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Biomedical subjects

J P Lin

Publications and source records attributed to J P Lin.

At least 19 recordsLinked to original sources

Berberine inhibits arylamine N-acetyltransferase activity and gene expression in mouse leukemia L 1210 cells.

N-acetyltransferases (NATs) are recognized to play a key role in the primary step of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow acetylators, which are being thought to involve cancer risk related to environmental exposure. Berberine has been shown to induce apoptosis and affect NAT activity in human leukemia cells. The purpose of this study is to examine whether or not berberine could affect arylamine NAT activity and gene expression (NAT mRNA) and the levels of NAT protein in mouse leukemia cells (L 1210). N-acetylated and non-N-acetylated AF were determined and quantited by using high performance liquid chromatography. NAT mRNA was determined and quantited by using RT-PCR. The levels of NAT protein were examined by western blotting and determined by using flow cytometry. Berberine displayed a dose-dependent inhibition to cytosolic NAT activity and intact mice leukemia cells. Time-course experiments indicated that N-acetylation of AF measured from intact mice leukemia cells were inhibited by berberine for up to 24 h. The NAT1 mRNA and NAT proteins in mouse leukemia cells were also inhibited by berberine. This report is the first demonstration, which showed berberine affect mice leukemia cells NAT activity, gene expression (NAT1 mRNA) and levels of NAT protein.

Animals↗

Decommissioning of a 60Co unit and estimation of personal doses.

Chang-hua Christian Hospital needs to uninstall the 60Co unit. The mode of this 60Co teletherapy unit is SHIMADZU RTGS-10. The original lead head was taken as the source container of this 60Co unit. The source head was dismantled and put into the prepared wooden box, after the source was sealed. This study describes the planning and dismantling of the retirement and transport of the 60Co unit, and personal doses measured during the procedure. This work estimates the doses of radiation received by exposed workers during the dismantling of the machine. The workers received doses of approximately 53 microSv. This study shows that the original lead head can be used as the source container of this 60Co unit. The 60Co machine was smoothly dismantled and transported by conscientious and careful workers, using planned and controlled radiation protection, following the ALARA (as low as reasonably achievable) rule.

Body Burden↗

Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study.

This study evaluated the efficacy and safety of three doses of botulinum toxin A (BTX-A; Dysport) in 125 patients (mean age 5.2 years, SD 2; 54% male)with dynamic equinus spasticity during walking. Participants were randomized to receive Dysport (10, 20, or 30 units/kg) or placebo to the gastrocnemius muscle of both legs. Muscle length was calculated from electrogoniometric measurements and the change in the dynamic component of gastrocnemius shortening at four weeks was prospectively identified as the primary outcome measure. All treatment groups showed statistically significant decreases in dynamic component compared with placebo at 4 weeks. Mean improvement in dynamic component was most pronounced in the 20 units/kg group, being equivalent to an increase in dorsiflexion with the knee extended at 19 degrees, and was still present at 16 weeks. The safety profile of the toxin appears satisfactory.

Botulinum Toxins, Type A↗

Luteolin-inhibited arylamine N-acetyltransferase activity and DNA-2-aminofluorene adduct in human and mouse leukemia cells.

N-Acetyltransferase enzyme is an important enzyme in the first step of arylamine compounds metabolism. Luteolin has been shown to exit antibacterial and antineoplastic activity. The purpose of this present study is to evaluate the question of whether luteolin could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adduct formation in human (HL-60) and mouse (L1210) leukemia cells. By using HPLC, N-acetylation of 2-aminofluorene was determined. Luteolin displayed a dose-dependent inhibition to cytosolic NAT activity and intact human and mice leukemia cells. Time-course experiments showed that N-acetylation of 2-aminofluorene measured from intact human and mice leukemia cells were inhibited by luteolin for up to 24 hours. Using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor to NAT activity in cytosols. The DNA-2-aminofluorene adduct formation in human and mouse leukemia cells were inhibited by luteolin. This report is the first demonstration to show that luteolin affects human and mice leukemia cells NAT activity and DNA-2-aminofluorene on adduct formation.

2-Acetylaminofluorene↗

Skin dose measurement by using ultra-thin TLDs.

