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Biomedical subjects

S C Wong

Publications and source records attributed to S C Wong.

At least 37 records · Page 2Linked to original sources
PubMed2001

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Aged↗
PubMed2001

Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1.

The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor alpha. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1.

Animals↗
PubMed2001

The adaptor protein BLNK is required for b cell antigen receptor-induced activation of nuclear factor-kappa B and cell cycle entry and survival of B lymphocytes.

B lymphocytes lacking the adaptor protein B cell linker (BLNK) do not proliferate in response to B cell antigen receptor (BCR) engagement. We demonstrate here that BCR-activated BLNK(-)/- B cells fail to enter the cell cycle, and this is due to their inability to induce the expression of the cell cycle regulatory proteins such as cyclin D2 and cyclin-dependent kinase 4. BCR-stimulated BLNK(-)/- B cells also do not up-regulate the cell survival protein Bcl-x(L), which may be necessary for the cells to complete the cell cycle. In addition, BLNK(-)/- B cells exhibit a high rate of spontaneous apoptosis in culture. Examination of the various BCR-activated signaling pathways in mouse BLNK(-)/- B cells reveals the intact activation of Akt and mitogen-activated protein kinases but the impaired activation of nuclear factor (NF)-kappaB that is known to regulate genes involved in cell proliferation and survival. The inability to activate NF-kappaB in BCR-stimulated BLNK(-)/- B cells is due to a failure to induce the degradation of the inhibitory kappaB protein. In all these aspects, BLNK(-)/- B cells resemble xid B cells that have a mutation in Bruton's tyrosine kinase (Btk). Recently, phospholipase C (PLC)-gamma2 has also been demonstrated to be essential for NF-kappaB activation. Since BLNK has been shown separately to interact with both Btk and PLC-gamma2, our finding of normal Btk but impaired PLC-gamma2 activation in BCR-stimulated BLNK(-)/- B cells strongly suggests that BLNK orchestrates the formation of a Btk-PLC-gamma2 signaling axis that regulates NF-kappaB activation. Taken together, the NF-kappaB activation defect may be sufficient to explain the similar defects in BCR-induced B cell proliferation and T cell-independent immune responses in BLNK(-)/-, Btk(-)/-, and PLC-gamma2(-)/- mice.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting.

BACKGROUND: Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis. METHODS: Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo). RESULTS: The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment. CONCLUSIONS: Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2001

Eclipse burns: a prospective study of solar retinopathy following the 1999 solar eclipse.

Looking at the sun can cause focal burns to the retina. We prospectively followed up all patients who presented to Eye Casualty of Leicester Royal Infirmary having observed the solar eclipse of August, 1999. 45 patients attended, of whom 20 had visual symptoms and five had visible changes in the retina; four patients were still symptomatic after 7 months.

Adolescent↗
PubMed2001

One-year survival following early revascularization for cardiogenic shock.

CONTEXT: Cardiogenic shock (CS) is the leading cause of death for patients hospitalized with acute myocardial infarction (AMI). OBJECTIVE: To assess the effect of early revascularization (ERV) on 1-year survival for patients with AMI complicated by CS. DESIGN: The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April 1993 through November 1998. SETTING: Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS: Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria. INTERVENTIONS: Patients were randomly assigned to an initial medical stabilization (IMS; n = 150) group, which included thrombolysis (63% of patients), intra-aortic balloon counterpulsation (86%), and subsequent revascularization (25%), or to an ERV group (n = 152), which mandated revascularization within 6 hours of randomization and included angioplasty (55%) and coronary artery bypass graft surgery (38%). MAIN OUTCOME MEASURES: All-cause mortality and functional status at 1 year, compared between the ERV and IMS groups. RESULTS: One-year survival was 46.7% for patients in the ERV group compared with 33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence interval [CI], 2.2%-24.1%; P<.03; relative risk for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses, only age (<75 vs >/= 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and 80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS: For patients with AMI complicated by CS, ERV resulted in improved 1-year survival. We recommend rapid transfer of patients with AMI complicated by CS, particularly those younger than 75 years, to medical centers capable of providing early angiography and revascularization procedures.

