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Biomedical subjects

C F Lee

Publications and source records attributed to C F Lee.

At least 19 recordsLinked to original sources

Devising an integrated methodology for analyzing energy use and CO2 emissions from Taiwan's petrochemical industries.

Input-output modeling and multiplier analysis are used to assess Taiwan's five petrochemical industries, based upon their economic contribution and potential impacts on energy consumption and CO2 emission. In addition, a consolidated index system was developed for evaluating energy and economic efficiencies as well as targets for CO2 reduction. Results indicate that petrochemical materials (PM) make a major contribution to economic development, with lesser contributions from plastic materials (PL) and artificial fibres (AF). PM has the highest energy multiplier while PL has the largest induced potential for energy consumption. Plastic and rubber products (PP, RP) are relatively insignificant energy consumers. AF has the highest CO2 multiplier, and its induced potential for CO2 emission is the most significant. The consolidated index shows that the upstream petrochemical industries perform rather poorly in an integrated view of economic, energy, and CO2 emission, and should be seen as the primary targets for CO2 reduction. Investment of the petrochemical industries in Taiwan should be adjusted to improve energy efficiency, economic bases, and lower CO2 emissions.

Carbon Dioxide↗

Increases of mitochondrial mass and mitochondrial genome in association with enhanced oxidative stress in human cells harboring 4,977 BP-deleted mitochondrial DNA.

In order to investigate the effect of aging- and disease-associated deletion of mtDNA on cellular functions, we used cytoplasm fusion to construct a series of the cybrids harboring varying proportions of mtDNA with 4,977 bp deletion from skin fibroblasts of a patient with chronic progressive external ophthalmoplegia. The cybrids were grown in the Dulbecco's modified Eagle medium supplemented with 5% fetal bovine serum, 100 microg/ml pyruvate and 50 microg/ml uridine. The population doubling time was longer for the cybrids containing higher proportions of 4,977 bp-deleted mtDNA. In addition, we found that the respiratory function was decreased with the increase of mtDNA with 4,977 bp deletion in the cybrids. Since impairment of the respiratory system of mitochondria increases the electron leak of the respiratory chain, we further determined the oxidative stress in these cybrids. The results showed that the specific contents of 8-hydroxy 2'-deoxyguanosine and lipid peroxides of the cybrids harboring > 65% of the 4,977 bp-deleted mtDNA were significantly increased as compared with those of the cybrids containing undetectable mutant mtDNA. On the other hand, we found that the mitochondrial mass and the relative content of the mitochondrial genome in the cybrids harboring 4,977 bp-deleted mtDNA were higher than those of the cybrids containing only wild type mtDNA. The relative content of mtDNA was increased 17% and 30%, respectively, in the cybrids harboring 17% and 56% of mtDNA with 4,977 bp deletion. Moreover, both mitochondrial mass and mtDNA content were concurrently increased by treatment of the cybrids with 180 microM of hydrogen peroxide. Taken these findings together, we conclude that increase of mitochondrial mass and mtDNA are the molecular events associated with enhanced oxidative stress in human cells with impaired respiratory function caused by mtDNA deletion.

8-Hydroxy-2'-Deoxyguanosine↗

Mitochondrial theory of aging matures--roles of mtDNA mutation and oxidative stress in human aging.

Mitochondrial theory of aging, a variant of free radical theory of aging, proposes that accumulation of damage to mitochondria and mitochondrial DNA (mtDNA) leads to aging of humans and animals. It has been supported by the observation that mitochondrial function declines and mtDNA mutation increases in tissue cells in an age-dependent manner. Age-related impairment in the respiratory enzymes not only decreases ATP synthesis but also enhances production of reactive oxygen species (ROS) through increased electron leakage in the respiratory chain. Human mtDNA, which is not protected by histones and yet is exposed to high levels of ROS and free radicals in the matrix of mitochondria, is susceptible to oxidative damage and mutation in tissue cells. In the past decade, more than one hundred mtDNA mutations have been found in patients with mitochondrial disease, and some of them also occur in aging human tissues. The incidence and abundance of these mutant mtDNAs are increased with age, particularly in tissues with great demand for energy. On the other hand, recent studies have revealed that the ability of the human cell to cope with oxidative stress is compromised in aging. Comparative analysis of gene expression by microarray technology has shown that a number of genes related to oxidative stress response are altered in aging animals. We discovered that the transcripts of early growth response protein-1, growth arrest and DNA damage-inducible proteins and glutathione S-transferase genes are increased in response to oxidative stress in human skin fibroblasts. Moreover, the activities of Cu,Zn-SOD, catalase and glutathione peroxidase decrease with age, whereas Mn-SOD activity increases with age up to 65 years and slightly declines thereafter in skin fibroblasts. Such an imbalance in the function of antioxidant enzymes may result in excess production of damaging ROS in the cell. This notion is supported by the observation that intracellular levels of H2O2 and oxidative damage to DNA and lipids are significantly increased with age of the fibroblast donor. Furthermore, the mitochondrial pool of reduced glutathione declines and DNA damage is enhanced in aging tissues. Taken together, these observations and our previous findings that mtDNA mutations and oxidative damage are increased in aging human tissues suggest that mitochondrial theory of aging is mature.

