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Biomedical subjects

S Y Ng

Publications and source records attributed to S Y Ng.

At least 37 records · Page 2Linked to original sources

A retrospective survey of attitudes toward acceptance of peritoneal dialysis in Chinese end-stage renal failure patients in Hong Kong--from a cultural point of view.

OBJECTIVE: We undertook to study the attitudes toward dialysis of patients approaching end-stage renal failure and to analyze those attitudes from a cultural perspective. SETTING: The study was performed in the pre-dialysis clinic of a tertiary referral renal center. PATIENTS: All patients of Chinese ethnic origin seen in the pre-dialysis clinic from 1995 to 2000 for assessment of dialysis therapy were included. METHOD: We performed a retrospective analysis of patient records with regard to attitudes of the patients toward dialysis, reasons for those attitudes, and factors that could lead to a subsequent change in attitude. RESULTS: We assessed 462 patients over the 6-year period. Their mean age was 65.5 +/- 13.3 years, and 43.9% of the patients had diabetes. Peritoneal dialysis (PD) was offered to 74% of the patients, and hemodialysis (HD) to 3.9%. Among the patients offered PD, only 44% accepted dialysis. After counselling, 54% of the patients who originally declined PD ultimately accepted it. The major reasons for refusing PD were the ideas of "having lived long enough" and "lack of family support." Most other reasons could be overcome by counselling. Only a minority of patients demanded hemodialysis. CONCLUSIONS: Declining an offer of dialysis was common. Counselling helped patients to accept PD. Certain cultural elements that hindered acceptance of dialysis were involved in the ideas of "having lived long enough" and "lack of family support." Those cultural elements should be tackled more specifically during counselling.

Adult↗

Development of a poly(ortho ester) prototype with a latent acid in the polymer backbone for 5-fluorouracil delivery.

A study has been carried out to determine whether the latest family of poly(ortho esters) can be converted into a practical delivery system. This polymer differs from the previously described polymers in that it incorporates a short segment of a latent acid in the polymer backbone. The following issues were specifically addressed: (a) can the erosion and drug release be reproducibly controlled to yield the desired drug release kinetics and erosion rates? (b) Is the polymer stable during radiation sterilization, on storage and on fabrication? (c) Can the polymer be prepared reproducibly at the desired molecular weights and molecular weight distribution? (d) Is the polymer safe for its intended application and does the in vivo erosion proceed to completion? (e) Can the polymer be easily fabricated into desired configurations? Studies have shown that if the synthesis is carefully controlled, the desired molecular weights can be reproducibly prepared, that the polymer is reasonably stable after irradiation at 24 kGy and during storage at room temperature under anhydrous conditions, and that it can be safely thermally fabricated at temperatures in the neighborhood of 120 degrees C. When polymer devices were implanted intraperitoneally in rats the polymer eroded to completion without any overt toxicity as determined by the measured parameters.

Acids↗

Poly(ortho esters) - their development and some recent applications.

Poly(ortho esters) have been under development since the early 1970s and four families of such polymers have been described. Of most interest are poly(ortho ester) III and poly(ortho ester) IV. Poly(ortho ester) III is a semisolid material that has been shown to be highly biocompatible and is currently being investigated as an adjunct to glaucoma filtering surgery and other ocular applications. However, the polymerization is difficult to control and is not readily scaled up. Poly(ortho ester) IV can be easily prepared in a highly reproducible manner, is very stable provided moisture is rigorously excluded and has also been shown to be highly biocompatible. It is currently under development for a variety of applications, such as ocular delivery, protein release, post-operative pain treatment and post-operative cancer treatment.

Animals↗

Ultrasound-guided retrieval of labial minor salivary gland sialoliths.

We report a case of minor salivary gland sialolithiasis presenting as acute, painful swelling of the upper lip. Conventional, unguided, incision and drainage removed three of the sialoliths. Diagnostic ultrasound identified two further sialoliths which were successfully removed with real-time, ultrasound-guided, needle localization. This technique of sialolith retrieval has not been previously reported.

