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ABSTRACT: The efficacy of Wen-Pi-Tang and each of its crude drug extracts on the proliferation of mouse mesangial cells was determined in terms of [3H]thymidine uptake. When Wen-Pi-Tang was added to the medium of mesangial cell cultures, it suppressed the proliferation of mesangial cells markedly. Similar to the effects of Wen-Pi-Tang, Rhei Rhizoma, its main ingredient, exerted an inhibitory effect on mesangial cell proliferation at a relatively low concentration. Ginseng Radix and Aconiti Tuber were also an effective crude drug. As for Zingiberis Rhizoma, an inhibitory activity at relatively high concentration was noted. However, the proliferation of mesangial cells in the presence of Glycyrrhizae Radix showed no particular alteration. As is clear from the results of the present study, Rhei Rhizoma, Ginseng Radix, Aconiti Tuber and Zingiberis Rhizoma alone each exert an inhibitory effect. The inhibition of mesangial cell proliferation by Wen-Pi-Tang can thus be explained by the action of these crude drugs.
Phytotherapy Research 01/2006; 8(3):170 - 173. · 2.09 Impact Factor
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Kazumasa Hamano,
Masayuki Iwano,
Yasuhiro Akai,
Hiroaki Sato,
Atsushi Kubo,
Yoshiharu Nishitani,
Hideto Uyama,
Yukiko Yoshida,
Masanobu Miyazaki,
Hideo Shiiki,
Shigeru Kohno, Kazuhiro Dohi
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ABSTRACT: Plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) are the major regulators of plasmin generation. Glomerular PAI-1/tPA balance is involved in extracellular matrix turnover, as well as fibrin deposition in glomeruli. Renal biopsy specimens were obtained from 80 patients with either primary or secondary glomerulonephritis (10 patients, minimal change nephrotic syndrome; 6 patients, focal segmental glomerulosclerosis [FSGS]; 10 patients, membranous nephropathy [MN]; 24 patients, mesangial proliferative glomerulonephritis; 15 patients, lupus nephritis; 14 patients, diabetic nephropathy; and 1 patient, membranoproliferative glomerulonephritis). We quantified glomerular PAI-1 and tPA messenger RNA (mRNA) by competitive polymerase chain reaction. We also determined PAI-1 mRNA localization by in situ hybridization. Glomerular PAI-1 mRNA levels in patients with FSGS and MN were significantly greater than those of controls. There was a sixfold increase in PAI-1-tPA mRNA ratio in patients with MN compared with the control group. In addition, glomerular PAI-1 mRNA level correlated with level of proteinuria. Conversely, there was no difference in tPA mRNA levels among types of glomerulonephritis. These results suggest that suppressed glomerular fibrinolytic and proteolytic activity may be associated with the pathogenesis of glomerulonephritis, especially in FSGS and MN.
American Journal of Kidney Diseases 05/2002; 39(4):695-705. · 5.43 Impact Factor
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ABSTRACT: Am J Hypertens (2001) 14, 81A–81A; doi:10.1016/S0895-7061(01)01761-7
P-152: Association of the missense Glu298Asp variant of eNOS gene with left ventricular hypertrophy and carotid atherosclerosis in patients with essential hypertension
Minoru Takaoka1, Shigeru Yamano1, Yasuhiro Akai1, Masayuki Iwano1 and Kazuhiro Dohi11First Department of Internal Medicine Nara Medical Univeresity Kashihara, Nara, Japan
American Journal of Hypertension 03/2001; · 3.18 Impact Factor
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ABSTRACT: In patients with dilated cardiomyopathy (DCM), the left ventricular (LV) inflow jet is narrow and has a high pressure gradient. A pulsed Doppler restrictive transmitral flow pattern is a characteristic feature of severe left ventricular disease. However, Doppler flow analysis is limited by the angle between the blood flow jet and the ultrasonic beam. In this study we used gated magnetic resonance imaging (MRI) to investigate the inflow velocity in the LV transverse directions during early diastole in patients with DCM. Methods: We studied 10 patients with DCM (mean age: 47 y). Ten age-matched healthy volunteers were also examined. Gradient echo images of the LV were obtained. Left ventricular short axis phase contrast images were obtained at the level of the mitral valve tip and 1 cm inside the LV. Long axis images were also obtained. Through-plane peak velocities at peak early diastolic filling were measured along the LV long axis, antero-posterior short axis, and right-left short axis. Blood velocity was measured in 50 ms blocks. Results: Early diastolic inflow velocity along the long axis, especially at the center of the LV, was well preserved in DCM. However, the inflow velocity in the antero-posterior transverse direction of the LV (i.e., in the direction of mitral valve excursion) was significantly reduced in DCM. Conclusions: Early diastolic inflow velocity in the antero-posterior transverse direction of the LV is reduced in patients with DCM indicating that the vector component of the forces acting in the antero-posterior transverse direction of the LV may be decreased in patients with DCM during early diastolic filling.
