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Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 127 records · Page 7Linked to original sources
PubMed1997

The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects.

Wet aerosols of 4.5% sodium chloride (NaCl) are often used to assess the bronchial responsiveness associated with asthma. We questioned whether dry NaCl could be used as an alternative. Dry powder NaCl was inhaled from capsules containing either 5, 10, 20 or 40 mg to a cumulative dose of 635 mg. The powder was delivered via an Inhalator or Halermatic. The airway sensitivity to the dry and wet NaCl was compared in 24 patients with asthma aged 19-39 yrs. All subjects responded to both preparations and the geometric mean (95% confidence intervals) for the provocative dose of NaCl causing forced expiratory volume in one second (FEV1) to fall 20% from baseline (PD[20,NaCl]) for dry NaCl was 103 mg (68-157) versus 172 mg (102-292), p<0.03 for the wet NaCl. The response to dry NaCl was reproducible and on repeat challenge the PD20 was 108 mg (75-153). The mean maximum fall in FEV1 was approximately 25% on each of the two test days. Spontaneous recovery occurred within 60 min after challenge with dry NaCl and within 5 min after bronchodilator. There were no serious side-effects requiring medical attention, however some patients coughed on inhalation of the 40 mg dose and three gagged. Arterial oxygen saturation remained within normal limits. We conclude that a suitably prepared dry powder of sodium chloride could potentially replace wet sodium chloride to assess bronchial responsiveness in patients with asthma, but further studies are required to establish the long-term stability of the dry powder preparation.

Administration, Inhalation↗
PubMed1997

Comparison of whole body MRI and radioisotope bone scintigram for skeletal metastases detection.

OBJECTIVE: To compare whole body magnetic resonance imaging (MRI) using fast sequences with radioisotope bone scintigraphy (BS) for the detection of metastases in the entire skeleton. METHODS AND RESULTS: In forty-four patients suffering from carcinoma of lung, breast and prostate whole body MRI could generally be accomplished in about 39 minutes and it was shown to have a higher skeletal metastases detection compared with BS in the spine, pelvis, limb bones, sternum, scapula, and clavicle, but lower in the ribs and skull. CONCLUSIONS: We think for addressing the status of skeletal metastases only, bone scintigram is still preferred over whole body MRI. When bone scintigram is unavailable, whole body MRI is a practical and acceptable alternative especially when extra-osseous metastases are also of concern.

Adult↗
PubMed1997

[Comparison of cardiopulmonary endurance and muscular fitness in teenagers between Hong Kong and inland cities].

A study on the data of the physique investigated in teenagers was carried out between Hong Kong and inland cities to compare their cardiopulmonary endurance and muscular fitness. Results revealed that cardiopulmonary endurance in school teenagers of both sex at different ages in inland cities was better than that in Hong Kong. Muscular strength and endurance of sports performance of teenagers, except for standing long jump, in Hong Kong were weaker than that in inland cities. It suggests that attention should be paid to the involvement of teenagers in physical education with the increase of people's living standard.

Adolescent↗
PubMed1996

NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development.

The locus control region of the beta-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the CNC ("cap 'n' collar") subfamily of the basic region-leucine zipper transcription factors, which exhibits strong homology at specific regions such as the "CNC" and the DNA binding and leucine zipper domains. Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia. To determine the function of NRF2, which we found to be widely expressed in vivo, we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated NRF2-/- mice. Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced. Our studies indicate that NRF2 is dispensable for mouse development.

Aging↗
PubMed1996

Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease.

We have disrupted the 5' locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes. The heterozygous knockout mice (.alpha/alpha alpha) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (.alpha/.alpha) show hemolytic anemia. Mice with three dysfunctional alpha-globin genes generated by breeding the 5' alpha-globin knockouts (.alpha/alpha alpha) and the deletion type alpha-thalassemia mice (../alpha alpha) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5' alpha-globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.

Animals↗
PubMed1996

Fibromyxoid sarcoma in a four-year-old child: case report and review of the literature.

We present a child with a rare and chemotherapy-resistant form of soft-tissue cancer, low-grade fibromyxoid sarcoma, first noted when he was 4 years old. He is the youngest patient reported to date. An 11-year-old white male presented to. The University of Texas M.D. Anderson Cancer Center's Department of Pediatrics with a 7-year history of right thigh mass and pulmonary nodules, confirmed on examination. He had undergone extensive prior chemotherapy and surgery. He received chemotherapy with high-dose cyclophosphamide (7 g/m2) and later etoposide (150 mg/m2/day x 5), with only slight shrinkage of the thigh mass and none in the lungs. Subsequently the tumor in his proximal thigh and his lung metastases were resected, and radiation therapy was administered to the thigh. His disease remained stable for 12 months, but he then developed a pleural-based metastasis on the left side and new bilateral lung metastases also. The tumors on the left side were removed; residual disease is stable after treatment for 6 months with subcutaneous alpha-interferon-2b. Low-grade fibromyxoid sarcoma is very uncommon in children. It grows slowly and metastasizes to distant organs, chiefly to the lungs. It is resistant to conventional chemotherapy, and thus far only surgery seems to have a life-prolonging effect. Newer chemotherapeutic and possibly biologic agents should be tried in future patients, in order to find an effective way to control the disease.

