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Biomedical subjects

C Tan

Publications and source records attributed to C Tan.

At least 19 recordsLinked to original sources
PubMed2000

Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars.

The antioxidant potential of eight clingstone peach cultivars was investigated by determining phenolic compounds and inhibition of low-density lipoprotein (LDL) oxidation. Cultivars low in polyphenol oxidase (PPO) were also selected to minimize enzymatic browning. Inhibition of LDL oxidation varied from 17.0 to 37.1% in peach flesh extract, from 15.2 to 49.8% in whole peach extract, and from 18.2 to 48.1% in peel extract. Total phenols were 432.8-768.1 mg/kg in flesh extract, 483.3-803.0 mg/kg in whole extract, and 910.9-1922.9 mg/kg in peel extract. The correlation coefficient between relative LDL antioxidant activity and concentration of total phenols was 0.76. Peel PPO activity was higher than flesh activity in most cultivars. The lowest PPO and specific activities were found in the Walgant cultivar, followed by Kakamas and 18-8-23. These three cultivars combine the desirable characteristics of strong antioxidant activity, low PPO activity, and lower susceptibility to browning reactions.

Antioxidants↗
PubMed2000

Inhibition of RNA polymerase I transcription in differentiated myeloid leukemia cells by inactivation of selectivity factor 1.

Transcription by RNA polymerase I (pol I) regulates the rate of ribosome biogenesis and the biosynthetic potential of the cell; therefore, it plays an important role in the control of cell growth. Differentiation of the human promyelocytic leukemic cell line U937 is accompanied by drastic decreases in pol I transcriptional activity. We have used cell-free extracts prepared from undifferentiated and differentiated U937 cells to investigate the molecular mechanisms responsible for this inhibitory process. Our analysis indicates that the activity of the TATA binding protein (TBP)/TBP-associated factor (TAF) complex selectivity factor 1 (SL1), one of the factors required for accurate and promoter-specific transcription by RNA pol I, is severely repressed in differentiated U937 cells. Moreover, the reduction in SL1 activity is not a consequence of a decrease in SL1, because there is no detectable difference in the abundance of TBP or TAFs before and after U937 cell differentiation. In conclusion, our results indicate that the selectivity factor SL1 is an important target for the regulation of pol I transcription during cell differentiation.

Cell Differentiation↗
PubMed1999

Gonadal function in young patients successfully treated for Hodgkin disease.

BACKGROUND: Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience. PROCEDURE: Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males). RESULTS: All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children. CONCLUSIONS: The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.

Adolescent↗
PubMed1999

Multicenter open-label sertraline study in adolescent outpatients with major depression.

OBJECTIVE: The aim of this multicenter outpatient study was to assess the therapeutic benefits, response patterns, and safety of sertraline in adolescent major depressive disorder (MDD). METHOD: Fifty-three adolescent outpatients with MDD were treated in an open-label, 10-week, acute-phase trial with sertraline and, if responders, for an additional 12-week continuation phase. Diagnostic and response assessments included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), 17-item K-SADS-derived depression severity score, Hamilton Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression Scale. RESULTS: By 2 weeks, when analyzed as continuous variables, all severity scores showed significant differences from baseline. This pattern persisted through 10 weeks, with a significantly greater response occurring when treatment was extended from 6 to 10 weeks. Both clinician- and patient-rated improvement was maintained during continuation treatment. Response rates varied considerably when depression rating scales were analyzed categorically. Sertraline was generally well tolerated and did not induce manic symptoms. CONCLUSIONS: In open treatment of adolescent MDD with sertraline, significant improvement occurred early on and was maintained for 22 weeks. Absolute response rates varied depending on the rating scales used, definition of response, and length of treatment. Maximal response rates were obtained by clinician-defined ratings after 10 weeks of treatment.

Adolescent↗
PubMed1999

Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependent manner.