Aged↗
PubMed2001

Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast.

In order to understand the intricate relationship of cell proliferation and apoptosis in tumour development, proliferation markers (Ki-67 and c-myc), apoptosis, cell-cycle inducers cyclin D1 and D3, and cell-cycle inhibitors p16(INK4), p21(CIP1), and p27(KIP1) were evaluated in ductal breast carcinoma. The heterogeneous nature of breast tumours provides a system by which the changes in cell-cycle genes can be explored under a wide range of proliferation and apoptotic indices. To address the above issues, immunohistochemical studies were conducted in 40 pairs of tumours and adjacent normal ductal tissues. The TUNEL method was used to identify apoptotic cells. Except for p27/KIP1, the proliferation (Ki-67, c-myc) and the apoptotic indexes together with levels of p16/INK4a, p21/CIP1, cyclin D1, and cyclin D3, were clearly elevated among tumour tissues, while absent in the adjacent normal tissues. Spearman correlation analysis indicated strong associations among apoptotic index, Ki-67, c-myc, and tumour grade. In addition, p21/CIP1 and cyclin D3 were positively correlated, while p16/INK4a, p27/KIP1, and cyclin D1 were negatively correlated with tumour grade. There was clear decoupling between p21 and p27, as well as decoupling between cyclin D1 and cyclin D3, in terms of their relationship to cell proliferation and apoptosis, indicating differential roles in tumour progression.

Apoptosis↗
PubMed2001

Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response.

Nipah virus is a newly discovered paramyxovirus transmitted directly from pigs to humans. During a large encephalitis outbreak in Malaysia and Singapore in 1998-9, most patients presented acutely. A 12 year old child is described who developed encephalitis 4 months after exposure to the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent assay (ELISA), which is also described. The late presentation and IgG subclass responses had similarities to subacute sclerosing panencephalitis. Nipah virus should be considered in patients with encephalitis even months after their possible exposure.

Animals↗
PubMed2000

Cytotoxic effect of gossypol on colon carcinoma cells.

Gossypol, a male contraceptive drug extracted from cottonseeds, has been found to have antiproliferative activity on tumour cells and is thought to be a potential anticancer drug. The aim of this study was to investigate the mechanisms of gossypol-induced cell death on two colon carcinoma cell lines, HT29 and LoVo. Firstly, we studied the effect of gossypol on the colony forming ability of these tumour cells, which is the main target of chemotherapeutic drugs. Using clonogenic assays, flow cytometry and DNA gel electrophoresis techniques, we have found that gossypol not only inhibited colony forming ability of these tumour cells, but we also observed cellular internucleosomal DNA fragmentation in the cells treated with 3 doses of gossypol and this was accompanied by the appearance of a sub-G1 apoptotic peak and morphological characteristics of apoptosis. Our results suggest that the gossypol induced cell death is via an apoptotic pathway and the effect of gossypol may not be cell cycle specific. Using Western blotting analysis, we found that the gossypol-induced apoptosis may not be involved in the regulation of p53 but possibly associated with the regulation of bcl-2 and Bax expression. Our evidence indicates that gossypol may provide a potential therapeutic benefit for the treatment of colon carcinoma and understanding the mechanisms of gossypol-induced cytotoxicity on tumour cells is essential for including this drug in clinical use.

Cell Cycle↗
PubMed2000

Cutting edge: B cell linker protein is dispensable for the allelic exclusion of immunoglobulin heavy chain locus but required for the persistence of CD5+ B cells.

