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Biomedical subjects

S H Tan

Publications and source records attributed to S H Tan.

At least 19 recordsLinked to original sources
PubMed1996

YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity.

YY1 is a multifunctional transcription factor that has been shown to regulate the expression of a number of cellular and viral genes, including the human papillomavirus (HPV) oncogenes E6 and E7. In this study, we have analyzed the YY1-mediated repression of the HPV type 16 (HPV-16) E6-E7 promoter. A systematic analysis to identify YY1 sites present in the HPV-16 long control region showed that of 30 potential YY1 binding motifs, 24 bound purified recombinant YY1 protein, but only 10 of these were able to bind YY1 when nuclear extracts of HeLa cells were used. Of these, only a cluster of five sites, located in the vicinity of an AP-1 motif, were found to be responsible for repressing the HPV-16 P97 promoter. All five sites were required for repression, the mutation of any one site giving rise to a four- to sixfold increase in transcriptional activity. The target for YY1-mediated repression was identified as being a highly conserved AP-1 site, and we propose that AP-1 may represent a common target for YY1 repression. We also provide data demonstrating that YY1 can bind the transcriptional coactivator CREB-binding protein and propose a potentially novel mechanism by which YY1 represses AP-1 activity as a result of this YY1-CREB-binding protein interaction.

DNA-Binding Proteins↗
PubMed1995

Skin cancers at Tertiary Referral Skin Hospital in Singapore.

BACKGROUND: Skin cancer is the seventh most common cancer in Singapore. This study was performed to determine the pattern of skin cancers seen in a tertiary referral skin hospital. METHODS: Histologically confirmed skin cancers, seen between 1980 and 1991, were analyzed according to age, sex, race, site, and presence/absence of preexisting skin conditions. RESULTS: Of a total of 520 patients, the commonest skin cancer was basal cell carcinoma (BCC) (36.5%), followed by squamous cell carcinoma (SCC) (24.4%), Bowen's disease (16.7%), and mycosis fungoides (9.0%). Malignant melanomas (2.7%) were rare. The sharp increase (26.2%) in BCC in the recent 3 years was largely contributed by a fivefold increase of non-resident Caucasian patients with BCC. All types of skin cancers were more common in Chinese (78.1%) and less frequent in the more pigmented races (9.4%). The men to women ratio was 1.72:1. The peak age distribution was in the 51-70-year group, with the exception of mycosis fungoides (31-50 years). The commonest site involved in BCC was the head and neck (67.0%) and in Bowen's disease the trunk (33.3%). Squamous cell carcinoma was found on the head and neck and the lower extremities with equal frequency (29.3%) and 46.2% of all SCC on the lower extremities occurred in leprosy patients with chronic trophic ulcers. Of patients with Bowen's disease involving the nonsunexposed parts (trunk and upper extremities), 42.6% had probable arsenic exposure evident either from the history or clinical examination. Malignant melanomas were commonly located on the foot (71.4%). CONCLUSIONS: The commonest skin cancers seen were BCC, SCC, Bowen's disease, and mycosis fungoides. There were differences in the site distribution of SCC, Bowen's disease, and malignant melanomas in our study when compared to studies in Caucasians.

Adult↗
PubMed1995

Upright tilt table testing in the evaluation of syncope.

OBJECTIVES: To review our experience with the upright tilt table test for the diagnosis of vasovagal syncope in a group of unselected patients with a history of syncope or presyncope. METHODS: 179 patients with a history of syncope or presyncope were subjected to upright tilt test. After carotid sinus massage to exclude carotid sinus hypersensitivity, the patients were tilted on a motorised tilt table with footplate support to an angle of sixty to seventy degrees for thirty minutes. If syncope was not induced, isoprenaline was then infused for a further fifteen minutes. A positive response was defined as fulfilling at least two out of three criteria: (i) syncope or presyncope similar to the spontaneous episodes of syncope, (ii) relative slowing of the heart rate at the onset of symptoms, (iii) drop of systolic pressure to less than 90 mmHg or by more than 50 mmHg. STATISTICAL METHODS: Continuous variables are expressed as mean values +/- one standard deviation and analysed for statistical significance by the unpaired Student's t-test. Chi-squared test with continuity correction was used for dichotomous variables. RESULTS: Ninety-four patients (53%) were positive for vasovagal syncope. Fourteen patients (8%) were positive at baseline tilt. An additional 80 patients (45%) were positive with the use of isoprenaline. Ten percent of the positive responses were purely cardioinhibitory, 10% purely vasodepressor and 80% mixed. The commonest cardiac rhythm during a positive response was junctional rhythm (46%) followed by sinus rhythm (44%). Sinus arrest with ventricular standstill occurred in only 5%. Accelerated idioventricular rhythm, 2:1 atrioventricular block and ventricular bigeminy accounted for the remaining 5%. CONCLUSION: The upright tilt table test is useful for the diagnosis of vasovagal syncope.