Integrin-mediated interactions of cells with components of the extracellular matrix regulate cell survival, cell proliferation, cell differentiation, and cell migration. Some of these physiological responses are regulated via activation of transcription factors such as activator protein 1 (AP-1). Integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase whose activity is rapidly and transiently stimulated by cell-fibronectin interactions as well as by insulin stimulation. ILK activates protein kinase B and inhibits the glycogen synthase kinase 3 (GSK-3) activity in a phosphatidylinositol-3-kinase (PI 3-kinase)-dependent manner. We now show that cell adhesion to fibronectin results in a rapid and transient stimulation of AP-1 activity. At the same time, the kinase activity of ILK is stimulated whereas that of GSK-3 is inhibited. This fibronectin-dependent activation of AP-1 activity is inhibited in a dose-dependent manner if the cells are transfected with wild-type GSK-3, and also by inhibitors of PI 3-kinase. Stable or transient overexpression of ILK results in a stimulation of AP-1 activity which is inhibited by cotransfection with wild-type GSK-3 and kinase-deficient ILK. Transient transfection of ILK in HEK-293 cells stimulates complex formation between an AP-1 consensus oligonucleotide and nuclear proteins containing c-jun. The formation of this complex is inhibited by cotransfection with active GSK-3 or kinase-deficient ILK, suggesting that ILK may regulate AP-1 activation by inhibiting GSK-3, which has previously been shown to be a negative regulator of AP-1. In the presence of serum, ILK has no effect on the phosphorylation of Ser-73 in the N-terminal transactivation domain of c-jun. These results demonstrate a novel signaling pathway for the adhesion-mediated stimulation of AP-1 transcriptional activity involving ILK and GSK-3 and the subsequent regulation of the c-jun-DNA interaction.

Animals↗
PubMed1998

Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase.

Integrin-linked kinase (ILK) is an ankyrin-repeat containing serine-threonine protein kinase capable of interacting with the cytoplasmic domains of integrin beta1, beta2, and beta3 subunits. Overexpression of ILK in epithelial cells disrupts cell-extracellular matrix as well as cell-cell interactions, suppresses suspension-induced apoptosis (also called Anoikis), and stimulates anchorage-independent cell cycle progression. In addition, ILK induces nuclear translocation of beta-catenin, where the latter associates with a T cell factor/lymphocyte enhancer-binding factor 1 (TCF/LEF-1) to form an activated transcription factor. We now demonstrate that ILK activity is rapidly, but transiently, stimulated upon attachment of cells to fibronectin, as well as by insulin, in a phosphoinositide-3-OH kinase [Pi(3)K]-dependent manner. Furthermore, phosphatidylinositol(3,4,5)trisphosphate specifically stimulates the activity of ILK in vitro, and in addition, membrane targetted constitutively active Pi(3)K activates ILK in vivo. We also demonstrate here that ILK is an upstream effector of the Pi(3)K-dependent regulation of both protein kinase B (PKB/AKT) and glycogen synthase kinase 3 (GSK-3). Specifically, ILK can directly phosphorylate GSK-3 in vitro and when stably, or transiently, overexpressed in cells can inhibit GSK-3 activity, whereas the overexpression of kinase-deficient ILK enhances GSK-3 activity. In addition, kinase-active ILK can phosphorylate PKB/AKT on serine-473, whereas kinase-deficient ILK severely inhibits endogenous phosphorylation of PKB/AKT on serine-473, demonstrating that ILK is involved in agonist stimulated, Pi(3)K-dependent, PKB/AKT activation. ILK is thus a receptor-proximal effector for the Pi(3)K-dependent, extracellular matrix and growth factor mediated, activation of PKB/AKT, and inhibition of GSK-3.

Amino Acid Sequence↗
PubMed1998

Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes.

Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8(+) lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.

Animals↗
PubMed1998

Covalent binding of carbamazepine reactive metabolites to P450 isoforms present in the skin.