Aging↗

Mediators and oxygen radicals in hyperpnea-induced airway constriction of guinea pigs.

Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to be important modulating factors for the hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen radicals modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs were divided into four groups: control, dimethylthiourea (DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of LT receptor, whereas A63162 is an inhibitor of lipoxygenase. Each group was further divided into three subgroups: baseline, hyperpnea, and recovery. Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory compliance (Crs), maximal expiratory flow at 50% total lung capacity (V(max(50))), and forced expiratory volume in 0.1 s (FEV(0.1)) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, V(max(50)), and FEV(0. 1), indicating HIB in the control group. Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (SP) levels increased progressively during the experiment in all groups. However, both FPL 55712 and A63162, but not DMTU, significantly decreased SP levels. Similarly, lung malondialdehyde (MDA) contents increased progressively during the experiment in the control group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly attenuated the increase in MDA during the recovery period. These results suggest that inhibition of LTs leads to suppression at SP levels and HIB, whereas DMTU attenuates HIB by means of other mechanisms.

Acetamides↗

The molecular biology of Schwanniomyces occidentalis klocker.

This review describes the molecular studies of Schwanniomyces occidentalis (Debaryomyces occidentalis) concerning transformation, genome, gene cloning, gene structure, gene expression and its characteristics to application. Schw. occidentalis appears to have at least five or seven chromosomes and no native plasmid from the yeast has been reported. Four transformation systems based on complement of Schw. occidentalis auxotrophic mutants were established. Vectors with the replicon of 2-micron plasmid and autonomous replication sequences (ARS) of Saccharomyces cerevisiae and Schw. occidentalis ARS replicated extrachromosomally in Schw. occidentalis transformants, without modification of the transformed vector DNA. So far, at least 21 Schw. occidentalis genes encoding 14 different proteins have been cloned. Most of the Schw. occidentalis genes have shown homologies (45 to 91%) with the corresponding genes of other organisms, especially of S. cerevisiae. However, some Schw. occidentalis genes possess other unique structures for their operators, promoters, transcription initiation sites, and terminators. Some foreign genes were expressed in Schw. occidentalis, while Schw. occidentalis genes functioned in other yeasts and bacteria, Escherichia coli, and Streptomyces lividans. Due to a strong ability of secretion and low level of glycosylation, Schw. occidentalis might be a promising host to produce heterologous proteins.

Amino Acid Sequence↗

Lac/Tet dual-inducible system functions in mammalian cell lines.

The Escherichia coli Lac repressor (Lac system) and tetracycline responsive promoter (Tet system) systems have been used individually to regulate gene expression at the cellular as well as the organismal levels. In this study, these two systems were combined (designated Lac/Tet dual-inducible system) to regulate two inducible genes simultaneously in a single cell. The isopropyl-beta-D-thiogalactopyranoside (IPTG) and tetracycline (used for the operation of the Lac and the Tet systems) were non-cytotoxic to the cells when added together into the cells at around the optimal concentrations (IPTG: < or = 5 mM; tetracycline: < 1.5 micrograms). The rate and efficiency of induction and repression of two inducible genes regulated by the Lac/Tet dual-inducible system were similar to the results obtained when one inducible gene is regulated by one inducible system in a single cell. The Lac/Tet dual-inducible system could function in many cell lines, which was demonstrated by regulating the expression of beta-galactosidase and luciferase reporter genes in five tumor cell lines by transient transfection analysis. The feasibility of introducing a second inducible system into an already established inducible cell line was confirmed. Finally, we showed that the Lac/Tet dual-inducible system functions at translational and at functional levels in a stable cell line named 7-4-b, which contains the Ha-ras and bc1-2 inducible genes. In conclusion, this study extends the application of prokaryotic inducible systems from the regulation of a single gene to two genes and helps clarify the relationship between two genes and the effects of two genes on the cells.

