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Biomedical subjects

K B Tan

Publications and source records attributed to K B Tan.

At least 19 recordsLinked to original sources
PubMed2006

Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression.

BACKGROUND: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. METHODS: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14. RESULTS: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated. CONCLUSION: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.

Adult↗
PubMed2005

Metastatic testicular carcinoma from the colon with clinical, immunophenotypical, and molecular characterization: report of a case.

We report a case of testicular metastasis from a colonic adenocarcinoma. The presentation of testicular metastasis, diagnosis, management, and possible modes of spread are reported. In addition to conventional investigations and histopathologic techniques, a molecular study of the testicular metastasis and colon primary, using microsatellite analysis, was performed to confirm the primary origin. Its potential uses are discussed.

Aged↗
PubMed2004

Uncommon benign intrascrotal tumours.

INTRODUCTION: Benign intrascrotal tumours are rare. CLINICAL PICTURE: Three patients with bilateral paratesticular leiomyomas, an adenomatoid tumour of the testis and a left paratesticular dermoid cyst coexisting with a synchronous left paratesticular epidermal cyst are presented. These tumours were discrete, hard and smooth lesions, in which the diagnosis of malignancy could not be safely excluded preoperatively even with ultrasonography. TREATMENT AND OUTCOME: The first patient had orchiectomy with contralateral testicular preserving surgery, the second patient underwent orchiectomy and the third had conservative testicular surgery. CONCLUSION: Awareness of these benign tumours may allow for testicular preservation.

Adenomatoid Tumor↗
PubMed2003

Cervical cytology: an audit in a Singapore teaching hospital.

OBJECTIVES: To describe the cervical cytology diagnoses and cyto-histological correlation in the Department of Pathology, National University of Singapore in 1997 and to compare the data with international figures. METHODS: A database search of all cervical cytology cases diagnosed in the department in 1997 as well as follow-up biopsies was carried out. The data was then critically analysed. RESULTS: 10,207 cases were reviewed. 96% of the cases had a diagnosis of "negative". Under 1% of cases were labelled as "inadequate". "Atypia" was diagnosed in 1% and dysplasia and/or malignancy was diagnosed in 1%. These figures correlate well with international data. Of the dysplasia cases, 78% were followed by biopsy. Of the high-grade dysplasia cases that were biopsied, 97% of the biopsy diagnoses were within the acceptable concordance range with the cytology diagnoses and in only 3% was there a significant discrepancy. Of the cases diagnosed as atypia, 39% were subsequently biopsied at the same institution as the next procedure and only one showed high grade dysplasia. A total of six cases showed a significant discrepancy between the cervical cytology result and the subsequent biopsy diagnosis and these were reviewed to elucidate the reasons for the discrepancies. CONCLUSION: The cervical cytology service is of a high diagnostic standard. A subset of patients is probably being prematurely biopsied and may benefit from having a repeat smear instead. Specific clinical protocols regarding subsequent therapy following cytology results and closer cyto-histological correlation are two main areas where the cytology service can be improved.

Biopsy↗
PubMed2002

Audit of transthoracic fine needle aspiration of the lung: cytological subclassification of bronchogenic carcinomas and diagnosis of tuberculosis.

INTRODUCTION: Transthoracic fine-needle aspiration cytology (FNAC) is a useful tool for evaluating neoplastic and inflammatory lung nodules. In view of the relative paucity of published audit studies regionally, such a study was undertaken to assess the use of the technique in our centre. METHODS: One hundred and fourteen FNACs were performed during 1997-1999. Immediate assessment for specimen adequacy was done. Diagnoses were correlated with clinical-pathological information and selective blind review performed. RESULTS: Cytologically, 65.8% of cases were malignant, 1.8% were atypical, 25.4% were inflammatory/non-malignant and 7% were inadequate. Cytological-histological tumour diagnostic concordance was 94.4%. Diagnostic sensitivity for malignancy: 93.4%, specificity: 95.8%, accuracy: 94%. Eight inadequate/ benign cases (7%) proved to be malignant with clinical-pathological follow-up. Tuberculosis was confirmed (acid-fast bacilli detected) in six cases (5.3%) and suggested in a further 10 cases (8.8%). The cytological review showed 96% concordance with the original benign/malignant diagnoses. Pneumothorax rate was 18%. CONCLUSION: FNAC is an accurate and safe method for the evaluation of lung nodules and it enables subclassification of bronchogenic carcinomas in the vast majority of cases. It is also useful for the diagnosis of tuberculous pulmonary nodules. Immediate assessment optimises specimen adequacy; inadequate/non-malignant smears in particular, need clinical correlation, close follow-up and re-biopsy, if necessary.

