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Biomedical subjects

V W Chan

Publications and source records attributed to V W Chan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Positive and negative roles of the tyrosine kinase Lyn in B cell function.

The function of Lyn in B cell activation has been studied recently by examining the properties of B cells from mice in which the lyn gene has been inactivated by gene targeting. These mice show evidence of B cell hyperreactivity in vivo, as the number of B lymphoblastoid cells greatly increase with age, IgM levels increase by 10-fold or more, and auto-antibodies to double-stranded DNA and other nuclear antigens become apparent. B cells from lyn -/- mice also exhibit enhanced BCR-induced activation of MAP kinases, intracellular calcium elevation and proliferative responses in vitro. These phenomena may relate to participation of Lyn in events that serve to decrease B cell responses to antigen. Among the leading candidates for these suppressive events are the inhibition of B cell antigen receptor function by Fc gamma RIIb1 and by CD22. Although Lyn also participates positively in the initial events of B cell antigen receptor signal transduction, this function can also be supplied by other tyrosine kinases, presumably other Src-family kinases. In contrast, some aspects of inhibition by CD22 appear to be almost completely dependent upon Lyn and Fc gamma RIIb1 inhibition is also diminished in the absence of Lyn. Thus, the net effect of Lyn action is negative rather than positive for B cell activation.

Animals↗
PubMed1998

Minimum effective anaesthetic concentration of hyperbaric lidocaine for spinal anaesthesia.

PURPOSE: Minimum effective anaesthetic concentration (MEAC) of lidocaine for spinal anaesthesia, defined as the concentration at which a spinal anaesthetic agent produces surgical anaesthesia within 20 min of administration in 50% of patients, was determined in a randomised, double-blind study in young patients undergoing knee and ankle surgery. METHODS: Using the combined spinal-epidural technique, 48 or 72 mg hyperbaric lidocaine containing dextrose 7.5% was administered intrathecally to 43 patients at concentrations ranging from 0.2-0.9%. The choice of lidocaine concentration was determined by Dixon's up-and-down method. Complete anaesthesia was defined as: (1) pinprick anaesthesia at or higher than T12, (2) anaesthesia to transcutaneous tetanic electric stimulation (50 Hz at 60 mA for five seconds) in the knees and (3) complete leg paralysis; all occurring in both lower extremities within 20 min. Epidural anaesthesia was initiated if anaesthesia was incomplete. RESULTS: In the 48 mg group, MEAC was 0.54% (95% CI-0.21-0.87). Anaesthetic effect was variable with mean duration of anaesthesia of 29 min (range: 20-50 min) and maximum pinprick sensory level ranging from T2-T10. In the 72 mg group, successful anaesthesia was achieved consistently at a concentration of 0.3%, i.e., MEAC was < 0.3%. Mean duration of complete anaesthesia was 46 min (range: 30-60 min) with maximum sensory level from T3-T8. DISCUSSION: Spinal anaesthesia can be accomplished with very dilute lidocaine solutions (< 0.9%). The value of MEAC is dose-dependent, i.e., complete anaesthesia can be accomplished with lower concentrations by increasing the dose of spinal anaesthetic administered.

Adolescent↗
PubMed1997

Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation.

Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen receptor (BCR) signaling. These mice had a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged lyn-/- mice developed splenomegaly, produced autoantibodies, and had an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from young lyn-/- mice initiated early BCR signaling events, although in a delayed fashion. Unexpectedly, lyn-/- B cells exhibited an enhanced MAP kinase activation and an increased proliferative response to BCR engagement. Stimulation of lyn-/- B cells with intact and F(ab')2 anti-IgM revealed defects in at least two mechanisms that negatively regulate BCR signaling, one of which involves Fc gammaRIIb1.

Aging↗
PubMed1997

Molecular defects in Hb H hydrops fetalis.

The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co-inheritance of a 'non-deletion' defect affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1 genotype. These two non-deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.

Gene Deletion↗
PubMed1996

Respiratory depression: an adverse outcome during patient controlled analgesia therapy.