The pre-B cell receptor (pre-BCR) and the BCR are required for B lymphopoiesis and for the allelic exclusion of Ig genes. Mice lacking B cell linker (BLNK) protein that is a component of the BCR signaling pathway have impaired B cell development. In this report, we show that allelic exclusion is intact in BLNK(-/-) mice harboring a V(H)12 transgene. This differs from mice lacking the tyrosine kinase Syk that is upstream of BLNK in BCR signaling and contrasts with mice lacking SLP-76 that is the equivalent adaptor molecule in TCR-signal transduction. We also show that, whereas most wild-type V(H)12-expressing B cells are CD5(+), the majority of the splenic V(H)12-expressing BLNK(-/-) B cells are CD5(-). A small population of V(H)12-expressing, BLNK(-/-) CD5(+) B cells is detectable in the peritoneal cavity of younger but not older mice. This suggests that BLNK deficiency affects not only the generation but also the persistence of B-1 cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Angiographic findings and clinical correlates in patients with cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction. BACKGROUND: Patients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking. METHODS: We compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications. RESULTS: Patients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3). CONCLUSIONS: Patients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade.

Aged↗
PubMed2000

Variation in the oxygen isotope ratio of phloem sap sucrose from castor bean. Evidence in support of the Péclet effect.

Theory suggests that the level of enrichment of (18)O above source water in plant organic material (Delta) may provide an integrative indicator of control of water loss. However, there are still gaps in our understanding of the processes affecting Delta. One such gap is the observed discrepancy between modeled enrichment of water at the sites of evaporation within the leaf and measured enrichment of the leaf water as a whole (Delta(L)). Farquhar and Lloyd (1993) suggested that this may be caused by a Péclet effect. It is also unclear whether organic material formed in the leaf reflects enrichment of water at the sites of evaporation within the leaf or Delta(L). To investigate this question castor bean (Ricinus communis L.) leaves, still attached to the plant, were sealed into a controlled-environment gas exchange chamber and subjected to a step change in leaf-to-air vapor pressure difference. Sucrose was collected from a cut on the petiole of the leaf in the chamber under equilibrium conditions and every hour for 6 h after the change in leaf-to-air vapor pressure difference. Oxygen isotope composition of sucrose in the phloem sap (Delta(suc)) reflected modeled Delta(L). A model is presented describing Delta(suc) at isotopic steady state, and accounts for 96% of variation in measured Delta(suc). The data strongly support the Péclet effect theory.

Ricinus communis↗
PubMed2000

Effects of elevated [CO(2)] and nitrogen nutrition on cytokinins in the xylem sap and leaves of cotton.

We measured the level of xylem-derived cytokinins (CKs) entering a cotton leaf, and the CK levels in the same leaf, thus enabling xylem sap and foliar CKs to be compared concurrently. Although zeatin was the dominant CK in xylem sap, zeatin, dihydrozeatin, and N(6)-(2-isopentenyl) adenine were present in approximately equimolar levels in leaves. Elevated [CO(2)] (EC) has an effect on the levels of cytokinins in sap and leaf tissues. This effect was modulated by the two levels of root nitrogen nutrition (2 and 12 mM nitrate). Growth enhancement (70%) in EC over plants in ambient [CO(2)] (AC) was observed for both nitrogen nutrition treatments. Low-nitrogen leaves growing in EC exhibited photosynthetic acclimation, whereas there was no sign of photosynthetic acclimation in high-nitrogen grown leaves. Under these prevailing conditions, xylem sap and leaf tissues were obtained for CK analysis. Higher nitrogen nutrition increased the delivery per unit leaf area of CKs to the leaf at AC. EC caused a greater increase in CK delivery to the leaf at low nitrogen conditions (106%) than at high nitrogen conditions (17%). EC induced a significant increase in CK content in low-nitrogen leaves, whereas CK content in leaf tissues was similar for high-nitrogen leaves growing in AC and EC.

Carbon Dioxide↗
PubMed2000

Differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia by protein and DNA analyses.

DNA analysis was used to confirm the Hb EE genotype and to differentiate from the possible genotype of Hb E-beta(0)-thalassemia in two Malay patients. The first patient was a 13-year-old Malay girl, whose parents were available for family studies. The second patient was a 69-year-old Malay woman with no living family members. The presence of Hb E in both propositi was confirmed by: (1) its characteristic electrophoretic mobilities on alkaline/acid gels; (2) its chromatographic properties on anion/cation exchangers, and (3) its mildly insoluble properties. However, differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia was challenging in these two cases. In the former, this was because of the possible interactions of the parents' phenotypes; i.e., the mother had a similar phenotype. In the latter, it was due to the lack of any living family members for family studies. In this communication, we present the protein and DNA analyses, including data on the use of the restriction enzyme Mnl I, for the definitive diagnosis of the Hb EE genotype in the propositi of these two Malay families.

