Search PubMed⌕ Search

Biomedical subjects

T Chan

Publications and source records attributed to T Chan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Selective alteration of personality and social behavior by serotonergic intervention.

OBJECTIVE: The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans. METHOD: A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N = 26), or placebo (N = 25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment. RESULTS: Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment. CONCLUSIONS: Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.

Adult↗
PubMed1997

Dehydroepiandrosterone (DHEA) treatment of depression.

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Aged↗
PubMed1997

The role of integrins and extracellular matrix in anchorage-independent growth of a mammary carcinoma cell line.

Anchorage-independent growth is a property of malignant cells. Extracellular matrix proteins are present in tumor spheroids but their function is not clearly defined. In this paper we show that a murine mammary carcinoma cell line, SP1, which expresses the fibronectin receptor alpha 5 beta 1 requires fibronectin for anchorage-independent growth in soft agar. Growth factors (hepatocyte growth factor and transforming growth factor-beta) also promote SP1 colony growth. In contrast, collagen types I and IV have an inhibitory effect on SP1 colony growth. A clone isolated from SP1 cells which expresses the collagen/laminin receptor alpha 2 beta 1 as well as the fibronectin receptor alpha 5 beta 1, demonstrates increased colony formation in the presence of fibronectin and collagen. These data suggest a role for both the alpha 5 beta 1 and alpha 2 beta 1 integrin receptors in the regulation of anchorage-independent growth of mammary carcinoma cells.

Animals↗
PubMed1996

Bicinchoninic acid protein assay in the determination of adriamycin cytotoxicity modulated by the MDR glycoprotein.

The development of simultaneous resistance to structurally unrelated drugs in cancer cells is a major obstacle to effective cancer chemotherapy. This multidrug-resistance (MDR) phenomenon is largely attributed to overexpression of a 170 kD glycoprotein, which serves as a transmembrane efflux pump in extruding a variety of natural anticancer drugs such as vinblastine, doxorubicin, and taxol from cancer cells. It is desirable, therefore, to discover compounds that can block the efflux mechanism and thus reverse drug resistance. The bicinchoninic acid protein assay has been adapted for use in a microtiter plate, into an easy, indirect method for screening MDR efflux blockers in plant extracts. This spectrophotometric assay is used to determine the enhancement of adriamycin cytotoxicity against resistant cancer cells by plant extracts or pure compounds indirectly. We have shown that the optical density measured (amount of cellular protein present) correlates with the number of viable cells and that fluorescence of Adriamycin associated with the cell correlates with the concentrations of Adriamycin added to the media. In addition, the relative efficacy of MDR reversal by various alkaloids has been determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Abu Dhabi third stage trial: oxytocin versus Syntometrine in the active management of the third stage of labour.

OBJECTIVE: To compare the effect of oxytocin and Syntometrine when used as part of active management of third stage of labour on postpartum haemorrhage, hypertension, nausea/vomiting and retained placenta. STUDY DESIGN: A randomised double blind trial was conducted in the Obstetric Unit of Corniche Hospital, Abu Dhabi in the United Arab Emirates. Between 1 January 1991 and 30 June 1991, 2040 women were randomly allocated either to the oxytocin (n = 1017) or the Syntometrine (n = 1023) group. Twelve patients had to be excluded from the trial (oxytocin, 5; Syntometrine, 7) after randomisation because they no longer fulfilled the inclusion criteria. All women in the trial received either oxytocin 10 units or Syntometrine 1 ml (oxytocin 5 units+ergometrine (ergonovine) 0.5 mg) by intramuscular injection with delivery of the anterior shoulder of the baby. Relative risk with 95% confidence intervals was calculated for each variable. RESULTS: Oxytocin (10 units) alone was as effective as Syntometrine (1 ml) in preventing post-partum haemorrhage without an increase in the incidence of retained placenta. Median blood loss was similar in both groups. The incidences of nausea, vomiting and headache were significantly lower in the oxytocin group, as was the occurrence of a mean rise in diastolic and systolic blood pressures of 20 and 30 mmHg or more, respectively. CONCLUSION: Prophylactic administration of oxytocin 10 U in the third stage of labour, as part of active management, reduces the incidence of maternal nausea, vomiting, headache and rise in blood pressure than does Syntometrine 1 ml without adversely affecting the rate of post partum haemorrhage.

Adult↗
PubMed1995

Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers.

