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Biomedical subjects

K Suga

Publications and source records attributed to K Suga.

At least 37 records · Page 2Linked to original sources

Intralobar bronchopulmonary sequestration: evidence of air trapping shown by dynamic xenon-133 SPECT.

Dynamic single photon emission computed tomography with xenon-133 gas in a 29-year-old male patient showed xenon-133 retention within an intralobar bronchopulmonary sequestration (BPS) with a focal hyperlucent lung area on CT. Left lower lobectomy showed no fistulous connection between the anomalous and normal bronchial trees, but non-contiguous, incompletely developed visceral pleura between the sequestration and the adjacent normally ventilated lung. These features strongly support the role of intralobar collateral air drift and air trapping in producing secondary changes of a focal hyperlucent lung area in BPS.

Adult↗

Constrained optimization of L-lysine production based on metabolic flux using a mathematical programming method.

Constrained optimization for microbial fermentation was studied. For optimization, we used not the maximum principle but a nonlinear programming method because of the need to consider many metabolic reactions. In the case of L-lysine fermentation, the optimization problem in L-lysine production was formulated as a nonlinear programming problem. In general, the state equations based on material balances are represented as differential equations, but such equations which are dependent on time can not be applied to a nonlinear programming problem. Therefore, the state equations were made discrete in a time base, and a new single vector which is not dependent on time was substituted. From these formulae, the objective function and the constraints using nonlinear programming problem were defined as the amount of L-lysine produced, and as a metabolic reaction model and empirical equations, respectively. Computer program was developed to solve this constrained nonlinear programming problem. The applied algorithm of the computer programming was a sequential quadratic programming method (SQP method). When the constrained nonlinear programming problem is solved using the SQP method, the maximum amount of L-lysine produced and the optimal feeding rate of L-threonine could be calculated. From the calculated results, it was clear that introduction of the equality and inequality constraints was easy. L-Lysine at a concentration up to 75.3 g/l could be produced when the fermentation was carried out under optimal conditions.

Journal Article↗

A kinetic model for a biopanning process considering antigen desorption and effective antigen concentration on a solid phase.

A phage display library is a powerful tool for screening ligands such as antibodies and peptides that specifically recognize a target. In this study, we established a kinetic model describing the affinity selection process of phage display libraries and verified the model experimentally. Desorption of target molecules from a solid phase and orientation of the epitopes of adsorbed target molecules are taken into account in this model. The ratio of the effective antigen density to the total antigen density was estimated to be 0.0127(+/-)0.0018 when bovine pancreatic ribonuclease A (RNase A) adsorbed on polystyrene beads was recognized by an anti-RNase A single-chain Fv phage antibody. The model can faithfully describe the recovery of the phage antibody in a round of biopanning based on the effective concentration of RNase A on the beads, the desorption rate constant of RNase A from the beads, the dissociation constant and dissociation rate constant of the phage antibody from RNase A, and the time for blocking, equilibrium and washing in the biopanning process. A recommended biopanning protocol based on the model is also described.

Journal Article↗

Measurement of association rate constant of antibody-antigen interaction in solution based on enzyme-linked immunosorbent assay.

A simple and rapid method based on enzyme-linked immunosorbent assay (ELISA) was developed for measuring the association rate constant of antibody-antigen interactions. An antibody and its antigen are mixed in a solution to initiate the equilibrium reaction. At different time intervals, the amount of the free antibody in the reaction mixture is estimated by an indirect ELISA. The association rate constant was estimated by nonlinear regression against an equation introduced from the derivation of the mass balance of antigen-antibody interaction. This method can determine the association rate constant of antibodies with a dissociation rate constant up to 5 x 10(-3) s(-1). The association rate constant of a single-chain Fv (scFv) to its antigen, bovine pancreatic ribonuclease A (RNase A), determined by the present method agreed well with those determined by the fluorescence polarization method and surface plasmon resonance method. No significant difference in the association rate constant was found between the soluble anti-RNase A scFv and the same scFv displayed on a phage (5.65 +/- 0.54 x 10(4) M(-1) s(-1) and 5.96 +/- 0.56 x 10(4) M(-1) s(-1), respectively).