Adolescent↗
PubMed1995

Cadmium hazard in silver brazing.

This study evaluates the usage of cadmium-containing silver brazing alloys in Singapore and the potential cadmium hazard from its use. Of the 137 factories which responded to the survey questionnaire, only 28 (20.4%) carried out brazing. Of these, only 7 factories used cadmium-containing filler alloys. One hundred and six out of 123 workers from one of these factories had cadmium-in-blood concentrations exceeding 10 mcg/l. Thirty-one (29.2%) of the workers with excessive cadmium absorption had urinary beta-2 microglobulin levels exceeding 28 mcg/g creat. Workers in the other factories who were intermittently exposed had cadmium-in-blood concentrations of 10 mcg/l and below.

Alloys↗
PubMed1994

Cryosubstitution technique reveals new morphology of flavivirus-induced structures.

Cryotechniques in combination with electron microscopy were used in an attempt to obtain more precise morphological details of flavivirus-induced structures. From conventional chemical fixation procedure, proliferation of endoplasmic reticulum, formation of microtubule paracrystals and clusters of smooth membrane vesicles (with 'thread-like' enclosures) were observed. These induced changes are typical for flavivirus infections. The images obtained from cryosections were disappointing as the structures were not well preserved. On the other hand, cryosubstituted-infected cells gave revealing images of the virus-induced structures. The most obvious difference between the cryosubstituted and chemical fixed processes was on the morphology of the 'thread-like' structure. The 'thread-like' structures instead appeared as dense cores. The morphology of the virus particles was also better defined. The envelope of the virus appeared clearly differentiated from the nucleocapsid. The most important finding was that the cryosubstituted technique was able to preserve the structures of the flavivirus nucleocapsids which so far has not been convincing reported with chemical processing.

Animals↗
PubMed1994

Efficient and rapid affinity purification of proteins using recombinant fusion proteases.

In the affinity purification of recombinant fusion proteins, the rate-limiting step is usually the efficient proteolytic cleavage and removal of the affinity tail and the protease from the purified recombinant protein. We have developed a rapid, convenient and efficient method of affinity purification which can overcome this limitation. In one example of the method, the protease 3C from a picornavirus (3Cpro), which cleaves specific sequences containing a minimum of 6-7 amino acids, has been expressed as a fusion with glutathione S-transferase. The resultant recombinant 'fusion protease' cleaves fusion proteins bearing (from the amino-terminus) the same affinity tail as the fusion protease, a 3Cpro cleavage recognition site, and the recombinant protein of interest. The recombinant protein is purified in a single chromatographic step which removes both the affinity tail and the fusion protease. The advantages over existing methods include much improved specificity of proteolytic cleavage, complete removal of the protease and the affinity tail in one step, and the option of adding any desired amount of fusion protease to ensure efficient cleavage. The potential flexibility of the method is shown by the use of various affinity tails and alternative fusion proteases.

3C Viral Proteases↗
PubMed1994

Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus.

Aberrant p53 immunoreactivity has been found in skin pre-malignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 +/- 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 +/- 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 +/- 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 +/- 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID.

The E6 promoters of all genital human papillomaviruses have a characteristic alignment of transcription factor binding sites. Activation of the basic transcription complex at the TATA box depends upon a sequence-aberrant Sp1 site. Repression of E6 promoters is achieved by two binding sites for the viral E2 protein positioned between the Sp1 site and the TATA box. We have purified the human papillomavirus type 16 E2 protein after expression in Escherichia coli and studied its binding and repression properties with oligonucleotides representing the homologous promoter sequences. A Kd value of 3 x 10(-10) M indicated binding properties expected for a native protein. We found low cooperativity in the binding of two E2 dimers to flanking sites, both when these sites were separated by 3 nucleotides, as in the natural promoter, and when they were further apart. E2 protein, bound close to the distal Sp1 site, displaced the Sp1 factor even when the aberrant sequence was replaced by a typical Sp1 core recognition site. The high affinity of E2 protein for its binding site even led to Sp1 displacement at concentrations of E2 protein nearly 2 orders of magnitude lower than those of Sp1. Functional analyses of mutated E6 promoter sequences showed repression by this distal E2 binding site in the complete absence of binding to the proximal E2 binding site. From our findings and observations published by others, we conclude that each of the E2 binding sites in the E6 promoter of genital human papillomaviruses plays a separate role by displacing the transcription factors Sp1 and TFIID.