The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are located on chromosome 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 (CDK4) and CDK6 and control cellular proliferation by preventing entry into the S phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers. In order to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 deletion in esophageal carcinogenesis, we have now analyzed 60 primary esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and CDKN2B by direct sequencing of PCR amplified genomic DNAs. In conjunction with our previously published data, we have identified a total of eight nucleic acid substitutions among 60 esophageal carcinomas; here, we describe one new CDKN2B nonsense mutation and one new silent CDKN2B mutation that occurred somatically. Taken together, these results suggest that intragenic mutations in CDKN2A and CDKN2B occur in esophageal cancer, but that they are infrequent events. In view of the known high frequency of loss of heterozygosity at the chromosome 9p21 locus in esophageal cancers, the current data suggest that intragenic mutation is not the predominant mode of inactivation of CDKN2A and CDKN2B or that other genes are targets of deletion at this locus in these cancers.

Base Sequence↗
PubMed1994

Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Adult↗
PubMed1994

Standardisation and adaptation of the Denver Developmental Screening Test (DDST) and Denver II for use in Singapore children.

OBJECTIVE: To modify and standardise the Denver Developmental Screening Test (DDST) and Denver II for developmental screening of children in Singapore. METHOD: The study used a quota sample of 2,194 Singapore children aged 4 weeks to 6 years. Logistic regression analysis established the 25th, 50th, 75th, and 90th percentile passing age for achieving the test tasks. Subgroup differences in Sex, Ethnicity, Social Class and Mother's Education were analysed by stepwise logistic regression; the composite norms for items with statistically significant subgroup differences (p < or = 0.10), were then adjusted by weighting based on the composition of Singapore children. The study protocol was based on the DDST (1975) and Denver II (1990), the latest version of the DDST. Modifications were introduced to improve on the sensitivity of the test and to make the test more suited to Singapore culture. MAIN FINDINGS: Out of the 215 items studied, 115 items were selected to form the new test, DDST, Singapore, DDST, Singapore shares 63% of the items with DDST (1975) and 67% of the items with Denver II. Among the comparable items, differences between the norms of Singapore and Denver children greater than 10% were demonstrated in more than 30 items, and differences of greater than 20% in 10 items. Within the study sample of Singapore children, there were relatively smaller differences among the subgroups studied. Only 10 items had clinically significant subgroup differences of more than 10%. None had more than 20% difference. CONCLUSION: DDST, Singapore is substantially different from the DDST (1975) and Denver II (1990). The use of the local standardised version for developmental screening of Singapore children is justified.

Child↗
PubMed1993

3-Nitro-3,4-dihydro-2(1H)-quinolones. Excitatory amino acid antagonists acting at glycine-site NMDA and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antagonist activity. Generally poor potency at the glycine site is observed when a variety of electron-withdrawing substituents are attached to the 3-position of 3,4-dihydro-2(1H)-quinolones. The analogues 5-9 (IC50 values > 100 microM, Table I) exist largely in the 3,4-dipseudoaxial conformation (as evidenced by 1H NMR spectra), whereas the 3-cyano derivative (10, IC50 = 12.0 microM) has a relatively high population of the 3-pseudoequatorial conformer. The 3-nitro analogue (4, IC50 = 1.32 microM) has a pKa approximately 5 and thus exists at physiological pH as an anion with the nitro group planar to the quinolone ring. The general requirement of acidity for high affinity binding at the glycine/NMDA site is supported with the good activity of the other 3-nitro derivatives (13-21), all of which are deprotonated at physiological pH. The 3-nitro-3,4-dihydro-2(1H)-quinolones and 2-carboxy-1,2,3,4-tetrahydroquinolines show quite different structure-activity relationships at the 4-position. The unselective excitatory amino acid activity of 21 is comparable with 6,7-dichloro-quinoxaline-2,3-dione and 6,7-dichloroquinoxalic acid and this suggests similarities in their modes of binding to excitatory amino acid receptors. The broad spectrum excitatory amino acid antagonist activity of the 4-unsubstituted analogue 21 (KbNMDA = 6.7 microM, KbAMPA = 9.2 microM) and the glycine/NMDA selectivity of the other 3-nitro derivatives allows the proposal of a model for AMPA receptor binding which differs from the glycine binding pharmacophore in that there is bulk intolerance adjacent to the 4-position. Compound 21 (L-698,544) is active (ED50 = 13.2 mg/kg) in the DBA/2 mouse anticonvulsant model and is the most potent combined glycine/NMDA-AMPA antagonist yet reported, in vivo, and may prove to be a useful pharmacological tool.

Amino Acids↗