Child↗
PubMed1996

Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics.

The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CGP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 microCi) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUC) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371.

Adult↗
PubMed1996

The role of helper lipids in cationic liposome-mediated gene transfer.

In the procedure for cationic liposome-mediated transfection, the cationic lipid is usually mixed with a "helper lipid" to increase its transfection potency. The importance of helper lipids, including dioleoylphosphatidylcholine (DOPC) and phosphatidylethanolamine (dioleoyl PE), DO was examined. Freeze-fracture electron microscopy of DNA:cationic complexes containing the pSV-beta-GAL plasmid DNA, the cationic lipid dioleoyl trimethylammonium propane, and these helper lipids showed that the most efficient mixtures were aggregates of ensheathed DNA and fused liposomes. PE-containing complexes aggregated rapidly when added to culture media containing polyanions, whereas PC-containing complexes did not. However, more granules of PC-containing complexes were formed on cell surfaces after the complexes were added to Chinese hamster ovary (CHO) cells in transfection media. Pronase treatment inhibited transfection, whereas dilute poly-L-lysine enhanced transfection, indicating that the attachment of DNA:liposome complexes to cell surfaces was mediated by electrostatic interaction. Fluorescence spectroscopy studies confirmed that more PC-containing complexes than PE-containing complexes were associated with CHO cells, and that more PC-containing complexes were located in a low pH environment (likely to be within endosomes) with time. Cytochalasin-B had a stronger inhibitory effect on PC-containing liposome-mediated than on PE-containing liposome-mediated transfection. Confocal microscopic recording of the fluorescently label lipid and DNA uptake process indicated that many granules of DNA:cationic liposome complexes were internalized as a whole, whereas some DNA aggregates were left out on the cell surfaces after liposomes of the complexes fused with the plasma membranes. For CHO cells, endocytosis seems to be the main uptake pathway of DNA:cationic liposome complexes. More PC-containing granules than PE-containing granules were formed on cell surfaces by cytoskeleton-directed membrane motion, after their respective DNA:liposome complexes attached to cell surfaces by electrostatic means. Formation of granules on the cell surface facilitated and/or triggered endocytosis. Fusion between cationic liposomes and the cell membrane played a secondary role in determining transfection efficiency.

Animals↗
PubMed1996

Total UK multi-centre experience with a novel arterial occlusion device (Duct Occlud pfm).

OBJECTIVE: To report the total UK multicentre experience of a novel arterial occlusion device (Duct Occlud pfm). DESIGN: Descriptive study of selected non-randomised paediatric patients with a variety of aortopulmonary connections. SETTING: Five UK tertiary referral centres for congenital heart disease. PATIENTS AND METHODS: Between March 1994 and February 1995, 57 children aged 2 weeks to 14 years (median 50 months) underwent attempted closure of their aortopulmonary connection. Fifty one had persistent arterial ducts and 9 of them had had a Rashkind umbrella device implanted. Five patients had superfluous modified Blalock-Taussig shunts (mBTS). In one there was also a native major aortopulmonary collateral artery (MAPCA). Another patient had a native major aortopulmonary connection (APC). Transcatheter occlusion was attempted in all cases through a 4 F delivery catheter. RESULTS: Devices were successfully deployed in 49/57 (86%) patients. Seven of 51 cases with persistent arterial ducts were judged too large for the device and a Rashkind umbrella was used. 40 (91%) of the 44 in whom the detachable coil device was used had complete occlusion at 24 hours on colour flow Doppler echocardiography. Devices were successfully deployed in all 6 remaining patients (4 mBTS, 1 mBTS + MAPCA, and 1 APC). Embolisation of a device occurred on 4 occasions. Two devices were not retrieved but caused no apparent clinical problems. CONCLUSION: This novel detachable coil type occlusion system compares favourably with other methods of transcatheter occlusion of native, residual, or surgically created aortopulmonary shunts. The delivery system allows its use in small children.

Adolescent↗
PubMed1996

Clinical pharmacokinetics of amonafide (NSC 308847) in 62 patients.