Adolescent↗
PubMed2001

Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study.

The diverse biological actions of extracellular nucleotides in tissues and cells are mediated by two distinct classes of P2 receptor, P2X and P2Y. The G protein-coupled P2Y receptors comprise at least six mammalian subtypes (P2Y(1,2,4,6,11,12)), all of which have been cloned from human tissues, as well as other species. The P2Y receptor subtypes differ in their pharmacological selectivity for various adenosine and uridine nucleotides, which overlap in some cases. Data concerning the mRNA expression patterns of five P2Y receptors (P2Y(1,2,4,6,11)) in different human tissues and cells are currently quite limited, while P2Y mRNA distribution in the human brain has not previously been studied. In this study, we have addressed this deficiency in receptor expression data by using a quantitative reverse transcription-polymerase chain reaction approach to measure the precise mRNA expression pattern of each P2Y receptor subtype in a number of human peripheral tissues and brain regions, from multiple individuals, as well as numerous human cell lines and primary cells. All five P2Y receptors exhibited widespread yet subtype-selective mRNA expression profiles throughout the human tissues, brain regions and cells used. Our extensive expression data indicate the many potentially important roles of P2Y receptors throughout the human body, and will help in elucidating the physiological function of each receptor subtype in a wide variety of human systems.

Actins↗
PubMed2001

Pseudo-outer product based fuzzy neural network fingerprint verification system.

Fingerprint identification has been used in law enforcement applications over the last century, and has become the de facto international standard for positive identification. With the emergence of automated fingerprint identification technologies, it has assisted in making the once labour-intensive process of classifying, searching and matching a thing of the past. As a biometrics proof of identification, not many have ventured into the world of fingerprint identification using fuzzy neural networks. In this paper, a database of fingerprint images is constructed and a fuzzy neural network called the pseudo outer product fuzzy neural network (POPFNN) [Zhou, R.W. & Quek, C. (1996). A pseudo outer-product based fuzzy neural network. Neural Networks, 9(9), 1569-1581] is trained to detect similarity between two fingerprints and decide whether they belong to the same person. The fundamental idea is that, given a person's fingerprints taken under different conditions, the POPFNN based fingerprint verification system should be sufficiently robust to distinguish the difference. The people providing the fingerprint samples are subjected to different 'adverse' conditions; from wetness to chemical treatments. Fingerprint images are taken after conditions such as: after a shower, holding pineapples (mild acid from fruit), after washing one's hands, etc. The characteristics of POPFNN, such as the learning, generalisation, and high computational abilities, make fingerprint verification particularly powerful when verifying authentic fingerprints subjected to external conditions and recognising spurious ones. In order to demonstrate the efficacy of POPFNN and its application in the fingerprint verification system (FVS), several types of experiments have been designed and implemented in this work. The experimental results and analysis are presented at the end of the paper for discussion.

Algorithms↗
PubMed2001

On-line computerized diagnosis of pain-related disability and psychological status of TMD patients: a pilot study.