Patient-controlled analgesia (PCA) is one of the more popular means of controlling postoperative pain. However, there is very little in the literature concerning the adverse outcome of respiratory depression in PCA. This report is a prospective study of 4,000 patients on PCA postoperatively. Nine of these patients experienced respiratory problems while on PCA. The respiratory depressions were associated with drug interactions, continuous narcotic infusion, nurse- or physician-controlled analgesia and inappropriate use of PCA by patients. This report identified the common precipitating factors in PCA-associated respiratory depression and its prevention.

Adolescent↗
PubMed1996

Propofol infusion for induction and maintenance of anesthesia in elderly patients: recovery and hemodynamic profiles.

STUDY OBJECTIVE: To evaluate the effect of propofol infusion for both induction and maintenance of anesthesia on hemodynamics and recovery in elderly patients compared with conventional thiopental-isoflurane anesthesia. DESIGN: Randomized, prospective, study. SETTING: Teaching hospital. PATIENTS: 60 nonpremedicated ASA physical status I, II, and III adult elderly patients scheduled to undergo total hip replacement surgery. INTERVENTIONS: Patients received either intravenous propofol infusion at 0.75 mg/kg/min or thiopental bolus 2 to 4 mg/kg for induction, followed by variable-rate propofol infusion up to 0.15 mg/kg/min or isoflurane 0.5% to 1.5% for maintenance of anesthesia. Nitrous oxide and fentanyl supplements were given in all patients. MEASUREMENTS AND MAIN RESULTS: Perioperative hemodynamic changes, patient recovery profile, and myocardial ischemia incidents were assessed in both anesthetic groups. Induction of anesthesia by propofol infusion (1.6 mg/kg) did not produce significant hypotension (-8.3% +/- 5.5%) or bradycardia; these changes were similar to induction by thiopental bolus injection (3.3 mg/kg). Furthermore, increases in blood pressure and heart rate (HR) during endotracheal intubation were limited to 6% following propofol induction compared with 22% for thiopental induction. During maintenance of anesthesia, the decrease in MAP and HR was comparable in both anesthetic groups. Postanesthetic recovery times for patient to achieve wakefulness, mental orientation, and a maximum Aldrete score (10) were significantly faster in the propofol group, by 4 minutes, 6 minutes, and 20 minutes, respectively; however, the time to discharge from the postanesthesia care unit was not different. Holter-monitored perioperative myocardial ischemic events detected in 23% of the patients occurred independent of hemodynamic changes or the type of anesthetic administered. CONCLUSION: Induction of anesthesia by propofol infusion in elderly patients produces greater attenuation of cardiovascular sympathetic response than thiopental bolus induction. Induction and maintenance of anesthesia by propofol infusion results in more rapid recovery in our elderly patients than thiopental isoflurane anesthesia.

Aged↗
PubMed1996

Molecular characterization of haemophilia A in southern Chinese.

41 unrelated southern Chinese haemophilia A patients were studied. The 5' promoter region, all 26 exons, their immediate 5' and 3' flanking splice junctions and the 3' untranslated region of the FVIII gene were amplified (including 16 different segments of exon 14) using GC-clamped primers. The GC-clamped PCR products were screened by denaturing gradient gel electrophoresis (DGGE) and fragments showing an abnormal migration pattern were sequenced. 17 mutations were identified, of which four were splicing defects, involving the first 1-6 nucleotide (nt) in the intervening sequences (IVS), six missense mutations, three nonsense mutations and four frameshift mutations. 14 other patients carried the type 1 inversion, affecting the distal copy of the FSA gene at the telomere of the X chromosome and the same gene in intron 22 of the FVIII gene. All the mothers studied (12/14) were carriers of the inversion. Two of these patients with inversion also have a co-existing missense mutation. In most cases the clinical severity of the disease corresponds to the genotype.

Base Sequence↗
PubMed1995

Signal transduction by the B-cell antigen receptor.

