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Biomedical subjects

C T Tan

Publications and source records attributed to C T Tan.

At least 19 recordsLinked to original sources

Glucocorticosteroids increase sodium transport in middle ear epithelium.

The effect of glucocorticosteroids on ion transport was investigated on a middle ear cell line with the short-circuit current (Isc) technique. Dexamethasone (DXM) produced a dose- and time-dependent increase in Isc. Concentration of half-maximal stimulation was 2.68 x 10(-8) M. This effect was blunted by the glucocorticoid antagonist RU-38486 and was related to Na+ transport, as evidenced by the inhibition induced by 1) apical addition of the Na+ channel inhibitor benzamil (10(-6) M) or 2) substitution of Na+ with N-methylglucamine in the incubation medium. The increase in Na+ transport resulted from a primary modulation of apical Na+ entry, since 1) the Na(+)-K(+)-ATPase activity of cellular homogenates was not modified by corticosteroids and 2) the DXM-induced increase in the ouabain-sensitive uptake of 86Rb was blunted by benzamil. Ribonuclease protection assay revealed 1) a constitutive expression of the mRNA encoding the alpha-subunit of the epithelial Na+ channel and 2) that DXM increased the expression of this transcript. This increase was dose dependent and paralleled changes in transepithelial Na+ transport. This study suggests that a component of the beneficial effect of steroid therapy for the treatment of otitis media might be related to increased fluid clearance.

Adenosine Triphosphate

Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups.

The aims of this study were to examine the clinical and laboratory features of Malaysian patients with systemic lupus erythematosus (SLE) and to identify any difference in disease expression between the different genders and among the three major ethnic groups of Malaysia. Retrospective analysis of all patients with SLE admitted to and followed-up at University Hospital Kuala Lumpur from 1974-90 was undertaken. Ethnic Chinese had the highest prevalence of SLE compared to other ethnic groups. There was a high incidence of renal disease, 74% of patient had significant proteinuria and half of these had associated nephrotic syndrome. Indian patients had significantly less incidence of skin manifestation compared to other racial groups. No difference in disease expression was detected between the ethnic Chinese and Indians and between the male and female patients. The overall 5 y and 10 y survival rates were 82% and 70% respectively. Indian patients had the poorest survival rates. Survival rates are similar among the Chinese and Malay patients. Our findings are in broad agreement with those previously reported.

Adolescent

Modulation of middle ear epithelial function by steroids: clinical relevance.

The efficacy of steroid therapy for the treatment of otitis media in children remains controversial, and a putative modulation of the middle ear epithelial function has to be demonstrated. Using the MESV cell line, short-circuit current (ISC) technique was used to evaluate changes in ion transport induced by glucocorticoids. Dexamethasone (DXM) produced a dose- and time-dependent increase in ISC in MESV cells. This effect was inhibited by specific glucocorticoid antagonist (RU-38486) and was related to a sodium transport, since the DXM-induced increase in ISC could be prevented or abolished i) by apical addition of the specific Na+ channel inhibitor benzamil; or ii) by substitution of sodium with N-Methyl-glucamine in the incubation medium. RNase protection assay revealed that DXM increased the expression of the alpha subunit sodium channel mRNA, which changes paralleled the modulation of ion transport. These data demonstrate that steroids up-regulate the trans-epithelial sodium transport in the middle ear epithelium. As far as these experimental data can be extrapolated to the in vivo situation, a component of the beneficial effect of steroid therapy for the treatment of otitis media may result from a corticosteroid-induced improvement in fluid clearance from the middle ear.

Amiloride

Arabidopsis profilins are functionally similar to yeast profilins: identification of a vascular bundle-specific profilin and a pollen-specific profilin.

Four members of the Arabidopsis profilin (pfn) multigene family have been cloned, sequenced and analyzed. By RNA gel blot analysis it has been shown that these four genes fall into two groups: one group (pfn1 and pfn2) is expressed in all organs of the plant and the other group (pfn3 and pfn4) in floral tissues only. Based on amino acid sequence alignment Arabidopsis profilins can be divided into the same two groups: PFN1 and PFN2 are 89% identical and PFN3 and PFN4 are 91% identical. Between these two groups they are 71-75% identical. The Arabidopsis profilins bind poly-L-proline and can complement both the Saccharomyces cerevisiae profilin deletion mutant and the Schizosaccharomyces pombe cdc3-124/profilin mutation, showing that the plant profilins are functionally similar to yeast profilins despite the low amino acid sequence homology. Analysis of pfn promoter-GUS fusion genes in transgenic Arabidopsis shows that pfn2 is specifically expressed in the vascular bundles of roots, hypocotyls, cotyledons, leaves, sepals, petals, stamen filaments and stalks of developing seeds, whereas expression of pfn4 is restricted to mature and germinating pollen grains.

