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M Okamoto

Publications and source records attributed to M Okamoto.

At least 37 records · Page 2Linked to original sources

Semileptonic decays of d mesons in three-flavor lattice QCD.

We present the first three-flavor lattice QCD calculations for D-->pilnu and D-->Klnu semileptonic decays. Simulations are carried out using ensembles of unquenched gauge fields generated by the MILC Collaboration. With an improved staggered action for light quarks, we are able to simulate at light quark masses down to 1/8 of the strange mass. Consequently, the systematic error from the chiral extrapolation is much smaller than in previous calculations with Wilson-type light quarks. Our results for the form factors at q(2)=0 are f(D-->pi)(+)(0)=0.64(3)(6) and f(D-->K)(+)(0)=0.73(3)(7), where the first error is statistical and the second is systematic, added in quadrature. Combining our results with experimental branching ratios, we obtain the Cabibbo-Kobayashi-Maskawa matrix elements |V(cd)|=0.239(10)(24)(20) and |V(cs)|=0.969(39)(94)(24), where the last errors are from experimental uncertainties.

Journal Article↗

Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions.

We examined chemical reactions in mouse lysozyme after incubation under physiological conditions (pH 7 and 37 degrees C). After incubation for 8 weeks, racemization was observed specifically at Asn127 among the 19 Asp/Asn residues in mouse lysozyme. Furthermore, analysis of the primary structure showed that the racemized residue was not Asp, but Asn, which demonstrates that deamidation and isomerization did not occur. These results mean that this racemization occurs without forming a succinimide intermediate. This is the first example of D-asparaginyl formation in a protein occurring during the racemization process under physiological conditions.

Amino Acid Sequence↗

Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients.

Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were used in a renal transplant transplant program since May 2000 including 67 patients in whom it was the primary drug. Acute rejection (AR) occurred in 9 cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK) studies of mycophenolic acid (MPA) were performed in 46 recent patients (total, 127 times). There was no correlation between dose (mg/kg) and blood concentration (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not with a single timepoint concentration. MPA AUC0-9 level was significantly higher among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR-positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after transplantation. MPA AUC0-9 level was higher among the adverse event (AE-positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation. These results suggest the necessity of measuring AUC for therapeutic drug monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present immunosuppressive regimen.

Adolescent↗

Twenty-five-year survival of living related kidney transplants: thirty-five years' experience.

AIM: Although better graft survival in patients treated with CsA has been obtained, chronic rejection continues to be a common complication in renal transplantation. In this study, we examined the graft survivals and complications among renal transplant patients followed for more than 25 years. METHODS: Between April 1970 and April 1979, 110 consecutive renal transplantations from living donors were performed in 110 patients. There were 83 men and 27 women of mean age of 27 +/- 7.0 years. A combination of azathioprine (AZ) and prednisolone (PSL) was used for the initial immunosuppressive therapy in all patients. RESULTS: Over 25 years postoperatively, 41 patients died with or without a functioning graft due to complications including infections and malignancies. Therefore, the 25-year patient survival was 62.5% and 34 patients returned to hemodialysis, yielding an actual 25-year graft survival of 36/110 (32.1%). The longest surviving graft is 30 years and 2 months. The main causes of death were infectious disease and malignancy; 73% of graft loss was due to chronic rejection. Mean serum creatinine of the patient with functioning grafts over 25 years is 1.2 mg/dL; 75% of patients displayed a value under 1.5 mg/dL. The mean dosage of Az was 52.3 mg/d and PSL was 5.6 mg/d.

Adult↗

Renovascular reconstruction of grafts with renal artery variations in living kidney transplantation.

INTRODUCTION: The shortage of grafts in living kidney transplantation has forced the use of marginal grafts with arterial disease or grafts with multiple renal arteries (MRA). We reviewed the outcomes of transplants using allografts with MRA procured by open donor nephrectomy and report two cases requiring vascular reconstruction. PATIENTS AND METHODS: We reviewed 31 cases where renovascular reconstruction of an MRA graft was performed. A ex vivo pantaloon (side-to-side) anastomosis to create a common channel was performed in 24 cases including two cases of renal artery aneurysms in the grafts, where vascular reconstruction was performed in the same fashion after resection of the aneurysm. In four cases, an accessory artery was anastomosed sequentially after revasculization of the main artery. In three cases of grafts with multiple renal arteries, multiple anastomoses were done in situ after various ex vivo renovascular reconstructions. RESULTS: Twenty one MRA grafts including grafts with a renal aneurysm are functioning well for a mean follow-up 135 months. The graft survival rate was 71.0% at 5 years after transplantation and 67.7% at 10 years. The donors whose grafts had a renal aneurysm were also well and normotensive with normal renal function at present. Ten grafts failed mainly due to chronic allograft nephropathy. CONCLUSION: MRA grafts procured by open nephrectomy, including those with renal artery aneurysms, were engrafted successfully by applying appropriate renovascular surgery. The use of those grafts was safe for both the recipient and the donor.

