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Biomedical subjects

Y C Lim

Publications and source records attributed to Y C Lim.

At least 19 recordsLinked to original sources
PubMed2004

Perivascular-submandibular lymph node metastasis in squamous cell carcinoma of the tongue and floor of mouth.

AIMS: The goal of this study was to investigate the incidence of occult metastasis in perivascular lymph node and nodal recurrence in these nodal pads in squamous cell carcinoma (SCC) of the tongue and floor of mouth. METHODS: We performed a prospective analysis of the incidence of an occult metastasis in the perivascular lymph nodes in 55 patients (41 with an oral tongue carcinoma and 14 with a mouth floor carcinoma) who underwent an elective supraomohyoid neck dissection (SOHND) for SCC of the tongue and floor of mouth, from 1997 to 2002. 99 SOHND procedures were performed as follows: 72 in tongue carcinomas and 27 in the mouth floor carcinomas. RESULT: Clinically occult, but pathologically positive perivascular lymph nodes occurred in four of 72 of the tongue carcinomas and two of 27 of the mouth floor carcinomas. The incidence of the regional recurrence at level I was three of 45. CONCLUSIONS: This preliminary report reveals a small incidence of perivascular lymph-node metastases and the infrequent nodal recurrence in this area after SOHND in early-staged tongue and floor of mouth SCC.

Adult↗
PubMed2001

IL-12, STAT4-dependent up-regulation of CD4(+) T cell core 2 beta-1,6-n-acetylglucosaminyltransferase, an enzyme essential for biosynthesis of P-selectin ligands.

TCR activation of naive T cells in the presence of IL-12 drives polarization toward a Th1 phenotype and synthesis of P- and E-selectin ligands. Fucosyltransferase VII (Fuc-T VII) and core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) are critical for biosynthesis of selectin ligands. P-selectin glycoprotein ligand-1 is the best characterized ligand for P-selectin and also binds E-selectin. The contributions of TCR and cytokine signaling pathways to up-regulate Fuc-T VII and C2GnT during biosynthesis of E- and P-selectin ligands, such as P-selectin glycoprotein ligand 1, are unknown. IL-12 signals via the STAT4 pathway. Here, naive DO11.10 TCR transgenic and STAT4(-/-) TCR transgenic CD4(+) T cells were stimulated with Ag and IL-12 (Th1 condition), IL-4 (Th2), or neutralizing anti-IL-4 mAb only (Th0). The levels of Fuc-T VII and C2GnT mRNA in these cells were compared with their adhesive interactions with P- and E-selectin in vitro under flow. The data show IL-12/STAT4 signaling is necessary for induction of C2GnT, but not Fuc-TVII mRNA, and that STAT4(-/-) Th1 cells do not traffic normally to sites of inflammation in vivo, do not interact with P-selectin, and exhibit a partial reduction of E-selectin interactions under shear stress in vitro. Ag-specific TCR activation in CD4(+) T cells was sufficient to trigger induction of Fuc-TVII, but not C2GnT, mRNA and expression of E-selectin, but not P-selectin, ligands. Thus, Fuc-T VII and C2GnT are regulated by different signals during Th cell differentiation, and both cytokine and TCR signals are necessary for the expression of E- and P-selectin ligands.

Animals↗
PubMed2001

Reduced expression of junctional adhesion molecule and platelet/endothelial cell adhesion molecule-1 (CD31) at human vascular endothelial junctions by cytokines tumor necrosis factor-alpha plus interferon-gamma Does not reduce leukocyte transmigration under flow.

