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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

At least 37 records · Page 2Linked to original sources

Synthesis and evaluation of a macrocyclic bifunctional chelating agent for use with bismuth radionuclides.

The detailed synthesis of the bifunctional chelating agent 2-(p-isothiocyanatobenzyl)-1,4,7,10,13-pentaazacyclopentadecane-N,N',N",N"',N""-pentaacetic acid (BF_PEPA) is reported. This ligand was conjugated to monoclonal antibody B3 and the resultant immunoconjugate radiolabeled with (205,206)Bi. The in vivo stability of the radiolabeled immunoconjugate, and targeting characteristics were determined by biodistribution studies in A431 xenograft tumor-bearing mice sacrificed at 0.5, 1, 2, 4, and 24 hr. Results indicate that BF_PEPA appears to not be a suitable bifunctional chelating agent for sequestering isotopes of Bi(III) for radioimmunotherapy applications.

Animals↗

Gene polymorphism in Netherton and common atopic disease.

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.

Amino Acid Sequence↗

Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: relevance to the arterial switch operation.

The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.

Animals↗

Comparison of sevoflurane-nitrous oxide anaesthesia with the conventional intravenous-inhalational technique using bispectral index monitoring.

Ninety-one patients were randomly allocated to one of two groups. Group A was induced with a single vital capacity breath of 6% (end-tidal) sevoflurane in nitrous oxide-oxygen (2 : 1 l.min-1), whereas group B was induced with intravenous fentanyl 1 microg.kg-1 + propofol 2 mg.kg-1 followed by nitrous oxide-oxygen (2 : 1 l.min-1) and sevoflurane. Induction was considered to have been achieved when the bispectral index value decreased to below 70. Mean induction time in group A (95.2 s, 95% CI 88.5-101.9 s) was longer than group B (70.3 s, 95% CI 66.3-74.3 s; p < 0.0001). Mild coughing was more common in group A, but relative hypotension was more common in group B. There was no difference in the emergence times. Thirty minutes after emergence, there was no difference in the incidence of adverse effects, with the exception of essentially mild abdominal pain which was more frequent in group A.

Adult↗

Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis.

OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure overload by means of pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. RESULTS: Acute pulmonary artery banding increased the right ventricular systolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard deviation]). Six weeks of treatment produced no significant differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals. CONCLUSION: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.

Adrenergic beta-Agonists↗

Breath-hold three-dimensional CT of the liver with multi-detector row helical CT.

PURPOSE: To compare image quality on transverse source images and coronal and sagittal reformations to determine the feasibility of using single-breath-hold three-dimensional liver computed tomography (CT) with multi-detector row helical CT in patients suspected of having hepatic metastases. MATERIALS AND METHODS: Fifty-three patients underwent the protocol. Coronal and sagittal reformations were constructed. Images were reviewed for duration of scan acquisition and length and adequacy of z-axis coverage. Reformations were scored for visualization of portal and hepatic vein branches, liver edge sharpness, cardiac pulsation and respiratory motion artifacts, noise due to mottle, and overall impression. RESULTS: Mean z-axis coverage was 207 mm +/- 33 (SD) (range, 145-280 mm), with a mean acquisition time of 10.96 seconds +/- 1.78 (range, 7.73-14.93 seconds). In 44 (83%) patients, the entire liver was imaged on a single helical scan. Artifact from cardiac motion was not identified on the transverse source images in any patient but was identified on coronal images in eight (15%) and on sagittal images in seven (13%). Similarly, noise due to mottle was not identified on the transverse source images but was identified on coronal images in seven (13%) patients and on sagittal images in six (11%). CONCLUSION: It is feasible to perform single-breath-hold three-dimensional liver CT with multi-detector row helical CT technology. Reformations provide a unique perspective with which to view the liver and may improve diagnostic capacity.

Adult↗

A standardized, uniform and universal dental chart for documenting state of dentition before anaesthesia.

