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Biomedical subjects

J C Tan

Publications and source records attributed to J C Tan.

At least 19 recordsLinked to original sources

The ability of the GDx nerve fibre analyser neural network to diagnose glaucoma.

PURPOSE: To evaluate the neural network used by the GDx in a group of normal subjects, patients with ocular hypertension (OHT) and patients with normal-pressure glaucoma (NPG). METHODS: The GDx neural network produces a "number" that indicates the likelihood that glaucoma is present. This number was compared in three groups representing different stages of health and disease, namely, normal controls (n = 101), OHT (n = 102) and NPG (105). The GDx number's ability to differentiate between normal and glaucoma individuals was then investigated. We also studied the relationship between the GDx number and retinal nerve fibre layer (RNFL) average thickness and visual field status to examine how well the GDx number reflects disease severity. RESULTS: The GDx number was significantly different among the groups (P < 0.01); it was highest in NPG and lowest in normal controls. The GDx number differentiated between glaucoma and normal with sensitivity of 92.3% and specificity of 96%. When combined with the parameter of RNFL average thickness, sensitivity and specificity were 88.5% and 100% respectively. In NPG a significant correlation was found between the GDx number and RNFL average thickness(rho = -0.88, P < 0.001) and visual field mean deviation (rho = -0.64, P < 0.001). CONCLUSION: The GDx number is able to differentiate between groups of normal, OHT and NPG subjects. Its close relationship with RNFL average thickness and visual field status in glaucoma indicates that it is able to reflect disease severity. Furthermore, its measured ability to distinguish between normal individuals and those with glaucoma demonstrates potential for use in glaucoma diagnosis.

Adult↗

Capsulotomy.

Research is continually seeking to better describe the relationship between pseudophakic capsular opacification and underlying cell biology, surgical technique, and intra-ocular lens biomaterial and design. Outcomes are reviewed from prospective, randomized studies that investigate the importance of capsulorhexis size, pharmacological treatment, and lens material in influencing capsular opacification and the need for capsulotomy. The results of several studies support the role of lens edge profile in inhibiting lens epithelial cell migration. A large post-mortem study also examines how lens type may affect anterior capsular opacification formation. Of particular interest is a histological report that sheds additional light on understanding cellular processes in posterior capsu-lar opacification.

Cataract↗

Post-operative pain in needlescopic versus conventional laparoscopic cholecystectomy: a prospective randomised trial.

BACKGROUND: Needlescopic cholecystectomy (NC) utilises instruments and ports smaller than 3 mm in diameter compared with the 5 mm ones used in conventional laparoscopic cholecystectomy (LC). Post-operative pain control and recovery has been thought to be superior in NC, when compared with historical controls with LC, but has not been proven in a prospective fashion. PATIENTS AND METHODS: A prospective randomised trial of NC versus LC for patients with symptomatic gallstone disease, with standardisation of post-operative analgesia and daily assessment of post-operative pain, using a 5-point visual analogue scale. RESULTS: There were 64 eligible patients randomised into NC (28) and LC (36). Four patients who had NC were converted to LC due to technical problems. Another three and six patients from the NC and LC groups, respectively, had conversion to open surgery. Post-operative pain scores were low in both groups. Mean pain scores for those with successful NC and LC were: 1.24 versus 1.43 for the day of operation (P = 0.49), 0.86 versus 0.83 for the first day post-operatively (P = 0.92) and 0.75 versus 0.81 for the second post-operative day (P = 0.87). The mean number of intra-muscular analgesic injections required were 0.76 versus 0.83 after NC and LC, respectively (P = 0.93). There were no significant differences between the two groups in the time taken to return to feeding, eating a normal diet and discharge from hospital. CONCLUSION: There is no advantage of NC over LC in terms of post-operative pain or recovery. Nevertheless, NC can be performed safely and expediently and has an excellent cosmetic outcome and high patient acceptability.

Adult↗

Longitudinal nerve fibre layer thickness change in normal-pressure glaucoma.