The combination of tumor necrosis factor (TNF)-alpha plus interferon (IFN)-gamma has been shown previously to promote redistribution of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (CD31), junctional adhesion molecule (JAM), and VE-cadherin away from lateral junctions of human umbilical vein endothelial cell monolayers. In parallel, neutrophil transmigration was significantly reduced. Because PECAM-1 and JAM have been implicated in leukocyte transmigration, the observed redistribution by cytokine activation was presumed to represent the mechanism causing decreased transmigration under static conditions. The current results confirm that culture of human umbilical vein endothelial cells with TNF-alpha plus IFN-gamma caused a decrease in surface-expressed and junctional-localized JAM and PECAM-1, but did not cause decreased leukocyte transmigration in an in vitro flow assay. Furthermore, blocking monoclonal antibody to PECAM-1 still significantly reduced monocyte transmigration, demonstrating that it retains a functional role even though its levels were reduced and redistributed away from junctions, whereas a panel of monoclonal antibodies to JAM failed to reduce leukocyte transmigration. Given the alterations in junction protein location, permeability function was assessed. IFN-gamma alone or TNF-alpha plus IFN-gamma significantly increased permeability, but TNF-alpha alone did not, suggesting lack of correlation between transmigration and loss of permeability. In conclusion, cytokine activation induced loss and redistribution of PECAM-1 and JAM away from lateral junctions, but per se does not negatively regulate either neutrophil or monocyte transmigration under flow.

Cell Adhesion↗
PubMed2001

Frequency of cytochrome P450 2C9 mutant alleles in a Korean population.

AIMS: To determine the frequencies of CYP2C9 variants in the Korean population and compare them with the frequencies in other ethnic populations. METHODS: Genotyping of CYP2C9*2 and CYP2C9*3 allelic variants was carried out in 574 Korean subjects by PCR and restriction fragment length pattern analysis. RESULTS: Thirteen of 574 subjects (2.3%) were heterozygous for CYP2C9*3 (Ile359Leu), but no subjects with a CYP2C9*2 allele or homozygous for CYP2C9*3 were identified. The allele frequency of CYP2C9*3 in Korean subjects (0.0113, 95% CI 0.0066-0.0193) was similar to that of other East Asian populations, but was considerably lower than that of Caucasian populations. CONCLUSIONS: CYP2C9*3 seems to be an allelic variant related to the functional polymorphism of CYP2C9, but this variant is rarely seen among Koreans compared with Caucasians. Routine genotyping of the CYP2C9*2 allele is considered to be unnecessary in Korean and East Asians, because this allele appears to be extremely rare or absent in these populations.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Renal dysfunction in workers exposed to inorganic lead.

INTRODUCTION: We studied the relationship between renal dysfunction and occupational lead exposure in a local factory. MATERIALS AND METHODS: A cross-sectional study with a cohort component was conducted with 55 male workers of a factory producing PVC stabilisers as subjects. Workers from this factory have been followed up with 6-monthly blood lead measurements since 1982. Two indices of overall lead exposure, i.e. the number of times a worker's blood lead exceeded 40 micrograms/dL (PbB40) and cumulative blood lead index (PbBint), were obtained from this data. Recent blood lead concentration (PbB) was measured. 4-hour creatinine clearance and various other urinary and serum markers of renal dysfunction were used as effect indices. RESULTS: There was no relationship between PbB and any of the renal markers. However, creatinine clearance decreased significantly (P < 0.001) with increasing PbB40 and PbBint after adjustment for age and smoking habits. Urinary albumin (Ualb), urinary alpha-1 microglobulin (U alpha 1m), urinary beta-2 microglobulin (U beta 2m) and urinary retinol-binding protein (URBP) increased significantly with both increasing PbB40 and PbBint. Total urinary activity of N-acetyl-beta-D-glucosaminidase (NAG-T) and its heat-stable isoenzyme (NAG-B) increased significantly with increasing PbB40. A significant difference in renal parameters occurred when PbB40 was 1 or more. CONCLUSIONS: We have found a positive association between overall lead exposure and renal dysfunction. The renal parameters were significantly higher among those who had at least one episode of blood lead above 40 micrograms/dL. Our findings also strengthen the case for the use of Ualb, U alpha 1m, U beta 2m, URBP, NAG-T and NAG-B as early markers of lead nephropathy.