Temporomandibular disorders (TMD) is a collective term embracing a number of clinical problems, which involve the masticatory musculature, the temporomandibular joint or both. Virtually all theories dealing with the aetiology and treatment of TMD have recognized the importance of psychological factors. This paper reports the development of a computerized on-line program (NUS TMD v1.1) for the diagnosis of pain-related disability and psychological status of TMD patients based on Axis II of the research diagnostic criteria (RDC)/TMD (Dworkin, S.F. & LeResche, L. 1992. Journal of Craniomandibular Disorders: Facial Oral Pain, 6, 301), which was developed to redress the lack of diagnostic criteria in TMD research. Methods adopted by RDC/TMD for use in assessing Axis II status include a seven-item questionnaire for grading chronic pain severity, the Symptom Checklist 90 Revised (SCL-90-R) and a jaw disability checklist. A pilot study, based on 37 new TMD patient records, was conducted to study the pain-related disability and psychological status of TMD patients using this newly developed program. The mean age of the predominantly Chinese population (86.5%) was 32.19 years (range 20-72 years) with a sex distribution of 24 females and 13 males. Most patients (78%) had low disability, with 12 patients having low intensity and 17 patients having high intensity pain. Approximately 73% of the sample population were moderately or severely depressed. Patients that were moderately and severely depressed had significantly higher scores for limitation related to mandibular functioning than normal patients. The three most frequent jaw disabilities were: eating hard foods (84%), yawning (78%) and chewing (65%).

Activities of Daily Living↗
PubMed2001

Application of finite element analysis in implant dentistry: a review of the literature.

Finite element analysis (FEA) has been used extensively to predict the biomechanical performance of various dental implant designs as well as the effect of clinical factors on implant success. By understanding the basic theory, method, application, and limitations of FEA in implant dentistry, the clinician will be better equipped to interpret results of FEA studies and extrapolate these results to clinical situations. This article reviews the current status of FEA applications in implant dentistry and discusses findings from FEA studies in relation to the bone-implant interface, the implant-prosthesis connection, and multiple-implant prostheses.

Biomechanical Phenomena↗
PubMed2001

Cloning, expression, and pharmacological characterization of a novel human histamine receptor.

Using a genomics-based reverse pharmacological approach for screening orphan G-protein coupled receptors, we have identified and cloned a novel high-affinity histamine receptor. This receptor, termed AXOR35, is most closely related to the H3 histamine receptor, sharing 37% protein sequence identity. A multiple responsive element/cyclic AMP-responsive element-luciferase reporter assay was used to identify histamine as a ligand for AXOR35. When transfected into human embryonic kidney 293 cells, the AXOR35 receptor showed a strong, dose-dependent calcium mobilization response to histamine and H3 receptor agonists including imetit and immepip. Radioligand binding confirmed that the AXOR35 receptor was a high-affinity histamine receptor. The pharmacology of the AXOR35 receptor was found to closely resemble that of the H3 receptor; the major difference was that (R)-alpha-methylhistamine was a low potency agonist of the AXOR35 receptor. Thioperamide is an antagonist at AXOR 35. Expression of AXOR35 mRNA in human tissues is highest in peripheral blood mononuclear cells and in tissues likely to contain high concentrations of blood cells, such as bone marrow and lung. In situ hybridization analysis of a wide survey of mouse tissues showed that mouse AXOR35 mRNA is selectively expressed in hippocampus. The identification and localization of this new histamine receptor will expand our understanding of the physiological and pathological roles of histamine and may provide additional opportunities for pharmacological modification of these actions.

Amino Acid Sequence↗
PubMed2000

Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor.

Opiate tolerance and dependence are major clinical and social problems. The anti-opiate neuropeptides FF and AF (NPFF and NPAF) have been implicated in pain modulation as well as in opioid tolerance and may play a critical role in this process, although their mechanism of action has remained unknown. Here we describe a cDNA encoding a novel neuropeptide Y-like human orphan G protein-coupled receptor (GPCR), referred to as HLWAR77 for which NPAF and NPFF have high affinity. Cells transiently or stably expressing HLWAR77 bind and respond in a concentration-dependent manner to NPAF and NPFF and are also weakly activated by FMRF-amide (Phe-Met-Arg-Phe-amide) and a variety of related peptides. The high affinity and potency of human NPFF and human NPAF for HLWAR77 strongly suggest that these are the cognate ligands for this receptor. Expression of HLWAR77 was demonstrated in brain regions associated with opiate activity, consistent with the pain-modulating activity of these peptides, whereas the expression in adipose tissue suggests other physiological and pathophysiological activities for FMRF-amide neuropeptides. The discovery that the anti-opiate neuropeptides are the endogenous ligands for HLWAR77 will aid in defining the physiological role(s) of these ligands and facilitate the identification of receptor agonists and antagonists.

