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Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 19 recordsLinked to original sources
PubMed2006

Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer.

We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.

Age Factors↗
PubMed2006

Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy.

BACKGROUND: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). OBJECTIVE: To determine if these patients share other common features. METHODS: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. CONCLUSIONS: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.

Atrophy↗
PubMed2006

Intestinal CYP3A4 is not involved in the enantioselective disposition of lansoprazole.

The contribution of (S)-lansoprazole to CYP3A4-catalysed sulfoxidation is greater than that of (R)-lansoprazole. The aim was to investigate the effect of grapefruit juice on the enantioselective disposition of lansoprazole among three CYP2C19 genotype groups. Eighteen healthy subjects, consisting of six each of homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs) and poor metabolizers (PMs), ingested a single oral dose of 60 mg racemic lansoprazole after taking either 200 ml grapefruit juice or water. There was no effect of grapefruit juice on the mean maximum plasma concentrations (C(max)) or the elimination half-life for each lansoprazole enantiomer in all three CYP2C19 genotype groups. Similarly, the pharmacokinetic parameters of lansoprazole sulfone remained unaltered by grapefruit juice in all three groups. The CYP3A4-mediated first-pass sulfoxidation of (R)- and (S)-lansoprazole were not influenced by grapefruit juice. In addition, stereoselectivity of the intestinal CYP3A4-catalysed sulfoxidation of (R)- and (S)-lansoprazole was not observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure.

Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.

Acylation↗
PubMed2006

Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive metabolizers and treated with tacrolimus.

OBJECTIVE: Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus. MATERIALS: 24 recipients who were CYP2C19 EMs were studied. METHODS: Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured. RESULTS: Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. CONCLUSIONS: (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Widening spectrum of a reversible splenial lesion with transiently reduced diffusion.

Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.

Brain Diseases↗
PubMed2005

Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.

OBJECTIVE: The objective of this study was to assess the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Japanese renal transplant recipients. METHOD: The pharmacokinetic parameters of tacrolimus were calculated in steady-state on day 28 after transplantation. Polymerase chain reaction-restriction fragment length polymorphism and direct sequence methods were used for CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The dose-adjusted area under the concentration-time curve (AUC0-12) was significantly lower among CYP3A5*1 carriers than those bearing CYP3A5*3/*3. (0.570 +/- 0.105 vs 0.865 +/- 0.343 ng.h/mL per mg/kg, P = .00322). The daily tacrolimus dose per body weight was significantly higher in CYP3A5*1 carriers than those of CYP3A5*3/*3 carriers (0.271 +/- 0.110 vs 0.150 +/- 0.056 mg/kg, P = .00016). In this study, a distinction was made between carriers of CYP3A5*1/*1+*1/*3 and CYP3A5*3/*3 to investigate the influence of the MDR1 C3435T mutation on tacrolimus pharmacokinetics. The MDR1 C3435T polymorphisms did not affect any tacrolimus pharmacokinetic parameter in either group. CONCLUSIONS: Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC0-12 of tacrolimus. In contrast, MDR1 C3435T polymorphism was not an important factor in tacrolimus pharmacokinetics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Incidence and risk factors of clinical characteristics, tacrolimus pharmacokinetics, and related genomic polymorphisms for posttransplant diabetes mellitus in the early stage of renal transplant recipients.

PURPOSE: Posttransplant diabetes mellitus (PTDM) is an important complication in a tacrolimus (TAC)-based immunosuppressive regimen. The present study investigated the incidence, clinical risk factors, TAC pharmacokinetics (PK), and genomic polymorphisms related to TAC-PK or diabetes mellitus (DM) under the TAC-based immunosuppressive protocol. PATIENTS AND METHODS: Seventy-one nondiabetic renal allograft recipients transplanted from February 1998 to March 2004 were studied. Patients with over 6.5 mg/dL of hemoglobin A1c on sequential blood samples or requiring insulin or oral antidiabetic agents around 6 months after transplantation were diagnosed as having PTDM. RESULTS: Six months after transplantation, 10 recipients (14.1%) developed PTDM. The positive risk factors were age (P = .003) and body mass index (P = .035). There were no significant differences in gender distribution, pretransplant dialysis period, dialysis modality, acute rejection rate, total steroid doses, TAC-PK, or its related genomic polymorphisms between the two groups. In the DM-related polymorphisms, the frequency of PTDM was significant higher in patients with the VDR TaqI tt or Tt genotype than in those with the TT genotype (P = .013). After a multivariate analysis, age over 50 years (P = .007, odds ratio 8.92) and the presence of VDR TaqI t allele (P = .043, odds ratio 6.71) were correlated with the development of PTDM. CONCLUSION: The incidence of PTDM in our series was 14.1%. Age over 50 years was a risk factor. The presence of VDR TaqI t allele might be a risk for PTDM. An association between TAC-PK and development of PTDM was not observed.

