Biomedical subjects

M Iwano

Publications and source records attributed to M Iwano.

At least 55 records · Page 3Linked to original sources

PubMed1997

[An elderly patient with purpura nephritis that appeared after extracorporeal shock wave lithotripsy].

We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.

Drug Administration Schedule↗

PubMed1996

Molecular cloning and expression of a novel peptide (LN1) gene: reduced expression in the renal cortex of lupus nephritis in MRL/lpr mouse.

A gene has been identified by mRNA differential display whose expression is reduced in the renal cortex of MRL/lpr mouse. The nucleotide sequence of the cDNA contains an open reading frame that encodes a protein of 338 amino acids (termed LN1). In situ hybridization showed that LN1 mRNA is present in glomeruli, and a 39 kDa protein was detected in the kidney by immunoblot. A human LN1 cDNA was also isolated, the deduced amino acid sequence of which is 78% identical to that of mouse LN1. Although the function of LN1 remains to be elucidated, its reduced expression may contribute to the pathogenesis of lupus nephritis.

Amino Acid Sequence↗

PubMed1996

Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.

Monocytes/macrophages (M phi) have been implicated in the pathogenesis of lupus nephritis (LN), but the precise molecular mechanism of recruitment and activation of M phi in LN remains unclear. To clarify the involvement of chemotactic cytokines (chemokines) in those events, we measured levels of monocyte chemotactic and activating factor (MCAF, also termed monocyte chemoattractant protein-1, MCP-1) in urines and sera derived from 42 patients with LN. Both urinary and serum MCAF levels were significantly higher in patients with LN as compared with 22 healthy volunteers (10.3 +/- 3.2 vs. 1.0 +/- 0.1 pg/ml . creatinine, 212.2 +/- 75.8 vs. 66.1 +/- 15.5 pg/ml, respectively, P < 0.05, mean +/- SEM). Histological examination of renal lesions from 41 patients classified 19 as active according to the WHO-defined classes IIIb, IVb and IVc, and 22 as inactive by the WHO-defined classes I, II, IIIc, IVd and V. Urinary MCAF levels in the patients with active lesions were significantly higher than those with inactive lesions (20.3 +/- 6.4 vs. 1.7 +/- 0.3 pg/ml . creatinine, P < 0.01). Moreover, elevated urinary MCAF levels were dramatically decreased during steroid therapy-induced convalescence in 29 patients examined serially (13.9 +/- 4.5 vs. 5.3 +/- 1.7 pg/ml . creatinine, P < 0.001), whereas serum MCAF levels did not change significantly. Endothelial cells, renal epithelial cells and infiltrating mononuclear cells in the tubulointerstitial regions were MCAF-positive in immunohistochemical as well as in situ hybridization analysis. These observations suggest that MCAF is probably involved in the pathogenesis of LN with active lesions, possibly through the recruitment and activation of M phi, and that measurement of urinary MCAF levels may be a useful clinical tool for monitoring the disease activity of LN.

Adolescent↗

PubMed1996

Quantification of glomerular TGF-beta 1 mRNA in patients with diabetes mellitus.

Transforming growth factor-beta 1 (TGF-beta 1) is a primary determinant of the mesangial expansion observed in diabetic nephropathy. In this study, we quantitated the levels of intraglomerular TGF-beta 1 mRNA in patients with diabetes mellitus using a competitive polymerase chain reaction (PCR) method. Renal biopsy specimens were obtained from 29 patients with non-insulin-dependent diabetes mellitus. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. We also used this competitive PCR method to measure TGF-beta 1 cDNA by co-amplifying mutant templates of TGF-beta 1. We observed higher expression of TGF-beta 1 mRNA in glomeruli of patients with diabetic nephropathy as compared with normal glomeruli. Intraglomerular TGF-beta 1 mRNA was elevated, even in the early stage of diabetic nephropathy. Moreover, levels of intraglomerular TGF-beta 1 mRNA correlated with values of HbA1c. These data suggest that hyperglycemia induces intraglomerular TGF-beta 1 mRNA expression in vivo, and that TGF-beta 1 overproduction may be associated with the progression of diabetic nephropathy.

Aged↗

PubMed1996

IL-6 mRNA synthesis by peripheral blood mononuclear cells (PBMC) in patients with chronic renal failure.