The antigen receptor of B lymphocytes (BCR) plays important roles in recognition of foreign antigens and self-components to allow the immune system to make appropriate antibody responses. The BCR is a complex between membrane immunoglobulin and the Ig-alpha and Ig-beta heterodimer. Site-directed mutagenesis experiments have shown that the mu heavy chain transmembrane domain plays a key role in the association of mIgM with Ig-alpha/Ig-beta. In the absence of complex formation, mIgM is retained in the endoplasmic reticulum, and this function is also specified by the mu chain transmembrane domain. The ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta correlates well with their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. Thus, the signaling ability of the BCR appears to reside in the Ig-alpha/Ig-beta heterodimer. The cytoplasmic domains of Ig-alpha and Ig-beta each contain an ITAM sequence, which is defined by its limited homology with subunits of the T-cell antigen receptor and of Fc receptors. Moreover, chimeric proteins containing these ITAMs and surrounding sequences from the cytoplasmic domains of Ig-alpha or Ig-beta exhibit signaling function characteristics of the intact BCR. The Ig-alpha and Ig-beta chimeras are each capable of inducing all of the BCR signaling events tested and thus represent redundant functions. Cross-linking these chimeras leads to their phosphorylation and to binding of the intracellular tyrosine kinases Lyn and Syk. The BCR expressed in the nonlymphoid AtT20 cells, which express the Src-family tyrosine kinase Fyn but not Syk, was not able to trigger vigorous signaling reactions. Introduction of the active form of Syk into these cells restored some signaling events. These results are consistent with a model in which the ITAMs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases.

Animals↗
PubMed1995

A post-anesthetic discharge scoring system for home readiness after ambulatory surgery.

STUDY OBJECTIVE: To evaluate the validity and reliability of an objective scoring system, the Post-Anesthetic Discharge Scoring System (PADSS), which was compared against existing Clinical Discharge Criteria in the ambulatory surgery unit of our hospital. DESIGN: randomized, open study. SETTING: Ambulatory surgery unit at a university teaching hospital. PATIENTS: 247 ambulatory surgery patients undergoing general anesthesia. INTERVENTIONS: One hour after the operation, the initial assessment using PADSS and the Clinical Discharge Criteria was made by an independent observer. Evaluations were repeated at 30-minute intervals until patients obtained a Post-Anesthetic Discharge Score of at least 9 and fulfilled the Clinical Discharge Criteria. MEASUREMENTS AND MAIN RESULTS: There was a close correlation between the end of anesthesia to time patients were fit for discharge using either PADSS or the Clinical Discharge Criteria (Pearson's Correlation Coefficient r = 0.89). The internal consistency reliability of PADSS (alpha = 0.65) was superior to that of the Clinical Discharge Criteria (alpha = 0.14). CONCLUSIONS: We have found PADSS to have superior measurement scaling and diagnostic properties.

Adult↗
PubMed1995

Continuous intravenous administration of ketorolac reduces pain and morphine consumption after total hip or knee arthroplasty.

The purpose of this study was to determine the analgesic efficacy, opioid-sparing effect, and tolerability of ketorolac administered as an intravenous (i.v.) bolus followed by a continuous infusion after total hip or knee arthroplasty. After general anesthesia, patients received either placebo or ketorolac 30 mg i.v. as a bolus over 15-30 s followed by a continuous i.v. infusion of ketorolac 5 mg/h for 24 h. All patients received patient-controlled i.v. morphine with no background infusion. Patients were assessed at 2, 4, 6, and 24 postoperatively with respect to analgesia, morphine consumption, side effects, and blood loss. Patients receiving ketorolac reported were less sedated and required fewer antiemetics. There was no difference in blood loss. Patients receiving ketorolac reported better analgesia and used less morphine (35% for hips and 44% for knees) than those receiving placebo.

Aged↗
PubMed1995

The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administered intrathecally in the rat.

