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Biomedical subjects

S Obara

Publications and source records attributed to S Obara.

At least 19 recordsLinked to original sources
PubMed2004

Monitoring of T-cell repertoire was useful for predicting graft-versus-host disease prognosis in a patient with chronic myelogeneous leukemia after allogeneic bone marrow transplantation.

We analyzed 24 T-cell receptor (TCR)beta chain subfamilies (Vbeta) and the chimerism of a patient with chronic myelogeneous leukemia who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed liver dysfunction at day 19 leading to worsening of his condition. He died on day 91 of hepatic failure. Complete donor chimerism was observed after day 19. The average complexity score of TCR-Vbeta, which was low on day 19 (5.50), because much lower on day 82 (3.77). The average value of normal volunteers is 7.69. Neither immunosuppressive therapy nor antiviral therapy was effective to treat his hepatic dysfunction. A liver specimen at autopsy showed necrotic tissue with invasion of lymphocytes under the endothelial cells of the bile ducts. These findings suggest that the liver dysfunction was due to graft-versus-host disease (GVHD). Careful monitoring of chimerism and TCR-Vbeta complexity may help to predict the prognosis of GVHD after allogeneic BMT.

Adult↗
PubMed2004

Successful non-T-cell-depleted nonmyeloablative hematopoietic stem cell transplantation (NST) from an HLA-haploidentical 2-loci-mismatched sibling in a heavily transfused patient with severe aplastic anemia based on the fetomaternal microchimerism.

A 37-year-old Japanese man with systemic hemochromatosis due to multiple transfusions was referred to us for the treatment of severe aplastic anemia (SAA), from which he had been suffering for 24 years. The patient had diabetes arising from the hemochromatosis, chronic anal fissures, and a kidney abscess due to neutropenia. He was treated with a nonmyeloablative preconditioning regimen followed by non-T-cell-depleted (non-TCD) allogeneic peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical 2-loci-mismatched sibling. Prompt engraftment of granulocytes and platelets was observed, and graft-versus-host disease was easy to control. Noninherited maternal antigens in the donor were confirmed prior to PBSCT, and they were also detected in small quantities in the recipient. This report describes the first successful nonmyeloablative hematopoietic stem cell transplant in a heavily transfused SAA patient from an HLA-haploidentical 2-loci-mismatched sibling donor. The result suggests that a long-term fetomaternal microchimerism-positive sibling can be a second-line donor if an alternative HLA-identical donor is not available.

Adult↗
PubMed2003

Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin's lymphoma.

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.

Aged↗
PubMed2001

Treatment modalities for oral verrucous carcinomas and their outcomes: contribution of radiotherapy and chemotherapy.

BACKGROUND: This clinical study focused, firstly, on the results of treatment and, secondly, on the anaplastic transformation, of oral verrucous carcinomas (OVCs) diagnosed and treated from 1981 to 1997 at the Department of Oral and Maxillofacial Surgery at Shimane Medical University Hospital. METHODS: We analyzed the treatment modalities and outcomes for 15 patients with OVC. RESULTS: Excluding the results for 4 palliatively treated patients, the disease-free survival rates of the patients after the initial treatments, were 82% at 5 years and 66% at 10 years; for all 15 patients, these rates were 57% and 46%, respectively. Surgery alone and surgery combined with other treatments (such as radiotherapy and chemotherapy) appeared to yield disease-free survival rates to those achieved superior with other treatments whether single or combined; (78% vs 33% for 5-year disease-free survival; 52% vs 33% for 10-year disease-free survival); however, the difference was not significant (P = 0.47). Well differentiated squamous cell carcinomas (W-SCCs) (n = 5) as well as spindle cell carcinoma (n = 1) were found in subsequent operative or biopsy specimens. CONCLUSION: Surgery was the most reliable treatment method for OVC; however, radiotherapy combined with chemotherapy was the next most preferable treatment when surgery was not undertaken. We also found that highly malignant transformation (anaplastic transformation) occasionally occurred during treatments for OVC.

Aged↗
PubMed2000

Anandamide induces apoptosis of PC-12 cells: involvement of superoxide and caspase-3.

Anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor ligand has been suggested to have physiological role in mammalian nervous system. However, little is known about the role of anandamide on neuronal cells. Here, we demonstrate that anandamide causes death of PC-12 cells, showing marked DNA condensation and fragmentation, appearance of cells at sub-G(0)/G(1) and redistribution of phosphatidyl serine, the hallmark features of apoptosis. Anandamide raised intracellular superoxide level and CPP32-like protease activity in PC-12 cells markedly. Furthermore, antioxidant N-acetyl cysteine prevented anandamide-induced superoxide anion formation and cell death, implying that intracellular superoxide is a novel mediator of anandamide-induced apoptosis of PC-12 cells.

