3-D microscopy to assess bone healing around dental implants.
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Adaptation, Physiological↗
Biomedical subjects
K Wong
Publications and source records attributed to K Wong.
L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.
A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a large left parieto-occipital haemorrhage 7 days after completion of induction chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L-asparaginase. The haemorrhage could not be attributed to thrombocytopenia, disseminated intravascular coagulopathy, arterio-venous malformation, berry aneurysm or leukaemic infiltration because each of these causes was carefully investigated into and excluded. We conclude that the intracranial haemorrhage was likely L-asparaginase induced, an uncommon but recognised complication associated with L-asparaginase therapy.
Adult↗
Pharmacological modulation of pressure-overload cardiac hypertrophy: changes in ventricular function, extracellular matrix, and gene expression.
BACKGROUND: Appropriate cardiac hypertrophy (CH) is necessary in several clinical settings, such as pulmonary artery banding in the two-stage arterial switch operation for transposition of the great arteries. Pressure-overload CH, however, produces ventricular dysfunction due to structural and molecular changes. The beta2-adrenergic receptor agonist clenbuterol has been shown to induce CH without such adverse effects to the rat heart. This study was performed to determine its effects on left ventricular (LV) function, structure, and gene expression in pressure-overload CH. METHODS AND RESULTS: Sprague-Dawley rats were assigned to one of four groups: 1, sham-operated (n=15); 2, banding of ascending aorta (n=22); 3, banding+clenbuterol (n=18); and 4, banding+thyroxine (n= 17). At the end of 3 weeks, groups 2, 3, and 4 showed an increase in LV mass index of 49.7+/-5.1%, 66.1+/-3.8%, and 47.6+/-4.6%, respectively, relative to group 1. A subgroup with severe CH (>50%) in group 2 was found to have significantly impaired developed pressure and diastolic relaxation and an increase in passive stiffness, with significantly reduced LV expression of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) mRNA and increased LV collagen concentration. In comparison, similarly hypertrophied animals in groups 3 and 4 demonstrated improved developed pressure, normal relaxation and diastolic stiffness with normal collagen concentration, and a greater abundance of SERCA2a mRNA. CONCLUSIONS: Clenbuterol administration in conjunction with pressure overload produces a specific type of CH with preserved LV function. In addition, an increase in LV mass was associated with less fibrosis and greater expression of SERCA2a mRNA than banding alone.
Analysis of Variance↗
Influence of Dynamic Surface Tension on the Spreading of Surfactant Solution Droplets Impacting onto a Low-Surface-Energy Solid Substrate
We have investigated the impact of single droplets of various surfactant solutions on a low-surface-energy solid substrate using a high-frequency visualization technique (one picture every 100 μs). Whatever the surfactant, the drop spreads and retracts in about 1 s under the action of inertia and capillarity, respectively. During retraction, the capillary waves can be amplified and, in some cases, even yield droplet bouncing. Then, the droplet may slowly spread again due to gravity and the unbalanced capillary forces at the contact line between the droplet and the substrate. During the fast spreading process (2-3 ms), the droplet surface increases by almost one order of magnitude since its shape changes from a sphere to a flat pancake; this causes a strong deviation from thermodynamic equilibrium. The relevant surface property is therefore the dynamic surface tension which we have evaluated using a maximum bubble pressure apparatus. We have shown that droplet retraction is drastically influenced by the adsorption kinetics of the surfactant which limits the return to equilibrium surface tension.
Journal Article↗
A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia.
Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal root ganglia (DRG), cellular expression, and functional analysis of a novel tetrodotoxin-sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many different tissues. Within the rat DRG, both the mRNA and PN1-like immunoreactivity are present in small and large neurons. The abundance of sodium channel mRNAs in rat DRG is rBI > PN1 >/= PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction analysis. Data from reverse transcription-polymerase chain reaction and sequence analyses of human DRG and other human tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel. In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium currents and is inhibited by tetrodotoxin with an IC50 of 4.3 +/- 0.92 nM. Unlike rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression of the beta-subunits.
Amino Acid Sequence↗
Subcellular locations of phosphatidylinositol 4-kinase isoforms.