Acute Disease↗

Extensive temporal bone pneumatization: incidental finding in a patient with TMJ dysfunction.

An 18-year-old male presented with symptoms of temporomandibular joint dysfunction. A panoramic radiograph revealed slight erosion of the condylar heads, and an incidental finding of multilocular radiolucencies in the zygomatic processes of the right and left temporal bones. CT scans were undertaken to exclude any sinister cause. The radiolucencies were shown to be extensive bilateral pneumatization of the temporal bones. Conservative management relieved the symptoms of TMJ dysfunction.

Adolescent↗

A case of Castleman's disease mimicking a multicystic ovarian tumour.

We report on a case of solitary Castleman's disease that had an unusual presentation. A 29-year-old Filipino woman who had a history of intermittent right lower abdominal pain for several years was admitted to the Princess Margaret Hospital because of a sudden exacerbation of the abdominal pain. Ultrasonography had previously detected a multilocular right ovarian cyst of approximately 6.5 cm in diameter. Intra-operative findings, however, revealed a retroperitoneal presacral cystic tumour of approximately 7 cm in diameter, which was unrelated to the ovaries. The tumour was removed and found to be well defined and measure 7 x 5 x 4 cm. The cut surface revealed homogenous light-brown tissue at the periphery. The central part showed cystic spaces of 1- to 3-cm diameter. Histological examination of the tumour led to the diagnosis of hyaline vascular-type Castleman's disease. Cystic spaces were visible within the infarcted tissue; extensive cystic changes in Castleman's disease are unusual and may have caused the diagnostic difficulty.

Journal Article↗

In vitro drug release from self-catalyzed poly(ortho ester): case study of 5-fluorouracil.

Self-catalyzed poly(ortho esters) are a new variation of linear poly(ortho esters) prepared by the addition of diols to the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane where dimer segments of lactic acid or glycolic acid are built into the polymer backbone. By varying the concentration of these segments, polymer erosion rate can be controlled. The present investigation describes the in vitro drug release characteristics from these new polymers. Because poly(ortho esters) have potential applications for the delivery of antifibroblastic agents for example after glaucoma-filtering surgery, the in vitro release studies were evaluated using 5-fluorouracil as the active compound. It was shown that a mole ratio of 90/10 or 80/20 diol/diol-lactate incorporated into the polymer lead to a release of 5-fluorouracil by an erosion process. Smaller amounts of diol-lactate lead to a concomitant drug release by diffusion and erosion. It was also shown that the release rate depends on the alkyl chain length of the diol in the polymer backbone but it does not depend on the drug loading.

Catalysis↗

Death-effector filaments: novel cytoplasmic structures that recruit caspases and trigger apoptosis.

The death-effector domain (DED) is a critical protein interaction domain that recruits caspases into complexes with members of the TNF-receptor superfamily. Apoptosis can also be induced by expressing certain DED-containing proteins without surface receptor cross-linking. Using Green Fluorescent Protein to examine DED-containing proteins in living cells, we show that these proteins cause apoptosis by forming novel cytoplasmic filaments that recruit and activate pro-caspase zymogens. Formation of these filaments, which we term death-effector filaments, was blocked by coexpression of viral antiapoptotic DED-containing proteins, but not by bcl-2 family proteins. Thus, formation of death-effector filaments allows a regulated intracellular assembly of apoptosis-signaling complexes that can initiate or amplify apoptotic stimuli independently of receptors at the plasma membrane.

Adaptor Proteins, Signal Transducing↗

CD28-costimulation activates cyclic AMP-responsive element-binding protein in T lymphocytes.