BACKGROUND: Recent reports of major and minor neurologic sequelae after spinal anesthesia have generated concern regarding the safety of some currently used intrathecal agents. The role of glucose, if any, in neurotoxic injury associated with spinal anesthesia is not known. The current experiments sought to determine whether the presence of 7.5% glucose alters the neurotoxicity of intrathecally administered 5% lidocaine. METHODS: Two experiments were performed. First, 48 rats were implanted with an intrathecal catheter and randomly divided into eight equal groups. Each animal received a single intrathecal infusion of 5% lidocaine (groups P1-P4) or 5% lidocaine with 7.5% glucose (G1-G4) for 0.5, 1, 2, or 4 h at a rate of 1 microliter/min. Sensory function was assessed using the tail-flick test; a deficit was defined as a complete lack of response to the heat stimulus at the proximal, mid or distal portion of the tail persisting 4 days after the infusion. In the second experiment, 60 rats were randomly divided into two groups to receive a 1-h intrathecal infusion of 5% lidocaine or 5% lidocaine with 7.5% glucose. Animals were evaluated for increase in the latency of the tail-flick reflex 4 days after infusion. RESULTS: In the first experiment, the two lidocaine solutions produced similar dose-dependent loss of sensory function. In the second experiment, the two solutions induced similar alterations in tail-flick latency. CONCLUSIONS: The presence of 7.5% glucose does not affect the potential of intrathecally administered 5% lidocaine to induce sensory impairment. These findings provide further support for the hypothesis that recent injuries after spinal anesthesia resulted from a direct neurotoxic effect of the local anesthetic.

Anesthesia, Spinal↗
PubMed1994

Mechanism of B cell antigen receptor function: transmembrane signaling and triggering of apoptosis.

The antigen receptor of B lymphocytes (BCR) plays important roles in virtually every stage in the development, inactivation, or activation of B cells. The BCR is a complex of membrane immunoglobulin (mIg) and a heterodimer of two transmembrane polypeptides called Ig-alpha and Ig-beta. Site directed mutation of the mu immunoglobulin heavy chain has demonstrated that the mu transmembrane domain plays a key role in the assembly of mIgM with Ig-alpha/Ig-beta. In addition, there is a strong correlation between the ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta and their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. The cytoplasmic domains of Ig-alpha and Ig-beta share a region of limited homology with each other and with components of the T cell antigen receptor and of the Fc receptor. The presence of regions of the cytoplasmic domains of Ig-alpha or Ig-beta including this conserved amino acid sequence motif is sufficient to confer signaling function on chimeric transmembrane proteins. Both Ig-alpha and Ig-beta chimeras are capable of inducing all of the BCR signaling events tested. Based on these and related observations, we propose that the motifs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases. Among the important events mediated by BCR signaling is induced expression of a series of genes referred to as early response genes. In B cells these include transcription factors and at least one component that regulates signaling events. One of these genes, c-myc, appears to play an important role in mediating apoptosis in B cells stimulated via the BCR complex.

Amino Acid Sequence↗
PubMed1994

Persistent sacral sensory deficit induced by intrathecal local anesthetic infusion in the rat.

BACKGROUND: Several cases of cauda equina syndrome after continuous spinal anesthesia have been recently reported. One possible etiology is toxic exposure of the sacral roots resulting from intrathecal maldistribution of a relatively large dose of local anesthetic. The current experiments sought to determine whether a local anesthetic solution, injected intrathecally to produce a restricted distribution of anesthesia, could result in a sacral deficit. In addition, we sought to test the hypothesis that, when equal volumes are administered intrathecally, significant differences exist in the potential to three commonly used anesthetic solutions to induce sensory impairment. METHODS: Thirty-two rats were implanted with intrathecal catheters to permit repetitive infusion of local anesthetic. Animals were randomly assigned to four groups of eight to receive either 5% lidocaine with 7.5% dextrose; 0.75% bupivacaine with 8.25% dextrose; 0.5% tetracaine with 5% dextrose; or normal saline. Each rat received, in sequence, a 1-h (60 microliters), a 2-h (120 microliters), and a 4-h (240 microliters) infusion; the infusions were separated by a 4-day rest period. Sensory function was assessed using the tail-flick test, which was performed immediately before each infusion and 6 days after the last infusion by an investigator blinded to the solution infused. RESULTS: There was no significant difference in baseline tail-flick latencies for the four groups. Tail-flick latency for the lidocaine group was significantly prolonged when compared with the bupivacaine, tetracaine, and saline groups. This difference was apparent after the first infusion and persisted throughout the study. CONCLUSIONS: In the rat, restricted anesthetic distribution can be achieved, and sensory impairment may result. These findings further support an etiology of local anesthetic neurotoxicity for recent clinical injuries after continuous spinal anesthesia. The functional model described appears to be suitable for in vivo study of local anesthetic neurotoxicity.