We measured levels of IL-6 mRNA in PBMC obtained from patients with chronic renal failure, using polymerase chain reaction (PCR). PBMC were isolated from 45 patients on haemodialysis (HD) at the start of HD. PBMC were also isolated from 35 patients on HD at the end of HD, 23 patients on continuous ambulatory peritoneal dialysis (CAPD), 24 undialysed patients with chronic renal failure (CRF), and 19 healthy controls. Total RNA was extracted from PBMC with RNA zol and reverse transcribed into cDNA. To prepare samples containing identical amounts of beta-actin cDNA, we performed competitive PCR by co-amplifying serial dilutions of mutant templates containing a single point mutation which generated a unique Eco RI site. Next, to measure IL-6 cDNA semiquantitatively in the samples containing identical amounts of beta-actin (100 pg), we performed PCR amplification using 2 fg of the IL-6 mutant template containing a unique Eco RI site. Higher levels of IL-6 mRNA in the PBMC were observed in the HD patients than in the CAPD patients and healthy controls. The levels of IL-6 mRNA in the PBMC at the end of HD were not significantly higher than those at the start of HD. These results suggest that the dialysis session itself did not significantly affect IL-6 mRNA levels in the PBMC, but that chronic stimulation by maintenance HD may be associated with higher levels of IL-6 mRNA observed in HD patients.

Adult↗

PubMed1996

Clinical and morphological predictors of renal outcome in adult patients with focal and segmental glomerulosclerosis (FSGS).

In this retrospective study, we examined 35 adult patients with biopsy-proven, primary focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome to determine whether any of the clinical and morphological features of FSGS were associated with a higher risk of a poor renal outcome. Clinical factors assessed were the age, sex, amount of urinary protein, and presence of microscopic hematuria, hypertension and renal dysfunction at onset in each patient. Morphological parameters included the number of segmental sclerosis and global sclerosis, sclerosis score, location of segmental sclerosis, mean glomerular diameter, grade of tubulo-interstitial changes, and presence of vascular lesions. Twenty-three patients (66%) were in complete or incomplete (partial) remission, and 12 (34%) were non-responders at the end of follow-up. On univariate analysis, the age at onset, sclerosis score, mean glomerular diameter, and grade of tubulo-interstitial changes in no response were significantly greater than those parameters in remission. Multivariate logistic regression analysis revealed that the degree of tubulo-interstitial changes and mean glomerular diameter were independent risk factors for a poor renal outcome. These findings suggest that the estimation of these latter two parameters allows the nephrologist to predict the probable course and prognosis of an adult with FSGS. Intensive and prolonged therapy is recommended for patients without these two morphological features.

Adult↗

PubMed1995

Pharmacokinetic studies of cortisol after oral administration of deuterium-labelled cortisol to a normal human subject.

A trace amount (5 mg) of stable isotopically labelled cortisol ([1,1,19,19,19-2H5]cortisol, cortisol-d5) was administered orally to a healthy human subject to examine the pharmacokinetic behaviour of exogenous cortisol and study the interconversion of cortisol to cortisone catalysed by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The use of a gas chromatographic/mass spectrometric method allowed the simultaneous measurement of the plasma concentrations of endogenous and exogenous cortisol and cortisone. The amount administered was sufficiently small not to disturb or decrease the endogenous cortisol secretion by negative feedback. The appearance of cortisol-d5 and cortisone-d5 was very rapid. In a blood sample taken 10 min after administration of cortisol-d5, plasma concentrations of 154.8 ng ml-1 cortisol-d5 and 2.7 ng ml-1 cortisone-d5 were detected. A peak value of 196.6 ng ml-1 cortisol-d5 was observed 30 min after cortisol-d5 administration. The peak value of cortisone-d5 was 15.5 ng ml-1 40 min after cortisol-d5 administration, and thereafter cortisone-d5 declined in parallel with the slower decline phase of cortisol-d5. The plasma concentrations fell as low as 26.9 ng ml-1 for cortisol-d5 and 4.6 ng ml-1 for cortisone-d5 4 h after cortisol-d5 administration. The ratio of cortisone-d5 to cortisol-d5 approached a plateau 2 h after cortisol-d5 administration, reaching a constant value of approximately 0.15 thereafter. The higher value of the cortisone/cortisol concentration ratio (0.14-0.81; average 0.30) than the cortisone-d5/cortisol-d5 ratio may provide important information about the possibility that cortisone might be formed not only via the pathway of the cortisol conversion but also through other biotransformation processes.

Adrenal Cortex Hormones↗

PubMed1994

Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.

Both PDGF and IL-1 play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis, using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.

Animals↗

PubMed1994

Intraglomerular expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA in patients with glomerulonephritis: quantitative analysis by competitive polymerase chain reaction.

