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Biomedical subjects

K Ng

Publications and source records attributed to K Ng.

At least 37 records · Page 2Linked to original sources
PubMed2000

STM studies of the electronic structure of vortex cores in Bi(2)Sr(2)CaCu(2)O(8+delta)

We report on low temperature scanning tunneling microscopy (STM) studies of the electronic structure of vortex cores in Bi 2Sr 2CaCu 2O (8+delta). At the vortex core center, an enhanced density of states is observed at energies near Omega = +/-7 meV. Spectroscopic imaging at these energies reveals an exponential decay of these "core states" with a decay length of 22+/-3 A. The fourfold symmetry sometimes predicted for d-wave vortices is not seen in spectroscopic vortex images. A locally nodeless order parameter induced by the magnetic field may be consistent with these measurements.

Journal Article↗
PubMed2000

Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial.

CONTEXT: Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator, but bleeding complications, including intracranial hemorrhage, are a recognized complication. OBJECTIVE: To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke. DESIGN: The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998. SETTING: Forty-eight centers, primarily community hospitals, in the United States and Canada. PATIENTS: A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis. INTERVENTIONS: Patients were randomly assigned to receive ancrod (n=248) or placebo (n =252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L. MAIN OUTCOME MEASURES: The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality. RESULTS: Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (< or = 3 or > 3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01). CONCLUSION: In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke.

Ancrod↗
PubMed2000

The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome.

In this study, serum stability and target-sensitivity of phosphatidylethanolamine (PE) immunoliposomes prepared with dioleoylphosphatidylethanolamine (DOPE), HYB-241 monoclonal antibody that targets p-glycoproteins, and various levels of polyethyleneglycol 2000 dioleoylphosphatidylethanolamine (PEG(2000)-DOPE) were determined. Incubation of calcein-laden pegylated immunoliposomes prepared with different levels of PEG(2000)-DOPE (0.3, 0.5 and 1.0 mol%) with p-glycoprotein rich bovine brain microvessel endothelial cells in 10% serum cell culture medium, all resulted in time-dependent release of calcein from the liposomes. The release of calcein was greatest for immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE (66% in 1 h). Contrarily, the release of calcein from the other two immunoliposomes reached only approximately 10-3% after same period of incubation. When serum-induced leakage of calcein was investigated for the above liposome preparations, liposomes prepared with 0.3 and 0.5 mol% PEG(2000)-DOPE had the highest leakage level (10% in 1 h). Contrarily, the release of calcein from liposomes prepared with 1.0 mol% PEG(2000)-DOPE reached only 3% after same period of incubation. Together, it would appear that release of calcein from the immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE is a result of both serum-induced and target-induced destabilization of liposomes. The net release of calcein due to target-induced destabilization of liposomes is calculated to be at approximately 56%. In contrast, there is no target-induced leakage of calcein from immunoliposomes prepared with either 0.5 or 1.0 mol% PEG(2000)-DOPE.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Neuronal-glial interactions and behaviour.

Both neurons and glia interact dynamically to enable information processing and behaviour. They have had increasingly intimate, numerous and differentiated associations during brain evolution. Radial glia form a scaffold for neuronal developmental migration and astrocytes enable later synapse elimination. Functionally syncytial glial cells are depolarised by elevated potassium to generate slow potential shifts that are quantitatively related to arousal, levels of motivation and accompany learning. Potassium stimulates astrocytic glycogenolysis and neuronal oxidative metabolism, the former of which is necessary for passive avoidance learning in chicks. Neurons oxidatively metabolise lactate/pyruvate derived from astrocytic glycolysis as their major energy source, stimulated by elevated glutamate. In astrocytes, noradrenaline activates both glycogenolysis and oxidative metabolism. Neuronal glutamate depends crucially on the supply of astrocytically derived glutamine. Released glutamate depolarises astrocytes and their handling of potassium and induces waves of elevated intracellular calcium. Serotonin causes astrocytic hyperpolarisation. Astrocytes alter their physical relationships with neurons to regulate neuronal communication in the hypothalamus during lactation, parturition and dehydration and in response to steroid hormones. There is also structural plasticity of astrocytes during learning in cortex and cerebellum.

Animals↗
PubMed2000

Factors influencing outcome following mild traumatic brain injury in adults.