It is vital to have adequate and precise documentation of the condition of a patient's dentition before commencing an anaesthetic. The incidence of dental damage during anaesthesia is not low. To the authors' knowledge, there is no standardized method used by anaesthetists to document the state of a patient's dentition. We propose the introduction of a standardized uniform dental chart to enable anaesthetists to accurately document the condition of their patients' teeth. This vital information can be easily obtained during the preanaesthetic assessment. With the increase in medical litigation and demands for adequate documentation, we believe this chart can become an invaluable part of every hospital's preanaesthetic assessment form. The dental chart is to be offered as a service to anaesthetists in the form of a copyright-free "Freeware" computer diskette or adhesive sticker and will be downloadable from the internet.

Adult↗

Prevertebral abscess with extension into the hip joint.

We present a case of a paravertebral abscess with extension into the hip joint. The presumed conduit of infection in this case is the iliopsoas bursa, which has been shown to provide direct communication between the retroperitoneal space and the hip joint in up to 15% of cadaveric specimens. The patient was treated with emergent open irrigation and debridement of the hip joint, as well as percutaneous drainage of the prevertebral abscess. The patient remains minimally symptomatic at the 2-year follow-up.

Abscess↗

Intercellular Ca(2+) waves in rat hippocampal slice and dissociated glial-neuron cultures mediated by nitric oxide.

Nitric oxide (NO) may participate in cell-cell communication in the brain by generating intercellular Ca(2+) waves. In hippocampal organotypic and dissociated glial-neuron (>80% glia) cultures local applications of aqueous NO induced slowly propagating intercellular Ca(2+) waves. In glial cultures, Ca(2+) waves and Mn(2+) quench of cytosolic fura-2 fluorescence mediated by NO were inhibited by nicardipine, indicating that NO induces Ca(2+) influx in glia which is dihydropyridine-sensitive. As NO treatments also depolarised the plasma membrane potential of glia, the nicardipine-sensitive Ca(2+) influx might be due to the activation of dihydropyridine-sensitive L-type Ca(2+) channels. Both nicardipine-sensitive intercellular Ca(2+) waves and propagating cell depolarisation induced by mechanical stress of individual glia were inhibited by pretreating cultures with either an NO scavenger or N(G)-methyl-L-arginine. Results demonstrate that NO can induce Ca(2+) waves in hippocampal slice cultures, and that Ca(2+) influx coupled to NO-mediated membrane depolarisation might assist in fashioning their spatio-temporal dynamics.

Animals↗

Electron capture by the image charge of a metal nanoparticle

We have measured absolute cross sections for the capture of low-energy electrons by large free sodium nanoclusters ( approximately 10(4) atoms, or 4 nm radius). To explain the results, it is necessary to go beyond the commonly used induced-dipole approximation and to employ the full image-charge interaction potential which accounts for the finite size of the particle. This potential yields an exact analytical expression for the capture cross section and leads to good agreement with the data. It is suggested that electron capture may provide a useful tool for size characterization of nanoparticle beams.

Journal Article↗

Neurotrophin 4/5 immunoassay: identification of sources of errors for the quantification of neurotrophins.