Amino Acid Sequence

A community-based prevalence study on headache in Malaysia.

This community study on headache in Malaysia was based on IHS diagnostic criteria and showed the last-year prevalence of migraine was 9.0%. Migraine with aura accounted for only 10.6% of the migrainous population. The last-year prevalence of tension headache was 26.5% (94.4% episodic, 5.6% chronic) and 28.2% for other types of headache. No case of cluster headache was found. Almost two thirds of the migraine subjects graded their headaches as severe, while almost 60% of the tension headache subjects and almost 70% of the other headache subjects graded their headaches as mild. Overall, there was higher prevalence in females for migraine and tension headache, and in males for the other types of headache. The prevalence of headache was lower among those younger than 15 and older than 65 years of age. No significant differences were found in the prevalence of headache among the different racial groups nor among the urban versus the rural population. All the headache types shared the same triggering factors suggesting that different physiological characteristics are responsible for the type of pain suffered. In the location of this community with its tropical climate, headache was attributed to sun exposure in 51.9% of the migraine subjects, 55.7% of the tension headache subjects, and 36.6% of the group with other headaches.

Adolescent

Traumatic luxation of the stapes evidenced by high-resolution CT.

We encountered a case of acquired perilymphatic fistula in which the origin of the disease, namely, the stapes begin medially displaced into the vestibule, was shown by thin-section CT. Accordingly, we recommend that every patient with suspected perilymphatic fistula of traumatic origin undergo high-resolution CT of the petrous bone.

Female

Incidence of second cancers in patients treated for Hodgkin's disease.

BACKGROUND: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. PURPOSE: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. METHODS: We conducted a study within a cohort that included 10,472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. RESULTS: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6-35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1-3.6), procarbazine (RR = 4.9; 95% CI = 2.6-9.1), vinblastine (RR = 1.7; 95% CI = 1.1-2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9-7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9-12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (RR = 1.5; 95% CI = 0.7-3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0-2.5). The RR of solid tumors following chemotherapy was 1.4 (95% CI = 1.1-1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7-5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7-20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1-3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1-6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1-5.4). CONCLUSIONS: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. IMPLICATIONS: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors.

Adolescent

Characterisation of HEVER, a novel stress-induced gene from Hevea brasiliensis.

A novel stress-induced gene, HEVER (Hevea ethylene-responsive) from the rubber tree, Hevea brasiliensis, has been isolated and characterised. HEVER is encoded by a multigene family. The HEVER transcript is expressed at basal levels in Hevea tissues and is developmentally regulated. In addition, the HEVER transcript and protein are induced by stress treatment with salicylic acid and ethephon. Sequence analysis shows that HEVER encodes a 33 kDa protein that has significant homology to the hypothetical protein SLEXORFA-1 from the plant, Stellaria longipes, and two bacterial proteins, BAC180K-75 from Bacillus subtilis and MVRNO3-1 from Methanococcus vannielii.

Amino Acid Sequence

A cDNA clone encoding Brassica calmodulin.

A 834 bp cDNA encoding calmodulin (CaM) has been isolated from Brassica juncea. On Northern analysis this cDNA hybridises this cDNA to mRNAs of about 0.9 kb in leaf, silique and peduncle. Genomic Southern analysis indicates the presence of a CaM multigene family in Brassica juncea. Comparison of the predicted amino acid sequence of Brassica CaM with that of Arabidopsis CaM ACaM-2 and ACaM-3 showed 100% homology, which is not unusual, since both plants belong to the family Cruciferae. In situ hybridisation studies on Brassica seedlings using a digoxigenin-labelled RNA probe showed that high levels of CaM mRNA were detected in the leaf primordia and the shoot apical meristem, and to a lesser degree, in the zone of root elongation of the root tip. The occurrence of a higher rate of cell division and growth in these regions than its surrounding tissue may possibly be related to higher levels of CaM mRNA.

Amino Acid Sequence

Fluoxetine in the treatment of depression in Asian (Chinese and Indian) patients in Singapore.

The aim of this paper is to study the efficacy and side-effects of fluoxetine. Fluoxetine is a specific serotonin reuptake inhibitor. Nineteen Asian (Chinese and Indian) patients who satisfied the DSM-3R criteria for major depressive episode were treated with fluoxetine 20 mg daily for 12 weeks. They were monitored two weekly. The results showed that during the period of treatment there was significant improvement in depressive symptoms and no serious side-effects. There were no significant changes in weight, temperature, blood pressure and pulse rate throughout the 12 weeks. This study showed that fluoxetine was well-tolerated and relieved the symptoms of depression effectively. Most of the results are supported by other studies.

Adult

Pharmacologic-guided trial of sequential methotrexate and thioguanine in children with advanced malignancies.

