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Biomedical subjects

Takashi Harada

Publications and source records attributed to Takashi Harada.

At least 19 recordsLinked to original sources
PubMed2006

Dopamine D(2) receptor expression and regulation of gonadotropin alpha-subunit gene in clonal gonadotroph LbetaT2 cells.

This study investigated the role of dopamine on the regulation of gonadotropin secretion at the gonadotroph cell line. We examined the function of the dopamine D(2) receptor in the regulation of pituitary gonadotropin gene expression using LbetaT2 cells, a mature, well differentiated clonal gonadotroph cell line. The presence of the dopamine D(2) receptor in the LbetaT2 cells was confirmed by both RT-PCR and Western blot. Gonadotropin releasing hormone (GnRH) stimulation resulted in gonadotropin LHbeta, FSHbeta and alpha-subunit promoter activation, and none were inhibited by quinpirol, a specific dopamine D(2) receptor agonist. Pituitary adenylate cyclase-activating polypeptide (PACAP) increased gonadotropin alpha-subunit promoter activity, but not LHbeta and FSHbeta promoter activity. The activity of PACAP was significantly inhibited in the presence of quinpirol. The protein kinase A inhibitor, H89, also inhibited PACAP-induced alpha-subunit gene expression. PACAP increased intracellular cAMP more than GnRH did in LbetaT2 cells, and the elevation of cAMP was strongly inhibited in the presence of various dopamine D(2) agonists. These results suggest that in pituitary gonadotrophs, the dopamine D(2) receptor is a negative regulator of gonadotropin alpha-subunit gene expression which is induced by cAMP-elevating factors in a cAMP-dependent pathway.

Animals↗
PubMed2005

Long-term mortality outcome in patients with reactive amyloidosis associated with rheumatoid arthritis.

It is well established that amyloidosis is a serious clinical complication that can influence the prognosis of patients with rheumatoid arthritis (RA). The purpose of the study was to obtain information on the survival and the hemodialysis (HD) of patients with amyloidosis. Eighty patients (9 men and 71 women) who were diagnosed with amyloidosis by biopsy and definite or classical RA were studied retrospectively. The average duration of RA prior to the diagnosis of amyloidosis was 15.4+/-9.4 years. The average period from the diagnosis of amyloidosis to death was 67.4 months. Forty-nine patients died of the disease (32 cases with HD and 17 cases without HD). Thirty-one patients lived (7 cases with HD and 24 cases without HD). Regarding the survival of these patients, 49 (61.3%) of the 80 patients have died. Survival rate at 28 months was 75%; at 67 months, it was 50%; and at 111 months, it was down to 25%. Mortality rate was 11.9% per year. Survival rate in dialysis at 9.8 months was 75%; at 60.6 months, it dropped to 50%; and at 100.0 months, to 25%. As for patients' survival, high onset age of amyloidosis was the major determining factor for poor survival in these patients (p<0.001). Furthermore, male patients also had poor survival (p=0.07). The long-term results were very encouraging to initiate HD in patients with end-stage renal disease due to reactive amyloidosis associated with RA.

Age of Onset↗
PubMed2005

Tissue-specific expression of renin-angiotensin system components in IgA nephropathy.

BACKGROUND: The renin-angiotensin II system (RAS) has been implicated in the development of glomerulonephritis. The aims of this study were to determine (1) the expression of RAS components, angiotensin (Ang II)-forming enzymes [angiotensin-I-converting enzyme (ACE) and chymase], and Ang II receptors, and (2) the correlation between RAS expression and severity of tissue injury in IgA nephropathy (IgAN). METHODS: The expression levels of ACE, chymase, and Ang II type 1 and type 2 receptor (AT1R and AT2R) mRNAs were determined by in situ hybridization in renal specimens from 18 patients with IgAN, 5 patients with non-IgA mesangial proliferative glomerulonephritis (non-IgAN) and 10 patients with nonmesangial proliferative glomerulonephritis (minimal change nephrotic syndrome, n = 5, and membranous nephropathy, n = 5). Normal portions of surgically resected kidney served as control. RESULTS: In normal kidney, a few mesangial cells and glomerular and tubular epithelial cells weakly expressed ACE, chymase and AT1R mRNAs. In IgAN and non-IgAN samples, ACE, chymase, AT1R and AT2R mRNAs were expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells and cells of Bowman's capsule. The glomerular expressions in IgAN were stronger than in minimal change nephrotic syndrome and membranous nephropathy. In IgAN, the expressions in glomeruli correlated with the degree of mesangial hypercellularity, whereas the expression levels were weaker at the area of mesangial expansion. IgAN with severe tubulointerstitial injury showed expression of ACE, chymase, AT1R and AT2R mRNAs in atrophic tubules and infiltrating cells and such expression correlated with the degree of tubulointerstitial damage. CONCLUSION: Our results suggest that renal cells can produce RAS components and that locally synthesized Ang II may be involved in tissue injury in IgAN through Ang II receptors in the kidney.