Phosphatidylinositol (PtdIns) 4-kinase catalyzes the synthesis of PtdIns-4-P, the precursor of an array of lipid second messengers generated by additional phosphorylation by PtdIns-4-P 5-kinase and PtdIns 3-kinase. PtdIns 4-kinase activity is conserved from yeast to higher eukaryotes. Multiple isoforms of mammalian PtdIns 4-kinase have been purified, and the activities have been detected in almost all subcellular locations. We previously reported the cloning and characterization of the first mammalian PtdIns 4-kinase named PI4Kalpha (Wong, K., and Cantley, L. C. (1994) J. Biol. Chem. 269, 28878-28884). Alternatively spliced forms of PI4Kalpha have also been identified from several sources including bovine brain (Gehrmann, T., Vereb, G., Schmidt, M., Klix, D., Meyer, H. E., Varsanyi, M., and Heilmeyer, L. M., Jr. (1996) Biochim. Biophys. Acta 1311, 53-63). Recently we isolated a distinct human PtdIns 4-kinase gene, named PI4Kbeta, that encodes an enzyme that is wortmannin sensitive (Meyers, R., and Cantley, L. C. (1997) J. Biol. Chem. 272, 4384-4390). Here we report the locations of these enzymes and provide evidence for other yet unidentified isoforms present in specific organelles. PI4Kalpha is mostly membrane-bound and located at the endoplasmic reticulum; whereas PI4Kbeta is in the cytosol and also present in the Golgi region. Neither of these isoforms accounts for the major type II PtdIns 4-kinase activity detected in the lysosomes and plasma membrane fraction.
1-Phosphatidylinositol 4-Kinase↗
Repression of c-myc transcription by Blimp-1, an inducer of terminal B cell differentiation.
Transcription of c-myc in plasma cells, which are terminally differentiated B cells, is repressed by plasmacytoma repressor factor. This factor was identified as Blimp-1, known for its ability to induce B cell differentiation. Blimp-1 repressed c-myc promoter activity in a binding site-dependent manner. Treatment of BCL1 lymphoma cells with interleukin-2 (IL-2) plus IL-5 induced Blimp-1 and caused a subsequent decline in c-Myc protein. Ectopic expression of Blimp-1 in Abelson-transformed precursor B cells repressed endogenous c-Myc and caused apoptosis; Blimp-1-induced death was partially overcome by ectopic expression of c-Myc. Thus, repression of c-myc is a component of the Blimp-1 program of terminal B cell differentiation.
Animals↗
Identification of the major synaptojanin-binding proteins in brain.
Synaptojanin is a nerve-terminal enriched inositol 5-phosphatase thought to function in synaptic vesicle endocytosis, in part through interactions with the Src homology 3 domain of amphiphysin. We have used synaptojanin purified from Sf9 cells after baculovirus mediated expression in overlay assays to identify two major synaptojanin-binding proteins in rat brain. The first, at 125 kDa, is amphiphysin. The second, at 40 kDa, is the major synaptojanin-binding protein detected, is highly enriched in brain, is concentrated in a soluble synaptic fraction, and co-immunoprecipitates with synaptojanin. The 40-kDa protein does not bind to a synaptojanin construct lacking the proline-rich C terminus, suggesting that its interaction with synaptojanin is mediated through an Src homology 3 domain. The 40-kDa synaptojanin-binding protein was partially purified from rat brain cytosol through a three-step procedure involving ammonium sulfate precipitation, sucrose density gradient centrifugation, and DEAE ion-exchange chromatography. Peptide sequence analysis identified the 40-kDa protein as SH3P4, a member of a novel family of Src homology 3 domain-containing proteins. These data suggest an important role for SH3P4 in synaptic vesicle endocytosis.
Amino Acid Sequence↗
Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases.
v-Abl is an oncogenic form of the c-Abl nonreceptor tyrosine kinase. v-Abl induces transcription of c-myc, and c-Myc function is a necessary but not sufficient component of the v-Abl transformation program. Previously we showed that the E2F site in the c-myc promoter is a v-Abl response element and that v-Abl appears to induce c-myc by initiating a phosphorylation cascade that ultimately activates E2F-binding proteins. In this work we have investigated the signaling pathway between the v-Abl tyrosine kinase and activated E2F proteins. We show that the Ras GTPase and Raf1 serine/threonine kinase are required in this pathway. However, in contrast to other aspects of v-Abl signaling, induction of c-myc transcription is independent of the Rac GTPase. Our results also establish a requirement for activated cyclin-dependent kinases (cdks), as v-Abl-dependent induction of c-myc transcription is blocked by cdk inhibitor p21 and induction of c-myc is accompanied by activation of cdk2 and cdk4. Finally, we show that v-Abl-dependent induction of c-myc is accompanied by hyperphosphorylation of pRb, p107, and p130. On the basis of these data, we propose a model for the signaling path from v-Abl to c-myc.
Animals↗
A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase.
Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha3beta1). The size (55 kDa) and other properties of the phosphatidylinositol 4-kinase (PI 4-K) (stimulated by nonionic detergent, inhibited by adenosine, inhibited by monoclonal antibody 4CG5) are consistent with PI 4-K type II. Not only was PI 4-K associated with alpha3beta1-CD63 complexes in alpha3-transfected K562 cells, but also it could be co-purified from CD63 in untransfected K562 cells lacking alpha3beta1. Thus, TM4SF proteins may link PI 4-K activity to the alpha3beta1 integrin. The alpha5beta1 integrin, which does not associate with TM4SF proteins, was not associated with PI 4-K. Notably, alpha3beta1-CD63-CD81-PI 4-K complexes are located in focal complexes at the cell periphery rather than in focal adhesions. The novel linkage between integrins, transmembrane 4 proteins, and phosphoinositide signaling at the cell periphery may play a key role in cell motility and provides a signaling pathway distinct from conventional integrin signaling through focal adhesion kinase.
1-Phosphatidylinositol 4-Kinase↗
Mortality studies in psoriatic arthritis: results from a single outpatient clinic. I. Causes and risk of death.
OBJECTIVE: To identify the causes of death and mortality risk in patients with psoriatic arthritis (PsA) who were being followed up at a single outpatient clinic in Toronto, Ontario, Canada. METHODS: Patients enrolled in the PsA Clinic between 1978 and 1993 were compared with the general population of Ontario. Deaths were identified from the clinic database and through linkage with the provincial mortality database, and causes were confirmed by death certificates. A standardized mortality ratio (SMR) was computed, based on the assumption that patients lost to followup were alive at the end of the study. RESULTS: Of the 428 patients with PsA (194 women and 234 men), 53 (26 women and 27 men) died. The 4 leading causes of death were diseases of the circulatory (36.2%) or respiratory (21.3%) system, malignant neoplasms (17.0%), and injuries/poisoning (14.9%). The SMR for the female cohort was 1.59, and for the men, it was 1.65, indicating a 59% and 65% increase in the death rate, respectively. Deaths due to respiratory causes were particularly increased in these patients. CONCLUSION: The results suggest that this PsA Clinic outpatient population had an increased mortality risk.
Adolescent↗
Effect of fibrin glue in the reduction of postthoracotomy alveolar air leak.
BACKGROUND: Intraoperative use of fibrin glue has been advocated in reducing postthoracotomy alveolar air leak, although most studies have not been randomized and have focused on its routine use after lung resection. METHOD: This study specifically addresses the effectiveness of fibrin glue in reducing alveolar air leak only in patients considered intraoperatively to have continued moderate to severe alveolar air leak after all conventional measures to reduce it have been used. RESULTS: During a 24-month period, 66 patients undergoing lobectomies, segmentectomies, or decortication were randomized either to serve as controls (n = 33) or to have fibrin glue sprayed on the "raw" lung surface (n = 33). The median duration of intercostal drainage and in-hospital stay was 6 and 9 days, respectively, in the control group and 6 and 8 days, respectively, when fibrin glue was used. Statistical analysis revealed no differences between the groups. CONCLUSION: Fibrin glue does not add to conventional techniques in reducing moderate to severe alveolar air leak after thoracic operations.
Adolescent↗
The combined differentiating effect of retinoic acid and vincristine on acute promyelocytic leukemia.
We have previously shown that HL-60 cells exposed to all-trans retinoic acid (ATRA) after treatment with a non-cytotoxic concentration of vincristine (VCR) result in granulocytic maturation and differentiation, suggesting that VCR might exhibit a synergistic action with ATRA in the treatment of acute promyelocytic leukemia. In this report, leukemic cells obtained from a patient with acute promyelocytic leukemia were exposed to 20 nM VCR for 1 h followed by 1 microM ATRA for 6 days. An increase in the expression of mature myelocyte antigens, CD11b and CD15, was observed as determined by flow cytometric analysis. Treatment of VCR or ATRA alone, however, did not have any effect on the expression of these mature myelocyte antigens of the leukemic cells. These results suggest that combined VCR and ATRA may be more efficient in the differentiation therapy of acute promyelocytic leukemia, particularly in those cases showing a slow response to ATRA therapy.
Antigens, CD↗
Are acoustic neuromas encapsulated tumors?