Anastomosis, Surgical↗

Improved graft survival in ABO-incompatible living donor kidney transplantation.

INTRODUCTION: We reviewed ABO-incompatible living donor kidney transplantations (LDKT) performed in our institute. PATIENTS: Fourteen ABO-incompatible LDKT were carried out in the first era (September 1990-August 1996) and 13 were in the second era (October 2001-July 2004). All patients were treated with sessions of plasmapheresis before transplantation to reduce antibody titers <1:8. In the second era, those with rebound increase of antibody titers >1:64 after repeated plasmapheresis were not subjected to transplantation. Posttransplantation immunosuppression consisted of cyclosporin, predonisone, azathioprine, gusperimus hydrochloride (DSG), and antilymphocyte globulin (ALG) in the first era, and tacrolimus, mycophenolate mofetil, predonisone, and DSG in the second era. Splenectomy was performed during the transplantation. Anticoagulant therapy was introduced in the second era. RESULTS: One-, 2-, and 5-year graft survival in the first era was 57%, 57%, and 50%, respectively, values that were significantly lower than those of ABO-compatible cases in the same period (n = 101), namely, 1-, 3-, and 5-year graft survival rates 93%, 83%, and 76%, respectively. The main reason for graft and patient losses was infectious complications. In the second era, no recipient suffered a severe infectious complication and 1- and 2-year graft survival rates were both 100%. Four patients in the first era and 1 in the second era experienced a graft rejection episode between 10 days and 14 months after transplantation, but they were successfully treated with steroid pulse therapy. CONCLUSION: Although patients with high blood group antibody titers remain problematic, ABO-incompatible LDKT is an increasingly viable option for patients whose only donor is blood group-incompatible.

ABO Blood-Group System↗

The relationship between self-reported difficulty with hearing in the worse ear and the better ear.

OBJECTIVES: To investigate the relationship of self-reported hearing difficulty with hearing in the worse ear and the better ear at 1 and 4 kHz. DESIGN: Receiver-operating characteristic (ROC) curve analysis in community-residing population. SETTINGS: The Settsu City Health Center (Osaka, Japan). PARTICIPANTS: A total of 919 consecutive participants who were provided health check-ups. MAIN OUTCOMES MEASURES: Comparison is based on the measurement of the area under the curve (AUC) of ROC. RESULTS: At 1 kHz, the area under the curve (AUC) of the worse ear (0.625 +/- 0.021) was significantly larger than that of the better ear (0.570 +/- 0.021) (P < 0.01). At 4 kHz, the AUC of the worse ear (0.665 +/- 0.019) was significantly larger than that of the better ear (0.622 +/- 0.020) (P < 0.01). Excluding the subjects with noise exposure, tinnitus and ear disease, at both frequencies, the AUC of the worse ear was not significantly larger than that of the better ear at both 1 and 4 kHz. Hearing in the worse ear was significantly more related to self-reported hearing difficulty than in the better ear without excluding those with noise exposure, tinnitus and ear disease. CONCLUSIONS: ROC curve analysis would provide a method to help us judge the difference between the worse hearing ear and the better hearing ear on the subject of hearing loss.

Adult↗

Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study.

BACKGROUND AND AIMS: Helicobacter pylori infection and gastric atrophy are both risk factors for gastric cancer. We aimed to elucidate the natural history of gastric cancer development according to H pylori infection and gastric atrophy status. SUBJECTS AND METHODS: A total of 9293 participants in a mass health appraisal programme were candidates for inclusion in the present prospective cohort study: 6983 subjects revisited the follow up programme. Subjects were classified into four groups according to serological status at initial endoscopy. Group A (n = 3324) had "normal" pepsinogen and were negative for H pylori antibody; group B (n = 2134) had "normal" pepsinogen and were positive for H pylori antibody; group C (n = 1082) had "atrophic" pepsinogen and were positive for H pylori antibody; and group D (n = 443) had "atrophic" pepsinogen and were negative for H pylori antibody. Incidence of gastric cancer was determined by annual endoscopic examination. RESULTS: Mean duration of follow up was 4.7 years and the average number of endoscopic examinations was 5.1. The annual incidence of gastric cancer was 0.04% (95% confidence interval (CI) 0.02-0.09), 0.06% (0.03-0.13), 0.35% (0.23-0.57), and 0.60% (0.34-1.05) in groups A, B, C, and D, respectively. Hazard ratios compared with group A were 1.1 (95% CI 0.4-3.4), 6.0 (2.4-14.5), and 8.2 (3.2-21.5) in groups B, C, and D, respectively. Age, sex, and "group" significantly served as independent valuables by multivariate analysis. CONCLUSIONS: The combination of serum pepsinogen and anti-H pylori antibody provides a good predictive marker for the development of gastric cancer.