Body Mass Index↗
PubMed2005

The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation.

PURPOSE: The present retrospective study investigated the influence of mycophenolate mofetil (MMF) instead of azathioprine (AZA) as part of tacrolimus-based immunosuppression. Mycophenolic acid (MPA) pharmacokinetic (PK) parameters were used for associations with the incidence of acute rejection (AR) episodes and infectious complications after renal transplantation. METHODS: The 66 consecutive renal transplant recipients reported herein excluded ABO-incompatible transplants or cytomegalovirus (CMV)-seronegative recipients. The immunosuppressive regimen consisted of tacrolimus, steroids, and AZA 1-2 mg/kg/d in 22 patients (between February 1998 and December 2000) or MMF 2 g/d in 44 patients (since January 2001). CMV infection was defined as positive CMV-antigenemia. MPA PK was studied on day 28 after transplantation in 21 recipients. RESULTS: AR occurred in 13.6% of patients in the MMF group compared with 18.2% in the AZA group. The viral infection (CMV, varicella zoster virus, adenovirus hemorrhagic cystitis, and malignancy related to Epstein-Barr [EB] virus) rate was 22.7% in the MMF group and 0% in the AZA group (P = .015). There were no bacterial or fungal infections observed in the 2 groups. MMF dose per body weight was significantly lower among patients with AR than those without AR (25.1 vs 35.6 mg/kg; P = .026). There were no differences in MPA PK parameters between patients with and without viral infections. CONCLUSIONS: Patients treated with MMF required less treatment for AR, however, there were no significant differences. MMF dose per body weight may play an important role in the occurrence of AR. Although virus infections occurred in recipients treated with MMF, MPA PK did not influence the infectious complications after renal transplantation.

Adult↗
PubMed2005

Comparison of enantioselective disposition of rabeprazole versus lansoprazole in renal-transplant recipients who are CYP2C19 extensive metabolizers.

The purpose of this study was to investigate the comparative pharmacokinetics of rabeprazole and lansoprazole enantiomers in renal-transplant recipients on tacrolimus who were CYP2C19 extensive metabolizers. Sixteen Japanese patients were randomly assigned after renal transplantation to receive repeated doses of one of the following two regimens for 28 days; tacrolimus, mycophenolate mofetil and prednisolone together with either 20mg of racemic rabeprazole (n=8) or 30 mg of racemic lansoprazole (n=8). The mean Cmax and AUC0-24 of (R)-lansoprazole compared to (S)-lansoprazole in renal transplant recipients were 12-fold (954+/-522 vs. 167+/-137 ngml(-1), respectively) and 6.9-fold (4787+/-3454 vs. 451+/-354 nghml(-1), respectively) greater, and its elimination half-life was 2.1-fold (2.3+/-1.0 vs. 1.2+/-0.6h, respectively) longer. In contrast, although the elimination half-life of (R)-rabeprazole was significantly longer than that of the (S)-enantiomer (2.1+/-0.5 vs. 1.3+/-0.9h, respectively; P<0.05), there was no difference in Cmax between the (R)- and (S)-enantiomer (186+/-40 vs. 200+/-92 ngml(-1), respectively). In conclusion, in renal-transplant recipients who are CYP2C19 extensive metabolizers, there is less stereoselective difference in the pharmacokinetic disposition between the (R)- and (S)-enantiomers of rabeprazole than those of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

OBJECTIVE: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. METHODS: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month (8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI (within 1 week in eight patients). CONCLUSION: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

Adolescent↗
PubMed2004

Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes.