Journal Article↗

Improvement of freezing tolerance in transgenic tobacco leaves by expressing the hiC6 gene.

A cryoprotective protein, HIC6, was expressed transgenically in tobacco, a cold-sensitive plant, and the localization of the protein within the cell as well as freezing tolerance of the transgenic tobacco was investigated. For constitutive expression of HIC6 in tobacco, its corresponding gene was subcloned into pBI121. Through the transformation with pBI121/hiC6, fifteen transgenic tobacco lines were acquired, out of which twelve lines expressed the HIC6 protein. None of the transgenic tobacco lines, however, showed significant differences in freezing tolerance from the control plants (wild-type and transformed with pBI121) at -1, -3, and -4 degrees C, with the exception that their freezing temperature was -2 degrees C. In order to increase the accumulation level of HIC6, pBE2113 with a stronger promoter was used. Eight lines expressed the protein out of thirteen lines transformed with pBE2113/hiC6. The accumulation levels of the protein were clearly higher in the tobacco plants transformed with pBE2113/hiC6 than in those with pBI121/hiC6. The HIC6 protein seemed to be localized in mitochondria of the transgenic tobacco plants. Freezing-tolerance tests at -1 - -4 degrees C showed that the degree of electrolyte leakage was significantly lower in the plants with pBE2113/hiC6 than in the control plants. A leaf browning observation also showed that high accumulation of HIC6 significantly suppressed injury caused by freezing to the transgenic tobacco at -3 degrees C.

Algal Proteins↗

Early retardation of 99mTc-DTPA radioaerosol transalveolar clearance in irradiated canine lung.

UNLABELLED: The alteration of 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) transalveolar clearance in an initial phase of radiation lung injury was experimentally investigated. METHODS: Fourteen dogs were irradiated to the hemithorax with a single dose of 20 Gy. A DTPA radioaerosol study was performed before irradiation and on day 12 after irradiation. On day 14, the DTPA study was repeated again, with seven animals undergoing the study after inhalation of an aerosolized synthetic surfactant. The penetration index (P.I.) and clearance half-time (T(1/2)) of DTPA were measured in each lung. To evaluate the changes in lung surfactant after irradiation, alveolar lipids were stained in the resected lungs (n = 14), and the amounts of alveolar surfactant phospholipid and protein were measured by a bronchoalveolar lavage study in another six irradiated dogs. RESULTS: In all of the 14 irradiated animals, DTPA radioaerosol distributed uniformly throughout the lungs without significant changes in P.I. The T(1/2) values in irradiated lungs were significantly prolonged compared with the matched baseline values and those in nonirradiated lungs (P < 0.05 and 0.001, respectively). The aerosolized synthetic surfactant retarded the DTPA clearance both in the irradiated and in the nonirradiated lungs (P < 0.001) without significant changes in P.I. The histologic and bronchoalveolar lavage studies revealed an increase of alveolar surfactant materials in the irradiated lungs without substantial histologic changes in the alveolar structures. CONCLUSION: DTPA transalveolar clearance was retarded soon after irradiation. Increased alveolar surfactant may be partly responsible for this retarded DTPA clearance because the aerosolized synthetic surfactant also prolonged the clearance in nonirradiated lungs. A DTPA clearance test is sensitive for the early detection of radiation lung injury and seems helpful for clarifying the association of epithelial integrity changes and lung surfactant in radiation lung injury.

Administration, Inhalation↗

In vivo estimation of bioartificial liver with recombinant HepG2 cells using pigs with ischemic liver failure.