Animals↗

Single dose pharmacokinetic study of lithium in Taiwanese/Chinese bipolar patients.

OBJECTIVE: The purpose of this study is to investigate the single dose pharmacokinetics of lithium in Taiwanese/Chinese bipolar patients for future interracial comparisons. METHOD: Eight bipolar patients took 900 mg of lithium carbonate after overnight fasting. Blood samples of 5 mL were taken after 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 7 h, 9 h, 15 h, 25 h and 31 h after dosing. The computer programs CSTRIP and PCNONLIN were used for pharmacokinetic analysis. RESULTS: The pharmacokinetic parameters obtained were as follows: Cmax, 0.970 +/- 0.170 (SD) mmol/L; Tmax, 1.59 +/- 0.78 h; AUC31 h = 548.9 +/- 135.4 mmol x m/L; AUC to infinity = 722.6 +/- 262.7 mmol x m/L; beta-half-life = 16.3 +/- 7.18 h; kappa-half-life = 0.613 +/- 0.442 h; Cl(oral) = 1.13 +/- 0.39 mL/min/kg; Vd/F = 1.43 +/- 0.387 L/kg. Most of the pharmacokinetic parameters were within the ranges reported in investigations of Caucasian subjects. CONCLUSIONS: This study showed that racial differences in lithium pharmacokinetics might not exist. We suggest that methodological designs, including method of blood sampling, measurement of lithium, and pharmacokinetic and statistical calculations, be standardised if future cross-ethnic comparisons are to be conducted.

Adolescent↗

Synthesis and cytotoxic evaluation of substituted sulfonyl-N-hydroxyguanidine derivatives as potential antitumor agents.

A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido moiety of the lead compound with hydroxyguanidine provided a stable cytotoxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivatives, such as N-(4-chlorophenyl)-N'-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N"- hydroxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calculations, and X-ray crystallography, indicated stacking of the two aromatic rings. The derivatives were evaluated for in vitro cytoxicity against five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds against the human tumor cell lines were equal to or greater than that of the lead compound. N-(4-Chlorophenyl)-N'-[[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]- N"- hydroxyguanidine (4n) and N-(4-chlorophenyl)-N'-[[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl] sulfonyl]-N"-hydroxyguanidine (4o) exhibited the greatest growth inhibition of solid tumor cell lines. Compound 4o was found to possess antitumor activity against murine K1735/M2 melanoma xenografts.

Animals↗

Epinephrine enhances glycogen turnover and depresses glucose uptake in vivo in rat heart.

In vivo effects of epinephrine on glucose uptake and glycogen turnover in rat heart were studied and compared to liver and skeletal muscle. Fasted ketamine-anesthetized rats were intravenously infused with saline or epinephrine. Both the low and high doses of epinephrine resulted in hyperglycemia (40-50%) and hyperlactemia (threefold) at the end of infusion. Glucose uptake, determined by the phosphorylation of the intravenously injected [14C]2-deoxyglucose, was found to decrease in the heart and skeletal muscle of epinephrine-infused rats. Glycogen in livers, skeletal muscles, and hearts of the epinephrine-infused rats decreased to varying degrees relative to the saline-infused rats, indicating enhanced glycogenolysis in all three organs. Glycogen synthesis, determined by the incorporation of the co-infused [3-(3)H]glucose into glycogen, was found to decrease in liver and skeletal muscle. However, glycogen synthesis in the heart was found to increase 50% in Epi-1 and 280% in Epi-2 compared to the saline-infused rats. We conclude that glucose utilization in the in vivo heart may be preferentially channeled through glycogen turnover in the presence of epinephrine. That both synthesis and degradation of glycogen can be simultaneously activated appears to be unique to the heart and is protective against a loss of glycogen at a time of enhanced glucose utilization.

Animals↗

The daily rhythm of tooth eruption.