PURPOSE: To investigate longitudinal retinal nerve fibre layer (RNFL) thickness change in patients with normal-pressure glaucoma (NPG) and to assess how this may be related to visual fields. METHODS: NPG patients and normal subjects who had had serial GDx nerve fibre layer Analyzer II imaging and Humphrey visual fields performed at least 18 months apart were selected for study. These measurements were compared between groups at baseline and at subsequent follow-up, for change over time. RESULTS: Seventy-five NPG patients and 35 normal subjects were studied. Significant differences in RNFL thickness were found between NPG patients and normal controls at baseline (P < or = 0.001). Over the same time, there was greater RNFL thinning in NPG patients than in normal subjects (P < or = 0.0001). RNFL thinning in NPG was negatively correlated with visual field log MD at baseline (P < 0.001) and change in MD over time (P < 0.001). CONCLUSION: Reduction of RNFL thickness over time was significantly greater in NPG patients than in normal subjects, indicating that NPG patients' RNFL had thinned at a faster rate. NPG patients with initially better visual fields had a greater reduction in RNFL thickness than did those with initially more advanced visual field defects, suggesting that more RNFL change may be observed when glaucoma is at an earlier stage. There was a direct relationship between RNFL thinning and visual field deterioration.

Aged↗

Removal of a dinner fork from the stomach by double-snare endoscopic extraction.

Long and pointed foreign objects in the stomach are difficult to remove by endoscopy, and they can cause complications such as perforation and impaction. The endoscopic removal of long and pointed objects involves the following principles: (1) presenting the blunt end cephalad to prevent perforation or impaction during extraction; (2) orienting the long axis of the object in the line of extraction; and (3) applying traction to the foreign body without losing grip. Currently practised methods of extraction, which use a protector hood or an overtube, do not address these three principles. We report on a case in which an ingested metal dinner fork was removed from the stomach by using a double wire-loop snare technique. This method uses two snares to hold the object and allows the endoscopist to change the presentation, orient the axis, and maintain traction to allow the safe removal of long and pointed objects.

Adult↗

The effect of neodymium: YAG capsulotomy on contrast sensitivity and the evaluation of methods for its assessment.

OBJECTIVE: To determine the most appropriate method for measuring the effect on contrast sensitivity of neodymium:YAG (Nd:YAG) posterior capsulotomy for early posterior capsular opacification (PCO). DESIGN: Prospective comparison of five different methods for luminous contrast sensitivity testing in patients undergoing capsulotomy. PARTICIPANTS: Sixteen patients with PCO involving the visual axis and visual acuities of 20/40 or better were recruited sequentially. INTERVENTION: All patients were tested with each of the five tests before and after Nd:YAG capsulotomy. MAIN OUTCOME MEASURES: The contrast sensitivity function was measured with variable contrast sine wave gratings using the Vistech VCTS 6500, Mentor B-VAT-II and a computer graphics system. Peak contrast sensitivity at 3 cyc/deg was compared with two letter tests, the Pelli-Robson chart, and a computer that generated optotypes. RESULTS: Significant generalized improvement that was not frequency selective was measured over the entire contrast sensitivity function after capsulotomy. The five tests did not significantly differ (P > 0.05) in their measurement of peak contrast sensitivity (3 cyc/deg) improvement after capsulotomy. Letter-based tests showed better agreement and lower variance than gratings tests. Visual acuity and contrast sensitivity improvement were poorly correlated. CONCLUSIONS: This study shows that contrast sensitivity is adequately documented by a single measurement at 3 cyc/deg, is an informative supplement to visual acuity, and that little extra information is to be gained by measuring further spatial frequencies in eyes with PCO. Peak contrast sensitivity is best determined using a letter-based test.

Aged↗

Development of a CD28 receptor binding-based screen and identification of a biologically active inhibitor.

CD28 is a T-cell costimulatory receptor which plays a pivotal role in antigen-induced T-cell response. We have developed a cell-free and scintillation-proximity assay-based screen to search for molecules that inhibit ligand binding to CD28. The assay was shown to be versatile and adaptable to automation for high-throughput screening. Using this assay, we identified an inhibitor of CD28, NP2214. The inhibitor was shown to be active in vitro by suppressing IL-2 synthesis and proliferation of peripheral blood mononuclear cells in response to CD28 costimulation. We also demonstrated the additive effects of NP2214 and cyclosporine A which act mechanistically distinctly in inhibiting costimulation-induced IL-2 synthesis.