PURPOSE: Based on in vitro studies that have shown synergistic effects of sequential administration of methotrexate (MTX) and thioguanine (6-TG), we conducted a pharmacologically guided trial of sequential MTX and 6-TG to determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6-TG given by this sequence and schedule. PATIENTS AND METHODS: Thirty-one children with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour infusion of 6-TG in escalating doses. RESULTS: Measurement of plasma MTX, 6-TG, and mononuclear 5-phosphoribosyl-1-pyrophosphate (PRPP) levels indicates that the desired biochemical modulation and serum levels were achieved. Nonhematologic toxicities were mild and the dose-limiting toxicity was bone marrow depression. A 300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in patients with lymphoma. CONCLUSION: Encouraging antitumor effects were produced with this regimen in heavily pretreated patients with lymphoma, particularly Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+ months. A phase II trial of the MTX/6-TG combination is warranted for the treatment of relapsed lymphoma.

Adolescent

An in vivo canine model for the study of phonation physiology by midbrain stimulation.

A versatile in vivo canine model is indispensable in studying the phonation function of the larynx. In this study, we attempted to build an in vivo phonation model in anesthetized dogs using stereotaxic electrical stimulation at a specific area in the midbrain. In each of the eight animals in this experiment, evoked phonation was successfully elicited by stimulating sites in the area ranging from 9 to 11 mm anterior, 3 to 5 mm lateral and 5 to 16 mm dorsal to the ear bar zero. This area was at the lateral border of the periaqueductal gray in the midbrain. The evoked-phonation process involved electrical stimulation of sites in this area, resulting in consistent responses by respiratory and laryngeal musculature accompanied by phonation. The evoked phonation could be consistently repeated. Different pitches of phonation were elicited by slightly moving the stimulation spots in this area. During evoked phonation, the subglottic aerodynamic power and individual laryngeal muscle action could be modified to study the effects of a single factor on the phonation process. The neuromuscular action for the control of phonation and the mechanical properties of the vocal folds can be investigated using an in vivo canine model.

Animals

Malaysian children with: "benign epilepsy of childhood with centrotemporal spikes".

Benign epilepsy of childhood with centrotemporal spikes (BECT) was studied in Malaysian children, and was observed in Chinese, Malay and Indian children in the ratio 10:6:5. There were 12 boys and 9 girls. Fit frequency varied from almost daily to a single fit. The age of onset ranged from 2-13 years and BECT was not noted in any child over 13 years old. There was a strong circadian rhythm and fits occurred mainly in sleep. Generalised seizures were more common than partial seizures. During the 3-year study from April 1989 to April 1992, 21 children with BECT were identified from the EEG records done at the University Hospital and it was found that this genetic epilepsy which is autosomal dominant with age dependent penetrance occurs in approximately 4.8% of our epileptic children. In addition there were 3 children in whom petit mal co-existed with a BECT EEG trait.

Adolescent

Wilson's disease--a review of cases at University Hospital, Kuala Lumpur.

The clinical course of 18 patients with Wilson's disease is reported. There were 13 males and five females of whom one is Malay. The prevalence of Wilson's disease in Malaysia is probably the same as elsewhere. Being a genetic syndrome, the genetic carrier rate for Wilson's disease is probably lower amongst the Malays. At diagnosis, the clinical signs were predominantly hepatic in 10 patients, neurological in five patients with three asymptomatic cases. All patients were commenced on penicillamine but poor compliance was observed in many patients. Two patients defaulted follow-up and seven patients died. Out of the nine surviving patients, only four are well with no clinical symptoms.

Adolescent

The hot bath test among Malaysian multiple sclerosis patients.

This is a study of 13 Malaysian patients with clinically definite Multiple sclerosis (MS) subjected to a hot bath test with VEPs, BAEPs, median nerve SSEPs before and after heating. Five patients (38%) developed neurological changes with the rise in body temperature. There was an average of 0.46 new sign per patient. Four patients had motor disturbances attributed mainly to aggravation of spinal cord dysfunction. Two patients had additional visual deterioration, one patient has associated VEP change. This study shows that though Uhthoff's phenomenon has not been noted in the reports of Asian MS patients, when subjected to rigorous testing, Asian MS patients also show sensitivity to body temperature change. However, the percentage of positivity of the hot bath test is much lower than that reported for Caucasians. Thus this study shows further differences between Asian and Caucasian MS patients.

Adult

Juvenile myoclonic epilepsy--a report of 11 patients at the University Hospital, Kuala Lumpur.

This is a report on 11 cases of Juvenile Myoclonic Epilepsy (JME) from the University Hospital, Kuala Lumpur, all of whom were diagnosed in the last one and a half years. This genetic syndrome is seen in all the three main racial groups: Chinese, Malays and Indians. It accounts for 2% of the epilepsy patients seen at the neurology clinic. Lack of awareness is the main hindrance to diagnosis.

Adolescent