Antibodies, Bacterial↗

Manganese superoxide dismutase activity in the rat adrenal.

In the light of studies suggesting that transcription of the gene coding for manganese superoxide dismutase (MnSOD) is induced by ACTH in the rat adrenal gland, northern blot analysis was used to determine its mRNA distribution. It was found that mRNA coding for MnSOD is primarily present in the inner zones of the rat adrenal cortex, and not the glomerulosa. To investigate the functional relationships between MnSOD activity and expression and adrenocortical function, adrenals and blood were taken from animals pretreated with corticotrophin or betamethasone (Betnesol), or subjected to a low-sodium diet. MnSOD activity in inner zone mitochondrial fractions was enhanced by corticotrophin and by a low-sodium diet, but suppressed by betamethasone. Apparent cytosolic MnSOD activity, total cytosolic MnSOD and CuZnMn-SOD, and glomerulosa mitochondrial MnSOD all were unaffected. Steroid assays showed a clear correlation between circulating corticosterone and inner zone mitochondrial MnSOD, but none between aldosterone and glomerulosa MnSOD. Immunoblot analysis of MnSOD showed two apparent isoforms, at approximately 25 kDa and 75 kDa. There was a partial relationship between expression of the 75 kDa isoform and MnSOD activity, in that it was induced by corticotrophin. However, there was also a slight induction with betamethasone, and a low-sodium diet had no effect. The 25 kDa MnSOD isoform was unaffected by the treatments. The results suggest that MnSOD may have a specific role in the steroidogenic function of the fasciculata/reticularis of the rat adrenal, but not in that of the glomerulosa.

Adrenal Cortex↗

Unique evolution of Bivalvia arginine kinases.

The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp(62) and Arg(193), which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp(62) and Arg(193) are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp(62) or Arg(193) by Gly in normal AK causes a considerable decrease in V(max) (6-15% of wild-type enzyme) and a two- to threefold increase in K(m) for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.

Amino Acid Sequence↗

Expression and localization of 25-Dx, a membrane-associated putative progesterone-binding protein, in the developing Purkinje cell.

Neurosteroids are synthesized de novo in the brain and the cerebellar Purkinje cell is a major site for neurosteroid formation. We have demonstrated that the rat Purkinje cell actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and synaptogenesis via its nuclear receptor in this neuron. On the other hand, 25-Dx, a putative membrane progesterone receptor, has been identified in the rat liver. In this study, we therefore investigated the expression and localization of 25-Dx in the Purkinje cell to understand the mode of progesterone actions in this neuron. Reverse transcription-PCR and Western immunoblot analyses revealed the expressions of 25-Dx mRNA and 25-Dx-like protein in the rat cerebellum, which increased during neonatal life. By immunocytochemistry, the expression of 25-Dx-like protein was localized in the Purkinje cell and external granule cell layer. At the ultrastructural level, we further found that 25-Dx-like immunoreactivity was associated with membrane structures of the endoplasmic reticulum and Golgi apparatus in the Purkinje cell. These results indicate that the Purkinje cell expresses the putative membrane progesterone receptor, 25-Dx during neonatal life. Progesterone may promote dendritic growth, spinogenesis and synaptogenesis via 25-Dx as well as its nuclear receptor in the Purkinje cell in the neonate.

Animals↗

Optimization of the use of cyclosporine in renal transplantation.

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant performed by Hume et al in 1952, there has been an elusive search for agents rendering the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ while sparing nonspecific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes; chemical (pharmaceutical), biological (immunological), physical (radiological), and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, azathioprine, cyclosporine (CsA), tacrolimus, mycophenolate mofetils and so on made an epoch at each stage in history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and /or B cells by inhibiting cytokine synthesis (CsA, FK506), cytokine action (Rapamycin), or cell differentiation (15-deoxyspergualin) pathways rather than to act on immune systems in a nonselective fashion. CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving the patient and graft survival. Sandimmun Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are under way to determine its effectiveness and safety. Therapeutic drug monitoring and combination therapy with CsA are investigated also.

Cyclosporine↗

Recurrence of focal glomerulosclerosis in post-renal transplant recipients: report of two cases.