Acetylcysteine↗
PubMed1999

The effect of trihexyphenidyl, an anticholinergic agent, on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease.

Cerebral blood flow and oxygen metabolism were studied in six previously untreated patients with Parkinson's disease (PD) before and after anticholinergic treatment using positron emission tomography (PET) and compared with six controls. The PET study and an assessment of the disability and cognitive impairment were performed before and after administration of 6 mg trihexyphenidyl for 5 to 11 weeks. All PD patients showed improvements in motor symptoms after the trihexyphenidyl treatment. Cognitive function did not significantly differ between before and after trihexyphenidyl treatment. However, after trihexyphenidyl treatment, rCBF and rCMRO2 decreased by 15% in the striatum and by 10% in all cortical areas contralateral to predominantly symptomatic limbs, and by 10% in the ipsilateral striatum and all cortical areas, significantly below the values of controls in most cerebral cortices and striatum. These findings suggest that trihexyphenidyl inhibits the cortical cholinergic system and significantly decreases rCBF and rCMRO2 in the cerebral cortices without cognitive impairment in untreated patients with PD.

Cerebrovascular Circulation↗
PubMed1999

Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195.

AIMS/HYPOTHESIS: Advanced glycation end products (AGEs) participate in the pathogenesis of diabetic nephropathy. We reported earlier that OPB-9195, a synthetic thiazolidine derivative and novel inhibitor of advanced glycation, prevented progression of diabetic glomerulosclerosis by lowering serum concentrations of advanced glycation end products and reducing their deposition in the glomeruli. Here, we examined their contribution and that of growth factors, such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF), to the progression of diabetic nephropathy. We also investigated the expression of type IV collagen in the kidneys of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model, after treatment with OPB-9195. METHODS: Using northern blots and immunohistochemical techniques, we determined the renal expression of TGF-beta and type IV collagen mRNAs and proteins in OLETF rats. We also examined OPB-9195's effects on renal expression of VEGF mRNA and protein. RESULTS: Concomitant increases in TGF-beta and type IV collagen expression were observed at each point in time in OLETF rats not given OPB-9195. In contrast, OPB-9195 treatment greatly suppressed the renal expression of TGF-beta, VEGF and type IV collagen mRNAs and proteins to that seen in non-diabetic rats. CONCLUSION/INTERPRETATION: Since OPB-9195, an AGE-inhibitor, prevented the progression of diabetic nephropathy by blocking type IV collagen production and suppressing overproduction of two growth factors, TGF-beta and VEGF, in diabetic rats, this compound warrants further investigation.

Animals↗
PubMed1999

Dry coating: an innovative enteric coating method using a cellulose derivative.

A novel enteric coating method was developed. This method involves direct feeding of coating polymer powder and simultaneous spraying of plasticizing agent, without either organic solvent or water, using a centrifugal granulator, fluidized bed, or tablet-coating machine. For film formation, a curing step was then necessary; this involved spraying a small amount (3-8% of core weight) of water or hydroxypropyl methylcellulose solution, followed by heating. Hydroxypropyl methylcellulose acetate succinate was used as the enteric coating polymer, and a combination of triethyl citrate and acetylated monoglyceride was used for plasticization. The coated beads and tablets were evaluated for gastric resistance, intestinal disintegration, and stability, in comparison with beads and tablets from a conventional aqueous coating with the same enteric polymer. The new method required a higher coating amount for gastric resistance compared with the conventional coating, but the processing time was dramatically reduced. The results show that this dry coating method is applicable to the preparation of enteric-coated beads and tablets using commercially available lab-scale apparatus.

Drug Stability↗
PubMed1999

A three-month repeated oral administration study of a low viscosity grade of hydroxypropyl methylcellulose in rats.

The toxicity of the lowest viscosity grade of hydroxypropyl methylcellulose (HPMC) that is currently commercially available was investigated by means of a three-month repeated oral administration study in male and female Crj:CD (SD) IGS rats at doses of 505, 1,020 and 2,100 mg/kg/day. Body weights of males and females in the 2,100 mg/kg group were lower than those of the control group on and after day 28 of administration, but the differences were not statistically significant. The degree of suppression of body weight gain in males was higher than that in females. This tendency was similar to the results in other toxicity studies of HPMC that have been reported. Males in the 2,100 mg/kg group showed a tendency (not significant) for decreased food consumption and urine volume. Examinations of general signs, hematology, blood chemistry, ophthalmology, absolute and relative organ weights, autopsy and histopathology revealed only a few, apparently coincidental, statistically significant differences from the control, and no evidence of any dose-dependent changes was found. It was concluded that the lowest viscosity grade of HPMC showed extremely low toxicity under the conditions of this study, as has been found for higher viscosity grades.

