including hereditary nephropathy, IRH, and renal stone and also in patients with proliferative glomerulonephritis lacking acute inflammatory lesions. Total urinary M phi of these patients were much less than those of patients having proliferative glomerulonephritis with acute inflammatory lesions. Transient expansion of the CD16+ M phi population in urine was observed during the acute exacerbation of urinary abnormalities, whereas the disappearance of CD16+ M phi closely preceded the amelioration of urinary abnormalities in patients with proliferative glomerulonephritis. In 38 of the 98 patients positive for CD16+ M phi population in urine, the CD16+ Mo population was negligible in peripheral blood. Immunohistochemically, CD16+ M phi were present in the glomeruli of active proliferative glomerulonephritis, whereas such cells were absent in inactive proliferative glomerulonephritis or nonproliferative glomerular diseases. CONCLUSION: CD16+ M phi may be effector cells involved in the acute inflammation common to all types of proliferative glomerulonephritis. Furthermore, the detection of CD16+ M phi in urine, as well as urinary M phi counts, may serve as a useful indicator of the active stage of proliferative glomerulonephritis.

Acute Disease↗
PubMed1999

[Usefulness of serum cystatin-C as a marker of the renal function: a comparative evaluation with beta 2-microglobulin, alpha 1-microglobulin and creatinine].

We evaluated the usefulness of cystatin-C as a marker of renal function. Serum cystatin-C level was measured using latex agglutination tests in 885 patients with various forms of renal disease and 200 healthy subjects. In addition to cystatin-C, serum beta 2-microglobulin, alpha 1-microglobulin and serum creatinine (Scr) were measured concomitantly in the same sample. The serum cystatin-C level inversely correlated more closely with creatinine clearance (Ccr) (r = -0.90) than serum beta 2-microglobulin (r = -0.85), alpha 1-microglobulin (r = -0.74) and Scr (r = -0.78). In patients with mildly impaired renal function (defined as Ccr 71-90 ml/min), a significant increase in cystatin-C level was observed in 24% of patients, whereas elevated beta 2-microglobulin and Scr were seen in 8% and elevated alpha 1-microglobulin was seen in 17%. In patients with normal renal function (defined as Ccr > or = 100 ml/min), increased cystatin-C level was observed in 7% of patients, whereas beta 2-microglobulin was seen in 2%, Scr in 2% and alpha 1-microglobulin in 11%. These data suggest that cystatin-C is a better marker of glomerular filtration than beta 2-microglobulin, alpha 1-microglobulin and Scr. Moreover cystatin-C measurement offers improved clinical sensitivity as a screening test for early renal damage.

Adult↗
PubMed1998

Membranoproliferative glomerulonephritis in the aged and its possible causal relationship with CD8+CD57+ lymphocytes.

Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive glomerulonephritis that occurs primarily in patients under the age of 30, and is rare in the elderly. We report eight aged patients with MPGN associated with CD8+CD57+ lymphocytosis. All eight patients showed a significant increase in CD8+CD57+ lymphocytes with a significant decrease in the ratio of CD4+ cells to CD8+ cells. Infiltration of CD8+CD57+ lymphocytes was observed within capillary lumens to various degrees according to the severity of endocapillary proliferation in each case. Expression of endothelial-leukocyte adhesion molecule-1 was observed in a focal and segmental manner on glomerular endothelial cells and on the endothelium of arterioles and arteries in kidney tissue in four cases in which a pronounced endocapillary proliferation was simultaneously seen. These findings suggest that cell-mediated cytotoxic mechanisms against glomerular endothelial cells may be involved in the pathogenesis of MPGN in the aged.

Age Factors↗
PubMed1996

Urinary macrophage counts and ratio to T lymphocytes: possible use in differential diagnosis and management of glomerular disease.