Cyclic AMP-responsive element binding protein (CREB) mediates gene expression in response to cAMP stimulation. The transcriptional activity of CREB depends on both the phosphorylation of Ser133 and the recruitment of cofactor for assembly of transcriptional complex. Extensive Ser133 phosphorylation of CREB was induced during T cell activation. This phosphorylation event is essential for IL-2 gene expression. However, phosphorylation of CREB at Ser133 was not sufficient for transcriptional activity by CREB. The presence of a second signal from CD28, a potent costimulatory molecule on T cells, stimulated CREB-mediated gene expression. CD28, an effective costimulator of T cell activation and IL-2 gene expression, is shown to induce CREB activation in the presence of anti-CD3 or O-tetradecanoylphorbol 13-acetate. These two signals together stimulated a CRE-dependent reporter gene, the proliferating cell nuclear Ag promoter, and transactivation by the GAL4-CREB fusion protein. Thus optimal induction of CREB, similar to the full activation of T lymphocytes, may be mediated by two distinct signal transductions. Using the specific kinase inhibitor, one of the two pathways appeared to involve mitogen-activated protein kinase kinase but not protein kinase C, protein kinase A, or p70 S6 kinase.

Activating Transcription Factor 1↗

Intra-oral ultrasound imaging of a submandibular duct calculus.

A case is presented showing the first reported use of a small, digitally-guided, intra-oral ultrasound probe to image a calculus in a submandibular salivary duct. This use of intra-oral ultrasound is discussed in the context of the overall current status of intra-oral and extra-oral ultrasound imaging. It is proposed that using a combination of intra-oral and extra-oral probes, the whole of the salivary apparatus may now be examined sonographically for the presence of calculi.

Adult↗

Serum response element associated transcription factors in mouse embryos: serum response factor, YY1, and PEA3 factor.

Many mammalian transcription factors, including human and mouse serum response factors (SRFs), are post-translationally modified with O-linked N-acetylglucosamine monosaccharides on multiple serine and/or threonine residues. Nuclear extracts were prepared from 9.5 to 19 days postcoitum mouse embryos and subsequently were fractionated by wheat germ agglutinin (WGA)-agarose affinity chromatography. SRF binds WGA-agarose and apparently is O-glycosylated. On the other hand, the low molecular weight serum response element (SRE)-binding proteins, including the previously named band I and band II factors, did not bind WGA-agarose. Furthermore, we showed that the fastest migrating complex contains the Yin-Yang 1 (YY1) factor. YY1 binds to the c-fos SRE and skeletal alpha-actin muscle regulatory element (MRE), but not the cardiac alpha-actin MRE. Nuclear extracts from NIH/3T3 fibroblasts contain similar, if not identical, SRE-binding complexes. Besides these SRE-binding factors, mouse PEA3-binding factor, presumably an ETS domain-containing protein, was found to bind SRF protein. This physical interaction, between SRF and ETS domain proteins, was shown to involve the DNA-binding domain-containing region of SRF and not the carboxyl-terminal transactivation domain.

Animals↗

Ras transformation results in an elevated level of cyclin D1 and acceleration of G1 progression in NIH 3T3 cells.

Ectopic overexpression of v-H-Ras protein in NIH 3T3 cells resulted in cellular transformation and an acceleration of G1 progression of these cells. A shortened G1 phase was found to be associated with an increased level of cyclin D1 but not cyclin E protein. Using an antisense blocking method, reduced synthesis of cyclin D1 in v-H-Ras transformants resulted in a slower G1 progression rate of these cells. Although constitutive overexpression of cyclin D1 in NIH 3T3 cells accelerated G1 progression, cells remained untransformed. Furthermore, inhibition of cyclin D1 synthesis greatly impaired the soft-agar cloning efficiency of v-H-Ras transformants. These results suggest that increased expression of cyclin D1 is necessary but not sufficient for the transforming activity of v-H-Ras. Similar effect on cell cycle progression was also observed in Raf-transformed cells. In addition to cyclin D1, cyclin E protein was found to be elevated in Src transformants. This may account for the further shortening of the G1 phase of these cells. Activation of an additional Ras-independent pathway was suggested to be responsible for the further acceleration of the G1 phase in Src transformants.