International Journal of Cardiac Imaging 01/2000; 16(1):43-48.
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ABSTRACT: Anti-neutrophil cytoplasmic antibodies (ANCA) of the immunoglobulin (Ig)G type are associated with rapidly progressive glomerulonephritis.
Such antibodies have been detected only rarely in patients with Henoch-Schönlein purpura (HSP) or IgA nephropathy (IgAN).
We report a patient with biopsy-proven IgAN with fibrous crescents in whom high titers of IgG ANCA occurred and were confirmed
to be anti-myeloperoxidase antibodies (MPO ANCA) by solid-phase enzyme-linked immunosorbent assay (ELISA) and inhibition studies.
During a 1-year follow-up period, high titers of MPO ANCA persisted but creatinine clearance remained over 50 ml/min per 1.48
m.2 This case suggests the lack of a reliable association between fulminant outcome of IgAN with crescents and high titers of
IgG MPO ANCA, and indicates the involvement of subsets of IgG MPO ANCA which recognize important or unimportant epitopes of
MPO in the pathogenesis.
Clinical and Experimental Nephrology 11/1999; 3(4):307-310. · 1.37 Impact Factor
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ABSTRACT: Aim: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). Methods: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (m) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n=5), fibrosis dominant group (n=5), dilated phase hypertrophic cardiomyopathy (n=2), and mixed type (n=3). Results: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 2.9, 8.3 2.7dB, respectively) than in normal subjects (14.4 2.9, 13.6 2.6dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 12.3%, and a mean myocyte diameter of 14.3 2.9m in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r=–0.56 in IVS, r=–0.56 in PW) and myocyte diameter (r=0.67 in IVS, r=0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. Conclusions: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.
International Journal of Cardiac Imaging 09/1999; 15(5):391-396.
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ABSTRACT: Background. Our objective was to investigate changes in left ventricular inflow jet width and long axis motion in patients on maintenance
hemodialysis by preload reduction due to a single hemodialysis.
Methods. We evaluated 20 patients on stable maintenance hemodialysis by Doppler echocardiography. Twenty age-matched controls were
also examined. Transmitral flow, left ventricular long axis M-mode (LAM) echocardiography, and two-dimensional color Doppler
early diastolic left ventricular inflow jet width (JW) were analyzed before and after a single hemodialysis.
Results. Before hemodialysis, compared with controls, JW was reduced in patients (2.1 ± 0.4 vs 2.4 ± 0.3 cm; P < 0.01), and early diastolic excursion of LAM (LAM-E) was also reduced. Peak velocity of the Doppler transmitral early diastolic
wave (E) and late diastolic wave (A) were both higher, while the E/A ratio was lower. After hemodialysis, compared with the
predialysis findings, JW and early diastolic excursion of LAM were unchanged; however, Doppler transmitral flow showed decreased
E and E/A. Thus, in hemodialysis patients, inflow jet width was narrow, and unchanged by a single hemodialysis, while the
Doppler transmitral flow pattern was changed mainly to dominant A waves and reduced E waves.
Conclusions. In patients on maintenance hemodialysis, the abnormal left ventricular inflow jet dynamics and early diastolic incoordinate
long axis motion are unmasked by a preload reduction due to single hemodialysis in a different way from a transmitral Doppler
flow pattern.