Neurotrophin 4/5 (NT4/5) is the least understood member of the mammalian neurotrophin family. Precise and reliable determinations of endogenous NT4/5 levels are essential to understand its physiology. Immunoassay has been used for neurotrophin quantification for over three decades. However, this apparently simple task has proved elusive: conflicting results have long been recognized for nerve growth factor (NGF; up to 10000-fold variations in serum values have been reported in the literature) and more recently, for brain-derived neurotrophic factor (as much as 50-fold reported in rat hippocampus). Reasons for these variations have been extensively investigated by researchers, but rarely explained. During the development of our NT4/5 immunoassay, we discovered that false positive reactions resulted when tissues were extracted and assayed under certain conditions. In this study, we examined the major factors that adversely affect the quantification of NT4/5. Tissue samples from Sprague-Dawley rats were dissected and extracted in a range of buffers. The assay was performed on 96 well vinyl plates using sheep anti-NT4/5 immunoglobulin (Ig) as the capture (first) antibody, and a monoclonal anti-NT4/5 as the detector (second) antibody, followed by anti-mouse IgG (third) conjugated with peroxidase or alkaline phosphatase from several manufacturers. Our results show that: (1) tissue extraction at high or low pH, a method previously found to increase the measurable amount of NGF, produced greater false positive results for NT4/5 when compared with extraction at neutral pH; (2) the most significant source of error derived from the use of conjugated antibodies capable of reacting with molecules within tissue extracts which bind to the plate, even after thorough blocking; and (3) quantification is also significantly affected by both the standards used and the ability of the antibodies to react with these standards. Our findings indicate that the precise determination of neurotrophin levels requires quality reagents and the optimization of extraction conditions for each neurotrophin. The use of a two - rather than a three - antibody assay system avoids most of the interactions which give rise to false positive reactions.

Animals↗

Collapse of stiff conjugated polymers with chemical defects into ordered, cylindrical conformations

The optical, electronic and mechanical properties of synthetic and biological materials consisting of polymer chains depend sensitively on the conformation adopted by these chains. The range of conformations available to such systems has accordingly been of intense fundamental as well as practical interest, and distinct conformational classes have been predicted, depending on the stiffness of the polymer chains and the strength of attractive interactions between segments within a chain. For example, flexible polymers should adopt highly disordered conformations resembling either a random coil or, in the presence of strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with strong intrachain interactions, in contrast, are expected to collapse into conformations with long-range order, in the shape of toroids or rod-like structures. Here we use computer simulations to show that the anisotropy distribution obtained from polarization spectroscopy measurements on individual poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is consistent with this prototypical stiff conjugated polymer adopting a highly ordered, collapsed conformation that cannot be correlated with ideal toroid or rod structures. We find that the presence of so-called 'tetrahedral chemical defects', where conjugated carbon-carbon links are replaced by tetrahedral links, divides the polymer chain into structurally identifiable quasi-straight segments that allow the molecule to adopt cylindrical conformations. Indeed, highly ordered, cylindrical conformations may be a critical factor in dictating the extraordinary photophysical properties of conjugated polymers, including highly efficient intramolecular energy transfer and significant local optical anisotropy in thin films.

Journal Article↗

A fundamental role for the nitric oxide-G-kinase signaling pathway in mediating intercellular Ca(2+) waves in glia.

In this study, we highlight a role for the nitric oxide-cGMP-dependent protein kinase (NO-G-kinase) signaling pathway in glial intercellular Ca(2+) wave initiation and propagation. Addition of the NO donor molsidomine (100-500 microM) or puffing aqueous NO onto primary glial cell cultures evoked an increase in [Ca(2+)](i) in individual cells and also local intercellular Ca(2+) waves, which persisted after removal of extracellular Ca(2+). High concentrations of ryanodine (100-200 microM) and antagonists of the NO-G-kinase signaling pathway essentially abrogated the NO-induced increase in [Ca(2+)](i), indicating that NO mobilizes Ca(2+) from a ryanodine receptor-linked store, via the NO-G-kinase signaling pathway. Addition of 10 microM nicardipine to cells resulted in a slowing of the molsidomine-induced rise in [Ca(2+)](i), and inhibition of Mn(2+) quench of cytosolic fura-2 fluorescence mediated by a bolus application of 2 microM aqueous NO to cells, indicating that NO also induces Ca(2+) influx in glia. Mechanical stress of individual glial cells resulted in an increase in intracellular NO in target and neighboring cells and intercellular Ca(2+) waves, which were NO, cGMP, and G-kinase dependent, because incubating cells with nitric oxide synthase, guanylate cyclase, and G-kinase inhibitors, or NO scavengers, reduced Delta[Ca(2+)](i) and the rate of Ca(2+) wave propagation in these cultures. Results from this study suggest that NO-G-kinase signaling is coupled to Ca(2+) mobilization and influx in glial cells and that this pathway plays a fundamental role in the generation and propagation of intercellular Ca(2+) waves in glia.

