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Biomedical subjects

W L Chan

Publications and source records attributed to W L Chan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Results of coronary stenting after delayed angioplasty of the culprit vessel in patients with recent myocardial infarction.

Little information is available concerning the effect of late coronary stenting in patients with recent myocardial infarction, especially long-term results. We retrospectively reviewed our results of 57 stent placements in 52 consecutive patients who received stents at an infarct-related lesion 24 hr to 30 days after an acute myocardial infarctions (median, 14 days). The average age was 67 years; 90% were male. Two patients who suffered from acute stent thrombosis received revascularization again and two early deaths were due to refractory cardiogenic shock before discharge. Mean patient clinical follow-up was 18.3 +/- 6.5 months. There were 1 subacute stent thrombosis, 1 cardiogenic death, and 10 patients (20.8%) in total suffering from angina class II to IV. Angiographic follow-up was performed in 36 patients (80%) at a mean of 7.5 +/- 3.1 months. Of these 36 patients, only 1 (3% of the total population undergoing follow-up angiography) had reocclusion at follow-up, but restenosis existed in 18 patients (50%). We conclude that there is still relatively high incidence of angiographic recurrence that is often silent in long-term follow-up, though the long-term result of late stenting in recent MI is low incidence of reocclusion.

Aged↗
PubMed1999

Immune effector mechanism in parasitic infections.

In this article is a summary of our recent findings on the role of nitric oxide (NO) as an effector mechanism against the intracellular parasite, Leishmania major. NO is produced in large amounts in murine macrophages following activation by IFNgamma synthesized by Th1 cells. NO production is inhibited by IL-4, a product of Th2 cells. A set of stable cell surface markers has now been identified. ST2L and IL-18R are selectively expressed on Th2 and Th1 cells respectively. Antibody against ST2L can down-regulate Th2 cells in the highly susceptible BALB/c mice leading to control of otherwise fatal L. major infection. These results show directly the critical role of the balance between Th1 and Th2 cells in cutaneous leishmaniasis.

Animals↗
PubMed1999

Retropharyngeal abscess on a Ga-67 scan: a case report.

A retropharyngeal abscess is a potentially fatal deep neck infection. Classical symptoms include fever, neck swelling, sore throat, dysphagia, and cervical rigidity. Sometimes small children present with nonspecific symptoms. We report a rare case whereby the Ga-67 citrate scan was the first investigation to reveal an inflammatory process in the retropharyngeal or submastoid region of a 3-year-old child with sepsis. This directed the line of investigation to a more precise anatomic imaging modality, CT scanning, to localize the abscess. With prompt administration of intravenous antibiotics, the child recovered quickly and did not require surgery. The Ga-67 scan is thus a useful screening test to detect inflammatory foci because of its high sensitivity. It is also valuable in the follow-up of the patient's response to therapy.

Anti-Bacterial Agents↗
PubMed1999

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Animals↗
PubMed1998

Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells.

Interleukin (IL)-18 induces interferon (IFN)-gamma synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rbeta2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R-derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin-T cell antigen receptor-alphabeta transgenic mice (D011.10). Anti-IL-18R antibody inhibited IL-18- induced IFN-gamma production by Th1 clones in vitro. In vivo, anti-IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-gamma and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.

Animals↗
PubMed1998

Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells.

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4(+) cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor-alpha/beta transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-gamma. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-gamma production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.

Animals↗
PubMed1998

Protective effect on Leishmania major infection of migration inhibitory factor, TNF-alpha, and IFN-gamma administered orally via attenuated Salmonella typhimurium.

The genes encoding murine macrophage migration inhibitory factor (MIF), IL-2, IFN-gamma or TNF-alpha were cloned individually into an expression plasmid under the control of the inducible promoter nirB and transfected into the aroA- aroD- deletion mutant strain of Salmonella typhimurium (BRD509). These S. typhimurium derivatives (henceforward called constructs and termed GIDMIF, GIDIL2, GIDIFN and GIDTNF) expressed their respective cytokines in vitro under anaerobic conditions and stably colonized BALB/c mice up to 14 days after oral administration. The highly susceptible BALB/c mice that had received the constructs orally and that had been subsequently infected via the footpad with Leishmania major, developed significantly reduced disease compared with control mice administered the untransfected Salmonella strain (BRD509). Importantly, a combination of GIDMIF, GIDIFN, and GIDTNF administered orally after L. major infection was able to significantly limit lesion development and reduced parasite loads by up to three orders of magnitude. Spleen and lymph node cells of mice administered this combination expressed markedly higher levels of inducible nitric oxide synthase (iNOS) compared with those from mice receiving an equivalent dose of the control strain of Salmonella (BRD509). These data therefore demonstrate the feasibility of therapeutic treatment in an infectious disease model using cytokines delivered by attenuated Salmonella. The protective effect observed correlates with the induction of inducible nitric oxide synthase in vivo.

Administration, Oral↗
PubMed1998

Mice lacking inducible nitric-oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses.