Amino Acid Sequence↗
PubMed1993

Immunological characterisation of the lichen planus infiltrate using monoclonal antibodies.

The immunological typing of cell populations in the skin biopsies of 20 cases of histologically proven lichen planus was done using monoclonal antibodies. The Avidin-Biotin-Complex immunoperoxidase technique was used. A predominance of T-helper/inducer cells in the dermal infiltrate was observed by a semiquantitative analysis. T-suppressor/cytotoxic cells and Langerhans cells were increased compared to eczema lesions. A comparison of the staining of Langerhans cells using monoclonal antibodies and the S100 protein stain showed that more Langerhans cells could be identified with the CD1 monoclonal antibody. The type of infiltrate did not correlate with the duration of disease. Direct immunofluorescence staining demonstrated fibrinogen at the dermo-epidermal junction and/or colloid bodies in the upper dermis. The immunophenotyping and immunofluorescence pattern in local cases of lichen planus are similar to previous reports from other countries. An interesting finding was the unexplained disproportionate predominance of Indians in the study cohort.

Adolescent↗
PubMed1992

During negative regulation of the human papillomavirus-16 E6 promoter, the viral E2 protein can displace Sp1 from a proximal promoter element.

The principal early promoter of human papillomaviruses (HPVs), designated P97 in the case of HPV-16, contains four characteristically aligned cis-responsive elements, namely one binding site for Sp1, two for the viral E2 proteins, and the TATA box. The Sp1 binding site is needed to mediate activation of P97 by the remote epithelial-specific enhancer, and the two E2 binding sites contribute to a negative feedback-loop of viral gene expression. The Sp1 consensus motif and the TATA-box distal E2 binding site are spaced in all genital papillomaviruses by a single nucleotide. We show here that at physiological concentrations, the binding of E2 proteins and Sp1 are mutually exclusive events, since a bandshift analysis with nuclear extracts from ID13, a mouse cell line transformed by BPV-1, showed only the E2 or the Sp1 bandshift, but no complex indicative of the concomitant binding of both factors. Increasing concentrations of in vitro translated E2 protein compete efficiently with the Sp1 factor for binding to an oligonucleotide containing both binding sites. Interference between Sp1 and E2 protein binding is apparently relevant for P97 repression in vivo, since a mutational analysis revealed that both E2 binding sites are necessary for negative transcriptional regulation: Alone, neither the distal site, where E2 protein can induce Sp1 displacement, nor the proximal site, where E2 protein interferes with formation and function of the pre-initiation complex, have a significant effect, but two functional E2 binding sites lead to repression of P97.

Animals↗
PubMed1991

Normal standard of pubertal development in Singapore school children.

A cross sectional study of the pubertal status of normal school children in Singapore was performed in 1987. The results of the data analysis are presented as an update from the last survey performed in 1977. The norms of pubertal development in boys and girls are thus defined.

Adolescent↗
PubMed1990

Synaptic junctions between sympathetic axon terminals and pinealocytes in the monkey Macaca fascicularis.

The distribution of axon terminals in the pineal gland of monkeys was studied by electron microscopy. Numerous terminals bearing small pleomorphic agranular and dense-cored vesicles were localized in the perivascular space and among the pinealocytes in the parenchyma in normal monkeys. Following bilateral superior cervical ganglionectomy, they underwent degenerative changes, including the accumulation of glycogen masses, appearance of dense residual bodies and the displacement of synaptic vesicles. Some of these degenerating terminals showed synaptic contacts with the cell bodies of pinealocytes. At the synaptic junction the postsynaptic membrane was thickened asymmetrically. Examples of synaptic contacts were most frequently observed in 5 and 7 days postoperative animals. In the longer surviving (30 days) monkey, most of the axon terminals showed round agranular vesicles, and they were mainly presynaptic to the intrapineal ganglion cells with some of the pinealocytes. They remained structurally unchanged following the resection of both the superior cervical ganglia. A few axon terminals containing small dense-cored vesicles appeared to have survived the initial insult, but some of their vesicles appeared swollen 30 days after the operation. It is concluded from this study that some of the pinealocytes are under the influence by the postganglionic neurons in the superior cervical ganglia through direct synaptic contacts. The intrapineal ganglion cells are postsynaptic to fibres originating exclusively from the central nervous system. Some of these fibres, however, may be presynaptic directly to pinealocytes.

