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Biomedical subjects

H Ogata

Publications and source records attributed to H Ogata.

At least 145 records · Page 8Linked to original sources

Short-term attenuation of natural killer cell cytotoxic activity in wheelchair marathoners with paraplegia.

OBJECTIVE: To investigate homeostasis of the immune system in athletes with spinal cord injuries during and after racing a wheelchair marathon. DESIGN: The study examined changes in the number and function of natural killer (NK) cells in nine male wheelchair marathon athletes (spinal cord injuries between T5 and T12) who completed the 15th Oita International Wheelchair Marathon Race. Blood samples were obtained the day before, immediately after, and 1 day after the race. Blood samples were also obtained from seven age-matched control subjects with spinal cord injuries but who did not exercise regularly. RESULTS: The number of peripheral leukocytes increased (p < .01) immediately after the race. In contrast, the number of peripheral NK cells and NK cell cytotoxic activity significantly decreased from 310+/-130/microL to 133 +/-61/microL and from 42.6%+/-3.0% to 38.2%+/-3.2%, respectively (mean+/-SD), immediately after the race. Plasma cortisol levels were increased after the race. However, all parameters returned to control levels within 24 hours. Measurements in control subjects did not change throughout the experiment. CONCLUSION: These findings suggest that racing a marathon suppressed peripheral NK cell number as well as NK cell cytotoxic activity in wheelchair athletes and that this was probably mediated by increased postrace cortisol levels. Wheelchair marathon athletes are advised to take extra precaution to avoid infection within 24 hours after racing because of the transient suppression of NK cell cytotoxic activity during this period.

Adult↗

Total surface bearing below-knee prosthesis: advantages, disadvantages, and clinical implications.

OBJECTIVE: To investigate the total surface bearing (TSB) prosthesis for below-knee amputee patients and to determine its clinical indications. DESIGN: Case series. SETTING: University hospital and the Welfare Center for the Disabled. PATIENTS: Thirty-two subjects who could walk with the TSB prosthesis and had already used the patellar-tendon bearing (or Kondylen-Bettung Münster) socket. MAIN OUTCOME MEASURE: Subjective assessment of the TSB socket, consisting of an overall rating and ratings of 13 individual items, was performed, and results were analyzed with Fisher's exact test. RESULTS: Seventy-five percent of the subjects were satisfied overall with the TSB socket. Of the 13 items, comfort, ease to swing, pain, piston movement, tightness, skin irritation, appearance, and durability were regarded as good by more than 75% of the patients. Donning, perspiration, odor, and staining were regarded as poor by more than 20%. Items that were significantly related with overall satisfaction with the TSB socket were comfort, ease to swing, and piston movement, while donning was significantly related to dissatisfaction. CONCLUSION: The TSB socket is suitable for and preferred by many amputee subjects, but some problems remain to be solved.

Adult↗

Enantioselective tissue distribution of the basic drugs disopyramide, flecainide and verapamil in rats: role of plasma protein and tissue phosphatidylserine binding.

PURPOSE: The stereoselective distribution of three basic drugs, disopyramide (DP), flecainide (FLC) and verapamil (VP), was studied to clarify the relationship between the tissue-to-unbound plasma concentration ratio (Kpf) and drug lipophilicity and binding to phosphatidylserine phs), which are possible factors determining the tissue distribution of these drug enantiomers. METHODS: The drug enantiomer or racemate was administered to rats by intravenous constant infusion. Their concentrations in plasma and tissues were determined using enantioselective high-performance liquid chromatography. Plasma protein binding, and buffer-octanol and buffer-hexane containing PhS partition coefficients were also determined. RESULTS: The stereoselectivity of the tissue-to-plasma concentration ratio (Kp) was partly associated with that of serum protein binding. However, the Kpf value of R(+)-VP in the lung was significantly higher than that of S(-)-VP. A linear correlation was observed between the Kpf values of these drug enantiomers in brain, heart, lung and muscle, and their buffer-hexane containing PhS partition coefficients. The in vitro data for the binding of these drugs to PhS suggest that stereoselective binding of VP to PhS may correspond to its stereoselective tissue binding. CONCLUSIONS: Our findings provide some evidence for a role of tissue PhS in the tissue distribution of basic drugs with respect to stereoselectivity of drug enantiomers distribution.

Animals↗

A use of Monte Carlo integration for population pharmacokinetics with multivariate population distribution.

This paper describes a use of Monte Carlo integration for population pharmacokinetics with multivariate population distribution. In the proposed approach, a multivariate lognormal distribution is assumed for a population distribution of pharmacokinetic (PK) parameters. The maximum likelihood method is employed to estimate the population means, variances, and correlation coefficients of the multivariate lognormal distribution. Instead of a first-order Taylor series approximation to a nonlinear PK model, the proposed approach employs a Monte Carlo integration for the multiple integral in maximizing the log likelihood function. Observations below the lower limit of detection, which are usually included in Phase 1 PK data, are also incorporated into the analysis. Applications are given to a simulated data set and an actual Phase 1 trial to show how the proposed approach works in practice.