Adult↗
PubMed2000

C-C and C-X-C chemokines trigger firm adhesion of monocytes to vascular endothelium under flow conditions.

In summary, our findings indicate that specific chemokines that are elaborated by endothelial cells after cytokine or endotoxin activation can play an essential role in monocyte recruitment beyond their chemoattractant activities. We show that this action is to translate initial monocyte tethering into firm adhesion via rapid leukocyte integrin activation. The in vitro model presented here provides a sensitive system for investigating the modulating ability of chemokines and reveals an important biological effect that is not predicted by results in simpler in vitro assays, such as measurement of calcium transients or chemotaxis. The surprising finding that the C-X-C chemokine IL-8 can trigger monocyte firm adhesion to vascular endothelium suggests a potential role for this chemokine in monocyte recruitment and underscores the biological complexity of the chemokine family.

Cell Adhesion↗
PubMed2000

Alpha4beta1-integrin activation is necessary for high-efficiency T-cell subset interactions with VCAM-1 under flow.

OBJECTIVE: The purpose of this study was to examine the relationship between alpha4beta1-integrin state of activation on CD4+ T-cell subsets and their adhesive interaction to VCAM-1 under flow. METHODS: Human CD4+ memory and naive T-cells were freshly isolated and effector-helper T-cell subsets. Th1 and Th2 cells, were differentiated in vitro from CD4+ naive T-cells. The expression of activation/ligand induced epitopes on beta1-integrins of each T-cell subset was assessed using mAb HUTS21 and mAb 15/7. T-cell subsets attachment and rolling on VCAM-1 was determined under defined flow conditions and the rates of attachment (ka), accumulation, and instantaneous rolling velocities were correlated to their beta1-integrin activation epitope expression. RESULTS: A subset of memory T-cells constitutively express activation/ligand induced epitopes on beta1-integrins recognized by mAb HUTS21 and 15/7, whereas expression levels on naive T-cells is low or not detectable. Consistent with an activated phenotype, memory T-cells exhibit significantly higher rates of attachment and accumulation on VCAM-1 under flow as compared to naive T-cells. Interestingly, the expression of activation/ligand induced epitopes on beta1-integrins on Th2 cells and the ability of these cells to interact with VCAM-1 are comparable to memory T-cells. In contrast, Th1 cells did not interact as efficiently with VCAM-1, which correlated with lower expression of activation/ligand induced epitopes on these cells. VCAM-1 interactions are inhibited completely by pretreatment of the T-cells with blocking mAb to alpha4-integrins or beta1-integrins, indicating that alpha4beta1 is the predominant T-cell integrin involved. CONCLUSIONS: Memory T-cells express constitutively active alpha4beta1-integrins, as compared to naive T-cells, which mediate high rates of initial attachment and sustained high-affinity adhesive interactions with VCAM-1 under flow conditions in vitro. Similarly, in vitro differentiated Th2 cells but not Th1 cells, which also express elevated levels of activated alpha4beta1-integrins, are capable of sustaining high-affinity adhesive interactions with VCAM-1. The differences observed in beta1-integrin activation on T-cell subsets may underlie selective recruitment patterns of T-cell subsets in vivo.

Cell Adhesion↗
PubMed2000

Renal functional responses to centrally administered ouabain in anesthetized rabbits.