Amonafide (A) demonstrates dose-related increases in area under the curve (AUC) and Cmax values. Total body clearance for A (ranging from 44.2 to 53.8 L/hr/m2) is relatively constant within the dosing range of this study. The dose-related increase of AUC was also observed for the two identified metabolites, acetylamonafide (AA) and noramonafide (NA). A and NA plasma data could be described by a four-compartmental model (two compartments for A, one compartment each for NA and AA). The fitting for NA was poor owing to its low plasma concentration. The terminal half-lives for A, NA, and AA were in the range of 3-6 hr. No cumulative accumulation of parent compound or metabolites was detected after daily administration, The concentrations of A, NA, and AA 24 hr after dosing were either below or very close to the quantitative limits of the assay. Polymorphic disposition of A was confirmed by a frequency distribution of AUC value versus dose plot.

Adenine↗
PubMed1995

The effect of the irreversible mu-opioid receptor antagonist clocinnamox on morphine potency, receptor binding and receptor mRNA.

In these experiments, the effect of the irreversible mu-opioid receptor antagonist clocinnamox on the potency of morphine, opioid receptor binding and mu-opioid receptor mRNA was examined. Mice were injected with clocinnamox (0.32-12.8 mg/kg) and the analgesic potency of morphine was examined 24 h later. Clocinnamox produced a dose-dependent decrease in the potency of morphine; and at the higher dose of clocinnamox the maximal analgesic effect was not observed following doses of morphine in excess of 500 mg/kg s.c. In saturation binding studies in brain, clocinnamox (0.32-25.6 mg/kg) dose-dependently decreased mu-opioid ([3H][D-Ala2,MePhe4,Gly-ol5]enkephalin; DAMGO) receptor Bmax with relatively minimal effects on Kd. Binding to delta-opioid receptor ([3H][D-Pen2,D-Pen5]enkephalin; DPDPE) and kappa-opioid receptor ([3H](5,7,8)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec -8-yl) benzeneacetamide; U69,593) was not affected by clocinnamox. The effect of clocinnamox was time-dependent in that the greatest changes in morphine potency and mu-opioid receptor density were observed within 24 h of administration and decreased with time (336 h). Although mu-opioid receptor density was decreased to less than 30% of control 24 h following clocinnamox (12.8 mg/kg) and had increased to 80% by 5 days, a solution hybridization assay for mu-opioid receptor mRNA transcript revealed no changes in the steady-state levels of this mRNA. These studies indicate that clocinnamox is an irreversible antagonist at the mu-opioid receptor since it appears to selectively affect receptor density with minimal effects on affinity. Furthermore, clocinnamox produces time- and dose-dependent changes in Bmax and these changes appear to be unrelated to changes in mu-opioid receptor mRNA. It is possible that the repopulation of brain by mu-opioid receptors following clocinnamox is mediated by an existing pool of receptors that are activated following treatment.

Animals↗
PubMed1995

Cocaine stimulation of ovine fetal swallowing.

Cocaine acts to block reuptake of neurotransmitters, resulting in elevated intra-synaptic norepinephrine levels. As monoaminergic systems may contribute to central regulation of swallowing motor activity as well as dipsogenic responses, and cocaine is known to alter fetal behavior, we examined the effect of intravenous cocaine on fetal swallowing. Six ovine fetuses (130 +/- 1 days) were chronically prepared with esophageal electrodes and an esophageal flow probe. Following a 1-h control period, fetuses received an intravenous injection of 1.0 mg/kg cocaine over 30 s. Fetal blood samples were withdrawn at timed intervals and fetal swallowing activity was monitored for 180 min after the cocaine bolus. Basal fetal swallowing activity during the control period was 0.6 +/- 0.1 swallows/min, with esophageal flow of 0.3 +/- 0.1 ml/min. At 10 min following cocaine, fetal swallowing rate increased to 1.4 +/- 0.4 swallows/min though esophageal flow did not change significantly (0.4 +/- 0.2 ml/min). Swallowing rate then returned to basal levels. Fetal heart rate increased in response to cocaine injection (149 +/- 14 to 174 +/- 24 bts/min at 180 min) though there was no change in fetal mean blood pressure. These results demonstrate acute stimulation of fetal swallowing activity in response to intravenous cocaine injection. Together with previous reports, these data further illustrate the diversity of fetal behavioral effects in response to in utero cocaine exposure.

Animals↗
PubMed1995

Simultaneous determination of moricizine and its sulphoxidation metabolites in biological fluids by high-performance liquid chromatography.

A simultaneous assay for moricizine, its two sulphoxidation metabolites, moricizine sulphoxide and moricizine sulphone, using high-performance liquid chromatography (HPLC) is described. The drug and metabolites and clozapine (internal standard) in biological fluids were extracted using pentanesulphonic acid into diethyl ether. The ethereal extract was evaporated to dryness and the residue was redissolved in the mobile phase (methanol-water-triethylamine, 65:35:0.5, v/v). The analyses were performed on a microBondapak reversed-phase C18 column housed in a Waters Z-module, linked to a C18 pre-column, with a run-time of 12 min. The retention times were 2.7, 3.5, 6.2 and 9.7 min for moricizine sulphone, moricizine sulphoxide, moricizine and clozapine, respectively. The recovery of the compounds from plasma ranged from 89.9% for the sulphoxide to 98.1% for clozapine. The limits of detection of the assay for moricizine, moricizine sulphoxide and moricizine sulphone were 20, 10 and 5 ng/ml, respectively.