Animals↗
PubMed1990

Ultrastructure of interstitial cells of Cajal at the gastro-oesophageal junction of the monkey (Macaca fascicularis).

The ultrastructure of the interstitial cells of Cajal (ICC) in the oesophagus of the monkey resembled that described in the oesophagus of other mammalian species but differed in their paucity and almost lack of smooth endoplasmic reticulum, caveolae and filaments. The plasmalemma of the ICC was in close contact (20- to 30-nm gaps) with that of smooth muscle cells. This may occasionally take the form of a desmosome, but gap junctions have not been observed. Vesiculated axon profiles, containing large granular or agranular vesicles were in close contact (20- to 30-nm gaps) with the plasmalemma of ICC. In a few vesiculated profiles a presynaptic density could be recognized. The intercalation of the ICC between the vesiculated axon profiles and the smooth muscle cells suggest a role in oesophageal motility. Between 3 and 21 days following bilateral vagotomy some ICC showed regressive changes such as increased electron density and shrinkage of the cytoplasm, crowding of the organelles and dissolution of the nuclear chromatin material. Axon profiles in the vicinity of the affected ICC contained glycogen granules suggesting injury. In late stages, the number of ICC and smooth muscle contacts was reduced. The results suggest that the vagus nerves exert a trophic influence on the ICC and that the intercellular relationships between ICC and smooth muscle cells possess a degree of plasticity. It is tentatively suggested that these vagal effects may be mediated via the oesophageal myenteric ganglia.

Animals↗
PubMed1990

TRH stimulation in non-toxic goitres in children and adolescence.

Non-toxic goitres are commonly encountered in clinical practice, but in the majority the aetiology is unknown. Possible aetiological factors include iodine deficiency, biosynthesis defects, immunologic factors or goitrogens. The consequential effect on thyroid function may be clinically undetectable. In this study, serum thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation was studied in a group of school children with non-toxic goitres to delineate those who may benefit from treatment. Evaluation of possible aetiological factors responsible for goitrogenesis was made by assessment of thyroid autoantibodies and history of exposure to goitrogens.

Adolescent↗
PubMed1990

Oculocardiac reflex in strabismus surgery under general anaesthesia--a study of Singapore patients.

A study of 80 patients with strabismus undergoing correctional surgery under general anaesthesia was done. A comparison was made with regards to the incidence of oculocardiac reflex between patients premedicated with intramuscular atropine 0.015 mg/kg and non-premedicated patients. We found that premedication with atropine reduces the incidence and the morbidity of the oculocardiac reflex.

Adult↗
PubMed1990

Basal cell carcinoma of the head and neck region--a five-year study (1984-88).

Two hundred and seventy-two patients with 292 lesions of basal cell carcinoma of the head and neck region treated at the Department of Plastic Surgery, Singapore General Hospital over a period of five years, were reviewed. Basal cell carcinoma is common in the face, the lesser pigmented mongoloid race of our population and has a higher incidence in the elderly age group. A large number (63%) of the basal cell carcinoma are of the pigmented variety, a very unusual feature. The commonest site of occurrence is the nose (37%). Of the 292 basal cell carcinoma excised, 27 (9%) had tumour involvement of the margins of excision. However, of these 27 cases, only 4 have presented with recurrent tumour. The place of close observation and immediate re-excision of positive margins is discussed. The 4 cases of recurrent basal cell carcinoma involved the nose and lip area, areas with a known higher incidence of recurrence. The results of treatment (98.7% cure rate) of this group are encouraging and compares well with those of other series and using other modalities of treatment. Longer follow-up is required.

Adult↗
PubMed1989

Ultrastructure of the pineal gland of the monkey, Macaca fascicularis, with special reference to the presence of synaptic junctions on pinealocytes.

The present study described the normal ultrastructure of the monkey pineal gland. The gland was composed of the principal pinealocytes, intramural neurons and glial cells. The nucleus of the pinealocytes was deeply infolded with evenly distributed chromatin materials. The abundant cytoplasm was rich in organelles including the well-developed Golgi apparatuses, multivesicular bodies, dense-cored vesicles and widely scattered free and polyribosomes. A variety of axon terminals was observed and the majority of them contained pleomorphic agranular vesicles with a few large dense-cored vesicles. A few terminals showed flattened vesicles or small dense cored vesicles. Some of the axon terminals formed synaptic contacts with the cell bodies of pinealocytes. These synapses were mainly concentrated in the posterior third of the gland. The occasional intramural neurons observed were postsynaptic to axon terminals containing round agranular vesicles. The sources of the nerve fibres and terminals forming synaptic junctions with pinealocytes and intramural neurons were discussed.

Animals↗