Biological efficacy of a recombinant human hepatic cell line, glutamine synthetase transfected HepG2 (GS-HepG2), was examined with large-scale culture in a circulatory flow bioreactor and in pigs with ischemic liver failure. GS-HepG2 cells were cultured in a circulatory flow bioreactor from 5 x 10(7) to 4 x 10(9) cells for 109 days. The cells showed ammonia removal activity even under substrate (glutamic acid)-free medium, suggesting that the GS catalyzed the activity using intracellular glutamic acid that had been pooled during conventional culture. When GS-HepG2 bioartificial liver (BAL) was applied to pigs with ischemic liver failure, survival time was prolonged to 18.8 +/- 6.1 h (mean +/- SD, n = 4) from 13.8 +/- 5.4 h (n = 6) and 10.7 +/- 4.1 h (n = 6) (groups treated with cell-free BAL and treated with plasma exchange and continuous hemodiafiltration, respectively). Laboratory data indicated the tendency for improvement in increase of blood ammonia level and decline of blood coagulation indices in the GS-HepG2 BAL-treated group. The advantages and potential for the cell line as a bioreactor in BAL is also discussed, comparing to those of isolated porcine hepatocytes.

Ammonia↗

[The new portable system for home enteral nutrition, Portermate, made a patient possible go out for a long time: report of a case].

The patient, who is received home enteral nutrition (HEN) for a long time in a day, has problems on moving all days. Now, we tried Portermate, which is new portable devices for HEN, in his clinical care. The patient is chronic pancreatitis, and his clinical problems becomes to be worse after he ate. He was under total enteral nutrition via jejunostomy. His clinical complications were almost controlled after HEN, but he has a few complains receiving enteral nutrition. He would not move easily, for an old HEN system was not compact to move. Portermate made him go everywhere he wanted any time. It extremely improved his QOL under HEN. He continues to use Portermate.

Activities of Daily Living↗

Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population.

BACKGROUND: One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer. Although this question has so far remained open, there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general population in 1986, using various immunological and biochemical markers. METHODS: Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes, and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up. FINDINGS: 154 cancer cases were used in the analysis. When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjusted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.16) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic activity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31-1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. INTERPRETATION: Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer.

Adult↗

Determination of 4-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate and other alkylphenols in fish and shellfish by high-performance liquid chromatography with fluorescence detection.

A simple and highly sensitive method is described for the HPLC determination of 4-nonylphenol (NP), 4-nonylphenol mono- (NP1EO) and diethoxylates (NP2EO) in fish and shellfish together with bisphenol A (BPA), 4-tert.-butylphenol (BP) and 4-tert.-octylphenol (OP). The NP, NP1EO, NP2EO and other alkylphenols in the samples are extracted with acetonitrile and the lipid in the sample extract is eliminated by partitioning between hexane and acetonitrile. After Florisil PR clean-up the sample extract is analyzed by HPLC with a fluorescence detection. Recoveries in Japanese smelt, carp and corbicura are 81.8-84.3% for NP, 83.5-84.3% for NP1EO, 90.5-96.2% for NP2EO, 70.7-72.9% for BPA, 71.0-73.4% for BP and 77.1-83.2% for OP spiked at 0.5 microg each chemical per 5 g of the fish and shellfish samples. The detection limits are 2 ng/g for NP, NP1EO and NP2EO, and 1ng/g for BPA, BP and OP.

Animals↗

Efficient production of desulfurizing cells with the aid of expert system.

An expert system was used to achieve the high production of desulfurizing cells of Rhodococcus erythropolis KA 2-5-1. By adding a proper amount of sulfur containing component with the aid of the expert system, we could avoid excess feeding which resulted in the lowering of desulfurizing activity and starvation which caused serious damage to cell growth. In order to determine the addition amount by the expert system, the data of the amount of chemical elements contained in the cells were used as a reference for comparison with the medium components present. Culture experiments were carried out using a 5l jar fermentor with several kinds of media whose components were determined based on the inferred results with the aid of the expert system. We could restrict the amount of the sulfur component addition so that sulfur was a growth-limiting factor; in contrast, the amounts of other elements were sufficient for growth.As a result, the maximum specific production rate of 2-hydroxy biphenyl (2HBP) and the maximum cell concentration were 20mmolkg-drycells(-1)h(-1) and of 45g-drycellsl(-1), respectively. At 100h of cultivation, 1g/l of dibenzothiophene (DBT) was converted to 2HBP within 20h, i.e., 10mmolkg-drycells(-1)h(-1) of specific desulfurization activity, and the specific activity remained stable for a long period in the culture experiment.