A video microscope system, which can resolve tooth movements to 1 to 2 microns, was used to monitor the eruption of 17 human maxillary second premolars in the prefunctional phase. Eruptive movement was detected by the change in position of an optical ruling on the erupting tooth relative to a reference ruling on the occluding adjacent teeth. Eruption was observed as the teeth erupted toward the occlusal plane over approximately a 41-hour period, from late Friday afternoon until Sunday noon. Half hourly observations were made during a 6 to 8-hour continuous laboratory session, which was during the day (9 AM to 5 PM) for nine of the subjects, and during the evening (5 to 11 PM) for eight. A similar pattern of eruption was seen for all subjects. The tooth intruded from before to after dinner on the first day, erupted significantly overnight, ceased eruption and approximately maintained its position during the next day, and erupted again during the second night. On the average, a slight intrusion was observed during the day, and statistically significant intrusion was associated with breakfast and dinner. Eruption occurred during the evening observation period, and the rate of evening eruption was significantly greater in children who were supine and relaxed than those who were upright and active. The 24-hour eruption rate was slower for teeth that were within 1.5 mm of the occlusal plane. The circadian eruption rhythm may be related to fluctuations of hormonal levels that affect metabolic activities within the periodontal ligament. It is also possible that a transient reduction in pressures by the cheeks, lips, and tongue during periods of rest allows eruption to occur then.

Adolescent↗

Amino acid sequences of trypsin inhibitors from the melon Cucumis melo.

Two squash family trypsin inhibitors, CMeTI-A and CMeTI-B, were isolated from the melon (Cucumis melo) seeds, by ion exchange chromatography, gel filtration, affinity chromatography, and high-performance liquid chromatography, and their amino acid sequences were determined. All inhibitors contain 29 amino acid residues including 6 half-cystine residues. They differ by twelve amino acid residues. These polypeptides are strong inhibitors of bovine trypsin, with Ki values of 1.6 x 10(-10) M (CMeTI-A) and 4.7 x 10(-10) M (CMeTI-B). The products of CMeTI-A and CMeTI-B cleaved at their reactive sites by tryptic digestion during the purification by trypsin-Sepharose 4B affinity column chromatography are active against trypsin activity, but a molar ratio of inhibitor to trypsin of 2:1 for trypsin-treated CMeTI-B or 1:1 for trypsin-treated CMeTI-A is required.

Amino Acid Sequence↗

2-Heteroaryl 2-substituted phenylketone derivatives and their inhibitory activity on platelet aggregation.

R 68070 and CV-4151 are two compounds possessing both thromboxane synthetase inhibitory activity and thromboxane receptor antagonist properties. 2-Heteroaryl 2-substituted phenylketone derivatives with a partial structural similarity to R 68070 and CV-4151, i.e. possessing a phenyl and a heteroaryl moiety, have been prepared and found to have antiplatelet activity. The compound 2-thienyl 2'-hydroxyphenyl ketone (4) was shown to completely inhibit platelet aggregation induced by arachidonic acid at a concentration of 5.0 microM. Structure-activity analysis indicated that the presence of a ketone group is an important requirement for this inhibitory activity. An o-hydroxyl substitution on the phenyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitory activity.

Animals↗

Different behavior of forearm blood flow during intermittent isometric handgrip in a thermo-neutral and a hot environment.

The purpose of the present study was to evaluate the different behavior of forearm blood flow (FBF) during intermittent isometric handgrip (IIHG, 6 seconds contraction +6 seconds relaxation) in a thermoneutral versus a hot environment. Six healthy men performed three times of 5-minute period IIHG at three different work loads (10%, 20% and 30% MVC). The IIHG was performed with the right hand. The experiments of IIHG were performed at two different air temperatures (25 degrees C and 40 degrees C, RH: 50%), and an experiment without work was also carried out at 40 degrees C (RH: 50%). The physiological responses measured involved heart rate (HR), cardiac output (CO), mean arterial blood pressure (MBP), FBF, and skin blood flow (SBF). HR, CO and SBF showed higher values during IIHG at 40 degrees C than at 25 degrees C. MBP had a tendency to increase with the intensity of work load at both 25 degrees C and 40 degrees C. Since intramuscular pressure might increase during contraction periods at 20% MVC and 30% MVC at 25 degrees C, FBF was significantly higher during relaxation periods than during contraction periods. FBF showed similar values between contraction and relaxation periods at 10% MVC at both temperatures. The present study suggested that FBF was sufficient for active muscles during IIHG at 10% MVC. FBF of contraction periods was close to that of relaxation periods at 40 degrees C due to the modulation of the sympathetic outflow to the muscles and/or the decreased efficiency of the muscle pump. It was suggested that FBF showed different behaviors during HHG at 25 degrees C versus at 40 degrees C.