Administration, Oral↗
PubMed1998

Cerebral blood flow and oxygen metabolism before and after a stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

Cerebral blood flow and oxygen metabolism were examined in two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) using positron emission tomography (PET). Regional cerebral blood flow (rCBF), regional cerebral oxygen metabolic rate (rCMRO2) and regional oxygen extraction fraction (rOEF) were determined with the steady-state technique using oxygen-15-labeled tracers (15O2, C15O2 and C15O). Case 1, a 45-year-old woman, presented with abrupt onset of fluent aphasia. T2-weighted magnetic resonance imaging (MRI) showed a high signal intensity lesion in the left temporoparietal region. The first PET study on day 16 showed increased rCBF and decreased rCMRO2 in the temporal region. In the second PET study, on day 35, rCBF in the temporal region had decreased. Case 2 was a 19-year-old male; the second son of Case 1. He complained of transient blurring of vision, and then generalized tonic-clonic convulsion occurred. A PET study six days before this stroke-like episode demonstrated increased rCBF in both frontal lobes and putamen, where MRI showed lesions after the episode. Focal hyperemia of the lesion antedated and lasted for at least sixteen days after the stroke-like episode in these MELAS patients. These stroke-like episodes appear to be the result of metabolic dysfunction in neural tissue, although the role of an ischemic vascular event cannot be ruled out.

Adult↗
PubMed1998

Application of extremely low viscosity methylcellulose (MC) for pellet film coating.

Pellet film coating has very limited applicability compared with tablet film coating, because of the problem of sticking during fluidized bed operation. We have prepared an extremely low viscosity methylcellulose (MC) (4 mPa.s), and examined its solution and film properties and its suitability for pellet film coating. MC lost its adhesiveness at a relatively high moisture content and pellet film coating could be achieved without agglomeration of the pellets within a reasonable operating time. The coated pellets were covered with a continuous film of MC, and drug release from the coated pellets was as rapid as that from the core. These findings suggest that MC (4 mPa.s) is applicable for pellet film coating in an aqueous system.

Gels↗
PubMed1998

Skin sensitization and photosensitization studies of hydrophobically modified hydroxypropyl methylcellulose in guinea pigs.

Skin sensitization and photosensitization tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, were conducted using guinea pigs. An aqueous dispersion of HM-HPMC (3 w/v %) was applied in the tests. Skin reaction was not observed in any animal in the HM-HPMC-treated group or control group. In the photosensitization test, no skin reaction was found in any animal in the test-preparation group or the control group. It was concluded that HM-HPMC dispersion does not exhibit skin sensitizing or photosensitizing activity under the condition of this test.

Adjuvants, Pharmaceutic↗
PubMed1997

Calcifying epithelioma (pilomatrixoma) of the head and neck: analysis of 37 cases.

OBJECTIVE: To review all cases of pilomatrixoma (calcifying epithelioma) of the head and neck published in Japanese dental journals 1977-1994. DESIGN: Retrospective review. SETTING: University hospital, Japan. SUBJECTS: 37 Patients with 38 tumours, mean age 23 years, female: male ratio 2.4:1. INTERVENTIONS: Enucleation alone (n=29, 78%), excision including covering skin (n=7, 19%), or excision including superficial lobe of parotid (n=1, 3%). MAIN OUTCOME MEASURE: Presentation, site, recurrence, and histological features. RESULTS: Two patients had multiple tumours (5%). Most of the tumours were firm nodules covered with normal skin varying in size from 5 to 30 mm. The most common site was the preauricular region; 22 (58%) were in the anterior part. The follow up period ranged from 7 to 43 months during which there was only one recurrence. Tumours were encapsulated and solid composed of either shadow and basophilic cells or shadow cells alone, and the stroma contained varying amounts of calcification, ossification, and keratinization. CONCLUSIONS: The diagnosis should be suspected when the mass is adherent to the skin but not fixed to the underlying tissue. It is difficult to distinguish between benign and malignant tumours by imaging methods alone, so the recommended treatment must be complete excision including adherent skin.

Adolescent↗