Adult↗
PubMed2005

Nephronophthisis in two siblings.

We describe here two sisters with nephronophthisis, which was not detected until the development of endstage renal failure. Twenty- and 15-year-old female siblings were admitted to our hospital for further examination of renal dysfunction. No urinalysis abnormalities had been found in yearly health checks in either patient. The serum creatinine level was 7.2 mg/dl in case 1 (the 20-year-old) and 6.4 mg/dl in case 2. Medical history, physical findings, and laboratory tests showed no evidence of urinary tract infection, use of any drugs, arthritis, or skin eruptions. To identify the cause of the renal failure, open left renal biopsies were performed in both patients. Histopathological findings were very similar in the two patients and included marked tubular and interstitial changes (tubular dilatation, focal tubular atrophy, interstitial fibrosis, and infiltration of mononuclear cells). The glomeruli were devoid of mesangial proliferation, mesangial expansion, and adhesion of Bowman's capsule. Based on the clinical and pathological findings, the final diagnosis was nephronophthisis in both patients. It is important to remember that some progressive renal diseases, including nephronophthisis, cannot be detected even by annual urinary screening tests, which are widely performed in Japan.

Adolescent↗
PubMed2005

Systemic lupus erythematosus in identical twins: a case report.

In this report we describe the case of identical twin sisters that developed systemic lupus erythematosus (SLE). These patients have in common major histocompatibility complex class I and class II alleles and identical red blood cell antigens, which is a clear indication of monozygotic twins. Both twins showed high titers of anti-dsDNA antibody. However, only one of them manifested signs of lupus psychosis and was positive for the LE test, rheumatoid factor, anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived together; therefore, the environmental factors were considered to be the same. Interestingly, these patients expressed different types of autoantibodies and the manifestation of disease was also quite different. When one of the twins was diagnosed with SLE, we began to closely follow up signs of the disease in the other twin periodically. This enabled us to promptly diagnose the second twin with SLE and she was successfully treated without progression of the disease. It is important to mention that following up the subsequent history of an identical twin diagnosed with SLE allowed early detection of the disease in the other twin.

Journal Article↗
PubMed2005

[Feasibility of cardiopulmonary rehabilitation in patients with idiopathic pulmonary arterial hypertension treated with intravenous prostacyclin infusion therapy].

OBJECTIVES: To evaluate cardiopulmonary rehabilitation in patients with idiopathic pulmonary arterial hypertension who had severe heart failure. METHODS: The subjects comprised 11 men and 13 women aged 5 to 37 years old with idiopathic pulmonary arterial hypertension, who received cardiopulmonary rehabilitation following the start of continuous intravenous prostacyclin administration between January 1999 and September 2003. Fifteen patients were categorized in New York Heart Association (NYHA) functional class-III and 9 were class-IV on admission. Patients received cardiopulmonary rehabilitation consisting of breathing exercise, training of upper extremity muscles, gait training, bicycle ergometer training, and treadmill walking for 30 to 60 min per day, 5 days a week. Cardiothoracic ratio, NYHA class, heart rate, pulse oximeter saturation, plasma levels of human atrial natriuretic peptide and brain natriuretic peptide, tricuspid regurgitation, and right ventricular myocardial index (RV Tei index) were evaluated by echocardiography, lower extremity muscle strength, ambulation ability, Barthel index, and 6-minute walking distance at the beginning and end of cardiopulmonary rehabilitation. RESULTS: The average period of cardiopulmonary rehabilitation was 6.7 weeks. There was no deterioration in cardiothoracic ratio, human atrial natriuretic peptide, brain natriuretic peptide levels, tricuspid regurgitation, RV Tei index and pulse oximeter saturation. The results also showed decreased heart rate at rest (p = 0.007), and improved NYHA class (p = 0.010), lower extremity strength (p < 0.001), ambulation ability (p < 0.001), Barthel index (p < 0.001), and 6-minute walking distance (p = 0.001). CONCLUSIONS: Cardiopulmonary rehabilitation is safe and effective for idiopathic pulmonary arterial hypertension patients in NYHA class-III and IV during intravenous prostacyclin infusion without deterioration of cardiac functions, despite the conventional contraindication.