Anesthesia, Local↗
PubMed1994

Anesthetic and hemodynamic effects of single bolus versus incremental titration of hyperbaric spinal lidocaine through microcatheter.

This study examined anesthetic development and hemodynamic changes during two techniques of hyperbaric lidocaine administration through 27-gauge intrathecal catheters for continuous spinal anesthesia in 55 elderly patients undergoing transurethral prostatic resection. Twenty-five patients were randomly assigned to receive hyperbaric lidocaine 5% solution in a single bolus of 75 mg to achieve blockade to approximately T6, and 30 patients to receive hyperbaric lidocaine 2.5% solution in increments of 25 mg to achieve T6 or to a maximum of three doses. Hemodynamic measurements of arterial pressure, heart rate, cardiac output, stroke volume, and ejection fraction were made serially after the induction of spinal anesthesia. Anesthesia failed to spread beyond the sacral region in 9/25 (36%) patients in the single-dose group (SD), but was successfully induced in all patients given titrated doses (TD) at total doses of 50 mg (n = 15) (TD50) and 75 mg (n = 15) (TD75). The mean maximal level of sensory block in all three groups was comparable: T5, T4, and T6 in groups SD, TD50, and TD75, respectively. The onset and progression of sensory block were rapid and similar in the SD and TD50 groups, in contrast to a gradual, stepwise development of block in group TD75. Grade 3 motor block occurred in response to the first dose of 25 mg lidocaine in 7/30 (23%) patients receiving titrated doses, but the overall incidence of leg paralysis did not differ among the three groups by the end of lidocaine dosing. Mean arterial pressure (MAP) decreased significantly relative to baseline in all three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn.

BACKGROUND: The 13 cell antigen receptor (BCR) is a multimeric protein complex consisting of an antigen recognition structure (membrane immunoglobulin) and two associated proteins, lg-alpha and Ig-beta It has been proposed that signalling through the BCR involves Ig-alpha and Ig-beta. Both of these proteins contain within their cytoplasmic domains an amino-acid motif that is present in a number of immune recognition receptors, including the BCR, T-cell antigen receptor and Fc receptor complexes. This motif, termed the antigen-receptor homology motif (ARH1), appears to have signal transduction ability. RESULTS: We now show that the presence of cytoplasmic regions containing the ARM motif from either Ig-alpha or Ig-beta is sufficient to confer signalling capability on an otherwise non-functional fusion protein. Both Ig-alpha- and Ig-beta-containing chimeras induced, in an apparently redundant fashion, signalling events seen upon membrane immunoglobulin crosslinking, including tyrosine phosphorylation of particular proteins, phosphoinositicle breakdown and calcium mobilization. Furthermore, crosslinking of the chimeras resulted in tyrosine phosphorylation of the Ig-alpha and Tg-beta tails and their association with the tyrosine kinases PTK72, p53/56(lyn) and p59(fyn). CONCLUSIONS: These observations indicate that Ig-alpha and Ig-beta are responsible for coupling membrane immunoglobulin to intracellular signalling components. Moreover, they demonstrate that a number of tyrosine kinases associate directly with the cytoplasmic domains of both Ig-alpha and Ig-beta. Stimulation of the chimeras, which results in tyrosine phosphorylation of the ig-alpha and Ig-beta tails, is a prerequisite for some of these associations. The implications of these findings for the mechanism by which the BCR initiates the signalling reactions are discussed.

Journal Article↗