Amino Acid Sequence↗
PubMed2000

Identification of an EDG7 variant, HOFNH30, a G-protein-coupled receptor for lysophosphatidic acid.

We have identified a cDNA, designated HOFNH30, which encodes a 354 amino acid G-protein-coupled receptor (GPCR). This receptor has 96% amino acid identity to the Jurkat-T cell-derived EDG7 and could be a splice variant. RT-PCR analysis demonstrated that HOFNH30 mRNA is expressed in placenta whereas EDG7 mRNA shows highest expression in prostate. The HOFNH30 gene is localized to human chromosome 1p22. 3-1p31.1. When HOFNH30 was expressed in RBL-2H3 cells, LPA and phosphatidic acid (PA) induced a calcium mobilization response with EC(50) values of 13 nM and 3 microM, respectively. LPA also induced phosphorylation of mitogen-activated protein kinase (p42(MAPK) and p44(MAPK)) in HOFNH30-transfected but not vector-transfected RBL-2H3 cells. In the present study, we have identified a novel variant from the EDG receptor family, a GPCR for which LPA is a high-affinity endogenous ligand.

Amino Acid Sequence↗
PubMed2000

Influence of water exposure on three-body wear of composite restoratives.

The objective of this investigation was to study the influence of water exposure on the three-body wear of composite restoratives. A three-body wear instrumentation was used to investigate the wear resistance of five composite restoratives [Silux Plus (SX), Z100 (ZO), Ariston pHc (AR), Surefil (SF) and Tetric Ceram (TC)] with and without exposure to water. An amalgam alloy [Dispersalloy (DA)] was used as control. Ten specimens were made for each material. The specimens were conditioned in artificial saliva at 37 degrees C for 24 h and randomly divided into two groups of 5. The first group was subjected to wear testing immediately after the 24 h conditioning period, while the second group was conditioned in distilled water at 37 degrees C for 7 days prior to wear testing. All materials were wear tested at 15 N contact force against SS304 counter-bodies for 20,000 cycles with millet seed slurry as third-body. Wear depth (microm) was measured using profilometry, and results were analyzed by ANOVA/Scheffe's and independent sample t-tests at significance level 0.05. Ranking of wear resistance was as follows: without water exposure: DA > ZO > SF > AR > SX > TC; with water exposure: DA > ZO > SX > SF > AR > TC. Wear factor ranged from 2.20 for ZO to 7.13 for TC without water exposure and from 46.00 for ZO to 143.00 for TC with exposure to water. Exposure to water significantly increased three-body wear for all composite restoratives, but did not affect wear of the amalgam alloy. The effects of water exposure must be considered for the evaluation of wear in all polymeric composite restoratives.

Composite Resins↗
PubMed2000

Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils.

