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Biomedical subjects

H Ogata

Publications and source records attributed to H Ogata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Population pharmacokinetic analysis of cisplatin and its metabolites in cancer patients: possible misinterpretation of covariates for pharmacokinetic parameters calculated from the concentrations of unchanged cisplatin, ultrafiltered platinum and total platinum.

BACKGROUND: Usually, total and filtered platinum concentrations in plasma are monitored after cisplatin administration. However, these concentrations represent a mixture of unchanged cisplatin and metabolites. In this work, we studied population pharmacokinetic analysis based on these platinum concentrations. METHODS: Twenty-seven patients (23 males, four females) were administered cisplatin (60-100 mg/m2) with intravenous constant infusion for 90 min. Blood samples were taken at about three points per patient. The concentrations of cisplatin and platinum in the plasma were determined by high-performance liquid chromatography and atomic absorption spectrometry, respectively. Population pharmacokinetic analysis was performed using the program NONMEM (Version V) with the one- or two-compartment model with zero-order infusion. RESULTS: The clearance and volume of distribution for all platinum species studied were significantly related to the body surface area of the patients. Only the clearance of filtered platinum was significantly related to urinary N-acetyl-beta-D-glucosaminidase and the other covariates were not related to these pharmacokinetic parameters with respect to unchanged cisplatin and total platinum concentrations. CONCLUSION: The dosage regimen based on the filtered platinum concentration which is usually monitored may result in possible misinterpretation because the detected covariate is different between unchanged cisplatin and filtered platinum.

Aged↗
PubMed2001

Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine.

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used frequently in the treatment of ulcerative colitis. However, there have been few reports investigating the relationship between colonic mucosal concentrations of 5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were administered. The aim of this study is to compare the mucosal concentrations of 5-ASA ensured by sulfasalazine or mesalamine, and to define the clinical significance of the measurement of 5-ASA concentrations in the treatment of distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow-release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal administration of 5-ASA. High-pressure liquid chromatography was used to measure the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA concentrations of the sulfasalazine group with the mesalamine group. Furthermore, we analyzed the relationship between tissue 5-ASA concentrations and the Disease Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in the sulfasalazine group were higher than those in the group taking oral mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the patients who received oral and rectal mesalamine in an enema than in the patients who had oral mesalamine alone. There was a significant inverse correlation between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001). CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was significantly higher in the sulfasalazine group than in the mesalamine group. Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the estimation of its efficacy in the treatment of ulcerative colitis.

Administration, Oral↗
PubMed2001

Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits.

The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 microM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was the sum of that elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

Action Potentials↗
PubMed2001

Assessment of gastric acidity of Japanese subjects over the last 15 years.

The gastric acidity of young to elderly Japanese subjects from 1989 to 1999 was assessed and compared with that obtained in 1984, using GA-Test capsules containing acid-dissolving granules of riboflavin. The percentage of achlorhydric subjects increased with age as observed before, however, an over all decrease in all age categories year by year was noted. The percentage of achlorhydric subjects aged 50 years in 1995-1999 was about 40%, which was lower than that (60%) in 1984. However, such a chronological change was not observed when the percentage of achlorhydric subjects was determined according to birth year, indicating that it is related to the birth year of subjects. The percentage of achlorhydric subjects correlated with infection by Helicobacter pylori. Considering the high percentage of achlorhydric elderly, bioavailability and bioequivalence studies should be performed taking into consideration the effects of gastric acidity on the in vivo performance of drug products.

Achlorhydria↗
PubMed2001

Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits.

We have estimated the pharmacokinetic and pharmacodynamic interactions of verapamil (VP) enantiomers and also the interaction between VP and its metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to their prolongation effect on PR intervals, which were used as an index of VP's antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant values at concentrations ranging from 0.022 to 1.10 microm. There were no interactions between enantiomers or between VP and NVP. The pharmacological effect of the S-enantiomer (S-VP), which was determined by linear regression analysis, showed it was about 20 times more potent than that of the R-enantiomer (R-VP). The effect of racemic VP was the simple sum of those elicited by both enantiomers. These relationships were not significantly different between intravenous infusion and bolus injection. Simultaneous intravenous infusion of NVP had no influence on the PR intervals. In conclusion, we demonstrated that the relationship between plasma unbound concentration of VP enantiomers and their pharmacological effect was the simple sum of two enantiomers.

Animals↗
PubMed2001

Evaluation of the effective drugs for the prevention of nausea and vomiting induced by morphine used for postoperative pain: a quantitative systematic review.