Algorithms↗

Reconstruction of amino acid biosynthesis pathways from the complete genome sequence.

The complete genome sequence of an organism contains information that has not been fully utilized in the current prediction methods of gene functions, which are based on piece-by-piece similarity searches of individual genes. We present here a method that utilizes a higher level information of molecular pathways to reconstruct a complete functional unit from a set of genes. Specifically, a genome-by-genome comparison is first made for identifying enzyme genes and assigning EC numbers, which is followed by the reconstruction of selected portions of the metabolic pathways by use of the reference biochemical knowledge. The completeness of the reconstructed pathway is an indicator of the correctness of the initial gene function assignment. This feature has become possible because of our efforts to computerize the current knowledge of metabolic pathways under the KEGG project. We found that the biosynthesis pathways of all 20 amino acids were completely reconstructed in Escherichia coli, Haemophilus influenzae, and Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as well, although it was necessary to assume wider substrate specificity for aspartate aminotransferases.

Amino Acids↗

Plasma exchange for thrombocytopenia in antiphospholipid syndrome: a case report.

The remarkable effect of plasma exchange (PE) was observed on thrombocytopenia in a patient with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus. Three times PE led to recovery from severe thrombocytopenia refractory to treatment with corticosteroid, anticoagulant, and antiplatelet drugs accompanied by a decrease in the serum cardiolipin beta2 glycoprotein I antibody level. This result suggests that PE is a valuable therapeutic tool for refractory thrombocytopenia in APS.

Adult↗

Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis.

A 64-year-old male was treated continuously with rifampin, isoniazid and streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii. Five weeks after beginning the treatment, the patient suddenly developed acute renal failure. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis with moderate interstitial changes. Serum antirifampin antibody was detected, and the cessation of rifampin treatment was followed by a rapid spontaneous recovery of the patient's renal function. This is, to our knowledge, the first case of rapidly progressive crescentic glomerulonephritis associated with rifampin treatment where circulating antirifampin antibody is demonstrated and the renal function spontaneously improved after discontinuing rifampin treatment.

Antibiotics, Antitubercular↗

Muscle sympathetic nerve activity during cold pressor test in patients with cerebrovascular accidents.

BACKGROUND AND PURPOSE: Autonomic dysfunction is frequently present in patients with cerebrovascular accidents (CVA). However, the pathophysiological mechanisms of these disorders are not clear. The purpose of the study was to assess the effects of CVA on the autonomic nervous system. METHODS: In eight male patients with a history of CVA with damage of the cortical or subcortical structures, we measured the cold pressor response during recording of muscle sympathetic nerve activity (MSNA) from the peroneal nerve on the hemiplegic side. We also studied 10 age-matched male control subjects. Tests were performed before, during, and after immersion of the nonhemiplegic hand in ice water for a period of 3 minutes in each phase. We also recorded changes in heart rate (HR), arterial blood pressure, skin temperature of the middle finger, and perception of pain using the Borg's score. RESULTS: During the control period, the mean burst count of MSNA in CVA (57.2 +/- 3.9 beats/100 HR) was higher than in control subjects (36.3 +/- 3.2 beats/100 HR) (P<.05). Total MSNA (the mean burst amplitude per minute times burst rate) increased significantly in CVA and control during the immersion period by 79.9 +/- 18.4% and 133.1 +/- 25.6%, respectively. The percent change in total MSNA in CVA was attenuated during immersion compared with control subjects. The HR and skin temperature responses as well as the Borg's score were similar in both groups during control, hand immersion, and recovery periods. CONCLUSIONS: The present results suggest that increased MSNA in CVA may be due to damage of cortical or subcortical structures or stroke-related changes in other areas or nonspecific changes that cause continuous increase in basal MSNA.

Aged↗

Population pharmacokinetics and pharmacodynamics of cisplatin in patients with cancer: analysis with the NONMEM program.