BACKGROUND: Eosinophils, basophils, and mast cells are believed to be the central tenet cells in allergic conditions including allergic rhinitis, asthma, and eczema. The molecular mechanisms underlying the recruitment of these cells to sites of allergic inflammation are poorly understood. OBJECTIVES: Our aim was to identify a common adhesion molecule that could potentially be responsible for mediating the recruitment of the allergic cell types to the lungs and other sites of allergy. METHODS: We have cloned a sialoadhesin molecule from a human eosinophil library with the use of expressed sequence tag technology and characterized its expression on allergic cells by the use of flow cytometry and specific mAbs. RESULTS: With the use of expressed sequence tag sequencing, we have identified a novel siglec molecule, SAF-2. SAF-2 has homology with other sialoadhesin family members (CD33 and siglec-5) and belongs to a subgroup of the Ig superfamily. SAF-2 is a 431-amino acid protein composed of 3 Ig domains with a 358-amino acid extracellular domain and a 47-amino acid tail. SAF-2 is highly restricted to eosinophils, basophils, and mast cells. Antibodies to SAF-2 do not modulate Ca(++) mobilization or chemotaxis of human eosinophils induced by eotaxin. CONCLUSION: SAF-2 is a highly restricted sialoadhesin molecule, which may be useful in the detection and/or modulation of allergic cells.

Antigens, CD↗
PubMed2000

Identification and cloning of a human urea transporter HUT11, which is downregulated during adipogenesis of explant cultures of human bone.

Bipotential cells in human trabecular bone explant cultures that express osteoblast characteristics are able to undergo adipogenesis in the presence of 3-isobutyl-1-methylxanthine plus dexamethasone (Nuttall et al. [1998] J Bone Miner Res 13:371-382). The initial studies of these bipotential cells in explant cultures have been extended to examine differential gene expression during osteoblast/adipocyte transdifferentiation. Using differential display, we have identified a gene expressed in trabecular bone explant cultures that is downregulated as these cells differentiate from an osteoblast to an adipocyte phenotype. Homology searching identified this gene as the human urea transporter HUT11. The expression and downregulation of HUT11 have been observed in multiple patient bone explant cultures. The size of the bone explant-derived HUT11 mRNA is approximately 4.4 kb, which is identical to the largest splice variant reported. In this article, we report the cloning and sequencing of this gene from primary human osteoblasts. In addition, we report tissue distribution for the bone explant-derived form of HUT11 mRNA and show a reciprocal relationship between the expression of HUT11 and the nuclear hormone receptor peroxisome proliferator-activated receptor gamma 2, which is a marker of adipocyte differentiation. Because the control of osteoblast/adipocyte transdifferentiation is unknown, selective downregulation of HUT11 during adipogenesis suggests that HUT11 expression may be a marker of the switch from an osteoblast to an adipocyte phenotype. Understanding the role of HUT11 in osteoblasts may provide insights into the mechanism controlling osteoblast and adipocyte differentiation.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth.

Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappaB and AP-1 through a TNF receptor-associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-related proteins derived from an expressed sequence tag data base. One of these, which we designated HVEM-L, specifically bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with soluble and membrane forms of both receptor and ligand. HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid protein. A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappaB-dependent transcription.

Amino Acid Sequence↗
PubMed1998

Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines.

TR2 (TNFR-related 2) is a recently identified member of the TNFR family with homology to TNFRII. We have demonstrated previously that TR2 mRNA is expressed in resting and activated human T cells and that TR2-Ig partially inhibits an allogeneic mixed leukocyte proliferation response. We now characterize TR2 further by the use of specific mAbs. Flow-cytometry analysis using TR2 mAbs confirmed that resting PBL express high levels of cell surface TR2, and that TR2 is widely expressed on all freshly isolated lymphocyte subpopulations. However, stimulation of purified T cells with either PHA or PHA plus PMA resulted in decreased surface expression within 48 h of activation before returning to resting levels at 72 h. TR2 mAbs inhibited CD4+ T cell proliferation in response to stimulation by immobilized CD3 or CD3 plus CD28 mAbs. Assay of culture supernatants by ELISA showed inhibition of TNF-alpha, IFN-gamma, IL-2, and IL-4 production, which, for IL-2 and TNF-alpha was also confirmed by intracellular cytokine staining. Furthermore, expression of activation markers on CD4+ T cells, including CD25, CD30, CD69, CD71, and OX40 (CD134), was inhibited. TR2 mAbs inhibited proliferation in a three-way MLR, and a response to soluble recall Ag, tetanus toxoid. In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers.

Animals↗