Postoperative nausea and vomiting (PONV) with morphine therapy develops in more than 60% of patients after surgery, markedly reducing patient QOL. The prophylactic effect of several antiemetics has already been studied, but evaluations, and even those using the same drug, are not uniform. The present research involved a meta-analysis of randomized controlled trials on prophylactic drug therapy for PONV in patients receiving morphine for the treatment of postoperative pain. The efficacy of the prophylactic administration of the drugs was examined. As a result, meta-analysis of five drugs was possible and the evidence of efficacy was shown for three drugs ranked in order of an increasing odds ratio (OR) and confidence interval (CI): dexamethasone (OR: 0.23, 95% CI: 0.15-0.35, p < 0.00001), droperidol (OR: 0.27, 95% CI: 0.21-0.34, p < 0.00001), and metoclopramide (OR: 0.48, 95% CI: 0.30-0.75, p < 0.001). These results suggest that the three drugs are effective in prophylactic treatment for PONV. Of them, dexamethasone used as a prophylactic drug for PONV provided the best results. Dexamethasone was shown to reduce the incidence of PONV from 66-80% to 16-50% with a dose of 1.25 to 10 mg and to be suitable as a first drug of choice.

Antiemetics↗
PubMed2001

Recent advances in computational genomics.

In the post-genomic era, the new discipline of functional genomics is now facing the challenge of associating a function (as well as estimating its relevance to industrial applications) to about 100,000 microbial, plant or animal genes of known sequence but unknown function. Besides the design of databases, computational methods are increasingly becoming intimately linked with the various experimental approaches. Consequently, bioinformatics is rapidly evolving into independent fields addressing the specific problems of interpreting i) genomic sequences, ii) protein sequences and 3D-structures, as well as iii) transcriptome and macromolecular interaction data. It is thus increasingly difficult for the biologist to choose the computational approaches that perform best in these various areas. This paper attempts to review the most useful developments of the last 2 years.

Computational Biology↗
PubMed2001

[Efficacy of mesalamine enema in the treatment of steroid-resistant or dependent distal ulcerative colitis].

The efficacy and safety of mesalamine enema were examined in 20 patients with steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after the start of mesalamine enema treatment, respectively. Mean clinical activity index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p < 0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3 mg) were also significantly lower than those before the treatment (12.8 mg) (p < 0.01). Four patients dropped out. Three patients could not retain the enemas because of abdominal discomfort and one patient had fever and rash. There were no significant differences in age, gender, disease duration, disease type, and mean doses of oral corticosteroid before the treatment between the response group (n = 8) and the non-response group (n = 8). However, clinical and endoscopic activities before mesalamine enema treatment in the non-response group (CAI 9.8, Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts score 5.5). These results suggest that mesalamine enema is useful for mildly to moderately active distal ulcerative colitis by improving clinical symptoms and reducing corticosteroid.

Adolescent↗
PubMed2001

Relationship between the slow component of oxygen uptake and the potential reduction in maximal power output during constant-load exercise.

BACKGROUND: The purpose of the present study was to examine the relationship between the slow component of oxygen uptake (VO2) and muscle fiber fatigue. Maximal power output (MPO) was used as an index of muscle fiber fatigue. METHODS: Two constant exercises were carried out at exercise intensities of 40% and 80% of maximal oxygen uptake (VO2max). Each exercise was repeated three times, once for the measurement for VO2, and the other two times for MPO testing, at 3 and 6 minutes after work output. RESULTS: Reproducibility of MPO at rest was assessed by correlation coefficient. Its value was 0.933. At 40% VO2max, MPO did not significantly decrease from the resting value. At 80% VO2max, MPO significantly decreased by 129+/-77 watts at 3 min and by 178+/-108 watts at 6 min. The VO2 kinetic at 40% VO2 was well described by a monoexponential function with a time constant of 0.432 min. However, at 80% VO2max, a slow component of the form of a linear drift superimposed on a monoexponential function with an essentially equal time constant (0.469 min) was unambiguously detected. This slow component was significantly related to the decrease in MPO (r=0.567). CONCLUSIONS: The present results suggested that the fatigue of muscle fibers may be one of the factors that produce the slow component of VO2 during high intensity exercise.

Adult↗
PubMed2001

[The alternative or simultaneous excretion of different species of mycobacteria in atypical mycobacteriosis--15 cases in 7 years].