The population pharmacokinetics and pharmacodynamics of cisplatin (CDDP) were evaluated based on a mixed-effect model using the NONMEM program. Unchanged CDDP in plasma was measured as a biologically active platinum species during CDDP chemotherapy, using high-performance liquid chromatography. Plasma concentration measurements (157) of unchanged CDDP from 26 patients with cancer receiving 80 mg/m2 CDDP by infusion over 2 hours, 3.5 hours, or 4 hours were analyzed according to a one-compartment model. The influences of individual characteristics such as body weight, dose schedule, course, and clinical laboratory values (renal function markers, albumin) on total body clearance (Cl) and volume of distribution (Vd) were examined. In the final pharmacokinetic model, body surface area and dose schedule affected Cl of unchanged CDDP. The Cl of CDDP was increased by 27.3% after the 2-hour infusion schedule compared with Cl after the longer infusions. The Vd was estimated as 13.4 L/m2. The interindividual variability for Cl and Vd and residual variability were 22.9%, 30.9%, and 35.5%, respectively. The relationships between maximum concentration (Cmax) of unchanged CDDP and maximum blood urea nitrogen (BUNmax), or minimum creatinine clearance (ClCr,min) over a 1-month period after CDDP administration were evaluated according to linear, exponential, or maximum response (Emax) models. The linear or Emax model described pharmacodynamics most successfully, with relatively large interindividual variability for both slope and EC50 (more than 25%). Residual variability was 15.3% and 17.1% in BUNmax and Clcrmin, respectively. The population means and interindividual and residual variability of pharmacokinetics and pharmacodynamics of CDDP were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic and pharmacodynamic approach could be useful to manage CDDP nephrotoxicity using sparse data in a clinical setting.

Adult↗

Isolation of a major metabolite (i-OHAP) of aprindine and its identification as N-[3-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol.

i-OHAP, a major metabolite of aprindine (AP), was isolated by TLC from rat feces and identified as N-13-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol, based on 1H-NMR, the H-H correlation spectroscopy (COSY) spectrum, MS and LC-MS. Its structure was also confirmed by comparison with the synthesized compound. The hydroxy group of i-OHAP was located at the 5-position of the indan ring. AP is a prochiral compound, and the metabolism of AP to i-OHAP was stereoselective. The ratio of (+)/(-)-i-OHAP in rat feces and in human urine was about 5 and 15, respectively.

Adult↗

Inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs in human liver microsomes in vitro.

We studied the inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs (NSAIDs) in human liver microsomes in vitro. After screening for potential inhibitors among ten NSAIDs using human recombinant cytochrome P450, inhibition kinetic parameters were estimated using human liver microsomes. Phenylbutazone and bucolome were suggested to increase the unbound steady-state level of S-warfarin about four- and five-fold, respectively, as estimated from these metabolic parameters.

Anti-Inflammatory Agents, Non-Steroidal↗

In vitro study of neutrophil apoptosis in liver cirrhosis.

Cirrhotic patients frequently manifest neutropenia and are predisposed to bacterial infections. We examined neutrophil apoptosis to determine if neutrophil survival in cirrhotic patients is shortened. Neutrophils isolated from 10 cirrhotic patients and 10 healthy volunteers were cultured for 24 hours. The time course of neutrophil viability was assessed by the trypan blue dye exclusion test and apoptosis was determined morphologically by light and electron microscopy. Apoptotic cells were also confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick and labeling (TUNEL) and DNA gel electrophoresis. Fas expression of neutrophils was examined by flow cytometry. Viabilities were significantly decreased in liver cirrhosis (p<0.0001). Neutrophils from cirrhotic patients exhibited significantly greater apoptosis. Fas expression of neutrophils was significantly reduced for cirrhotic patients (p=0.0001). Neutrophils from cirrhotic patients exhibited markedly accelerated apoptosis in vitro. Shortening of neutrophil survival via apoptosis may explain in part the mechanism of neutropenia in cirrhotic patients.

Adult↗

Liddle's syndrome in an elderly woman.

A 78-year-old woman with hypertension was hospitalized with acute bronchitis. However, she was also found to have hypernatremia, hypokalemia, and metabolic alkalosis. Detailed examination showed a low plasma renin activity and plasma aldosterone concentration. A provisional diagnosis of Liddle's syndrome was established and the patient was successfully treated with triamterene. Although Liddle's syndrome is generally considered an inherited hypertensive disease found in young people, a review of the literature indicated that muscle weakness is an important clinical finding in elderly patients with this disease. Liddle's syndrome should be considered in the differential diagnosis of hypertension even in elderly individuals.

Aged↗

Measurement of reticulated platelets in thrombocytopenia--methodology and clinical utility.

In this study, we explored the methodology and clinical utility of reticulated platelets analysis. Reticulated platelets were measured using flow cytometry in peripheral circulation with thiazole orange (TO). We chose fixed platelet-rich plasma as the sample since it has been known to give stable results. The percentage of reticulated platelets in 7 patients with idiopathic thrombocytopenic purpura (ITP) was significantly increased (8.41 +/- 5.35%; mean +/- SD), compared with that in 21 normal subjects (1.92 +/- 1.27%). The value in 16 patients with liver cirrhosis was slightly below normal (1.86 +/- 0.85%). These findings suggested that thrombopoiesis was not promoted under the condition of hypersplenism or of abnormal pooling, and that any elevation in the percentage level of reticulated platelets could be clinically useful in the diagnosis of ITP.