Journal Article↗

Phantom study of fusion image of CT and SPECT with body-contour generated from external Compton scatter sources.

PURPOSE: A phantom study was conducted to evaluate the feasibility of body contour definition with Compton scatter photons from external sources of technetium-99m pertechnetate (Tc-99m) to create a fusion image of CT and SPECT images. METHODS: External sources of 1 mCi (37 MBq) Tc-99m were placed on each collimator, and body-contour SPECT images were obtained with an energy window of 100 keV +/- 25% for detecting 90 degrees and 180 degrees Compton scatter photons of Tc-99m from the body surface in water-filled cylindrical and hexagonal phantoms, and in a chest phantom with a Tc-99m-avid simulated lung nodule and multimethod surface markers. In the chest phantom, each transaxial SPECT slices was registered with the corresponding CT slice by using image-matching soft ware. A summation of the registered images yielded a three-dimensional (3-D) fusion image of this phantom. RESULTS: This method clearly visualized the body contour on all the SPECT slices in all the phantoms except for the complex hexagonal phantom. There was no significant difference between the known and SPECT-measured diameters of the cylindrical phantom. The fit of CT and SPECT images of the chest phantom was achieved with a mean alignment error of 5% in visual inspection, which was improved to 0.2% after correction of the magnification of the SPECT images according to the resultant dimensional differences. The 3-D fusion image of this phantom effectively visualized the anatomic location of the lung nodule and surface markers. CONCLUSION: This simple method effectively provided boundary information on the cold phantoms. Although further improvements in the registration technique with CT images are desirable, the body-contour SPECT image obtained by this method has the potential for accurately creating a 3-D fusion image with CT images, and is a feasible way of anticipating the anatomical localization of a target tissue.

Humans↗

Overexpression of the OLE1 gene enhances ethanol fermentation by Saccharomyces cerevisiae.

The fermentation characteristics of Saccharomyces cerevisiae strains which overexpress a constitutive OLE1 gene were studied to clarify the relationship between the fatty acid composition of this yeast and its ethanol productivity. The growth yield and ethanol productivity of these strains in the medium containing 15% dextrose at 10 degrees C were greater than those of the control strains under both aerobic and anaerobic conditions but this difference was not observed under other culture conditions. During repeated-batch fermentation, moreover, the growth yield and ethanol productivity of the wild-type S. cerevisiae increased gradually and then were similar to those of the OLE1-overexpressing transformant in the last batch fermentation. However, the unsaturated fatty acid content (77.6%) of the wild-type cells was lower than that (86.2%) of the OLE1-recombinant cells. These results suggested that other phenomena caused by the overexpression of the OLE1 gene, rather than high unsaturated fatty acid content, are essential to ethanol fermentation by this yeast.

Culture Media↗

Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET.

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2)) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T(1/2) in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T(1/2) values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease.

Case-Control Studies↗

Alteration of myocardial metaiodobenzylguanidine uptake after treatment of phaeochromocytoma and neuroblastoma.