Clinical and Experimental Nephrology 07/1999; 3(3):192-197. · 1.37 Impact Factor
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ABSTRACT: OBJECTIVE: The goal of the study was to determine whether the central velocity of the left ventricular outflow tract represents the mean velocity of the total outflow area. METHODS: Thirteen healthy men (mean age, 30 +/- 6 years) and nine patients with aortic valve disease (seven with aortic regurgitation and two with aortic valve stenosis) were examined. Cine gradient echo images were obtained in the left ventricular outflow long axis. Cine images with velocity mapping were obtained in the short axis of the outflow tract. Values for peak velocity were obtained on the right-left axis and on the anteroposterior axis. Distances were measured along the axes from the right and anterior edges of the outflow tract at the point of peak velocity. Percentages of the distances for outflow diameter were calculated. Peak velocity at the left ventricular outflow tract using pulsed-Doppler method were also measured. RESULTS: In normal subjects and in patients, on the right-left axis, the peak velocity was 87 +/- 16 and 72 +/- 11 cm/sec, respectively, and the distance from the right edge of outflow tract corresponded to 19% +/- 8% and 21% +/- 7%, respectively. On the anteroposterior axis, the peak velocity was 86 +/- 16 and 60 +/- 9 cm/sec, and the corresponding distance from the anterior edge was 30% +/- 13% and 41% +/- 12% for normal subjects and patients, respectively. The central velocity of the outflow tract was 74 +/- 15 cm/sec, whereas the mean of the total outflow tract was 74 +/- 13 cm/sec. Central and mean velocities of the outflow tracts as revealed by magnetic resonance imaging showed a close and highly significant correlation in both groups. Velocity obtained by pulsed-Doppler method and mean velocity of the outflow tract by magnetic resonance imaging also showed significant correlation in both groups. CONCLUSIONS: Central velocity at the left ventricular outflow tract represented the mean of the total outflow tract both in normal subjects and in patients with aortic valve disease. The stroke volume measured by pulsed Doppler is therefore considered reliable if the sampling point is placed exactly at the center of the outflow.
Echocardiography 02/1999; 16(1):11-16. · 1.24 Impact Factor
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ABSTRACT: Right ventricular function can be evaluated echocardiographically by assessing the longitudinal motion of the tricuspid ring recorded in the apical four chamber view. In this study, we applied this technique to assess the right ventricular diastolic function in 10 healthy Japanese men (mean age : 286 years; age range : 20–43 years). Echocardiographic studies were performed with a phased-array imaging system using a 2.5 MHz probe. Tricuspid ring motion was measured by two-dimensional echo guided M-mode echocardiogram of the right lateral tricuspid ring. The excursion of the tricuspid ring during early diastole (dS; mm) and the peak rate of change of the excursion (dS/dt; mm/sec) were measured. We also assessed the right ventricular function by cine magnetic resonance imaging (MRI). Cine gradient echo images were obtained along the short axis of the right ventricle. The right ventricular volume at each phase of the cardiac cycle was calculated by Simpson's method and time–volume curves were constructed. The peak filling rate (dV/dt; ml/s) was determined from these time–volume curves. The dS was 12.82.5 mm, dS/dt was 13227 mm/sec and dV/dt was 26966 ml/s. There were significant positive correlations between dS and dV/dt (r=0.80, P
International Journal of Cardiac Imaging 11/1998; 14(6):391-395.
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ABSTRACT: Aims. To validate the use of three-dimensional transthoracic echocardiography compared with the magnetic resonance imaging for determination of right ventricular volume and ejection fraction. Methods and results: We recorded transthoracic echocardiographic images starting from the apical four-chamber view in which the RV is clearly visualized in 15 healthy volunteers. The scanning plane of the RV was obtained by the rotational scanning technique in 2 degree angular increments for three-dimensional reconstruction. The RV volumes in end-diastole and end-systole were calculated using a Tomtec three-dimensional reconstruction computer. We also assessed the RV by cine magnetic resonance imaging using the Siemens Magnetom Impact Expert (1.0 T). Cine gradient echo images were obtained in the short axis of the RV. The RV volume at each phase was calculated by Simpson's method. We also calculated the RV ejection fraction. The RV volumes in end-diastole and end-systole were 11122 ml and 5213 ml, respectively as determined by three-dimensional echo, and 11518 ml and 5514 ml determined by MRI. The right ventricular volumes at end-diastole and end-systole determined by three-dimensional echo were correlated with the volumes determined by MRI (r=0.94 and 0.97, respectively, p
International Journal of Cardiac Imaging 11/1998; 14(6):385-390.
