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Biomedical subjects

Masayuki Tomita

Publications and source records attributed to Masayuki Tomita.

12 recordsLinked to original sources
PubMed2006

Reducing the dose of antipsychotic agents ameliorates visual hypersensitivity attack: an ideal treatment option in terms of the adverse effect.

There are sporadic reports of antipsychotic-induced visual hypersensitivity attack (VHA). VHA is characterized by hypersensitivity of perception mainly in the visual modality and sometimes accompanied by an oculogyric crisis. However, some researchers regard VHA as a schizophrenia symptom. To determine whether VHA is an adverse effect of antipsychotic agents, we examined the effect of dose reduction on VHA. This was an open-label 36-week study. We randomized 34 patients with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures were the frequency and duration of VHA, assessed with patients' self-reports, and the Clinical Global Impressions (CGI). Assessment also included the Drug-induced Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric hospitals in Tokyo.VHA diminished in 16 patients (94.1%) in the reduced-dose group in the CGI score, the frequency (number of episodes per week), and the duration of the episodes (from 4.06 to 1.77, P < 0.001; from 2.59 to 0.82, P = 0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no changes in the fixed-dose group. There were no changes in the underlying illness as measured by the PANSS in both groups. Reducing the dose of antipsychotic agents ameliorates VHA and represents the ideal treatment option for patients with VHA.

Adolescent↗
PubMed2005

Monoclonal antibody 1-22-3-induced glomerulonephritis in uninephrectomized rats as a model of progressive renal failure.

BACKGROUND: At present, there are few available animal models of progressive renal failure originating from mesangial proliferative glomerulonephritis (GN). In the current study, we examined the usefulness of anti-Thy-1 monoclonal antibody (mAb) 1-22-3-induced GN in uninephrectomized rats as a model of progressive renal failure by analysing the similarities to human disease. METHODS: GN was induced by intravenous injection of mAb 1-22-3 into uninephrectomized male Wistar rats. The natural course of the disease was analysed in this model for 47 weeks. The effect of treatment with the angiotensin-converting enzyme inhibitor, captopril, on renal functional outcome was also examined in this model for 23 weeks, beginning from 1 week after antibody injection. RESULTS: Injection of mAb 1-22-3 induced a persistent proteinuria during the entire study period. Animals showed a progressive decline in renal function and 63% died by week 47. Severe glomerular and tubulointerstitial lesions were consistently observed. Treatment with captopril significantly inhibited increases in proteinuria and blood pressure, and attenuated renal injury. Captopril also retarded the progression of renal failure, and decreased mortality. Finally, the level of proteinuria was significantly correlated with the rate of decline in renal function, and the reduction in proteinuria by captopril was accompanied by a slower progression of renal failure. CONCLUSIONS: The mAb 1-22-3-induced GN in a uninephrectomized rat model simulates the clinical manifestations of human disease, indicating that this model may be useful for studying progressive renal failure and for investigating new therapeutic strategies against renal failure.

Animals↗
PubMed2005

Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists.

Two novel classes of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective EP(4) antagonists have been discovered. The optimized diphenyloxzole 8 and Ndelta-Z-ornithine 11 effectively competed with [(3)H]PGE(2) binding to human recombinant EP(4), with K(i) values of 0.30 nM and 0.91 nM, respectively, and were selective for all members of the human prostanoid receptor family. 8 was shown to exhibit good pharmacokinetic properties in rats and dogs and potent inhibitory activity toward in vitro PGE(2)-promoted IgE synthesis.

Adjuvants, Immunologic↗
PubMed2005

[Primary, nonviral, hepatocellular carcinoma in patients with prostate cancer treated by hormone therapy: 2 case reports].

We studied two cases of primary, hepatocellular carcinoma (HCC) that occurred following hormone therapy (estrogen therapy in one case and total androgen blockade therapy in another) for stage D2 prostate cancer. Prostate cancer is considered to be hormone-dependent, and androgens appear to be important hormonal factors. However, hepatocellular carcinoma has been shown to have both estrogen and androgen receptors, suggesting that this may be dependent on estrogen or androgen. Reported here are two unique cases of hepatocellular carcinoma in patients with prostate cancer; the pathogenesis of HCC in these patients was suspected to be related to diethylstilbestrol (DES) therapy and antiandrogen therapy for their prostate cancer.

Aged↗
PubMed2004

Decreased collagen-degrading activity could be a marker of prolonged mesangial matrix expansion.