Activities of Daily Living↗
PubMed2004

Establishment of immortalized human glomerular endothelial cell lines and their application.

BACKGROUND: The experimental use of cultured endothelial cells derived from the microvasculature such as glomerular endothelial cells possesses many problems, including limited growth rates, heterogeneity and loss of specific cell properties dependent on culture passage. In this study, we attempted to establish immortalized, human glomerular endothelial cell (HGEC) lines. METHODS: HGECs of up to 5 passages were transformed by infection with simian virus (SV)-40. After 4-6 weeks the surviving, foci-forming cells were harvested and cloned. Each cell line obtained was examined by immunofluorescence with antibodies to antigens specific for vascular endothelial cells. The expression of adhesion molecules on cells incubated with or without TNF-alpha was also examined by cellular ELISA. RESULTS: Three of twelve cell lines obtained expressed SV40 large T-antigen and von Willebrand's factor, as well as endothelial cell adhesion molecules including ICAM-1 (CD54), PECAM-1 (CD31) and E-selectin (CD62E). In these cells, ICAM-1 and E-selectin expression was up-regulated by TNF-alpha, as in native cultured HGEC. CONCLUSIONS: These cell lines maintain the morphologic and functional characteristics of HGEC even after 60 passages. Immortalized HGEC will be useful for research on glomerular cell biology and provide a standardized substrate for anti-endothelial cell antibody detection.

Antigens↗
PubMed2004

Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells.

The hepatitis C virus (HCV) envelope E2 glycoprotein is a key molecule regulating the interaction of HCV with cell surface proteins. E2 binds the major extracellular loop of human CD81, a tetraspanin expressed on various cell types including hepatocytes and B lymphocytes. Regardless, information on the biological functions originating from this interaction are largely unknown. Since human hepatic stellate cells (HSC) express high levels of CD81 at the cell surface, we investigated the E2/CD81 interaction in human HSC and the possible effects arising from this interaction. Matrix metalloproteinase-2 (MMP-2; gelatinase A), a major enzyme involved in the degradation of normal hepatic extracellular matrix, was up-regulated following the interaction between E2 and CD81. In particular, by employing zymography and Western blot, we observed that E2 binding to CD81 induces a time-dependent increase in the synthesis and activity of MMP-2. This effect was abolished by preincubating HSC with an anti-CD81 neutralizing antibody. Similar effects were detected in NIH3T3 mouse fibroblasts transfected with human CD81 with identical time course features. In addition, E2/CD81 interaction in human HSC induced the up-regulation of MMP-2 by increasing activator protein-2/DNA binding activity via ERK/MAPK phosphorylation. Finally, suppression of CD81 by RNA interference in human HSC abolished the described effects of E2 on these cells, indicating that CD81 is essential for the activation of the signaling pathway leading to the up-regulation of MMP-2. These results suggest that HSC may represent a potential target for HCV. The interaction of HCV envelope with CD81 on the surface of human HSC induces an increased expression of MMP-2. Increased degradation of the normal hepatic extracellular matrix in areas where HCV is concentrated may favor inflammatory infiltration and further parenchymal damage.

Animals↗
PubMed2004

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).

BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study. RESULTS: There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed. CONCLUSIONS: The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.

Adult↗
PubMed2004

Clinical and immunohistochemical study of immunoglobulin A nephropathy (IgAN) before and after tonsillectomy.

Tonsillectomy often improves clinical features in immunoglobulin A nephropathy (IgAN), however, the mechanisms mediating clinical modifications are unclear. In the present study, we examined the immunohistological alterations in biopsy specimens obtained from IgAN patients before and after tonsillectomy. We investigated eight IgAN patients who underwent repeated renal biopsy in the present study. Immunohistochemistry for alpha-smooth muscle actin (alpha-SMA), CD68 and proliferating cell nuclear antigen (PCNA) were performed and histological findings were compared before and after tonsillectomy. None of the patients were treated with steroids or immunosuppressive drugs before second renal biopsy. The expression of alpha-SMA and the number of CD68 positive cells were significantly decreased in IgAN patients with improvement of proteinuria and hematuria after tonsillectomy. The degree of mesangial cell proliferation, expansion of mesangial area and the number of PCNA positive cells were not changed after tonsillectomy. These results suggest that the reduced number of activated mesangial cells and macrophages may be involved in the improvement of hematuria after tonsillectomy. They also suggest that tonsillectomy may improve proteinuria and hematuria in some patients with IgAN through reduction of mesangial cell activation and macrophage infiltration.

Actins↗