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T F Chan

Publications and source records attributed to T F Chan.

10 recordsLinked to original sources
PubMed2003

Arsenite-induced nitric oxide generation is cell cycle-dependent and aberrant in NBS cells.

Exposure to arsenic has been reported to cause DNA damage and eventually the occurrence of bladder, lung and skin cancers. A previous report has demonstrated that arsenite-induced phosphorylation of Mre11, a protein involved in the repair of DNA double strand breaks (DSBs), is M phase-dependent and requires the Nijmegen breakage syndrome (NBS) protein, NBS1 [DNA Repair 1 (2002) 137]. Furthermore, arsenite treatment arrests cells at the M phase and the cells eventually go through apoptosis [Biochemical Pharmacology 60 (2000) 771]. Here we demonstrate that arsenite treatment enhances the generation of nitric oxide (NO), and that the enhanced NO generation is dominant at the G2/M phase. Arsenite-induced NO generation is impaired in DSB repair-defective NBS cells, but not in NBS1-reconstituted NBS cells, suggesting NBS1 is required for effective NO generation. In summary, our study showed, for the first time, that arsenite-induced NO generation is cell-cycle- and NBS1-dependent.

Arsenites↗
PubMed2002

Preparation of patients for anaesthesia - achieving quality care.

Implementation of anaesthesia begins with a preoperative assessment of the surgical patient and development of an anaesthetic plan. Preparation of the patient includes the preoperative assessment, review of preoperative tests, optimisation of medical conditions, adequate preoperative fasting, appropriate premedication, and the explanation of anaesthetic risk to patients. The goals of preoperative preparation are to reduce the morbidity of surgery, to increase the quality while decreasing the cost of perioperative care, and to return the patient to desirable functioning as quickly as possible. A knowledgeable anaesthesiologist is the 'final clinical gatekeeper', who coordinates perioperative management and ensures that the patient is in the optimal state for anaesthesia and surgery.

Adult↗
PubMed2000

Regulation of APG14 expression by the GATA-type transcription factor Gln3p.

Gln3p is a nitrogen catabolite repression-sensitive GATA-type transcription factor. Its nuclear accumulation was recently shown to be under the control of TOR signaling. Gln3p normally resides in the cytoplasm. When cells are starved from nitrogen nutrients or treated with rapamycin, however, Gln3p becomes translocated into the nucleus, thereby activating the expression of genes involved in nitrogen utilization and transport. To identify other genes under the control of Gln3p, we searched for the Gln3p-binding GATAA motifs within 500 base pairs of the promoter sequences upstream of the yeast open reading frames in the Saccharomyces Genome Database. APG14, a gene essential for autophagy, was found to have the most GATAA motifs. We show that nitrogen starvation or rapamycin treatment rapidly causes a more than 20-fold induction of APG14. The expression of APG14 is dependent on Gln3p; deletion of Gln3p severely reduced its induction by rapamycin, whereas depletion of Ure2p caused its constitutive expression. However, overexpression of APG14 led to only a slight increase in autophagy in nitrogen-rich medium. Therefore, these results define a signaling cascade leading to the expression of APG14 in response to the availability of nitrogen nutrients and suggest that the regulated expression of APG14 contributes to but is not sufficient for the control of autophagy.

5' Untranslated Regions↗
PubMed2000

A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR).

The target of rapamycin protein (TOR) is a highly conserved ataxia telangiectasia-related protein kinase essential for cell growth. Emerging evidence indicates that TOR signaling is highly complex and is involved in a variety of cellular processes. To understand its general functions, we took a chemical genomics approach to explore the genetic interaction between TOR and other yeast genes on a genomic scale. In this study, the rapamycin sensitivity of individual deletion mutants generated by the Saccharomyces Genome Deletion Project was systematically measured. Our results provide a global view of the rapamycin-sensitive functions of TOR. In contrast to conventional genetic analysis, this approach offers a simple and thorough analysis of genetic interaction on a genomic scale and measures genetic interaction at different possible levels. It can be used to study the functions of other drug targets and to identify novel protein components of a conserved core biological process such as DNA damage checkpoint/repair that is interfered with by a cell-permeable chemical compound.

Cell Cycle Proteins↗
PubMed2000

Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases.