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ABSTRACT: We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7)
as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified
to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various
substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide
(LPS), and interferon-γ (IFN-γ) increased AM production 1.5–7-fold in RAW 264.7 cells in a dose- as well as time-dependent
manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted
a synergistic effect when administered with TPA, LPS, or IFN-γ, whereas IFN-γ completely suppressed AM production in RAW 264.7
cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-β dose-dependently suppressed
AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage
secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM
was found to increase basal secretion of tumor necrosis factor α (TNF-α) from RAW 264.7 cells, whereas AM suppressed the secretion
of TNF-α and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources
of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented,
and the secreted AM is deduced to function as a modulator of cytokine production.
Journal of Biological Chemistry 07/1998; 273(27):16730-16738. · 4.77 Impact Factor
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ABSTRACT: A 53-year-old man with aortic regurgitation was admitted to our hospital because of fever. A diagnosis of ruptured mitral valve aneurysm was made by Doppler echocardiography. Aortic regurgitant flow along the anterior mitral leaflet may have predisposed to mitral valve endocarditis, aneurysm formation, and its rupture.
Echocardiography 06/1998; 15(4):401-404. · 1.24 Impact Factor
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ABSTRACT: BackgroundWe evaluated levels of plasma interleukin-1β (IL-1β) and IL-1β mRNA in peripheral blood mononuclear cells (PBMCs) from patients
with chronic renal failure.
MethodsPatients with chronic renal failure included 13 patients not undergoing dialysis, 10 patients undergoing continuous ambulatory
peritoneal dialysis, and 16 patients underoing hemodialysis. The levels of plasma IL-1βwere measured by enzyme-linked immunosorbent
assay and IL-1βmRNA levels were evaluated by using the competitive polymerase chain reaction (PCR) method. PCR was performed
by coamplifying the IL-1β mutant template containing a uniqueSac
I site in samples that contained identical amounts of β-action.
ResultsThe levels of plasma IL-1β were below a delectable level. The levels of IL-1βmRNA in each group with chronic renal failure
were significantly higher than that in healthy subjects. Levels of IL-1β mRNA in the PBMCs were augmented at the end of dialysis
sessions compared to those at the start of dialysis.
ConclusionsResults suggest that the overexpression of IL-1β mRNA in PBMCs may be induced by uremic substances, as well as by dialysis
per se.
Clinical and Experimental Nephrology 04/1998; 2(1):25-30. · 1.37 Impact Factor
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ABSTRACT: Stroke volume can be calculated by using noninvasive Doppler techniques. The products of pulsed Doppler stroke distance of left ventricular outflow and left ventricular outflow area can often be used to calculate stroke volume. However, left ventricular outflow also moves longitudinally toward the apex of the ventricle during systole, so that zero velocity flow cannot be detected by the usual pulsed Doppler studies. We evaluated the contribution of these zero velocity flow to the noninvasive estimation of left ventricular stroke volume in 20 patients with left ventricular disease and in 20 age matched healthy controls. Left ventricular stroke distance was calculated by summing the Doppler stroke distance and the outflow long axis motion. The percentage of zero velocity flow for total stroke volume was calculated in each group. Cardiac output was also measured by thermo-dilution technique. The percentage of zero velocity flow for total noninvasive stroke volume in patients with left ventricular disease was 2.51.1 ml (4.01.5%), significantly lower than in normal subjects, 3.61.0 ml (5.51.5%) (p
International Journal of Cardiac Imaging 01/1998; 14(1):37-42.
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ABSTRACT: To investigate the velocity profiles of transtricuspid inflow, we examined 20 normal subjects (17 males and 3 females, mean age 27 7) by the magnetic resonance imaging (MRI). Electrocardiographic gating was performed in all anatomical and flow studies, and sequences were triggered by the R wave. Cine gradient echo images (echo time, 14 ms) were acquired in the right ventricular horizontal long axis, and from these, cine images with velocity mapping were obtained in the short axis of the right ventricle. Velocity mapping of right ventricular inflow was obtained at peak early diastolic filling. Velocity profile curves across the tricuspid inflow were obtained at each 1 cm interval from the tricuspid ring to 3 cm into the cavity. Maximum/mean velocity was 1.1 0.1 at ring level, unchanged at 1 cm from the tricuspid ring, and thereafter increased to 1.4 0.3 at 2 cm, and 1.5 0.3 at 3 cm as peak velocity fell. The ratio of the longest and shortest jet width cross section was 1.3 0.3 at ring level, and increased to 1.5 0.3 at 3 cm from ring level. Jet cross sectional area was 10.4 2.1 cm2 at ring level, and was unchanged at 3 cm level. Thus, tricuspid inflow velocity showed a relatively flat profile at the tricuspid ring and tip level, becoming more dispersed at 2 and 3 cm from the ring. Right ventricular inflow jet cross section was elliptic, and appeared to be relatively constant in the cross- sectional area.