Five hundreds and five cases of Mycobacterium tuberculosis infection admitted to our hospital during 7 years from 1993 to 1999. Numbers of newly diagnosed cases were 390, of which 329 (84.4%) were bacilli positive with sputum examination on admission. The recurrent cases were 115, of which 55 (47.8%) were bacilli positive cases. During the same period, mycobacteria other than tuberculosis (atypical mycobacteria) were detected in the sputum of other 121 cases. The 63 (52.1%) out of these 121 cases were diagnosed as atypical mycobacteriosis (AM) due to repetitive detection of bacilli with fulfilled the criteria according to the Japanese Mycobacteriosis Research Group of the National Chest Hospitals. The ratio of 63 AM cases to 329 bacilli positive TB cases was 19.1%, but it range from 8.2% to 31.3% year by year. In these 63 AM cases, 9 (14.3%) cases excreted AM bacilli simultaneously or alternately with TB bacilli. The other 15 (23.8%) cases excreted different AM bacilli simultaneously or alternately. The changes or combinations with M. avium and M. intracellulare were most frequently observed (in 12 cases). The manners of changes and combinations with different species were described in detail.

Humans↗
PubMed2001

Alteration of regional cerebral metabolism in patients with cirrhosis in positron emission tomography.

To evaluate the alteration of cerebral blood flow and oxygen metabolism in cirrhosis, we measured regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (rCMRO2), and oxygen extraction fraction (rOEF) in twelve patients with cirrhosis (six with a history of hepatic encephalopathy and six without) and six age-matched controls using positron emission tomography. Regional CBF in whole brain was not different in cirrhotic patients from that in controls. In six cirrhotic patients with a history of hepatic encephalopathy, rCMRO2 was significantly lower in the frontal, temporal, parietal and occipital cortices, hippocampus, thalamus, cerebellum and brain stem, than that in each region of controls. On the other hand, rCMRO2 in six cirrhotic patients without a history of hepatic encephalopathy did not differ from the controls in all regions except for the frontal cortex. Regional OEF in cirrhotic patients without a history of hepatic encephalopathy was higher in the hippocampus and striatum than that in each region of controls. Among twelve cirrhotic patients, rCMRO2 in the occipital cortex and striatum correlated directly with plasma leucine levels, and rCMRO2 in the striatum directly correlated with plasma valine levels. Regional CMRO2 in the frontal cortex, temporal cortex, parietal cortex, white matter as well as brain stem correlated inversely with plasma phenylalanine levels, and rCMRO2 in the occipital cortex correlated inversely with plasma tyrosine levels. Brain oxygen metabolism is impaired in cirrhotic patients with a history of hepatic encephalopathy, but preserved in those without a history or in the early stage of cirrhosis. Reduced oxygen metabolism is related with altered amino acid metabolism.

Aged↗
PubMed2001

Primary biliary cirrhosis associated with ulcerative colitis.

A rare case of concurrent primary biliary cirrhosis and ulcerative colitis is described in a 61 year-old Japanese male. Primary biliary cirrhosis was diagnosed on the basis of characteristic histologic findings and a positive serum mitochondrial antibody test. Ulcerative colitis was diagnosed from typical findings on colonoscopy and the histologic features of a sigmoid colon biopsy specimen. This is the 12th report of a patient presenting with the combination of primary biliary cirrhosis and ulcerative colitis. The potential autoimmune relationships on the basis of these conditions are discussed.

Colitis, Ulcerative↗
PubMed2001

Population pharmacokinetics, protein binding and antiarrhythmic effects of disopyramide enantiomers in arrhythmic patients.

Disopyramide (DP) is widely used as an antiarrhythmic agent. The antiarrhythmic effects of its enantiomers differ from each other and its metabolism and protein binding are also stereoselective. Population pharmacokinetic parameters of DP racemate, enantiomers (S(+)-DP, R(-)-DP), and their unbound concentrations (uDP, S(+)-uDP and R(-)-uDP) were analyzed using the nonlinear mixed effect model (NONMEM) program. Data were available from 108 points of 33 arrhythmic patients on maintenance therapy with DP racemate. We evaluated the factors to which pharmacokinetic parameters are attributed and the relationships between each serum concentration and the antiarrhythmic effect. A one-compartment model was fitted to the data using NONMEM. For DP, S(+)-DP and R(-)-DP, elimination rate constants (kes) were estimated as 0.0648, 0.0663 and 0.0691/h, respectively and the mean apparent volume of distribution (Vd/F) were estimated as 63.2, 54.1 and 71.6 l, respectively. Using the ke and Vd/F values estimated by NONMEM, time-concentration curves were well fitted to the observed data. Unbound fractions of both DP enantiomers showed nonlinearity and the binding ratio of S(+)-DP was 0.84 +/- 0.07, which was higher than that of R(-)-DP [0.70 +/- 0.11 (p < 0.01)]. Unbound fractions of both DP enantiomers correlated with alpha1-acid glycoprotein (AGP) (p < 0.01). On the other hand, using NONMEM, a significant proportion of the variability of Vd/F could be attributed only to AGP (p < 0.001). NONMEM was able to clarify the pharmacokinetic features in the protein binding of DP. Individual steady state concentrations were estimated by NONMEM using the Bayesian method. The average unbound concentrations of all nine responders were higher than those of the four non-responders, even though this difference was not significant. Unbound concentrations may reflect drug concentrations in the tissue, which suggests that these concentrations may indicate an antiarrhythmic effect rather than the total concentration.