This study aimed to investigate outcome in adults with mild traumatic brain injury (TBI) at 1 week and 3 months postinjury and to identify factors associated with persisting problems. A total of 84 adults with mild TBI were compared with 53 adults with other minor injuries as controls in terms of postconcussional symptomatology, behavior, and cognitive performance at 1 week and 3 months postinjury. At 1 week postinjury, adults with mild TBI were reporting symptoms, particularly headaches, dizziness, fatigue, visual disturbance, and memory difficulties. They exhibited slowing of information processing on neuropsychological measures, namely the WAIS-R Digit Symbol subtest and the Speed of Comprehension Test. By 3 months postinjury, the symptoms reported at 1 week had largely resolved, and no impairments were evident on neuropsychological measures. However, there was a subgroup of 24% of participants who were still suffering many symptoms, who were highly distressed, and whose lives were still significantly disrupted. These individuals did not have longer posttraumatic amnesia (PTA) duration. They were more likely to have a history of previous head injury, neurological or psychiatric problems, to be students, females, and to have been injured in a motor vehicle accident. The majority were showing significant levels of psychopathology. A range of factors, other than those directly reflecting the severity of injury, appear to be associated with outcome following mild TBI.

Adolescent↗
PubMed1999

Atomic-scale quasi-particle scattering resonances in Bi2Sr2CaCu2O8+delta

Low-temperature scanning tunneling spectroscopy of the high transition temperature (high-Tc) cuprate Bi2Sr2CaCu2O8+delta reveals the existence of large numbers of identical regions with diameters of about 3 nanometers that have a relatively high density of low-energy quasi-particle states. Their spatial and spectroscopic characteristics are consistent with theories of strong quasi-particle scattering from atomic-scale impurities in a d-wave superconductor. These characteristics include breaking of local particle-hole symmetry, a diameter near twice the superconducting coherence length, and an inverse square dependence of their local density-of-states on distance from the scattering center. In addition to the validation of d-wave quasi-particle scattering theories, these observations identify a source for the anomalously high levels of low-energy quasi-particles in Bi2Sr2CaCu2O8+delta at low temperatures.

Journal Article↗
PubMed1999

A preliminary study of healing of superpulsed carbon dioxide laser incisions in the hard palate of monkeys.

BACKGROUND AND OBJECTIVE: Prior studies of laser wound healing using different animal models have shown a delayed tissue response after carbon dioxide (CO2) laser application. This article reports on the preliminary findings of healing of superpulsed CO2 laser and scalpel incisions in the hard palate of monkeys. STUDY DESIGN/MATERIALS AND METHODS: Twelve parallel incisions using a superpulsed, continuous wave CO2 laser and a scalpel were performed in the hard palate of each of two adult monkeys at 3, 7, and 14 days time schedules. Power levels of 2.0, 4.0, and 6.0 Watts were used for the laser incisions. Wounds were harvested, fixed in 10% formalsaline for at least 48 hours and processed routinely. Each specimen was embedded in paraffin wax at 90 degrees to the surface epithelium and 5 microm thick sections prepared for staining with haematoxylin and eosin, Periodic acid Schiff and Masson-trichrome at a step-serial interval of 100 microm. Sections were evaluated independently. RESULTS: According to the clinical findings we showed a wound closure in all of the wounds (laser and scalpel incisions) at 3, 7, and 14 days of healing. Histologically, we showed that laser incisions at three and seven days demonstrated an increased, power setting-dependent tissue necrosis and marked inflammatory response with minimal organization compared to scalpel incisions. At 14 days both types of incisions exhibited complete wound healing of the epithelium and connective tissue. DISCUSSION AND CONCLUSIONS: According to these preliminary results, superpulsed CO2 laser tends to produce more pronounced changes (due to tissue thermal damage) with corresponding greater inflammatory reaction and delay in tissue organization only initially.

Animals↗
PubMed1999

Combined NK(1)and NK(2)receptor antagonists on the bronchoconstrictor response to NKA in dogs.

The major pulmonary effects of tachykinins, including bronchoconstriction, are mediated by activation of both neurokinin-1 (NK(1)) and neurokinin-2 (NK(2)) receptors. In guinea-pigs NK(1)and NK(2)receptor antagonists interact synergistically to inhibit the bronchoconstriction induced by neurokinin-A (NKA). However, the effect of combined NK(1)and NK(2)receptor antagonists on tachykinin-induced bronchoconstriction in most other species has not been evaluated. In this study, the interactive effects of CP 99994, an NK(1)receptor antagonist and SR 48968, an NK(2)receptor antagonist, were evaluated against NKA-induced brochospasm in dogs. Pulmonary resistance (R(L)) and dynamic lung compliance (C(Dyn)) were measured in anesthetized, spontaneously breathing dogs to measure the bronchoconstrictor response to aerosolized NKA (1%). Mean arterial blood pressure (MAP) and minute volume (MV) were also measured to assess the NK(1)receptor mediated cardiorespiratory response to substance P (100 ng/kg, iv). Pretreatment with SR 48968 (0.3-3 mg/kg, po) in the presence of an NK(1)antagonist dose of CP 99994 (10 mg/kg, po) inhibited the NKA-induced bronchospasm. However, the inhibition produced by SR 48968 plus CP 99994 was no greater than that previously shown for SR 48968 alone. Therefore, dual NK(1)/NK(2)receptor antagonists do not interact synergistically against NKA-induced bronchospasm in dogs. This may relate to the fact that dogs, like humans, have the NK(2)receptor as the predominant receptor subtype producing bronchoconstriction.