The noninvasive method that can differentiate hematuria-positive patients has not yet been developed. We evaluated the clinical value of the analysis of mononuclear cells in urine in combination with urinary erythrocytes as a noninvasive differential diagnostic tool of glomerular disease. The number of macrophages (CD14+ cells/ml.urine) and T-lymphocytes (CD3+ cells/ml.urine) were measured by flow cytometry using samples of freshly voided urine from 203 patients with hematuria. They had various types of proliferative glomerular disease, including rapidly progressive glomerulonephritis (RPGN), IgA nephropathy (IgAN), and membranoproliferative glomerulonephritis (MPGN), or nonproliferative glomerulopathy including idiopathic renal hematuria and hereditary nephropathy. Urinary macrophage counts increased significantly with the severity of glomerulonephritis; their number consistently exceeded that of T-lymphocyte counts in patients with active proliferative glomerulonephritis. Urinary macrophage counts in patients with proliferative GN were consistently higher than those of hematuriamatched nonproliferative GN. Moreover, urinary macrophage counts in patients with RPGN were significantly higher than those of MPGN and IgAN. Most of the patients with inactive proliferative glomerulonephritis or with nonproliferative glomerulopathy showed no marked increase in urinary macrophages. Although some patients with nonproliferative glomerulopathy who exhibited gross hematuria showed a slight increase in urinary macrophage counts, such counts were consistently lower than those of T lymphocytes. These observations suggests that urinary macrophage count and its ratio to T-lymphocyte count may provide useful information for clinicians in managing patients with proliferative glomerular disease as well as deciding whether to conduct renal biopsy in patients with hematuria.

CD4 Lymphocyte Count↗
PubMed1996

Possible relationship between hyperinsulinemia and glomerular hypertrophy in nephrosclerosis.

Hyperinsulinemia is potentially associated with the development of vascular sclerosis. On the other hand, the relationship between hyperinsulinemia and nephrosclerosis has not been elucidated. In this investigation clinicopathological studies were performed in 40 patients with nephrosclerosis, with special attention to the relationship between hyperinsulinemia and glomerular hypertrophy. Forty patients with biopsy-proven nephrosclerosis were divided into two groups by the 75-g oral glucose tolerance test (OGTT): group A, 2-hr plasma glucose concentration > 140 mg/dL (n = 25); group B, 140 < or = 2-hr plasma glucose < 200 mg/dL (n = 15). Patients with diabetes mellitus or diabetic nephropathy were not included. Morphometric analysis of the glomeruli revealed a significantly larger mean glomerular volume in subjects with nephrosclerosis in both subgroups. In addition, the mean glomerular volume was significantly correlated with the fasting insulin level, while no significant correlation was observed between the mean glomerular volume and creatinine clearance or degree of global sclerosis. These results indicate that hyperinsulinemia may be intimately related to glomerular hypertrophy in patients with nephrosclerosis.

Biopsy, Needle↗
PubMed1996

Long-term effects of intensive therapy combined with tonsillectomy in patients with IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of glomerular disease in the world. However, there is currently no established therapy for IgAN. To assess treatment regimens for IgAN, we investigated a retrospective long-term follow-up study comparing an intensive therapy with a conventional therapy. Clinical outcomes 5 years after the initiation of treatment in two centers were compared. In one center, patients were treated with tonsillectomy combined with steroid pulse, cyclophosphamide, anti-platelet drugs and warfarin (intensive therapy group, Group A, n = 50). In the other center patients were treated with anti-platelet drugs, warfarin or no treatment (conventional therapy group, Group B, n = 50). At the beginning of treatment, the two groups were well matched in terms of age, sex, blood pressure, urinalysis, and creatinine clearance. Five years after the initiation of treatment, proteinuria was remarkably reduced from 1.6 g/day to 0.5 g/day in Group A, whereas no significant change in proteinuria was observed in Group B. Creatinine clearance significantly improved from 77.6 ml/mm to 89.4 ml/min in Group A, whereas creatinine clearance deteriorated from 70.9 ml/min to 62.5 ml/min during 5 years in Group B. Our results indicate that early intensive therapy for IgAN is potentially of great value, and warrants close investigation.

Adult↗
PubMed1995

Mesangiolysis associated with severe glomerular endocapillary proliferation of CD57 large granular lymphocytes.