Adolescent↗
PubMed2001

[Pathogenesis of adynamic bone disease].

Both relative hypoparathyroidism and low turnover bone play crucial roles in the pathogenesis of adynamic bone disease (ABD), which is the most common form renal osteodystrophy (ROD). In addition to individual factors, including diabetes, elder age, and/or uremic toxins, dialysis therapy and treatment for ROD, administration of calcium-containing phosphorus binder or active vitamin D (VD) metabolite, are associated with the pathological processes. Recently it has been suggested a potential association ABD and VD receptor polymorphism, or malnutrition state.

English Abstract↗
PubMed2000

A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters.

The availability of computerized knowledge on biochemical pathways in the KEGG database opens new opportunities for developing computational methods to characterize and understand higher level functions of complete genomes. Our approach is based on the concept of graphs; for example, the genome is a graph with genes as nodes and the pathway is another graph with gene products as nodes. We have developed a simple method for graph comparison to identify local similarities, termed correlated clusters, between two graphs, which allows gaps and mismatches of nodes and edges and is especially suitable for detecting biological features. The method was applied to a comparison of the complete genomes of 10 microorganisms and the KEGG metabolic pathways, which revealed, not surprisingly, a tendency for formation of correlated clusters called FRECs (functionally related enzyme clusters). However, this tendency varied considerably depending on the organism. The relative number of enzymes in FRECs was close to 50% for Bacillus subtilis and Escherichia coli, but was <10% for SYNECHOCYSTIS: and Saccharomyces cerevisiae. The FRECs collection is reorganized into a collection of ortholog group tables in KEGG, which represents conserved pathway motifs with the information about gene clusters in all the completely sequenced genomes.

Algorithms↗
PubMed2000

Automatic detection of conserved gene clusters in multiple genomes by graph comparison and P-quasi grouping.

We previously reported two graph algorithms for analysis of genomic information: a graph comparison algorithm to detect locally similar regions called correlated clusters and an algorithm to find a graph feature called P-quasi complete linkage. Based on these algorithms we have developed an automatic procedure to detect conserved gene clusters and align orthologous gene orders in multiple genomes. In the first step, the graph comparison is applied to pairwise genome comparisons, where the genome is considered as a one-dimensionally connected graph with genes as its nodes, and correlated clusters of genes that share sequence similarities are identified. In the next step, the P-quasi complete linkage analysis is applied to grouping of related clusters and conserved gene clusters in multiple genomes are identified. In the last step, orthologous relations of genes are established among each conserved cluster. We analyzed 17 completely sequenced microbial genomes and obtained 2313 clusters when the completeness parameter P: was 40%. About one quarter contained at least two genes that appeared in the metabolic and regulatory pathways in the KEGG database. This collection of conserved gene clusters is used to refine and augment ortholog group tables in KEGG and also to define ortholog identifiers as an extension of EC numbers.

Algorithms↗
PubMed2000

Selfish DNA in protein-coding genes of Rickettsia.

Rickettsia conorii, the aetiological agent of Mediterranean spotted fever, is an intracellular bacterium transmitted by ticks. Preliminary analyses of the nearly complete genome sequence of R. conorii have revealed 44 occurrences of a previously undescribed palindromic repeat (150 base pairs long) throughout the genome. Unexpectedly, this repeat was found inserted in-frame within 19 different R. conorii open reading frames likely to encode functional proteins. We found the same repeat in proteins of other Rickettsia species. The finding of a mobile element inserted in many unrelated genes suggests the potential role of selfish DNA in the creation of new protein sequences.

Bacterial Proteins↗