The effects of intracerebroventricularly administered ouabain on renal function were studied in rabbits. Ouabain, when given intracerebroventricularly in doses ranging from 0.1 to 10 micrograms/kg, dose-dependently produced antidiuretic, antinatriuretic and antikaliuretic effects, along with decreases in renal perfusion and glomerular filtration rate. Systemic blood pressure also increased significantly in a dose-related fashion. No increase in free water reabsorption was noted. Intravenously administered ouabain (10 micrograms/kg) caused less pronounced antidiuresis and antinatriuresis, with the renal hemodynamics tending slightly to decrease. No significant increment of systemic blood pressure with intravenous ouabain was observed. In rabbits with one kidney denervated and the contralateral left intact, ouabain 10 micrograms/kg i.c.v. produced the typical renal effects on the intact kidney, while the denervated kidney responded with prominent natriuresis and diuresis, showing the maximal response in the second 10-min period after administration. Renal nerve activity increased significantly upon administration of ouabain 10 micrograms/kg i.c.v. and reached a peak at around 10 to 20 min after drug administration, a period in which the most remarkable antidiuresis and antinatriuresis is produced by i.c.v. ouabain. These observations suggest that the antidiuresis and antinatriuresis elicited by centrally administered ouabain results mainly from the decrease of renal hemodynamics, which is caused by the increased renal nerve activity.

Anesthesia↗
PubMed2000

Cross-sectional study of near-work and myopia in kindergarten children in Singapore.

INTRODUCTION: In view of the high and increasing myopia rates amongst young Singaporean children, we aimed to assess the relationship between near-work and myopia in 414 pre-school children aged 4 to 6 years. MATERIALS AND METHODS: We measured near-work indices such as tuition classes outside school and other possible risk factors via a questionnaire. We then measured myopia with a hand-held autorefractor. RESULTS: Children who had 3 or more hours per week of near-work classes outside school had a higher rate [odds ratio 1.39 (95% confidence interval 1.02, 2.53)] of myopia. CONCLUSIONS: This suggests that there may be an association between near-work and myopia, even at such a young age. Given the increasing emphasis on near-work in Singapore, it may be important to call for increased visual health awareness, although further studies will be needed to establish if near-work causes myopia.

Age Distribution↗
PubMed1999

Acquisition of selectin binding and peripheral homing properties by CD4(+) and CD8(+) T cells.

Different T cell subsets exhibit distinct capacities to migrate into peripheral sites of inflammation, and this may in part reflect differential expression of homing receptors and chemokine receptors. Using an adoptive transfer approach, we examined the ability of functionally distinct subsets of T cells to home to a peripheral inflammatory site. The data directly demonstrate the inability of naive T cells and the ability of effector cells to home to inflamed peritoneum. Furthermore, interleukin (IL)-12 directs the differentiation of either CD4(+) or CD8(+) T cells into effector populations that expresses functional E- and P-selectin ligand and that are preferentially recruited into the inflamed peritoneum compared with T cells differentiated in the presence of IL-4. Recruitment can be blocked by anti-E- and -P-selectin antibodies. The presence of antigen in the peritoneum promotes local proliferation of recruited T cells, and significantly amplifies the Th1 polarization of the lymphocytic infiltrate. Preferential recruitment of Th1 cells into the peritoneum is also seen when cytokine response gene 2 (CRG-2)/interferon gamma-inducible protein 10 (IP-10) is used as the sole inflammatory stimulus. We have also found that P-selectin binds only to antigen-specific T cells in draining lymph nodes after immunization, implying that both antigen- and cytokine-mediated signals are required for expression of functional selectin-ligand.

Adoptive Transfer↗
PubMed1999

MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions.

Monocytes contribute to the development of atherosclerotic lesions in mouse models. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in vascular lesions. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear how it could recruit monocytes. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with vascular endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte-endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium reveals an unexpected role for this chemokine in monocyte recruitment.

Cell Adhesion↗
PubMed1999

Expression of functional selectin ligands on Th cells is differentially regulated by IL-12 and IL-4.