Adult↗

Properties of the flexible pressure sensor under laboratory conditions simulating the internal environment of the total surface bearing socket.

The purpose of this study was to investigate the properties of the flexible pressure sensor under laboratory conditions simulating the internal environment of the total surface bearing (TSB) socket to determine optimal conditions for measuring normal stresses on the stump. The equipment used in the study was the Pressure Distribution Sensor System for Sockets. In a climatic chamber maintained at 37 degrees C and 70% humidity the sensor sheet was mounted on a measuring apparatus loaded with three 10 kg weights, and output from the sensor was recorded. Because of sensor creep, a sample 60 seconds after loading was adopted as the measured output. Output was greater when weight was decreased than when weight was increased because of hysteresis (paired t-test, p<0.05). The sensor had temperature sensitivity but differences in output were not statistically significant (paired t-test, 0.10>p>0.05). There were no significant differences in output among five sensor sheets or among five sections of four sensor sheets (two-way ANOVA, p>0.05), but repeated loading on the same section of the sensor sheet increased output (two-way ANOVA, p<0.05). Reproducibility and sensitivity distribution of the sensor are considered satisfactory under laboratory conditions, but measurements of rapid and repetitive movements may not be accurate and comparing subtle changes in output from a single sensor is not suitable. The reliability of the sensor in a clinical setting for measuring normal stresses on the stump with the TSB socket should be examined.

Amputation Stumps↗

Systematic Prediction of Orthologous Units of Genes in the Complete Genomes.

In order to fully make use of the vast amount of information in the complete genome sequences, we are developing a genome-scale system for predicting gene functions and cellular functions. The system makes use of the information of sequence similarity, the information of positional correlations in the genome, and the reference knowledge stored as the ortholog group tables in KEGG (Kyoto Encyclopedia of Genes and Genomes). The ortholog group table summarizes orthologous and paralogous relations among different organisms for a set of genes that are considered to form a functional unit, such as a conserved portion of the metabolic pathway or a molecular machinery for the membrane transport. At the moment, the ortholog group table is constructed for the cases where the genes are clustered in physically close positions in the genome for at least one organism. In this paper, we describe the system and the actual analysis of the complete genome of Pyrococcus horikoshii to identify ABC transporters.

Journal Article↗

Sensing stability and dynamic response of the F-Scan in-shoe sensing system: a technical note.

The objective of this study was to gain a better understanding of the F-Scan to determine its appropriate clinical application. Vertical pressure was applied to a sensor foil over the range of 10-80 kPa with or without the intervention of 0.2-0.8 mm thick felt. Sensor sensitivity reached a maximum without the felt, and decreased with increasing felt thickness, stabilizing at 48-74% of the maximum level when felt thickness exceeded 0.4 mm. This sensitivity change was caused by the slight difference in thickness of sensing areas from that of non-sensing areas. Dynamic response time was delayed by a mean of 0.32 s. Although the cause of this dynamic response delay remains unclear, it was considered to be inappropriate for accurate dynamic measurements. Therefore, rather than using F-Scan measurement to accurately obtain actual values, it should be used for relative comparisons of the plantar pressure distributions under constant conditions.

Biomechanical Phenomena↗

Self-rating Barthel index compatible with the original Barthel index and the Functional Independence Measure motor score.

To confirm concurrent validity of the final revision of the self-rating Barthel index (SB) and its test-retest reliability, we investigated 171 stroke outpatients without severe aphasia or dementia who were seen by a doctor on predetermined days at eight different hospitals. For 41 patients, the differences in scores among the original Barthel index (BI) and Granger's BI and SB were examined by the Friedman two-way analysis of variance and Wilcoxon matched-pairs signed-ranks test, and the difference in scores between Functional Independence Measure motor score (FIM-MS) and three-level scale FIM-MS was determined by the Wilcoxon's matched-pairs signed-ranks test. Concurrent validity of the SB was confirmed by Spearman's correlation coefficients with the original BI and FIM-MS, and internal consistency of the five measuring instruments was examined. For all 171 patients test-retest reliability of the SB was examined with the Spearman's correlation coefficient for total scores and kappa coefficients for each ADL item. Regression analysis was performed to determine what factors were related with test-retest reliability. Total scores of the SB and Granger's BI and the three-level scale FIM-MS were significantly higher than those of the original BI and FIM-MS, respectively. Correlation coefficients of the SB with the original BI and FIM-MS were 0.994 and 0.904, respectively, and its alpha-coefficient was 0.842. Test-retest reliability of the total score was 0.835 by the correlation coefficient, and kappa coefficients of 1 and 12 ADL items were fair and good, respectively. Regression analysis revealed that self-rating by a patient with a high SB total score is more accurate. Therefore, the SB has good concurrent validity and is well-related with the original BI and FIM, and its test-retest reliability is sufficiently high for practical use.

Activities of Daily Living↗