International Journal of Cardiac Imaging 09/1997; 13(5):433-436.
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ABSTRACT: BackgroundA protein called “secreted protein acidic and rich in cysteine” (SPARC) may be important in the progression of diabetic nephropathy.
Recent animal studies have shown a possible correlation between SPARC levels and diabetes-related kidney growth.
MethodsWe measured serum levels of SPARC in patients with diabetic nephropathy and compared them to the severity of glomerular lesions
as determined by renal biopsy. A total of 50 non-insulin-dependent diabetic patients were divided into 2 groups; patients
with endstage diabetic nephropathy (ESDN, n=10) or without ESDN (DM, n=40). Renal biopsies were performed in all patients
without ESDN. Serum levels of SPARC were measured by enzyme-linked immunosorbent assay (ELISA) in the 50 patients with diabetes,
in 10 healthy controls, and in 10 patients with immunoglobulin (Ig) A nephropathy. Values for serum creatinine, creatinine
clearance, β2-microglobulin, and hemoglobin A1C also were obtained.
ResultsThe mean serum SPARC levels (ng/mL) were 29±12, 41±21, 43±20, and 85±28, for healthy controls, IgA nephropathy, DM, and ESDN
patients, respectively. Serum SPARC levels showed a significant increase with an increase in severity of glomerular diffuse
lesions. Serum levels of SPARC were significantly higher in the DM group than in controls, and significantly higher in the
ESDN group than in the control, IgA nephropathy and DM groups.
ConclusionThe findings suggest that SPARC may contribute to the progression of diabetic nephropathy.
Clinical and Experimental Nephrology 05/1997; 1(2):115-120. · 1.37 Impact Factor
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ABSTRACT: Severe ballooning of the glomerular tufts was observed in a 65-year-old man who was treated with mitomycin C (MMC) and had typical MMC-induced renal lesions. He developed renal failure and severe anaemia 6 months after initiation of chemotherapy. Ballooned tufts were caused by enormous expansion of the sub-endothelial space simultaneously associated with mesangiolysis. Glomerular cysts, described in a variety of disorders including thrombotic microangiopathy and diabetes mellitus, are derived from cystically dilated and united capillary luminae secondary to mesangiolysis. The morphogenesis of this unusual lesion when induced by MMC differs from that of the glomerular cysts previously reported.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/1992; 420(6):545-551. · 2.49 Impact Factor
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ABSTRACT: A sinus of Valsalva aneurysm rupture into the right atrium was detected by intravenous contrast echocardiographic negative jet, although transthoracic color Doppler flow mapping suggested that the rupture communicated with the right ventricle.
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ABSTRACT: We report the case of a 57-year-old woman with systemic lupus eryth- ematosus associated with a ruptured sinus of Valsalva aneurysm. The physical examina- tion showed a holosystolic murmur at the left fourth intercostal space. Aortography revealed that the sinus of Valsalva aneurysm had ruptured into the right ventricle. Surgical closure of the ruptured aneurysm was successfully carried out. This aneurysm and its rupture may have been due to endocarditis involving the sinus of Valsalva.
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ABSTRACT: Bacteriophage λ surface display was used to isolate cDNA clones encoding autoantigens recognized by sera from patients with Sjögren's syndrome (SS). We made cDNA libraries from human HeLa and HepG2 cells, using the expression vector λfoo. By repeating affinity selection of the libraries with the sera immobilized in microtiter wells, we isolated three clones that encode previously unknown antigens as well as four clones previously known as SS autoantigens. The newly identified autoantigens include TRK-fused gene product (TFG), survival motor neuron gene product (SMN) and pM5, which has a similarity to the metal-binding domain of human fibroblast collagenase. Thus, the bacteriophage λ surface display is powerful for isolating cDNA clones by affinity screening.
Gene.