Carbamazepine is an anticonvulsant associated with a high risk for severe cutaneous reactions. Upon metabolism by cytochrome P450, carbamazepine may produce reactive metabolites. We evaluated in vitro the covalent binding of carbamazepine reactive metabolites on human P450s and then the presence of these P450s in human epidermis. Carbamazepine reactive metabolites covalent binding to human liver microsomes involved P450 subfamilies 1A, 2C and 3A. Specific covalent binding to yeasts expressing different P450s showed that carbamazepine reactive metabolites bound specifically to P450 1A2 and 3A4. We confirmed the constitutive presence of P450 3A in human epidermis and after induction with coaltar of P450 1A. Consequently, the production in epidermis of carbamazepine reactive metabolites is theoretically possible with formation of P450 adduct metabolites.

Adult↗
PubMed1998

Unusual features of the Drosophila melanogaster telomere transposable element HeT-A are conserved in Drosophila yakuba telomere elements.

HeT-A was the first transposable element shown to have a bona fide role in chromosome structure, maintenance of telomeres in Drosophila melanogaster. HeT-A has hallmarks of non-long-terminal-repeat (non-LTR) retrotransposable elements but also has several unique features. We have now isolated HeT-A elements from Drosophila yakuba, showing that the retrotransposon mechanism of telomere maintenance predates the separation of D. melanogaster and D. yakuba (5-15 million years ago). HeT-A elements from the two species show significant sequence divergence, yet unusual features seen in HeT-Amel are conserved in HeT-Ayak. In both species, HeT-A elements are found in head-to-tail tandem arrays in telomeric heterochromatin. In both species, nearly half of the HeT-A sequence is noncoding and shows a distinctive imperfect repeat pattern of A-rich segments. Neither element encodes reverse transcriptase. The HeT-Amel promoter appears to be intermediate between the promoters of non-LTR and of LTR retrotransposons. The HeT-Ayak promoter shows similar features. HeT-Amel has a frameshift within the coding region. HeT-Ayak does not require a frameshift but shows conservation of the polypeptide sequence of the frameshifted product of D. melanogaster.

Animals↗
PubMed1998

Structuring a safer donor-replacement program.

BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new-donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors.

Blood Donors↗
PubMed1998

Trabeculectomy survival with and without intra-operative 5-fluorouracil application in an Asian population.

PURPOSE: To define and compare the trabeculectomy survival with regard to intra-ocular pressure (IOP) control without further surgery or anti-glaucoma medication n an Asian population. METHODS: A retrospective review of two consecutive groups of patients who had trabeculectomy surgery in a university eye department setting. The first group of patients (group A) did not receive any adjunctive 5-fluorouracil (5-FU), while the second group (group B) had intra-operative sponge application of 5-FU. Only the first trabeculectomy of patients who had bilateral trabeculectomy and the first trabeculectomy performed in patients who had repeated surgery was analysed. Combined procedures were excluded. Survival analysis was performed using the Kaplan-Meier product limit method. RESULTS: Eighty-nine patients (51 in group A and 38 in group B) were studied, with a mean follow up of 37.5 and 27.0 months, respectively (P = 0.014). There were no statistical differences in age, gender, mean pretreatment IOP, pre-operative medication, proportion of patients with previous ocular surgery, or proportion of primary compared with secondary glaucoma between the two groups. The probability of trabeculectomy survival (IOP < 22 mmHg without additional medication/surgery) at 12 and 36 months was 54.3 and 36.4%, respectively, in group A and 75.8 and 65.8%, respectively, in group B. The differences in survival were significant (P = 0.006, log rank test). CONCLUSIONS: Our experience with trabeculectomy survival in the Asian population showed poorer success when compared with Caucasian populations reported by other investigators. The survival of trabeculectomy surgery was improved significantly with intra-operative 5-FU. There may be justification for advocating a more liberal use of intra-operative 5-FU in such a population.

Administration, Topical↗
PubMed1998

Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.

Wnts are secreted signaling molecules implicated in a large number of developmental processes. Frizzled proteins have been identified as likely receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for vertebrate frizzleds has not yet been defined. To assess the endogenous role of frizzled proteins during vertebrate development, we have identified and characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep cells of the Spemann organizer prior to dorsal lip formation and in the early involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to complete secondary axis formation and can synergize with Xwnt-8 while an inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal cells has profound effects on morphogenesis during gastrulation and neurulation that result in dramatic shortening of the anterior-posterior axis. Our results suggest a role for xfz8 in morphogenesis during the gastrula stage of embryogenesis.