TGF-beta 1 is involved in the pathogenesis of glomerular sclerosis. We studied the intraglomerular expression of TGF-beta 1 mRNA in patients with glomerulonephritis using competitive polymerase chain reaction (PCR). This method is sensitive enough to quantify cDNA copies of mRNA present in small amounts of samples. Renal biopsy specimens were obtained from 42 patients with various kinds of glomerulonephritis. Ten glomeruli were dissected from renal biopsy specimens. Normal glomeruli were also obtained from the resected kidneys of eight patients with renal cell cancer. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. Next, to measure TGF-beta 1 cDNA, we performed competitive PCR by co-amplifying mutant templates of TGF-beta 1. We observed a higher glomerular expression of TGF-beta 1 mRNA in cases of mesangial proliferative glomerulonephritis having a moderate increase in mesangial matrix, diabetic nephropathy and diffuse proliferative lupus nephritis, compared with normal glomeruli. Results suggest that the intraglomerular synthesis of TGF-beta 1 may be involved in the progression of glomerulonephritis in humans.

Actins↗

PubMed1994

Angiotensin II receptor antagonist, TCV-116, prevents myocardial hypertrophy in spontaneously hypertensive rats.

Recently, it has been suggested that angiotensin II (AII) might be associated with cardiac hypertrophy and fibrosis. We investigated the preventive effect of an AII receptor antagonist, TCV-116, on the development of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats (SHR) at 24 weeks of age through histopathological study and an AII receptor assay. Treatment with TCV-116, enalapril (an angiotensin-converting enzyme inhibitor, ACEI), and hydralazine for 20 weeks lowered systolic blood pressure (SBP) significantly (-39 mmHg, -45 mmHg, and -45 mmHg, respectively). The heart weight/body weight ratio, cardiac myocyte diameter, and percent cardiac fibrosis were significantly reduced by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The AII receptor density was significantly increased by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The results of this study suggest that AII receptors are involved in the development of cardiac hypertrophy and fibrosis in SHR. It was demonstrated that the AII receptor antagonist, TCV-116, was comparable to the ACEI, enalapril, in inhibiting the progression of cardiac hypertrophy and fibrosis via the AII receptor.

Angiotensin II↗

PubMed1994

Distribution of thrombomodulin in patients with focal and segmental glomerulosclerosis (FSGS).

Thrombomodulin (TM), an endothelial cell surface glycoprotein, is a regulatory factor in the intravascular anticoagulant system. Furthermore, its plasma level is believed to reflect injury to the endothelial cell. In searching for changes in intraglomerular coagulation and endothelial cell injury during the clinical course of 14 patients with focal and segmental glomerulosclerosis (FSGS), we evaluated the distribution of thrombomodulin (TM) in the kidney by immunohistochemical methods. In the nephrotic stage, intraglomerular staining for TM was weak and segmental and occurred in 6 out of 9 patients (67%), but the incidence of TM expression was not different significantly from that in the normal kidney. Sclerotic lesion was negative for TM. In all patients with incomplete remission and with complete remission, strong and diffuse staining was seen in intra- and extraglomerular endothelial cells. Moreover, TM was scattered in sclerotic lesions. The present study suggest that the over-expression of TM in remission may be linked to recovery from endothelial cell damage and that TM may be closely involved in the repair of FSGS.

Adolescent↗

PubMed1994

Inhibitory effects of ginseng on proliferation of cultured mouse mesangial cells.

To evaluate the pharmacological action of ginseng, its effects on the proliferative activity of mesangial cells, which are thought to play an important role in the regulation of renal function, were determined in terms of [3H]thymidine uptake. When the extract was added to the medium of mesangial cell cultures, it suppressed the proliferation of mesangial cells, and similar proliferation-inhibitory activity was found in the total saponin and ginsenoside-Rd fractions, consistent with the renal effects observed in our previous in vivo studies. The inhibition of mesangial cell proliferation by the extract can thus be explained by the action of ginsenoside-Rd.

Animals↗

PubMed1994

Rapid measurement of urinary IL-6 by ELISA: urinary IL-6 as a marker of mesangial proliferation.