Adult↗

Circulatory regulation during supine and sitting intermittent isometric handgrip in a hot environment.

We studied the circulatory regulation during intermittent isometric handgrip (IIHG, six seconds contraction + six seconds relaxation) in supine and sitting postures in a hot environment (40 degrees C, RH: 50%). Eight healthy male subjects performed thrice 5-minute period IIHG at three different work loads (10%, 20% and 30% MVC). The IIHG was performed with the right hand in the two postures. Heart rate (HR), cardiac output (CO), mean arterial blood pressure (MBP), forearm blood flow (FBF), skin blood flow (SBF), foot swelling (FSW) and tympanic temperature (Tty) were measured during IIHG, resting and recovery periods. During IIHG in a hot environment, HR, MBP, FSW and Tty showed higher values in the sitting than in the supine posture. FBF during relaxation showed higher values at high work load than at low work load in the two postures. FBF showed higher values in the sitting than in the supine posture, except during relaxation at 30% MVC. It was concluded that the decrements of blood volume of splanchnic organs might be greater in the sitting than in the supine posture due to sympathetic vasoconstrictor activity, and were responsible for the redistribution of blood flow. Posture had an effect on FBF because of hydrostatic pressure.

Adult↗

Screening for defects of branched-chain amino acid metabolism.

Screening for defects of branched-chain amino acid metabolism is a sequential process involving clinical evaluation of the patient, plasma carnitine determination, urinary organic acid analysis, and enzyme studies in cultured or isolated peripheral cells. This report will summarize clinical and metabolite features and enzymological methods available for the diagnosis of the more common defects of branched-chain amino acid metabolism, including isovaleryl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, 3-methylglutaconic aciduria due to 3-methylglutaconyl-CoA hydratase deficiency and other less well characterized defects, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, and 2-methylacetoacetyl-CoA thiolase deficiency. Newer enzymatic methodologies utilizing NaH14CO3 fixation coupled assays are described which allow for the estimation of six enzyme activities in the catabolic pathways of L-leucine and L-isoleucine catabolism. These coupled assays facilitate the rapid identification of five of the six enzyme abnormalities described above. Their ease of use should allow them to be implemented in any laboratory which screens for inborn errors of metabolism.

Amino Acid Metabolism, Inborn Errors↗

Synonymy of Candida methylica with Candida boidinii and of Candida methanolophaga with Candida succiphila.

Some Candida species which can use methanol as a sole carbon source were studied by performing chemotaxonomic tests; we determined the ubiquinone systems of these organisms, their DNA base compositions, their electrophoretic karyotypes, and their DNA relatedness values. The type strains of Candida methanolophaga and Candida succiphila had similar DNA base compositions and exhibited 90% DNA relatedness. All Candida boidinii and Candida methylica strains had DNA G + C contents of 30.8 to 31.0 mol%, and these organisms exhibited 87 to 101% DNA relatedness to the type strain of C. boidinii. We propose that C. methanolophaga and C. methylica should be synonyms of C. succiphila and C. boidinii, respectively.

Base Composition↗

[Responses of electroencephalogram to different odors].

The responses of electroencephalogram (EEG) to different odors and their densities were studied on four men and two women at rest while sitting. The odors examined were citrus, floral and lavender, and their densities were 100 ppb and 200 ppb. The odors were released for ten minutes from a duct to fill the room completely. The subjective estimation indicated that citrus had a tendency to be the most comfortable odor in this study, but it was not significant. To evaluate changes of EEG, the power spectra of frequency-fluctuation of alpha wave (Fz) and the rate of alpha, beta, and beta/alpha wave (Oz, Fz) were calculated. The rate of alpha wave (Oz) in the period of giving out the citrus at 100 ppb was significantly (p < 0.05) higher than that of the lavender. The rate of beta wave (Oz) in the period of giving out the floral at 200 ppb was significantly (p < 0.05) higher than that of the lavender. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave in the period of giving out the lavender at 100 ppb was significantly higher than those in the other periods of the experiment. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave for lavender given out at 200 ppb was significantly (p < 0.01) higher than those for the other odors given out. It seems that the regression coefficient of the power spectra of frequency-fluctuation of alpha wave can be used for the evaluation of psychophysiological responses.

Adult↗