Animals↗
PubMed1995

Comparative pharmacokinetics and bioavailability of nitroglycerin and its metabolites from Transderm-Nitro, Nitrodisc, and Nitro-Dur II systems using a stable-isotope technique.

The pharmacokinetics and bioavailability of nitroglycerin (GTN) and its metabolites, 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN), were compared after a single 14-hour application of Transderm-Nitro (Ciba-Geigy, Summit, NJ), Nitrodisc (GD Searle, Chicago, IL), and Nitro-Dur II (Key Pharmaceuticals, Kenilworth, NJ) systems to 18 healthy male subjects on 3 separate occasions. A 14-hour intravenous infusion of 15N-labeled GTN was given simultaneously to correct for changes in systemic clearance during the application of each system. Plasma concentrations of 15N-labeled GTN, unlabeled GTN, and their corresponding dinitrate metabolites were measured using a gas chromatography/mass spectrometry method. Results showed that the plasma concentration profiles of nitroglycerin and its metabolites for the three systems were similar during and after system removal. Mean (SD) total amounts (AUCp x CLiv) of GTN transdermally available after adjustment for 15N-labeled GTN clearance were 5.3 (2.1), 5.3 (2.0), and 5.4 (2.6) mg for Transderm-Nitro, Nitrodisc, and Nitro-Dur II, respectively. Mean (SD) AUC values for 1,2-GDN were 44.6 (15.8), 44.3 (16.1), and 42.8 (19.3) ng.h/mL for the 3 systems. Corresponding AUC values for 1,3-GDN were 9.3 (2.9), 9.7 (2.9), and 8.7 (3.0) ng.h/mL. Statistical analysis of the log-transformed data based on 90% conventional confidence interval showed that all 3 systems delivered equivalent amounts of nitroglycerin into the systemic circulation. The AUC ratios for 1,3-GDN to GTN, but not 1,2-GDN to GTN, were statistically different for the intravenous and transdermal routes during all 3 system applications, indicating that the formation and metabolism of 1,3-GDN was dependent on route of administration.

Administration, Cutaneous↗
PubMed1995

Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization.

A family of human genes encoding basic-leucine zipper (bZIP) transcription factors, p45-NF-E2, Nrf1 and Nrf2, have been isolated independently. Whereas the encoded proteins of the three genes share highly conserved regions distinct from other bZIP families such as Jun or Fos, remaining regions diverged considerably from each other. Chromosomal localization by fluorescence in situ hybridization demonstrates that these genes are non-syntenic. p45-NF-E2 mapped to chromosome 12q13.1-13.3, whereas Nrf1 and 2 mapped to 17q21.3 and 2q31, respectively. However, these three genes were probably derived from a single ancestor by chromosomal duplication as other genes that also map in these regions are related to one another.

Amino Acid Sequence↗
PubMed1995

A 3-dimensional model for the insulin-like growth factor binding proteins (IGFBPs); supporting evidence using the structural determinants of the IGF binding site on IGFBP-3.

It is generally accepted but not established that the insulin-like growth factor (IGF) binding site on the IGF binding proteins (IGFBPs) is in the N-terminal region. However, other workers have reported C-terminal fragments with IGF binding determinants. Therefore, we tested the hypothesis that both the N- and C-terminal regions of IGFBPs are involved in binding. Using a protein A gene fusion system, a cDNA encoding residues 1-147 (N147) was cloned into the plasmid pRIT2T and expressed in E. coli as a fusion protein. Since an Asn N-terminal to the gly of IGFBP-3 had been engineered into the cDNA construct, protein A was cleaved from N147 by hydroxylamine. Purified N147 was refolded in a DTT/cystamine redox system at pH 8.4 under nitrogen atmosphere. Both ligand binding Westerns and solution binding assays demonstrated that the recombinant derived N147 bound IGFs. The 147 and 176 residue N-terminal fragments, including a C-terminal fragment (residues 151-263) of IGFBP-3 were also expressed in pichia (yeast) as glycosylated proteins. Solution binding assays showed that they all bound labelled IGF-1. In conclusion, IGFBP-3 contains at least two binding determinants, one on the N- and one on the C-terminal domain. There may also be a possible contribution from the intermediate (I) domain. Our molecular genetic approach to mapping the binding region for IGFs on IGFBP-3 can now be tested on the other mutants we have prepared. Subsequently, site directed mutagenesis can be used to pinpoint key functional residues.

Binding Sites↗