Animals↗
PubMed1998

A single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment) from incorporating ribonucleotides.

Although nucleic acid polymerases from different families show striking similarities in structure, they maintain stringent specificity for the sugar structure of the incoming nucleoside triphosphate. The Klenow fragment of E. coli DNA polymerase I selects its natural substrates, deoxynucleotides, over ribonucleotides by several thousand fold. Analysis of mutant Klenow fragment derivatives indicates that discrimination is provided by the Glu-710 side chain which sterically blocks the 2'-OH of an incoming rNTP. A nearby aromatic side chain, at position 762, plays an important role in constraining the nucleotide so that the Glu-710 "steric gate" can be fully effective. Even with the E710A mutation, which is extremely permissive for addition of a single ribonucleotide to a DNA primer, Klenow fragment does not efficiently synthesize pure RNA, indicating that additional barriers prevent the incorporation of successive ribonucleotides.

Binding Sites↗
PubMed1998

Sulfate activation and transport in mammals: system components and mechanisms.

Extensive studies on the mammalian sulfate-activating enzymes and PAPS translocase have enhanced our understanding of the overall pathway of sulfate activation and utilization. Isolation of the PAPS-synthesizing activities from rat chondrosarcoma and preparation of stable non-hydrolyzable analogs of APS and PAPS have facilitated the kinetic characterization of mammalian ATP sulfurylase and APS kinase. These studies provided the basis for further experimental work showing that APS, the labile intermediate product, is channeled directly between the sulfurylase and kinase active sites. The defect in the brachymorphic mutant mouse lies in this channeling mechanism, thus interfering with efficient PAPS production. The rat chondrosarcoma ATP sulfurylase and APS kinase activities, in fact, reside in a single bifunctional cytoplasmic protein, which has now been cloned and expressed. The mechanism by which PAPS reaches its sites of utilization in the Golgi lumen has also been elucidated: The PAPS translocase is a 230-kDa integral Golgi membrane protein which functions as an antiport.

Animals↗
PubMed1998

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)- one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites.

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzol[b][1,8]naphthyrid in-5(7H)-one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6-, 7-, and 9-carbinols, the glucuronide of the 6-carbinol, and the 6-ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non-physiological ratio of substrate to liver, the 6-carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6-ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6-carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample.

Animals↗
PubMed1998

Symptoms and attitudes of 100 consecutive patients admitted to an acute hospice/palliative care unit.

One hundred patients admitted to an acute hospice/palliative care unit in a U.S. teaching hospital were evaluated using a standardized data acquisition tool that assessed the presence of physical symptoms and attitudes concerning admission to such a specialty unit. Patients entering the unit between June 1995 and October 1995 completed the tool within 24 hours of admission. Symptoms reported were fatigue in 81 patients, anorexia in 70, dyspnea in 61, xerostomia in 58, cough in 52, pain in 49, confusion in 37, depression in 37, constipation in 35, nausea in 30, insomnia in 23, and vomiting in 22. Of the 59 patients and family/friends that responded to the question "How do you feel about hospice care?", 53 gave a positive response. When asked about the best aspects of the unit, the most common response related to the care the patient and family received (23 responses, 39%). We conclude that patients admitted to an acute inpatient hospice/palliative care unit have multiple symptoms and a high degree of satisfaction with the environment.

Adult↗
PubMed1997

Biochemical and mutational studies of the 5'-3' exonuclease of DNA polymerase I of Escherichia coli.

In order to improve our understanding of the 5'-3' exonuclease reaction catalyzed by Escherichia coli DNA polymerase I, we have constructed expression plasmids and developed purification methods for whole DNA polymerase I and its 5'-3' exonuclease domain that allow the production of large quantities of highly purified material suitable for biophysical and other studies. We have studied the enzymatic properties of the 5'-3' exonuclease, both as an isolated domain and in the context of the whole polymerase, using a variety of model oligonucleotides to explore the enzyme-substrate interaction. The 5'-3' exonuclease is known to be a structure-specific nuclease that cleaves a 5' displaced strand at the junction between single-stranded and duplex regions. Since the isolated domain shows the same structure specificity as the whole polymerase, the correct geometry of substrate binding is achieved without the assistance of the polymerase domain. The 5'-3' exonuclease reaction has a strict requirement for a free 5' end on the displaced strand; however, the upstream template and primer strands are dispensable. Site-directed mutagenesis of the ten carboxylate residues that are highly conserved among bacterial and bacteriophage 5'-3' exonucleases indicates that nine of them are important in the reaction. This finding is discussed in relation to structural and mutational data for related 5' nucleases.