In articles and chapters on the subject of acoustic neuroma, it is almost invariably stated that they are well-encapsulated tumors. During surgical procedures, blunt mechanical dissection defines a natural subsurface cleavage plane that leaves intact a several millimeter thick rind of tumor surface. Occasionally, as a concession to neural integrity, less than complete resection is elected, leaving behind this "capsular" remnant. To clarify the nature of the surface of acoustic neuromas and to test whether this long held description is indeed correct, a microscopic analysis of 10 surgical specimens was performed. A wedge was harvested from the free surface of the tumor in the mid cerebellopontine angle that included a large, undisturbed section of the tumor surface. Histologic analysis showed that for most of the tumor surface only an extremely thin (3 to 5 microm) layer of connective tissue envelops the tumor. Neoplastic Schwann cells, which extend essentially to the margin of the tumor, were found to be somewhat flattened and compressed in the vicinity of the surface. Although acoustic neuromas are surrounded by a continuous layer of connective tissue, it is so exceptionally thin (on average less than the diameter of a red blood cell) that its edge cannot be visualized intraoperatively by a surgeon. Because the pathologic definition of a capsule is a thick, enveloping layer of connective tissue that is both micro- and macroscopically evident, it must be concluded that acoustic neuromas are nonencapsulated, at least in the conventional sense of the term. The surface peel observed intraoperatively is surgically produced during tumor debulking by cleaving of the looser central component from the more compressed portion of neoplastic cells that lies immediately beneath the free margin of the lesion.
Connective Tissue↗
Confirmation of ethanol compressed gas standard concentrations by an NIST-traceable, absolute chemical method and comparison with wet breath alcohol simulators.
This study compares compressed-gas Ethanol Breath Standards (EBS) with wet simulators as calibration standards for breath alcohol analyzers. After reviewing the technical basis and traceability for the two calibration sources, new analytical data verifying the ethanol content of EBS gas are presented. Based on collection of ethanol in an impinger and titration using a modified California Department of Health method, the data confirm the alcohol content of EBS compressed gas standards by an absolute, wet chemical method. These results establish the concentration accuracy and the NIST traceability of the EBS gas by two independent methods, gas chromatographic analysis traceable to NIST standards and the new wet chemical method. Effluent gas from a wet simulator standard is then analyzed by the wet method to show its equivalence with EBS gas.
Breath Tests↗
Inhibition of junction assembly in cultured epithelial cells by hepatocyte growth factor/scatter factor is concomitant with increased stability and altered phosphorylation of the soluble junctional molecules.
Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived glycoprotein with a strong scattering effect on epithelial cells. A receptor tyrosine kinase encoded by the met proto-oncogene has been identified as the cellular receptor for HGF/SF. Following stimulation with HGF/SF, cell scattering occurs concurrent with decreased cell-cell adhesion and disassembly of junctional components. In culture, junction formation is cell-cell contact dependent and can be regulated by modulating the Ca2+ concentrations of the growth media. Decreasing the Ca2+ concentrations below 50 microM causes rapid disassembly of junctions, whereas increasing the Ca2+ concentrations to 1.8 mM induces cell-cell contact and junction assembly. Although associated with decreased cell-cell adhesion and disassembly of the junctional complex, HGF/SF-induced scattering occurs under high extracellular Ca2+ concentrations. To gain insight into the mechanisms of HGF/SF-induced scattering of epithelial cells, we have studied the effect(s) of HGF/SF on junction assembly by examining the solubility, stability, phosphorylation, and subcellular localization of the major components of the adhering junctions, plakoglobin (Pg) and E-cadherin, in Madin-Darby canine kidney (MDCK) epithelial cells and in a MDCK cell line expressing an exogenous chimeric met receptor (CSF-MET) that scatters in response to colony-stimulating factor 1 (CSF-1). The results have shown that in HGF/SF-stimulated MDCK cells, adhering junctions were not assembled upon induction of cell-cell contact. Immunofluorescence analyses showed that larger amounts of Pg and E-cadherin were Triton X-100 extractable, and more significantly, these proteins were homogeneously distributed along the membrane and were not concentrated at the areas of cell-cell contact. Similar results were obtained for CSF-MET expressing MDCK cells in response to CSF-1. In contrast, none of the above effects were detected in MDCK cells expressing a mutant CSF-MET chimera containing a phenylalanine substitution at tyrosine 1356 in met, which fails to scatter in response to CSF-1. When compared with the unstimulated cells, the inhibition of cell adhesion promoted by HGF/SF correlated with an increased stability of the newly synthesized soluble E-cadherin and Pg and an altered phosphorylation pattern of E-cadherin, as determined by partial proteolytic peptide mapping.
Animals↗
Moroto morass. A fossil ape unexpectedly resembles modern apes and humans.
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Animals↗
Neanderthal notes. Did ancient humans play modern scales?
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Animals↗