A 54-year-old man developed renal failure, with renal biopsy findings of diffuse mesangiolysis with severe endocapillary proliferation. Immunohistochemical studies revealed that CD3-CD56-CD57+ large granular lymphocytes were present predominantly within glomerular tufts. Intercellular adhesion molecule-1 was more preferentially expressed in the glomerular endothelial cells with severe endocapillary proliferation as compared to those without endocapillary proliferation. These findings suggest that CD57+ large granular lymphocytes caused glomerular endothelial injury by a cell-mediated cytolytic mechanism, resulting in the development of mesangiolysis and microaneurysm formation.

Antigens, CD↗
PubMed1994

Analysis of mononuclear cells in urine using flow cytometry in glomerular diseases.

Analysis of urinary substances, such as low molecular weight proteins and enzymes localized in the proximal tubulus and cytokines, has been proposed as being useful in monitoring the disease activity of glomerulonephritis [1-4]. However, most of these markers are more closely associated with renal tubulointerstitial injury than glomerular injury. It has been demonstrated that mononuclear cells (macrophages and lymphocytes) are involved in the pathogenesis of various types of human glomerulonephritis, as well as in animal models [5-7]. If mononuclear cells are involved in glomerular injury, it can be assumed that such cells could be detected in urine; however, to our knowledge, the characterization of mononuclear cells in urine has not been investigated. We have recently demonstrated that increased numbers of mononuclear cells are observed in the urine of patients with active IgA nephropathy and that the extent of active crescents in biopsy specimens is significantly correlated with the number of urinary macrophages and natural killer cells [8]. The aim of the present study is to evaluate the clinical usefulness of analyzing mononuclear cells in urine as a non-invasive diagnostic tool for glomerular injury.

Flow Cytometry↗
PubMed1993

Analysis of CD14+ cells and CD56+ cells in urine using flow cytometry: a useful tool for monitoring disease activity of IgA nephropathy.

The interrelationship between glomerular inflammatory activity and urinary leukocytes was investigated in IgA nephropathy (IgAN). The numbers of T cells, macrophages, and natural killer (NK) cells in urine were evaluated using flow cytometry. The glomerular changes were studied by routine histopathological methods and by immunohistochemical methods using monoclonal antibodies. Biopsies were classified into three categories: non-crescentic IgAN (n = 44), inactive-crescentic IgAN (n = 17), and active-crescentic IgAN (n = 18). Macrophages (Leu M3/CD14) and NK cells (Leu 19/CD56) were predominantly present within active crescents, whereas T cells (Leu 4/CD3) were less frequently observed. A significant increase of mononuclear cells in urine was observed in patients with active-crescentic IgAN as compared with other groups. Moreover, the extent of active crescents in biopsies was significantly correlated with the number of CD14+ cells and CD56+ cells in urine (CD14: r = 0.6858, p < 0.01; CD56: r = 0.6373, p < 0.01). These findings suggest that analysis of CD14+ cells and CD56+ cells in urine using flow cytometry can be a useful tool for monitoring disease activity of IgAN.

Adult↗
PubMed1992

[Analysis of mononuclear cells in urine using flow cytometry: a useful tool for monitoring disease activity of proliferative glomerulonephritis].

We investigated CD56+ cells (natural killer cells), CD14+ cells (macrophage) and CD3+ cells (pan T cells) in urine using flow cytometry in various renal diseases including idiopathic crescentic glomerulonephritis, IgA nephropathy, membranoproliferative glomerulonephritis membranous nephropathy, pyelonephritis and idiopathic renal hematuria. A remarkable increase of CD56 cells in urine was observed in glomerulonephritis with marked necrotizing/and or crescentic (NC) lesions. The ratio of CD56+ cells/CD3+ cells was correlated with the severity of NC lesions. The ratio of CD14+ cells/CD3+ cells was increased in glomerulonephritis with endocapillary proliferation. Using immunohistochemical methods, CD56+ cells were also observed to be present in cellular crescents in biopsy specimens. These observations suggest that an analysis of these cells in urine using flow cytometry may be a useful tool for monitoring disease activity in proliferative glomerulonephritis.

Antigens, CD↗