Immune responses may be qualitatively distinct depending on whether Th1 or Th2 cells predominate at the site of Ag exposure. T cell subset-specific expression of ligands for vascular selectins may underlie the distinct patterns of recruitment of Th1 or Th2 cells to peripheral inflammatory sites. Here we examine the regulation of selectin ligand expression during murine T helper cell differentiation. Large numbers of Th1 cells interacted with E- and P-selectin under defined flow conditions, while few Th2 and no naive T cells interacted. Th1 cells also expressed more fucosyltransferase VII mRNA than naive or Th2 cells. IL-12 induced expression of P-selectin ligands on Ag-activated naive T cells, even in the presence of IL-4, and on established Th2 cells restimulated in the presence of IL-12 and IFN-gamma. In contrast, Ag stimulation alone induced only E-selectin ligand. Interestingly, restimulation of established Th2 cells in the presence of IL-12 and IFN-gamma induced expression of P-selectin ligands but not E-selectin ligands; IFN-gamma alone did not enhance expression of either selectin ligand. In summary, functional P- and E-selectin ligands are expressed on most Th1 cells, few Th2 cells, but not naive T cells. Furthermore, selectin ligand expression is regulated by the cytokine milieu during T cell differentiation. IL-12 induces P-selectin ligand, while IL-4 plays a dominant role in down-regulating E-selectin ligand.

Animals↗
PubMed1998

Important contributions of P-selectin glycoprotein ligand-1-mediated secondary capture to human monocyte adhesion to P-selectin, E-selectin, and TNF-alpha-activated endothelium under flow in vitro.

In this study, an in vitro flow model and a blocking mAb to P-selectin glycoprotein ligand-1 (PSGL-1) were used to define the role of PSGL-1 in monocyte attachment and rolling on E- and P-selectin and in attachment and accumulation on 6-h TNF-alpha-activated HUVEC. KPL1, an adhesion-blocking mAb directed against the tyrosine sulfate motif of PSGL-1, abolished monocyte-adhesive interactions with P-selectin, but only partially blocked monocyte interaction with E-selectin. Further analysis showed that on E-selectin, KPL1 blocked only secondary (i.e., monocyte/monocyte) interactions, but did not block primary (i.e., monocyte/E-selectin) interactions, with secondary adhesion accounting for 90% of the total adhesive interactions on either E- or P-selectin. On cytokine-activated HUVEC, monocytes initially attached and formed linear strings of adherent cells, which involved both primary and secondary adhesion. PSGL-1 or L-selectin mAb reduced string formation, and the combination of PSGL-1 and L-selectin mAb prevented monocyte strings and inhibited 86% of accumulation. Monocyte attachment and rolling on purified adherent monocytes were also critically dependent on PSGL-1 on the adherent monocytes. These studies document that secondary interactions between monocytes, mediated by PSGL-1, are crucial for monocyte initial attachment, rolling, and accumulation on activated endothelium under laminar shear flow.

Animals↗
PubMed1998

Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: implications for atherogenesis.

To study the role of vascular cell adhesion molecule-1 (VCAM-1) in monocyte recruitment and atherogenesis, we constructed a recombinant adenovirus, AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previously shown that AdRSVrVCAM-1-transduced human umbilical vein endothelial cells (HUVECs) support the adhesion of CD4+ CD45RO+ memory T lymphocytes under laminar flow conditions. We now demonstrate that AdRSVrVCAM-1-transduced HUVECs support the adhesion of peripheral blood monocytes at a shear stress of < or = 1.5 dyne/cm2. Although VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate monocyte rolling, firm adhesion, and transmigration when expressed in the context of otherwise unactivated vascular endothelium. VCAM-1-transduced HUVECs supported the adhesion of as many as 4-fold more monocytes than T cells under laminar flow. The greater monocyte adhesion was explained at least in part by leukocyte-leukocyte interactions (secondary adhesions), which were not seen with T cells. These secondary monocyte interactions were specifically blocked by monoclonal antibodies to L-selectin and P-selectin glycoprotein ligand-1. These data demonstrate that VCAM-1 expressed in the context of unactivated vascular endothelium supports the adhesion of the leukocyte populations present in atherosclerotic plaque and may contribute to the predominance of monocytes over lymphocytes.

Adenoviruses, Human↗