The treatment schedule for radiation therapy is often interrupted because of complicated skin reactions. Quantitative information relating beam parameters and skin reactions will be helpful. Measurements were performed for 6-15 MV photons and 6-21 MeV electrons with ultra thin TLD films (GR-200F, surface area 0.5 x 0.5cm2, nominal thickness 5 mg cm(-2)). The skin doses for various field sizes, ranging from 10 x 10 to 40 x 40 cm2, and various incident angles of beam from 0 degrees to 80 degrees were measured. The ratios of skin dose to maximum dose in phantom for 10 x 10 cm2 are 16.10+/-0.68%, 14.03+/-1.04% and 10.59+/-0.64% for 6, 10 and 15 MV, respectively. Such ratios increase with a larger field size. For electrons the ratios are 72.59+/-1.72%, 78.52+/-2.99%, 78.89+/-2.86%, 86.08+/-2.62%. 87.75+/-1.94% and 86.33+/-3.09% for 6, 9, 12, 15, 18 and 21 MeV, respectively. They also increase with a larger size. The oblique factors also increase with larger incident angle.

Electrons↗

The measurement of photoneutrons in the vicinity of a Siemens Primus linear accelerator.

This study involves the measurement of photoneutron contamination emitted from a Siemens Primus medical linear accelerator by using BD-PND bubble detectors. Various bubble detectors were arranged around the linac head with the interval of I m and at the same height as the isocenter to measure the dose equivalent distribution in the treatment room. The measurements were performed for 15 MV X-rays with 40 x 40cm2 and 0 x 0cm2 fields and for 15,18, and 21 MeV electrons with 25 x 25 cm2 electron cone. Neutron dose equivalent rate at the points of measurement in the treatment room decreased with increasing distance to the isocenter. The maximum neutron dose equivalents were at the isocenter, and the values for 15MV 40 x 40 and 0 x 0 cm2 were 1843+/-90 and 169.9+/-59.9 microSv per Gy X-ray, respectively. The values for 15, 18 and 21 MeV electrons with 25 x 25 cm2 cones were 100.0+/-20.4, 262.7+/-61.2 and 349.0+/-29.6 microSv per Gy electron, respectively. The neutron contamination of electrons less than 12 MeV was below the detection limit.

Journal Article↗

Dose compensation of the total body irradiation therapy.

The aim of the study is to improve dose uniformity in the body by the compensator-rice and to decrease the dose to the lung by the partial lung block. Rando phantom supine was set up to treat bilateral fields with a 15 MV linear accelerator at 415cm treatment distance. The experimental procedure included three parts. The first part was the bilateral irradiation without rice compensator, and the second part was with rice compensator. In the third part, rice compensator and partial lung block were both used. The results of thermoluminescent dosimeters measurements indicated that without rice compensator the dose was non-uniform. Contrarily, the average dose homogeneity with rice compensator was measured within +/- 5%, except for the thorax region. Partial lung block can reduce the dose which the lung received. This is a simple method to improve the dose homogeneity and to reduce the lung dose received. The compensator-rice is cheap, and acrylic boxes are easy to obtain. Therefore, this technique is suitable for more studies.

Humans↗

Monte Carlo simulation of a clinical linear accelerator.

The effects of the physical parameters of an electron beam from a Siemens PRIMUS clinical linear accelerator (linac) on the dose distribution in water were investigated by Monte Carlo simulation. The EGS4 user code, OMEGA/BEAM, was used in this study. Various incident electron beams, for example, with different energies, spot sizes and distances from the point source, were simulated using the detailed linac head structure in the 6 MV photon mode. Approximately 10 million particles were collected in the scored plane, which was set under the reticle to form the so-called phase space file. The phase space file served as a source for simulating the dose distribution in water using DOSXYZ. Dose profiles at Dmax (1.5 cm) and PDD curves were calculated following simulating about 1 billion histories for dose profiles and 500 million histories for percent depth dose (PDD) curves in a 30 x 30 x 30 cm3 water phantom. The simulation results were compared with the data measured by a CEA film and an ion chamber. The results show that the dose profiles are influenced by the energy and the spot size, while PDD curves are primarily influenced by the energy of the incident beam. The effect of the distance from the point source on the dose profile is not significant and is recommended to be set at infinity. We also recommend adjusting the beam energy by using PDD curves and, then, adjusting the spot size by using the dose profile to maintain the consistency of the Monte Carlo results and measured data.

Computer Simulation↗

Safety profile and efficacy of botulinum toxin A (Dysport) in children with muscle spasticity.

Botulinum toxin A (BTX-A) is widely used in the management of muscle spasticity in children. However, at present the dose of BTX-A for a given patient is selected empirically. The aim of this study is to provide dosage guidelines that are based on risk/benefit assessment. This was a multicentre retrospective study of the safety profile and efficacy of BTX-A in children with chronic muscle spasticity. Data in 758 patients who received a total of 1594 treatments were analysed (mean age 7.2 years; 429 males, 329 females). Spastic cerebral palsy (CP) was the most common diagnosis (94% of the study sample). Of all treatments 7% resulted in adverse events; incidence was related to the total dose rather than the dose calculated on the basis of body weight. The highest incidence of adverse events was observed in patients who received >1000 IU of BTX-A per treatment session. The odds of an adverse event was 5.1 times greater for this group of patients than for those who had 250 IU or less (p<0.001). A good overall response to treatment was reported in 82% and treatment goals were fully or partially achieved in 3% and 94% of participants respectively. More patients in the highest dose group reported functional deterioration. Interestingly, multilevel treatments resulted in a better response than single-level treatments (odds ratio 1.7, 95% CI 1.3 to 2.2,p=0.001).