Mice deficient in the inducible nitric-oxide synthase (iNOS), constructed by gene-targeting, were significantly more susceptible to herpes simplex virus (HSV)-1 infection, displayed a delayed clearance of virus from the dorsal root ganglia (DRG) and exhibited an increase in the frequency of virus reactivation in DRG compared with similarly infected heterozygous mice. The infected iNOS-deficient mice developed enhanced Th1-type immune responses and their spleen cells produced higher concentrations of IL-12 than similarly infected heterozygous mice. This finding suggests that iNOS plays an important role in resistance against HSV-1 infection. Furthermore, nitric oxide (NO) may block the development of Th1 cells via inhibition of IL-12 synthesis and thereby play a role in immune regulation.

Animals↗
PubMed1998

Polymorphisms of the apolipoprotein B 3' variable number of tandem repeats region associated with coronary artery disease in Taiwanese.

We studied the allelic frequency of the variable number of tandem repeats region 3' of the apolipoprotein B gene (apoB 3' VNTR) and its impact on coronary artery disease (CAD) in 150 patients with CAD and 153 normal controls in a Taiwan population. apoB 3' VNTR alleles were classified according to the number of repeats of a 15-bp hypervariable elements (HVE), the sequence of which was determined using the polymerase chain reaction and direct sequencing. Thirteen alleles comprising from 26 to 54 HVEs were identified. The CAD patients had greater heterozygosity (0.58 vs 0.42) and a higher frequency of long (> 36-HVE) apoB 3' VNTR alleles than the controls (18.7% vs 10.8%, p < 0.01). CAD patients with two HVE-36 alleles and no HVE-32 alleles (the two most common forms) had significantly higher concentrations of LDL-cholesterol, apolipoprotein B, and triglycerides, and significantly lower values of HDL-cholesterol and apolipoprotein AI than the control group (p < 0.01 for all comparisons). The length of the apoB 3' VNTR was not correlated with the plasma concentrations of any of the lipids. We conclude that long apoB 3' VNTR alleles occur more frequently in CAD patients, but that apoB 3'VNTR genotypic variation has little impact on the risk of dyslipidemia in Taiwanese.

Aged↗
PubMed1997

Acute renal failure and proximal tubule lesions after trichosanthin injection in rats.

The structural basis of the recently recognized renal impairment after infusion of trichosanthin (TCS), a type I ribosome inactivating protein, is uncertain, but functionally it appears to be related to a lesion in the renal tubules. In this study, renal dysfunction in experimental rats was induced by a single dose of TCS. Creatinine clearance and tubular proteinuria were used to assess renal function. Light microscopy and ultrastructure of the kidneys were examined and apoptosis in proximal tubules was evaluated by the in situ TdT-mediated nick end labeling technique. TCS-treated rats demonstrated a significant dose-dependent decrease in creatinine clearance together with a mild degree of low-molecular-weight proteinuria. The proximal convoluted tubule was the site of lesions showing individual tubular cell death, which was more abundant in rats receiving high doses of TCS. Apoptotic cell death, together with heterophagosomes and large residual bodies, was observed. DNA fragmentation was confirmed by the in situ technique. There was also a dose-dependent density of apoptotic cells. Other portions of the nephron were spared, and it was not accompanied by any inflammatory infiltrate. In conclusion, these findings are consistent with TCS-induced proximal tubular toxicity resulting in reduction of glomerular filtration rate and tubular proteinuria. The extent of injury is dosage dependent. Both necrotic cell death and apoptosis participated in the loss of cells from the proximal tubules. Such toxicity may be mediated through intracellular events induced by trichosanthin.

Acute Kidney Injury↗
PubMed1997

Differential T cell response induced by certain recombinant oligopeptides of herpes simplex virus glycoprotein B in mice.

Much attention is presently focused on the quality of the immune response produced by helper T or regulatory cells because of its implications for vaccine development and immunomodulation. Glycoprotein B (gB) of herpes simplex virus (HSV) has been shown to induce a protective T cell response. To further characterize the nature of the T cell response, oligopeptides were expressed from the open reading frame of gB from HSV-2 (gB-2) as fusion proteins with beta-galactosidase (GZ) in E. coli. After immunopurification using an anti-GZ affinity column, oligopeptides p59 and p65, spanning amino acid residues 339-394 and 424-484 of gB-2 respectively, were examined for immunogenic response by delayed type hypersensitivity (DTH) in vivo and for antigenic response by T cell proliferation in vitro. p59 but not p65 was able to prime for both DTH and proliferative T cell response to whole HSV-2 and protect against challenge infection. However, when mice were pretreated with cyclophosphamide, p65 primed for a strong DTH response to a level similar to that induced by p59 in mice either pretreated or not treated with cyclophosphamide. This suggests that p65 contains epitopes capable of inducing both DTH and immunosuppression. Thus, when mice were primed with p65 before immunizing with HSV-2, their in vitro HSV-specific proliferative response was suppressed. Therefore, p59 is a good immunogen able to induce significant, though incomplete, protection. It could be considered for inclusion in a cocktail of subunit vaccines against HSV-2 whereas p65 or parts thereof should be excluded for this purpose.