BACKGROUND: Mesangial matrix expansion is caused by the overproduction and/or the impaired proteolytic degradation of the extracellular matrix. However, the relative contribution of these changes to the development of prolonged mesangial matrix expansion is still poorly understood. We aimed to elucidate the relative role of the matrix metalloproteinase (MMP)/tissue inhibitors of metalloproteinases (TIMPs) system in the development of prolonged mesangial matrix expansion. METHODS: We prepared two rat models, showing reversible or prolonged mesangial matrix expansion, induced by a single injection or two consecutive injections of anti-Thy-1.1 monoclonal antibody 1-22-3, respectively. We analyzed the glomerular expression of type I and type IV collagens; MMP-2, -9, and -13; membrane type 1-MMP (MT1-MMP); TIMP-1; and urinary type I collagen-degrading activity in both models. RESULTS: There were no differences in glomerular mRNA levels of type I and type IV collagens between the reversible and the prolonged models. MMP-9 mRNA expression and protein level was lower in the prolonged model than in the reversible one, whereas there were no differences in mRNA levels of MMP-2, -13, MT1-MMP, or TIMP-1 between the two models. Urinary type I collagen-degrading activity in the prolonged model was lower than that in the reversible one. Furthermore, there was a significant correlation between the mesangial matrix expansion and urinary type I collagen-degrading activity. CONCLUSIONS: Impaired expression of MMP-9 may contribute to the development of prolonged mesangial matrix expansion. Analysis of urinary type I collagen-degrading activity may provide additional diagnostic information in mesangial proliferative glomerulonephritis. Mesangial matrix expansion is caused by the overproduction and/or the impaired proteolytic degradation of the extracellular matrix. However, the relative contribution of these changes to the development of prolonged mesangial matrix expansion is still poorly understood. We aimed to elucidate the relative role of the matrix metalloproteinase (MMP)/tissue inhibitors of metalloproteinases (TIMPs) system in the development of prolonged mesangial matrix expansion.

Animals↗
PubMed2003

Phosphodiesterase type 5 inhibition ameliorates nephrotoxicity induced by cyclosporin A in spontaneous hypertensive rats.

Our recent study suggests that there is a reciprocal mechanism to maintain cGMP content, via both a decrease in cGMP degradation (decrease in cGMP-phosphodiesterase activity) and an increase in synthesis of cGMP (increase in guanylate cyclase activity) in the kidney of cyclosporin A-treated rats. We undertook this study to clarify the role of cGMP-phosphodiesterase in cyclosporin A nephrotoxicity by evaluating N-(3,4-dimethoxybenzyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide (FR226807), a phosphodiesterase type 5 inhibitor, in an animal model. Male spontaneous hypertensive rats (SHR) were treated with cyclosporin A (50 mg/kg) for 2 weeks or with cyclosporin A and FR226807 (3.2 mg/kg or 10 mg/kg) for 2 weeks. Cyclosporin A-treated rats showed renal dysfunction and histological change compared with vehicle-treated rats. Administration of FR226807 improved the renal dysfunction (increase in serum creatinine and fractional excretion of sodium, and decrease in creatinine clearance) as well as the pathological changes (tubular vacuolization) induced by cyclosporin A in SHR. At the molecular level, administration of FR226807 resulted in a further increase in cGMP content in the kidney, aorta and platelets from cyclosporin A-treated rats. Our present study demonstrates that cGMP-phosphodiesterase plays an important role in the cyclosporin A nephrotoxicity and also suggests that further inhibition of cGMP-phosphodiesterase is a potential pharmacological target for preventing cyclosporin A nephrotoxicity.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia.

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.

Adolescent↗
PubMed2002

FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3.

BACKGROUND: We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. METHODS: The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. RESULTS: FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-gamma (IFN-gamma; 1.0 mg/kg BW FK506, 32.4% to the placebo group, P < 0.01) and IL-2 (55.6%, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 +/- 0.89 vs. 19.8 +/- 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 +/- 3.1 vs. 80.2 +/- 7.4, P < 0.01; matrix expansion, 0.90 +/- 0.30 vs. 1.34 +/- 0.27, P < 0.05; alpha-smooth muscle actin (alphaSMA) expression; 1.20 +/- 0.12 vs. 1.96 +/- 0.29, P < 0.01] on day 14. CONCLUSION: Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.

Animals↗
PubMed2002

[A case of complete self-mutilation of penis].

Self-mutilation of the penis is extremely rare. A 69-year-old man was admitted after having amputated his own penis completely from its root. He had no history of psychiatric illness, but his physical condition on admission was abnormal. We performed urethrocutaneostomy, rather than replantation of the penis, because of the danger that he would reinjure himself. The patient was treated by a psychiatrist under a diagnosis of alcoholic dementia. To our knowledge, this is the 24th case of self-mutilation of the penis reported in the Japanese literature.

Aged↗
PubMed2002

[Malignant fibrous histiocytoma of perirenal tissue: a case report].

A 75-year-old woman was admitted to our hospital with an extremely large retroperitoneal tumor that had been detected with ultrasound on a routine health check. She had no complaint except lumbar pain. Computed tomography revealed a heterogenous tumor located outside the right kidney which was enhanced gradually. Doppler ultrasound showed mild vascularity in the tumor. We performed tumorectomy and right nephrectomy because the tumor was adherent to the right kidney. The tumor was 16 x 11 x 7 cm in size and weighed 621 g. The histopathological diagnosis was malignant fibrous histiocytoma. The tumor was considered to have arisen from perirenal tissue.

Aged↗
PubMed2002

[A case of lung collapse caused by endobronchial metastasis from renal cell carcinoma reinflated with laser and electrosurgical snaring].

A 62-year-old woman, who had undergone left nephrectomy for renal cell carcinoma and had received interferon-alpha for metastasis to the lung, was hospitalized because of cough, dyspnea and anorexia 16 months after nephrectomy. Chest radiography showed collapse of the right lung. We performed bronchoscopy and found a red polypoid tumor completely obstructing the right bronchus. Biopsy specimens showed clear cell carcinoma, similar to previous specimens of renal cell carcinoma. We removed the endobronchial tumor with laser and electrosurgical snaring, after which the right lung reinflated.

Bronchial Neoplasms↗