Age Factors↗

Effects of (-)-menthol on arylamine N-acetyltransferase activity in human liver tumor cells.

To evaluate whether or not (-)-menthol affects arylamine N-acetyltransferase (NAT) activity, we selected human liver tumor cell line (J 5) for examination. By using high performance liquid chromatography, NAT activity for acetylation of 2-aminofluorene (AF) was determined. (-)-Menthol displayed a dose-dependent inhibition to cytosolic NAT activity. Time-course experiments showed that NAT activity measured from intact human liver tumor cells was inhibited by (-)-menthol for up to 24 hrs. But in human liver tumor intact cells, the low doses (0.0032 and 0.032 mM) of (-)-menthol promoted the NAT activity and the high doses (3.2 and 32 mM) of (-)-menthol inhibited NAT activity and the 0.32 mM (-)-menthol did not show any significant differences between control and (-)-menthol treated groups. Using standard steady-state kinetic analysis, it was demonstrated that (-)-menthol was a possible uncompetitive inhibitor (decrease Km and Vmax) to NAT activity in cytosols. This report is the first demonstration which showed (-)-menthol affect on human liver tumor cells NAT activity.

Antineoplastic Agents↗

Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita.

Limitation of movement during fetal development may lead to multiple joint contractures in the neonate, termed arthrogryposis multiplex congenita. Neuromuscular disorders are among the many different causes of reduced fetal movement. Many congenital myasthenic syndromes (CMSs) are due to mutations of the adult-specific epsilon subunit of the acetylcholine receptor (AChR), and, thus, functional deficits do not arise until late in gestation. However, an earlier effect on the fetus might be predicted with some defects of other AChR subunits. We studied a child who presented at birth with joint contractures and was subsequently found to have a CMS. Mutational screening revealed heteroallelic mutation within the AChR delta subunit gene, delta 756ins2 and delta E59K. Expression studies demonstrate that delta 756ins2 is a null mutation. By contrast, both fetal and adult AChR containing delta E59K have shorter than normal channel activations that predict fast decay of endplate currents. Thus, delta E59K causes dysfunction of fetal as well as the adult AChR and would explain the presence of joint contractures on the basis of reduced fetal movement. This is the first report of the association of AChR gene mutations with arthrogryposis multiplex congenita. It is probable that mutations that severely disrupt function of fetal AChR will underlie additional cases.

Action Potentials↗

Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification.

OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced-stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.

Adult↗

[Studies on lipase production from Candida rugosa].

We studied some factors affecting the lipase production from candida rugosa, they mainly included medium compositions and culture condition. The result showed that the optimal medium compositions for lipase production are 0.1% glucose 4.0% olive oil (carbon source), 0.3% NH4NO3(nitrogen source), 1.2% K2HPO4 and 0.4% MgSO4.7H2O. And the optimal culture condition is initial pH6.5, temperature 30 degrees C, agitation 180 r/min and time 60 h. As a result, and the lipase activity could reach 19.5 u/mL. Meanwhile we found that the surfactant could be helpful to the lipase production, and the optimal surfactant concentration was 0.03% GPE. The lipase activity was improved by more than 170% after we optimized the medium compositions and culture condition. While in a 5L fermentator, the lipase activity of fermentation broth could reach 33.5 u/mL within 48 hours.

Candida↗

Liquid products from oxidative thermal treatment of oil sludge with different oxygen concentrations of air.