Gln3p is a GATA-type transcription factor responsive to different nitrogen nutrients and starvation in yeast Saccharomyces cerevisiae. Recent evidence has linked TOR signaling to Gln3p. Rapamycin causes dephosphorylation and nuclear translocation of Gln3p, thereby activating nitrogen catabolite repressible-sensitive genes. However, a detailed mechanistic understanding of this process is lacking. In this study, we show that Tor1p physically interacts with Gln3p. An intact TOR kinase domain is essential for the phosphorylation of Gln3p, inhibition of Gln3p nuclear entry and repression of Gln3p-dependent transcription. In contrast, at least two distinct protein phosphatases, Pph3p and the Tap42p-dependent phosphatases, are involved in the activation of Gln3p. The yeast pro-prion protein Ure2p binds to both hyper- and hypo-phosphorylated Gln3p. In contrast to the free Gln3p, the Ure2p-bound Gln3p is signifcantly resistant to dephosphorylation. Taken together, these results reveal a tripartite regulatory mechanism by which the phosphorylation of Gln3p is regulated.

DNA-Binding Proteins↗
PubMed2000

TOR signaling regulates microtubule structure and function.

The functional diversity and structural heterogeneity of microtubules are largely determined by microtubule-associated proteins (MAPs) [1] [2]. Bik1p (bilateral karyogamy defect protein) is one of the MAPs required for microtubule assembly, stability and function in cell processes such as karyogamy and nuclear migration and positioning in the yeast Saccharomyces cerevisiae [3]. The macrocyclic immunosuppressive antibiotic rapamycin, complexed with its binding protein FKBP12, binds to and inhibits the target of rapamycin protein (TOR) in yeast [4] [5]. We report here that TOR physically interacts with Bik1p, the yeast homolog of human CLIP-170/Restin [6] [7]. Inhibition of TOR by rapamycin significantly affects microtubule assembly, elongation and stability. This function of TOR is independent of new protein synthesis. Rapamycin also causes defects in spindle orientation, nuclear movement and positioning, karyogamy and chromosomal stability, defects also found in the bikDelta mutant. Our data suggest a role for TOR signaling in regulating microtubule stability and function, possibly through Bik1p.

Fungal Proteins↗
PubMed1997

Radiofrequency catheter ablation of left-sided accessory pathways using a transeptal technique and specialized long intravascular sheaths. Efficacy, recurrence rate and complications.

49 patients with 51 left-sided accessory pathways underwent radiofrequency catheter ablation for symptomatic supraventricular tachycardia via the transeptal route using specialised long vascular sheaths with compound curves. The procedure was successful in 45 patients (92%). The mean fluroscopic time was 22.5 +/- 15.2 mins and the mean procedure time was 1.7 +/- 0.5 hours. Pericardial tamponade occurred in 2 patients (4%) and 2 patients (4%) required switching to the retrograde transaortic route for successful ablation of the pathways. During the period of follow-up of 16.8 +/- 6.9 months, clinical recurrence occurred in 2 patients (4%). In conclusion, the transeptal route of radiofrequency catheter ablation is a useful alternative strategy to the transaortic approach with good long term results. The use of specialised sheaths may help in stabilisation of the catheter during the procedure which can generate more adequate lesions and consequently a lower recurrence rate.

Adolescent↗
PubMed1996

Is there psychopathology in the coparents of schizophrenic adoptees' half-siblings?

An excess of schizophrenia has been observed in the biological relatives of adoptees with schizophrenia. The present analysis examined the possibility that illness observed among 90 half-siblings may have been influenced by assortative mating resulting in excess illness in the biological parents of the half-siblings not biologically related to the adoptees (the coparents). We found no difference in the prevalence of mental illness between 44 index and 26 control coparents.

Adoption↗
PubMed1995

The variation of radon exhalation rates from building surfaces of different ages.

Standardized activated charcoal canisters (according to the U.S. EPA) have been used to collect radon exhaled from concrete surfaces covered with thin plaster (categorically different from thick plaster) of 32 buildings of different ages (0.5-31 y) in Hong Kong. Concrete surfaces covered with thin plaster is the commonest wall configuration in Hong Kong. The canisters are analyzed using gamma spectroscopy to obtain the radon exhalation rates. The results show that the radon exhalation rate decreases with the building age.

Air Pollution, Indoor↗