Aminoquinolines↗

Forced expression of a dominant-negative chimeric tropomyosin causes abnormal motile behavior during cell division.

Forced expression of the chimeric human fibroblast tropomyosin 5/3 (hTM5/3) in CHO cell was previously shown to affect cytokinesis [Warren et al., 1995: J. Cell Biol. 129:697-708]. To further investigate the phenotypic consequences of misexpression, we have compared mitotic spindle organization and dynamic 2D and 3D shape changes during mitosis in normal cells and in a hTM5/3 misexpressing (mutant) cell line. Immunofluorescence microscopy of wild type and mutant cells stained with monoclonal anti-tubulin antibody revealed that the overall structures of mitotic spindles were not significantly different. However, the axis of the mitotic spindle in mutant cells was more frequently misaligned with the long axis of the cell than that of wild type cells. To assess behavioral differences during mitosis, wild type and mutant cells were reconstructed in 2D and 3D and motion analyzed with the computer-assisted 2D and 3D Dynamic Image Analysis Systems (2D-DIAS, 3D-DIAS). Mutant cells abnormally formed large numbers of blebs during the later stages of mitosis and took longer to proceed from the start of anaphase to the start of cytokinesis. Furthermore, each mutant cell undergoing mitosis exhibited greater shape complexity than wild type cells, and in every case lifted one of the two evolving daughter cells off the substratum and abnormally twisted. These results demonstrate that misexpression of hTM5/3 in CHO cells leads to morphological instability during mitosis. Misexpression of hTM5/3 interferes with normal tropomyosin function, suggesting in turn that tropomyosin plays a role through its interaction with actin microfilaments in the regulation of the contractile ring, in the localized suppression of blebbing, in the maintenance of polarity and spatial symmetry during cytokinesis, and in cell spreading after cytokinesis is complete.

Animals↗

Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome.

Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.

Ataxia↗

The development of computer ethics: contributions from business ethics and medical ethics.

In this essay, we demonstrate that the field of computer ethics shares many core similarities with two other areas of applied ethics. Academicians writing and teaching in the area of computer ethics, along with practitioners, must address ethical issues that are qualitatively similar in nature to those raised in medicine and business. In addition, as academic disciplines, these three fields also share some similar concerns. For example, all face the difficult challenge of maintaining a credible dialogue with diverse constituents such as academicians of various disciplines, professionals, policymakers, and the general public. Given these similarities, the fields of bioethics and business ethics can serve as useful models for the development of computer ethics.

Commerce↗

Stepwise pain score analysis of the effect of local lignocaine on outpatient hysteroscopy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of lignocaine gel in reducing the overall pain and pain of individual steps during outpatient hysteroscopy in comparison with placebo (no anesthesia). DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient hysteroscopy clinic in a regional hospital in Hong Kong. PATIENT(S): A total of 500 Chinese patients undergoing outpatient hysteroscopy. INTERVENTION(S): Application of lignocaine gel to the cervix during outpatient hysteroscopy. MAIN OUTCOME MEASURE(S): Mean pain score using present pain intensity, overall pain score measured by total area under the curve, and the pain score of individual steps in the procedure in patients receiving lignocaine gel were compared with those of patients having no anesthesia. The failure rate and poor-view rate in both groups were also compared. RESULT(S): There were no statistically significant differences in mean pain score, overall pain score, and pain score of individual steps between the lignocaine group and controls. The failure rate and poor-view rate also showed no statistically significant differences. CONCLUSION(S): Outpatient hysteroscopy without anesthesia is acceptable to most Chinese women, and the local application of lignocaine gel is not effective in reducing pain.

Adult↗