Oxidative thermal treatment of oil sludge with different oxygen concentrations of air by using a dynamic thermogravimetric (TG) reaction system is investigated. The experimental conditions employed are: gas flow rate of 50 cm3/min (value at 298 K) for 300 mg dry waste, a constant heating rate of 5.2 K/min, the oxygen concentrations in air of 1.09, 8.62 and 20.95 vol. % O2, and the temperature (T) range of 378-873 K. From the experimental results, the residual mass fractions (M) are about 78.95, 28.49, 8.77 and 4.13 wt. % at the oxidative T of 563, 713, 763 and 873 K for the case with 20.95 vol. % O2, respectively. The values of M with 8.62 and 1.09 vol. % O2 at T of 873 K are 4.87 and 9.44 wt. %, respectively. The distillation characteristics of the oil portion of liquid products (condensates of gas at 298 K) from the oxidative thermal treatment of oil sludge with 20.95 vol. % O2 at T of 378-873 K is close to those of commercial gasoline. Nevertheless, the liquid product contains a large amount of water. The distillation characteristics of the oil portions of liquid products with 8.62 and 1.09 vol. % O2 at T of 378-873 K are close to those of diesel and fuel oils, respectively. The oil quality with 8.62 vol. % O2 is better than that with 1.09 vol. % O2. However, the liquid product with 8.62 vol. % O2 still contains a large amount of water; nonetheless, that with 1.09 vol. % O2 is with negligible water. Compared with the oil product of nitrogen pyrolysis, the oil quality with 1.09 vol. % O2 is better. Certainly, low oxygen conditions (i.e. 1.09 vol. % O2) not only accelerate the thermal reaction of oil sludge, but also at the same time avoid or reduce the production of water. Further, from the analysis of benzene (B), ethylbenzene (E), toluene (T) and iso-xylene (X) concentrations of the oil portion of liquid products, the BETX concentrations of oil with 20.95 vol. % O2 are higher than those with 8.62 and 1.09 vol. % O2. The yields of liquid products with 20.95, 8.62 and 1.09 vol. % O2 at T of 378-873 K are 31.96, 34.42 and 37.3 wt. %, respectively. From the experimental results, the improvement effects of oxygen on the qualities of the oil portion of liquid products are obvious. The above technique not only formats good quality gasoline and diesel oils but also reduces large amount of oil sludge. If the oil exists with water, it may be obtained by further separation or collected by fractional condensation.

Air↗

Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex.

Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome, which has been linked to loci on 2p16 and 17q22-24. We recently reported that PRKAR1A, which codes for the type 1A regulatory subunit of protein kinase A (PKA), is a tumor suppressor gene on chromosome 17 that is mutated in some CNC families. To evaluate the spectrum of PRKAR1A mutations, we identified its genomic structure and screened for mutations in 54 CNC kindreds (34 families and 20 patients with sporadic disease). Fourteen families were informative for linkage analysis: four of four families that mapped to 17q had PRKAR1A mutations, whereas there were no mutations found in seven families exhibiting at least one recombination with 17q. In six of the latter, CNC mapped to 2p16. PRKAR1A mutations were also found in 12 of 20 non-informative families and 7 of 20 sporadic cases. Altogether, 15 distinct PRKAR1A mutations were identified in 22 of 54 kindreds (40.7%). In 14 mutations, the sequence change was predicted to lead to a premature stop codon; one altered the initiator ATG codon. Mutant mRNAs containing a premature stop codon were unstable, as a result of nonsense-mediated mRNA decay. Accordingly, the predicted truncated PRKAR1A protein products were absent in these cells. We conclude that (i) genetic heterogeneity exists in CNC; and (ii) all of the CNC alleles on 17q are functionally null mutations of PRKAR1A. CNC is the first human disease recognized to be caused by mutations of the PKA holoenzyme, a critical component of cellular signaling.

Amino Acid Sequence↗

Dissolution rates of limestones of different sources.

The dissolution characteristics of limestones from six sources in Taiwan have been studied by using the pH-stat method in a stirred tank at 60 degrees C, pH values of 4 and 6, stirrer speeds of 500-1000 rpm, and a particle size of 75-125 microm aperture width. The dissolution rates of the limestones were found to be controlled by the mass transfer of hydrogen ions with chemical reactions in the liquid film surrounding the limestone particle. The measured value of mass transfer coefficient increases with an increasing pH value and stirrer speed and remains constant with particle size. For the six limestones at the same particle size, the measured dissolution rates per unit area are the same due to the mass-transfer control kinetics; however, the time taken to reach a certain fraction of dissolution is proportional to the molar concentration of the soluble species in the limestone and the initial particle size.

Air Pollutants↗

A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22).

Familial hyperaldosteronism type II (FH-II) is caused by adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted in an autosomal dominant fashion. Unlike FH type I (FH-I), which results from fusion of the CYP11B1 and CYP11B2 genes, hyperaldosteronism in FH-II is not glucocorticoid remediable. A large family with FH-II was used for a genome wide search and its members were evaluated by measuring the aldosterone:renin ratio. In those with an increased ratio, FH-II was confirmed by fludrocortisone suppression testing. After excluding most of the genome, genetic linkage was identified with a maximum two point lod score of 3.26 at theta=0, between FH-II in this family and the polymorphic markers D7S511, D7S517, and GATA24F03 on chromosome 7, a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II; its molecular elucidation may provide further insight into the aetiology of primary aldosteronism.

Chromosome Banding↗