Abatacept↗

Comparison of methods to assess visual impairment from glare and light scattering with posterior capsule opacification.

PURPOSE: To compare 2 glare tests to determine their relative usefulness in the assessment of posterior capsule opacification (PCO) and to evaluate the potential benefits of combined visual, acuity, contrast sensitivity, and glare testing. SETTING: Teaching hospital ophthalmology department. METHODS: Sixteen patients had glare, visual acuity, and contrast sensitivity testing before and after neodymium:YAG (Nd:YAG) capsulotomy. Results with the Brightness Acuity Tester (BAT, Mentor), which measures disability glare, and the Straylightmeter (Foundation for Eye Research, The Netherlands), which quantifies forward scatter by direct compensation techniques, were compared. The correlation between glare, ETDRS visual acuity, and Pelli-Robson contrast sensitivity was determined. RESULTS: Pretreatment visual acuity was significantly correlated with contrast sensitivity (P < .01). However, visual acuity and contrast sensitivity were poorly correlated with both the BAT and Straylightmeter (P > .05), indicating that visual acuity is predictive of contrast sensitivity but a poor predictor of glare. Glare was significantly improved (Straylightmeter, P < .0001; BAT, P < .05) following capsulotomy. While the Straylightmeter consistently measured precapsulotomy forward scatter that improved with treatment, corresponding BAT disability glare was unmeasurable in 18.8% of patients with PCO, as their visual acuities improved rather than deteriorated with glare testing. CONCLUSIONS: Glare testing provided more information than contrast sensitivity when combined with visual acuity in the evaluation of PCO. Glare related to PCO is better assessed using the Straylightmeter because the BAT may yield aberrant disability glare results.

Aged↗

Perforated leiomyosarcoma of Meckel's diverticulum.

Two cases of perforated leiomyosarcoma of Meckel's diverticulum are presented. There are only 59 cases reported in current literature, including 4 perforations. Although the condition is rare, leiomyosarcoma is the commonest tumour of Meckel's diverticulum. Its clinical presentation include abdominal pain, intestinal bleeding, abdominal mass, intestinal obstruction and less commonly, acute perforations. Both our cases presented with perforations which is unusual. Despite this late presentations both were resectable and both had no distant or local metastasis. One of our patients was 89 years old at presentation and has been disease-free 3 years after resection. The other patient was 69 years old and has also been disease-free.

Aged↗

The role of dysphoric mood and gender in interpersonal responses to nondysphoric others.

There now exists a sizeable body of research on interpersonal responses to dysphoric individuals, yet relatively few studies have addressed responses of dysphoric individuals toward others. This study compared responses of dysphoric and nondysphoric individuals toward a nondysphoric person within same sex and opposite-sex dyads. Dysphoric and nondysphoric subjects did not differ in their desire for future interaction with their interactional partner. Dysphoric subjects reported a greater reduction in feelings of sadness, hostility, and impatience following the interaction, and among dysphoric subjects, those who interacted with a female reported a greater decrease in anxiety than did those who interacted with a male. Dysphoric subjects also perceived their partners to act in a more dysphoric fashion than did nondysphoric subjects.

Adult↗

The functional characterization of interleukin-10 receptor expression on human natural killer cells.

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.

Antigens, CD↗

Characterization of recombinant extracellular domain of human interleukin-10 receptor.