The relationships between changes in myocardial uptake of metaiodobenzylguanidine (MIBG) and those in circulating catecholamines and cardiac function after treatment of phaeochromocytoma and neuroblastoma were evaluated. Iodine-123 or iodine-131 MIBG scintigraphy was performed before and after surgical resection and/or chemotherapy for primary tumours in nine patients with phaeochromocytoma and 13 patients with neuroblastoma. Changes in myocardial MIBG uptake after treatment were estimated by the heart-to-upper mediastinum (H/M) uptake ratios on the images obtained 24 h after MIBG injection, which were compared with serum levels of noradrenaline (NA) and adrenaline (A). Cardiac function was assessed by echocardiography, with measurements of the left ventricular ejection fraction (LVEF). Before treatment, eight patients with phaeochromocytoma and three with neuroblastoma showed poor myocardial MIBG uptake, with highly elevated circulating NA and A. Echocardiography, however, did not show cardiac dysfunction in these patients with the exception of two patients with phaeochromocytoma. With normalization of NA and A levels after treatment, all of these patients except for the two with persistent cardiac dysfunction showed restoration of myocardial MIBG uptake. The H/M ratios increased significantly after treatment in both patient groups, i.e. with phaeochromocytoma and with neuroblastoma (P<0.0001 and P<0.05, respectively), and these ratios correlated inversely with circulating NA and A before and after treatment. By contrast, there was no significant correlation between H/M ratios and LVEF in these two groups. These results indicate that suppression of myocardial MIBG uptake usually may not be related to cardiac dysfunction and may be reversible following normalization of excess catecholamine levels after treatment in patients with neuroadrenergic tumours. However, the suppression may persist in the presence of catecholamine-induced cardiac dysfunction. The assessment of myocardial MIBG uptake can be a helpful adjunct in monitoring the normalization of circulating catecholamine levels and also in identifying the presence of cardiac dysfunction in treated patients with neuroadrenergic tumours.

3-Iodobenzylguanidine↗

Irreversible long-term pulmonary functional impairments after adenovirus type-7 pneumonia: assessment with xenon-133 ventilation and Tc-99m MAA perfusion studies.

A 3-year-old child presented with severe type-7 adenoviral pneumonia, after the resolution of diffuse pulmonary infiltrates of the pneumonia. Xenon-133 ventilation and Tc-99-m macroaggregated albumin (MAA) perfusion studies revealed a localized airflow obstruction and matched perfusion defect, and marked air trapping in the remaining lungs, and these abnormalities were not detected and not suspected even with CT. Thereafter, in a relatively short period, the child developed persistent bronchiectatic changes and pulmonary hyperinflation throughout the lungs. However, the scintigraphic findings were not significantly changed. This is the first description of radionuclide scintigraphic findings which clearly showed an irreversible long-term functional effect of adenoviral pneumonia.

Adenovirus Infections, Human↗

Increase in desulfurization activity of Rhodococcus erythropolis KA2-5-1 using ethanol feeding.

Rhodococcus erythropolis KA2-5-1 is one of the best strains for the desulfurization of dibenzothiophene (DBT) via a sulfur-specific pathway in which DBT is converted to the end product, 2-hydroxybiphenyl, by releasing sulfite via DBT-sulfone and 2-(2'-hydroxyphenyl) benzene sulphinate. The objective of this research is to develop a culture method in order to attain a high cell density with a high level of specific desulfurization activity. Compared with glucose or glycerol, ethanol was found to be a preferable carbon source for obtaining a high specific activity (SA) of desulfurization. When the amount of DBT fed was restricted by feeding 2.9 mg-DBT/g-ethanol solution, the maximum SA and final cell concentration were 135.5 (mmol-2HBP/kg-dry cell weight-h) and 37 (g-dry cell weight/l), respectively. On the other hand, when glucose or glycerol was used as a carbon source, the SA was lower than 50 (mM-2HBP/kg-dry cell weight-h) and the final cell concentration was also lower than 27 (g-dry cell weight/l). The activities of the desulfurization enzymes in R. erythropolis KA2-5-1 grown on ethanol were remarkably higher than when the strain was grown on glucose or glycerol. It was also suggested that NADH, which is produced by the biochemical reaction of NAD with ethanol catalyzed by alcohol dehydrogenase, might contribute to the conversion of FMN to FMNH2, which is a coenzyme for the activities of desulfurization enzymes.

Journal Article↗