Amino Acid Sequence↗
PubMed1998

Effect of nickel chloride on mouse T-lymphocyte subsets.

The study was carried out to observe the effect of nickel chloride (NiCl2) on T-lymphocyte subsets, CD4, CD8 and CD4/CD8 ratios in vivo. BALB/C mice were injected i.p. with NiCl2 every other day for 2 w. The NiCl2 doses were 1, 3, 6, 9 or 12 mg/kg. Lymphocytes were obtained from mouse spleen and cultured in the presence of monoclonal antibody FITC conjugated, anti-CD4 or anti-CD8. Samples were determined with a flow cytometer. A suppressive effect on CD4-positive cells was found in the 6 mg/kg group, but this subset was restored to the control level in the 9 and 12 mg/kg groups, suggesting that there was an "immune tolerance" effect. No significant changes were found in CD8-positive cells and CD4/CD8 ratios. The results suggested the NiCl2 had a deleterious effect on mouse T-lymphocytes in short-term in vivo exposure, but the effects may depend on the dose and cell subset.

Animals↗
PubMed1998

Discharge planning in a community hospital--a multidisciplinary approach.

The population of Singapore is ageing rapidly. Acute hospitals in Singapore are also experiencing an acute bed shortage. However, many elderly admitted to acute hospitals require a longer period of convalescence before they are able to go home. Community hospitals are most suitable to provide such care for the elderly patient. Patients could be discharged to the community hospitals to continue rehabilitation and convalescence. In addition this would also free the beds in the acute hospitals. However, there is a risk that without adequate discharge planning, the community hospitals would in turn also reach full capacity and no longer be able to accept patients. A discharge planning programme has been set up in a community hospital to address the following needs: 1) caring for a rapidly ageing population with increasing degrees of disability; 2) the shortage of beds in the acute hospitals; (3) the provision of holistic care and care-giver education, and 4) to prevent long term institutionalisation of the elderly as much as possible.

Aged↗
PubMed1997

Recombinant retroviruses pseudotyped with the vesicular stomatitis virus G glycoprotein mediate both stable gene transfer and pseudotransduction in human peripheral blood lymphocytes.

It is essential for the study of T-cell function and the improvement of adoptive cell therapies to efficiently generate large populations of human primary T cells that reliably express foreign genes. This goal is achieved by using recombinant retroviruses pseudotyped with either the gibbon ape leukemia virus (GaLV) envelope or the vesicular stomatitis virus G (VSV-G) glycoprotein. We show here that both retroviral particles mediate stable gene transfer in CD4+ and in CD8+ peripheral blood lymphocytes cultured under optimized conditions. However, VSV-G-pseudotyped virions may cause transduction artifacts that must be carefully excluded. The VSV-G virions require 10- to 100-fold higher concentrations of infectious particles to achieve levels of gene transfer comparable to GaLV-virions. Nonetheless, the physical stability of VSV-G-coated particles enables the concentration of viral stocks to 10(9) infectious particles per milliliter or more.

3T3 Cells↗
PubMed1997

Molecular cloning and characterization of a new receptor for galanin.

Galanin (GAL) is a widely distributed neuropeptide with diverse biological effects including modulation of hormone release, antinociception and modification of feeding behavior. Its effects are mediated through G-protein-coupled receptors (GPCR) for which only a single type has been cloned, GAL receptor 1 (GALR1). We describe the cloning of a second galanin receptor type, GALR2, from rat hypothalamus. The GALR2 amino acid sequence is 38% identical to GALR1 and is pharmacologically similar to GALR1 when expressed in COS-7 cells. GALR2 is encoded by a single gene containing at least one intron and expressed in a diverse range of tissues.

Amino Acid Sequence↗