Amino Acid Sequence↗
PubMed1997

Structure of a protein photocycle intermediate by millisecond time-resolved crystallography.

The blue-light photoreceptor photoactive yellow protein (PYP) undergoes a self-contained light cycle. The atomic structure of the bleached signaling intermediate in the light cycle of PYP was determined by millisecond time-resolved, multiwavelength Laue crystallography and simultaneous optical spectroscopy. Light-induced trans-to-cis isomerization of the 4-hydroxycinnamyl chromophore and coupled protein rearrangements produce a new set of active-site hydrogen bonds. An arginine gateway opens, allowing solvent exposure and protonation of the chromophore's phenolic oxygen. Resulting changes in shape, hydrogen bonding, and electrostatic potential at the protein surface form a likely basis for signal transduction. The structural results suggest a general framework for the interpretation of protein photocycles.

Bacterial Proteins↗
PubMed1997

The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum.

We have previously shown that a radioiodinated photoreactive analogue of chloroquine, [125I]N-(4-(4-diethylamino-1-methylbutylamino)quinolin-6-yl) -4-azido-2-hydroxybenzamide ([125I]ASA-Q), specifically labels two proteins in Plasmodium falciparum with apparent molecular weights (Mr) of 42 and 33 kDa (Foley M, Deady LW, Ng K, Cowman AF, Tilley L. J Biol Chem 1994:269:6955-6961). We now report the identification of the 33 kDa protein. The 33 kDa protein was purified from Plasmodium falciparum using photoaffinity labeling with [125I]ASA-Q to monitor the enrichment process. N-terminal sequence analysis of the purified protein revealed exact identity of the first 35 amino acids with P. falciparum lactate dehydrogenase (PfLDH). The plasmodial enzyme was cloned and expressed in E. coli and the recombinant protein used to produce a rabbit antiserum. Immunoprecipitation using affinity-purified anti-PfLDH antibodies confirmed the identity of the 33 kDa CQ-binding protein. The enzyme activity of purified PfLDH was not significantly affected by chloroquine indicating that PfLDH is not a direct target of CQ. PfLDH was, however, shown to be exquisitely sensitive to inhibition by free heme and chloroquine protected against this inhibitory effect.

Affinity Labels↗
PubMed1997

Use of circular dichroism spectroscopy in determining the conformation of a monoclonal antibody prior to its incorporation in an immunoliposome.

Attachment of antibodies to liposomes endows target specificity to liposomes for a certain cell or organ that express the targeted antigenic determinant. These so-called immunoliposomes hold high promise as targeted drug carriers. One approach of immunoliposome preparation involves conjugating antibodies to hydrophobic anchors (e.g. fatty acids or phospholipid molecules) for incorporation into the liposome membrane. Often, these conjugation reactions are harsh and may result in undesirable chemical and structural changes in the antibody molecule. This necessitates confirmation of the target specificity of the derivatized antibody prior to its incorporation into the liposome. Our approach to this problem is to utilize circular dichroism spectroscopy, which can detect subtle structural differences in proteins with high reproducibility and accuracy in relatively short period of time. In addition, circular dichroism is a non-destructive technique. In this study, we demonstrate the ability of circular dichroism to confirm the conformation of a model antibody, HYB-241, conjugated to N-glutarylphosphatidylethanolamine, prior to its mixing with dioleoylphosphatidylethanolamine/dioleoylphosphatidic acid to form a target-sensitive immunoliposome.

Antibodies, Monoclonal↗
PubMed1997

Medical physics is alive and well and growing in South East Asia.

In recent years there has been a significant economic growth in South East Asia, along with it a concurrent development of medical physics. The status of four countries--Malaysia, Thailand, the Philippines and Indonesia are presented. Medical physicists in these countries have been experiencing the usual problems of lack of recognition, low salaries, and insufficient facilities for education and training opportunities. However the situation has improved recently through the initiative of local enthusiastic medical physicists who have started MS graduate programs in medical physics and begun organizing professional activities to raise the profile of medical physics. The tremendous support and catalytic roles of the American Association of Physicists in Medicine (AAPM) and international organizations such as International Organization for Medical Physics (IOMP), International Atomic Energy Agency (IAEA), World Health Organization (WHO), and International Center for Theoretical Physics (ICTP) have been instrumental in achieving progress. Contributions by these organizations include co-sponsorship of workshops and conferences, travel grants, medical physics libraries programs, and providing experts and educators. The demand for medical physicists is expected to rise in tandem with the increased emphasis on innovative technology for health care, stringent governmental regulation, and acceptance by the medical community of the important role of medical physicists.

Asia, Southeastern↗