INTRODUCTION: Focal segmental glomerulosclerosis (FGS) has a tendency to recur frequently after kidney transplantation. To evaluate the incidence and outcome of recurrence of FGS, we report 2 cases of recurrence. PATIENTS: Among 12 patients with renal failure caused by biopsy-proved FGS who received kidney allografts from living related donors, 2 experienced recurrent FGS. CASE REPORTS: Case 1 was a 28-year-old man who received a renal transplant from his mother. The recurrence of FGS happened just after the scheduled reduction in immunosuppressants at 36 months after the transplantation. He developed subsequently end-stage renal failure (ESRD) 50 months after transplantation. Case 2 was a 22-year-old man who received a renal transplant from this ABO disparate mother. A few days after renal transplantation, he displayed a severe nephrotic syndrome due to recurrent FGS, reaching ESRD at 23 months. To treat recurrent FGS, plasma exchange was partially effective, reducing the proteinuria but not stopping the progression of disease. DISCUSSION: Two recipients with severe proteinuria were diagnosed as having recurrent FGS. The incidence of recurrent FGS was 16.7% with 5-year and 10-year graft survival rates among recipients with ESRD caused by FGS of 79.6% and 68.2%, respectively. The incidence and graft survival rates were better than those expected based upon previous reports. Once the recurrence occurred, it was difficult to halt the progression of disease. Effective prevention of FGS and careful observations with maintained of immunosuppression are necessary in these patients.

Adult↗

Inhibitory effect of green tea catechins on cysteine proteinases in Porphyromonas gingivalis.

The purpose of this study was to examine the effects of catechins and their derivatives on the activities of Arg-gingipain (Rgp) and Lys-gingipain (Kgp) in Porphyromonas gingivalis. Catechin derivatives, which included (-)-epigallocatechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-catechin gallate, significantly inhibited the Rgp activity. The 50% inhibitory concentrations (IC50s) of these catechin derivatives for Rgp ranged from 3 to 5 microm. While (-)-epigallocatechin and (-)-gallocatechin moderately inhibited Rgp activity (IC50s, 20 microm), (-) -epicatechin, (+)-catechin, and gallic acid were not effective, with IC50s greater than 300 microm. Further, some of the catechin derivatives tested also inhibited the Kgp activity, though to a lesser extent than inhibition of the Rgp activity. These findings suggest that green tea catechins may have the potential to reduce periodontal breakdown resulting from the potent proteinase activity of P. gingivalis.

Adhesins, Bacterial↗

Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer.

BACKGROUND: By using array comparative genomic hybridization (CGH), the increased copy number of CYP24 (which encodes vitamin D 24-hydroxylase) at 20q13.2 was previously reported, leading to the identification of CYP24 as a candidate oncogene in breast cancer. CYP24 leads to abrogate growth control mediated by vitamin D. MATERIALS AND METHODS: We examined CYP24 expression as well as VDR (vitamin D receptor) gene expression in 42 esophageal cancer cases using semi-quantitative RT-PCR assay. We induced CYP24 in seven esophageal cancer cell lines using 25-hydroxyvitamin D3 [25(OH)D3] and compared cell growth rate, measured using the 3-(4, 5-dimethylthiazol-2-y)-2, 5-diphenyltetrazolium bromide (MTT) assay system. RESULTS: The overall survival rate was significantly higher in 25 cases of lower CYP24 expression than 17 cases of higher CYP24 expression (P <0.05); on the other hand, 23 cases of low VDR expression had a poorer prognosis than 19 cases of high VDR expression. Moreover, we disclosed that the inverse correlation between CYP24 and VDR expression is significant in esophageal cancer cases (P <0.05). Furthermore, the cell growth evaluated by MTT assay was greatly increased in CYP24-induced and VDR-diminished cells than non-responding cells by 25(OH)D3 activity (P <0.01). CONCLUSIONS: Overexpression of the candidate oncogene CYP24 is inversely correlated to vitamin D receptor expression, and may play an important role in determination of the malignant potential of esophageal cancer.

Adult↗

Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy, pulmonary function, and high-resolution computed tomography lung densitometry in elderly patients with asthma.

BACKGROUND: Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics. METHODS: Forty-eight asthmatics over 70 years old (25 ex-smokers and 23 never-smokers) and 20 patients with COPD over 70 years old (all ex-smokers) were studied to determine the influence of cigarette smoking on IgE-mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper-responsiveness (BHR), generation of leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung showing attenuation values less than -950 Hounsfield units (RA950) on high-resolution computed tomography scans. RESULTS: The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B4 (LTB4) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex-smokers with asthma and COPD compared with never-smokers with asthma. Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics. CONCLUSION: Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in elderly asthmatics. Increased hyper-inflation or emphysematous changes of the lungs expressed by increased RA950, closely related to %RV, was more frequently observed in ex-smokers compared with never-smokers.

Aged↗