Animals↗
PubMed1997

Malfunction of an active fixation J-shaped screw-in atrial electrode lead: a case report.

Active fixation leads, using active grasping devices, ensure good postoperative lead fixation, long-term performance, and make possible later lead removal on demand. However, these delicate designs have not been without practical difficulties. We present two cases of fixation stylet fracture during helix extension and retraction maneuver respectively with resultant lead inoperability and abandonment. The fixed leads could be removed by torquing the entire lead counterclockwise.

Adult↗
PubMed1997

New stenosis on proximal coronary segment after directional atherectomy. Two case reports.

Two patients with new coronary stenotic lesions subsequently developed proximal to the sites accepting directional coronary atherectomy (DCA) are reported. One lesion developed at the left main coronary artery and the other at the proximal segment of the left anterior descending artery. The mechanisms of the development of such new stenotic lesions after DCA were studied and procedure-related mechanical trauma over the proximal segment of the primary lesion may be the possible mechanism for such complication.

Aged↗
PubMed1997

Right ventricular electrode lead implantation via a persistent left superior vena cava. An improved technique.

Persistent left superior vena cava occurs in approximately 0.5% of the population. This may complicate pacemaker implantation by making lead insertion difficult and causing lead instability through the left cephalic vein and the subclavian vein approach. We used a wide loop technique in the right atrium and successfully advanced the lead in the right ventricle apex. A persistent left superior vena cava does not preclude successful lead placement.

Aged↗
PubMed1996

Changes in cardiac autonomic activities in patients with syndrome X. A study of spectral analysis of heart rate variability.

The present study was designed to assess cardiac autonomic activities, coronary microvascular function, and their relationship in patients with syndrome X. Control of coronary blood flow is complex, and impaired coronary flow reserve has been attributed as the cause of myocardial ischemia in patients with syndrome X. It is unknown whether cardiac autonomic activities are altered in the presence of coronary microvascular dysfunction in patients with syndrome X. Eighteen patients with syndrome X were studied. Great cardiac vein flow was measured by the thermodilution method and the coronary flow reserve was determined by intravenous dipyridamole (0.56 mg/kg) infusion. Twenty-four-hour ambulatory electrocardiograms were obtained in a drug-free state. Another 14 age- and sex-matched normal subjects served as a control group. The amplitude (in ms) of ultralow (ULF), very-low (VLF), low (LF), and high (HF) frequency bands and total spectra of heart rate variability were measured for twenty-four-hour and every four-hour interval of the day.

Adult↗
PubMed1996

Effects of right ventricular pacing on ventriculoatrial conduction and systemic venous responses in sick sinus patients.

This study was designed to assess the ventriculoatrial (VA) conduction and systemic venous responses to right ventricular pacing at different pacing rates and the feasibility of identifying patients prone to pacemaker syndrome by means of a Doppler and two-dimensional echocardiographic technique. Twenty-two sick sinus patients who received ventricular-demand permanent pacemakers constituted the study group. The proximal inferior vena cava (IVC) diameters were measured by two-dimensional echocardiography. Fourteen patients had VA conduction by preimplant electrophysiologic study or paced electrocardiogram (Group II), while the other 8 patients presented no VA conduction (Group I). Abnormal systolic retrograde flow in the hepatic vein following each paced beat could be demonstrated in those patients with VA conduction in the basal state. In the 8 patients without VA conduction, the IVC diameters were significantly increased during rapid right ventricular pacing in those with left ventricular dysfunction (n = 4) as compared with those with normal left ventricular function (n = 4) (% increment at 120 beats per minute.

Blood Flow Velocity↗
PubMed1996

Hemodynamic mechanism of vasovagal syncope.

Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. Thirty two patients with recurrent unexplained syncope were studied using a head-up (60 degrees) tilt test. The electrocardiogram, arterial blood pressure, pulmonary arterial pressure and central venous pressure were monitored continuously, and the cardiac output was measured by the thermodilution method. Twenty patients (62.5%) had positive tilt test responses, of which 12 developed typical vasovagal syncope with marked hypotension and bradycardia; the others developed hypotension without bradycardia. There were five women and seven men with a mean age (+/- SD) of 53.3 +/- 15 years. The effect of head-up tilt resembled that of hypovolemia. The central venous pressure, pulmonary capillary wedge pressure and cardiac output declined with an increase of heart rate and systemic vascular resistance. However the mean blood pressure was maintained. During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.22 +/- 0.43 to 1.51 +/- 0.32 liters/min/m2 (p value < 0.05) and the systemic vascular resistance index decreased from 3,689 +/- 859 to 1,999 +/- 543.9 dynes s cm5/m2 (p value < 0.05). The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.

Adult↗