The extracellular region of the human interleukin-10 (hIL-10) receptor was expressed using a myeloma cell line and was purified to homogeneity by ligand-affinity chromatography. SDS-polyacrylamide gel electrophoresis analysis indicated that the soluble receptor is glycosylated and has an apparent molecular mass of 35,000-45,000. Under native conditions, soluble hIL-10 receptor was determined by gel filtration to be a monomeric protein. Soluble hIL-10 receptor was able to inhibit the binding of 125I-hIL-10 to the full-length receptor and was able to antagonize the effect of human IL-10 in cell proliferation and cytokine synthesis inhibition. The apparent dissociation constant (Kd) of soluble hIL-10 receptor was determined to be 563 +/- 59 pM, approximately 2- to 10-fold higher than that found on intact cells (Tan, J. C., Indelicato, S. R., Narula, S. K., Zavodny, P. J., and Chou, C.-C. (1993) J. Biol. Chem. 268, 21053-21059; Liu, Y., Wei, S. H.-Y., Ho, A. S.-Y., de Waal Malefyt, R., and Moore, K. W. (1994) J. Immunol. 152, 1821-1829). When hIL-10 binds soluble hIL-10 receptor in solution, a single complex was detected by gel filtration, and the complex was found to consist of two hIL-10 dimers and four soluble receptor monomers, suggesting that hIL-10 may induce a novel mode of oligomerization of the receptor upon binding.

Amino Acid Sequence↗

Lymphomagenesis in the SCID-hu mouse involves abundant production of human interleukin-10.

Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be important cofactors in the survival and growth of lymphoblastoid cell lines infected with Epstein-Barr virus (EBV). When mice with severe combined immune deficiency (SCID) are injected with human peripheral blood lymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymphoproliferative disease (EBV-LPD) of human B-cell origin, not unlike some cases of EBV-LPD that are seen in immunocompromised individuals. The role of huIL-10 or vIL-10 in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that develop EBV-LPD have significant elevation of serum huIL-10 levels compared with mice that do not develop EBV-LPD (P = .005). vIL-10 was undetectable in all animals. The EBV+ tumor samples express transcript for huIL-10 and huIL-10 receptor, express huIL-10 protein by immunohistochemical staining, and show specific binding of recombinant (r) huIL-10. In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV+ tumor cells shows that rhuIL-10 can prevent programmed cell death as well as promote proliferation and can do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 production by EBV+ tumor cells may contribute directly to their malignant outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: prevention of programmed cell death and proliferation. The implications of such findings with regard to EBV-LPD in humans is discussed.

Animals↗

Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells.

The pleiotropic effects of the Kit receptor system are mediated by Kit-Ligand (KL) induced receptor autophosphorylation and its association with and activation of distinct second messengers, including phosphatidylinositol 3'-kinase (PI3-kinase), p21ras and mitogen-activated protein kinase (MAPK). To define the role of PI3-kinase, p21ras and MAPK in Kit-mediated cell proliferation, survival and adhesion in bone marrow-derived mast cells (BMMC), mutant Kit receptors were expressed in Wsh/Wsh BMMC lacking endogenous c-kit expression. The introduction of both murine Kit(S) and KitL (isoform containing a four amino acid insert) into Wsh/Wsh BMMC restored KL-induced proliferation, survival and adhesion to fibronectin, as well as activation of PI3-kinase, p21ras and MAPK, and induced expression of c-fos, junB, c-myc and c-myb mRNA. Substitution of tyrosine 719 in the kinase insert with phenylalanine (Y719F) abolished PI3-kinase activation, diminished c-fos and junB induction, and impaired KL-induced adhesion of BMMC to fibronectin. In addition, the Y719F mutation had partial effects on p21ras activation, cell proliferation and survival, while MAP kinase activation was not affected. On the other hand, Y821F substitution impaired proliferation and survival without affecting PI3-kinase, p21ras and MAPK activation, and induction of c-myc, c-myb, c-fos and c-jun mRNA, while KL-induced cell adhesion to fibronectin remained intact. In agreement with a role for PI3-kinase in Kit-mediated cell adhesion, wortmannin blocked Kit-mediated cell adhesion at concentrations known to specifically inhibit PI3-kinase. We conclude, that association of Kit with p85PI3-K, and thus with PI3-kinase activity, is necessary for a full mitogenic as well as adhesive response in mast cells. In contrast, tyrosine 821 is essential for Kit-mediated mitogenesis and survival, but not cell adhesion.

Animals↗