3T3 Cells↗

Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle.

Cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen (PCNA) are three important cell cycle regulatory proteins. Recently, their promoters have been isolated, thus facilitating molecular analysis of transcriptional control mechanisms of these genes. Transcription of these three promoters in stable K562 transfectants during different cell cycle phases was analyzed after cell cycle synchronization. About 1 kb of 5' flanking region from either cyclin D1 or DNA topoisomerase I gene is sufficient to confer G1- or S-phase-specific transcription activity to chloramphenicol acetyltransferase (CAT) reporter genes, respectively. In contrast, 2.8 kb of 5' flanking sequences from the PCNA gene led to constitutive transcription, but the inclusion of a segment of the PCNA gene first intron, which contains evolutionarily conserved sequences, could enhance transcription in G1/S-enriched nuclei. This PCNA intron region contains a binding site recognized by the transcription factor E2F. To test whether this site is functional, we cotransfected PCNA-CAT genes with E2F-1 and DP-1 expression plasmids. Expression of the E2F-1/DP-1 heterodimer activated the CAT gene with the PCNA intron. Therefore, this intron region, involved in transcriptional activation at the cell cycle G1/S boundary, is also E2F inducible.

Base Sequence↗

Serum response factor associated ETS proteins: ternary complex factors and PEA3-binding factor.

An ETS protein binding motif CAGGAT adjoins the 5' side of the Serum Response Element in the c-fos promoter. This sequence is recognized by several ETS proteins which are able to form ternary complexes in the presence of Serum Response Factor. Related sequences, capable of ternary complex formation, are also found in the promoters of immediate early zinc finger proteins. However, similar sequences found in the gamma-actin and c-ets-2 promoters could not bind Ternary Complex Factor. We purified a 60-kDa human ETS protein which could bind the sequence recognized by Ternary Complex Factor, and this protein could bind DNA in the absence of Serum Response Factor. Interestingly, this protein also binds Serum Response Factor in vitro. Therefore the Serum Response Factor DNA-binding/oligomerization domain has affinities for distinct ETS oncoproteins.

Base Sequence↗

Functional divergence of the MAP kinase pathway. ERK1 and ERK2 activate specific transcription factors.

Growth factor-receptor interactions at the cell surface eventually leading to the transcriptional activation of immediate early genes is mediated by the mitogen-activated protein kinase (MAP kinase/MAPK) cascade. Here we show that overexpression of extracellular signal-regulated kinase 1 (ERK1) cDNA, encoding p44mapk, results in the activation of Elk-1, the serum response factor accessory protein. We also show that overexpression of ERK2, encoding p42mapk, activates Myc, but not Elk-1. Therefore, the MAP kinase cascade diverges with at least one specific target for each MAP kinase isoform and provides a novel mechanism for differential regulation of this signaling pathway.

3T3 Cells↗

Muscle homeodomain protein MHox inhibits ternary complex formation at the c-fos serum response element.

The Serum Response Element in the c-fos promoter is the target of growth factor-regulated signal transduction pathways. The ternary complex of Serum Response Element-binding protein Serum Response Factor and its accessory protein Ternary Complex Factor are important for transcriptional stimulation of the c-fos promoter in fibroblasts. However, this promoter is repressed in differentiating muscle cells. We discovered that MHox, a muscle homeodomain protein, was capable of inhibiting formation of the ternary complex by direct physical interaction between MHox and Serum Response Factor accessory protein-1 (SAP-1), one member of the Ternary Complex Factor family of proteins. Furthermore, exogenous MHox protein inhibited serum-inducibility of a Serum Response Element-dependent reporter gene in permeabilized fibroblasts. Taken together, these results imply that MHox is involved in blocking mitogenic signals during myogenesis.

3T3 Cells↗