To determine whether the urinary level of interleukin 6 (IL-6) measured by enzyme-linked immunosorbent assay (ELISA) can be used as a marker of mesangial proliferation, we studied urinary levels of IL-6 in 124 patients with primary and secondary glomerulonephritis, using ELISA. Although urinary levels of IL-6 were correlated with the degree of mesangial proliferation, there was no correlation between urinary levels of IL-6 and urinary protein excretion or renal function. Urinary levels of low-molecular-weight proteins, which are parameters of tubular dysfunction, were not correlated with the urinary excretion of IL-6. These results suggest that the urinary level of IL-6 may be a useful marker for mesangial proliferation.

Adolescent↗

PubMed1993

Inhibitory effect of tannin in green tea on the proliferation of mesangial cells.

The effect of green tea tannin on the proliferation of mesangial cells was determined in terms of [3H]thymidine uptake. When green tea tannin was added to the medium of mesangial cell cultures, it suppressed the proliferation of mesangial cells markedly. In particular, (-)-epigallocatechin 3-O-gallate, the predominant component of the green tea tannin mixture, exerted an inhibitory effect at a relatively low concentration, suggesting a direct corroboration of the renal effects.

Animals↗

PubMed1993

Inhibitory effects of crude drug components on the proliferation of cultured human mesangial cells.

The effects of a component of an Oriental medicine and green tea plants utilized for the traditional beverage on the proliferation of mesangial cells were determined in terms of the 3H-thymidine uptake. When magnesium lithospermate B was added to the medium of the mesangial cell culture, it suppressed the proliferation of mesangial cells at a concentration of 50 micrograms/ml. The 3H-thymidine uptake began to display an inhibitory action from the 6.25 micrograms/ml (-)-epicatechin 3-O-gallate, (-)-epigallocatechin 3-O-gallate or green tea tannin mixture, showing a more conspicuous inhibition at 50 micrograms/ml that did the magnesium lithospermate B at the corresponding concentration. In particular, (-)-epigallocatechin 3-O-gallate, the predominant component of the green tea tannin mixture, exerted an inhibitory effect at a relatively low concentration.

Catechin↗

PubMed1993

Urinary levels of IL-6 in patients with active lupus nephritis.

Using the IL-6 dependent hybridoma, MH60.BSF2, we measured urinary levels of interleukin 6 (IL-6) in 29 patients with active lupus nephritis. We detected IL-6 activity in the urine of 24 (83%) of 29 patients before the initiation of therapy. The median value of urinary IL-6 levels in patients with a histologic diagnosis of WHO class IV on renal biopsy was significantly higher than that in patients with other classes (p < 0.01). After treatment, urinary levels of IL-6 decreased significantly (p < 0.001). These data suggest that urinary levels of IL-6 may be a valuable tool for monitoring the progression of lupus nephritis.

Biomarkers↗

PubMed1993

Role of interleukin-6 in the progression of mesangial proliferative glomerulonephritis.

Mesangial proliferative glomerulonephritis (mesPGN) is histologically characterized by proliferation of mesangial cells (MC), suggesting the involvement of a growth factor for MC in the pathogenesis of mesPGN. We have previously shown that interleukin-6 (IL-6) induces proliferation of cultured rat mesangial cells, and urine samples from patients with IgA nephropathy contain high level of IL-6 activity. We have also demonstrated that transgenic mice carrying a human IL-6 genomic gene showed severe mesangial proliferation and matrix enlargement. Urinary samples of patients with lupus nephritis as well as IgA nephropathy contain significant IL-6 activity. Over a ten month follow-up, a positive correlation between the urinary IL-6 and pathological score was observed. Hence, measurement of urinary IL-6 can be used as a good indicator for monitoring IgA nephropathy and lupus nephritis. Using RT-PCR methods, IL-6 mRNA was detected in the glomeruli of renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis.

Animals↗

PubMed1992

Induction of interleukin 6 synthesis in mouse glomeruli and cultured mesangial cells.

Interleukin 6 (IL-6) is an autocrine growth factor of cultured mesangial cells (MC) and intraglomerular IL-6 production is suggested to be closely associated with the pathogenesis of human mesangial proliferative glomerulonephritis (mesPGN). In this study, to elucidate the mechanisms regulating the intraglomerular production of IL-6, we examined what kinds of stimuli are significant in the induction of IL-6 synthesis in vitro and in vivo. Incubation of cultured mesangial cells with interleukin 1 (IL-1) or bacterial lipopolysaccharide (LPS) induced significant IL-6 production, and intravenous injection of IL-1 or LPS into normal BALB/c mice induced significant intraglomerular IL-6 mRNA expression. Furthermore, we indicated in this study that IL-6 mRNA expression was augmented in the glomeruli of mice with immune complex-mediated glomerulonephritis.

Animals↗