Adolescent↗
PubMed1999

Synthesis of C-11 methyl-substituted benzocycloheptapyridine inhibitors of farnesyl protein transferase.

[formula: see text] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic compounds has been achieved via two different methods. Methylation of C-11 has been effected by treatment of amine 4 with BuLi followed by Mel quenching. In a similar procedure, introduction of a C-11 substituent with concomitant rearrangement of the exocyclic double bond has been carried out. Potent farnesyl protein transferase inhibitors have been synthesized using the above methodologies.

Alkyl and Aryl Transferases↗
PubMed1999

Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak.

BACKGROUND: In mid-1997, several children died in Sarawak, Malaysia, during an epidemic of enterovirus-71 (EV71) hand, foot, and mouth disease. The children who died had a febrile illness that rapidly progressed to cardiopulmonary failure and the cause was not satisfactorily resolved. We describe the isolation and identification of a subgenus B adenovirus from the children who died. METHODS: We studied two groups of children presenting to Sibu Hospital from April 14 to Sept 30, 1997. For children who died, the inclusion criterion was death after febrile illness, and for those who did not die it was acute flaccid paralysis (AFP). Serum and cerebrospinal fluid samples were tested for IgM antibodies to Japanese encephalitis and dengue viruses. Viruses isolated were identified by immunofluorescence, reverse-transcriptase PCR, or PCR and DNA sequencing. FINDINGS: Enterovirus was isolated in three (19%) of 16 children who died and in none of the eight surviving children with AFP. However, an agent that was initially difficult to identify was found in ten (63%) children who died and five (63%) surviving children who had AFP. The agents isolated from ten (66.7%) of these 15 children were eventually identified as adenoviruses and were isolated mainly from clinically important sterile sites or tissues. All the enterovirus-positive children who died had this second agent. INTERPRETATION: Our data raises doubts that EV71 was the only aetiological agent in these deaths.

Adenoviridae↗
PubMed1999

Impaired membrane transport in methotrexate-resistant CCRF-CEM cells involves early translation termination and increased turnover of a mutant reduced folate carrier.

The basis for impaired reduced folate carrier (RFC) activity in methotrexate-resistant CCRF-CEM (CEM/Mtx-1) cells was examined. Parental and CEM/Mtx-1 cells expressed identical levels of the 3. 1-kilobase RFC transcript. A approximately 85-kDa RFC protein was detected in parental cells by photoaffinity labeling and on Western blots with RFC-specific antiserum. In CEM/Mtx-1 cells, RFC protein was undetectable. By reverse transcriptase-polymerase chain reaction and sequence analysis, G to A point mutations were identified in CEM/Mtx-1 transcripts at positions 130 (P1; changes glycine 44 --> arginine) and 380 (P2; changes serine 127 --> asparagine). A 4-base pair (CATG) insertion detected at position 191 (in 19-30% of cDNA clones) resulted in a frameshift and early translation termination. Wild-type RFC was also detected (0-9% of clones). Wild-type RFC and double-mutated RFC (RFCP1+P2) cDNAs were transfected into transport-impaired K562 and Chinese hamster ovary cells. Although RFC transcripts paralleled wild-type protein, for the RFCP1+P2 transfectants, disproportionately low RFCP1+P2 protein was detected. This reflected an increased turnover of RFCP1+P2 over wild-type RFC. RFCP1+P2 did not restore methotrexate transport; however, uptake was partially restored by constructs with single mutations at the P1 or P2 loci. Cumulatively, our results show that loss of transport function in CEM/Mtx-1 cells results from complete loss of RFC protein due to early translation termination and increased turnover of a mutant RFC protein.

Animals↗