OBJECTIVE: The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects. METHODS: Healthy subjects ( n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose. RESULTS: The plasma concentrations of ( R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding ( S)-enantiomer. The mean maximum plasma concentration ( C(max)) of ( S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the ( R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of ( R)- and ( S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to lansoprazole for the ( R)- and ( S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the ( S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding ( R)-enantiomer. CONCLUSIONS: The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of ( S)-lansoprazole was greater than that of the ( R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Clinical comparison of the scanning CO2 laser and conventional surgery in the treatment of ingrown nail deformities.

AIM: To compare statistically the clinical effects and postoperative course of the scanning CO(2) laser and conventional surgical method to evaluate the clinical effectiveness of the former for the treatment of ingrown nail deformities. METHODS: We performed vaporization of the nail matrix using the scanning CO(2) laser in 25 cases with ingrown nail deformities. RESULTS: In 21 cases, the recurrence of ingrown nail deformity was not observed during follow-up. All cases were free of postoperative infection. Use of the scanning CO(2) laser reduced postoperative pain, and all patients were able to return to their daily activities by day 3 post-surgery without any problems. CONCLUSIONS: Statistically, the operating time and the duration of postoperative pain were reduced significantly by the scanning CO(2) laser. Furthermore, patients treated with CO(2) laser were able to return to daily life significantly sooner.

Adult↗
PubMed2003

Facile and rapid high-performance liquid chromatography method for simultaneous determination of allopurinol and oxypurinol in human serum.

OBJECTIVE: To develop a rapid and sensitive assay for the simultaneous determination of allopurinol and oxypurinol in serum. METHOD: High-performance liquid chromatography (HPLC) with UV-detection. Sample preparation consists of protein precipitation by an addition of trichloracetic acid. RESULTS: Percentage recovery and intra-assay coefficient of variation (CV%) for allopurinol were 97.4-101.3 and 0.66-5.13, respectively, in the concentration range 0.5-5.0 microg/mL. For oxypurinol, the percentage recovery and the intra-assay CV% were 93.2-98.1 and 0.88-5.62, respectively, in the concentration ranges 0.4-20 microg/mL. There was no interference of endogenous compounds in this assay. CONCLUSION: This method is useful for routine therapeutic drug monitoring of allopurinol in a clinical setting.

Administration, Oral↗
PubMed2003

Proteolysis of ICAM-1 on human oral epithelial cells by gingipains.

Cysteine proteinases (gingipains) from Porphyromonas gingivalis are considered key virulence factors of severe periodontitis and host immune evasion. Since expression of intercellular adhesion molecule-1 (ICAM-1) on gingival epithelium is indispensable in polymorphonuclear leukocyte (PMN) migration at the site of periodontitis, we examined the effects of gingipains on the expression of ICAM-1 on human oral epithelial cell lines (KB and HSC-2) by flow cytometry and Western blotting. We found that three purified forms of gingipains efficiently reduced ICAM-1 expression on the cells in a time- and dose-dependent manner. Gingipains reduced the expression on fixed cells and degraded the ICAM-1 in the cell membranes, indicating that the reduction resulted from direct proteolysis. They then disturbed the ICAM-1-dependent adhesion of PMNs to the cells. These results indicate that gingipains cleave ICAM-1 on oral epithelial cells, consequently disrupting PMN-oral epithelial cell interaction, and are involved in immune evasion by the bacterium in periodontal tissues.

Adhesins, Bacterial↗
PubMed2002

A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors.

A low concentration (10 nM) of adenosine potentiated hippocampal neuronal activity via A(2a) adenosine receptors without affecting presynaptic glutamate release or postsynaptic glutamatergic conductance. Adenosine inhibited glutamate uptake through the glial glutamate transporter, GLT-1, via A(2a) adenosine receptors. In addition, adenosine stimulated GLT-1-independent glutamate release from astrocytes, possibly in response to a rise in intracellular Ca(2+), via A(2a) adenosine receptors involving PKA activation. Those adenosine actions could lead to an increase in synaptic glutamate concentrations responsible for the potentiation of hippocampal neuronal activity. The results of the present study thus represent a novel neuromodulatory pathway with a glial contribution, bearing both inhibition of GLT-1 function and stimulation of glial glutamate release, as mediated via A(2a) adenosine receptors.

Adenosine↗