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Biomedical subjects

A S Wong

Publications and source records attributed to A S Wong.

At least 19 recordsLinked to original sources

Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer.

Epithelial ovarian carcinomas arise in a simple mesothelium (ovarian surface epithelium, OSE) but exhibit properties of oviductal and endometrial epithelia. Thus, during malignant progression, their differentiation proceeds from simple to complex, in contrast to carcinomas in other tissues. Related changes in OSE of women with a history of familial ovarian cancer indicate that this aberrant differentiation is initiated very early in neoplastic progression. The mechanisms underlying this process are not understood. Because cadherins are known regulators of differentiation, we investigated the relationship of the cadherins E, N and P to OSE morphology, growth patterns and differentiation in cultures of normal and metaplastic OSE from women with (FH-OSE) and without (NFH-OSE) a family history of ovarian cancer and in the ovarian carcinoma lines OVCAR-3 and CaOV3. We used immunofluorescence, RT-PCR, in situ hybridization and Western blotting. Our results define N-cadherin as the constitutively expressed cadherin of normal and metaplastic OSE and indicate that P-cadherin is undetectable while E-cadherin expression is conditional and related to genotype, stage of neoplastic progression and growth pattern. The altered expression of E-cadherin in apparently normal OSE of women with hereditary ovarian cancer syndromes in conjunction with the known capacity of E-cadherin to induce epithelial characteristics implicates this adhesion molecule as a possible inducer of the aberrant Mullerian differentiation which characterizes epithelial ovarian carcinomas. Abnormal differentiation in such (pre)-neoplastic tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression.

Adult

Conformational preferences in a benzodiazepine series of potent nonpeptide fibrinogen receptor antagonists.

Previously, we reported the direct design of highly potent nonpeptide 3-oxo-1,4-benzodiazepine fibrinogen receptor antagonists from a constrained, RGD-containing cyclic semipeptide. The critical features incorporated into the design of these nonpeptides were the exocyclic amide at the 8-position which overlaid the Arg carbonyl, the phenyl ring which maintained an extended Gly conformation, and the diazepine ring which mimicked the gamma-turn at Asp. In this paper, we investigate conformational preferences of the 8-substituted benzodiazepine analogues by examining structural modifications to both the exocyclic amide and the seven-membered diazepine ring and by studying the conformation of the benzodiazepine ring using molecular modeling, X-ray crystallography, and NMR. We found that the directionality of the amide at the 8-position had little effect on activity and the (E)-olefin analogue retained significant potency, indicating that the trans orientation of the amide, and not the carbonyl or NH groups, made the largest contribution to the observed activity. For the diazepine ring, with the exception of the closely analogous 3-oxo-2-benzazepine ring system described previously, all of the modifications led to a significant reduction in activity compared to the potent 3-oxo-1, 4-benzodiazepine parent ring system, implicating this particular type of ring system as a desirable structural feature for high potency. Energy minimizations of a number of the modified analogues revealed that none could adopt the same low-energy conformation as the one shared by the active (S)-isomer of the 3-oxo-1, 4-benzodiazepines and 3-oxo-2-benzazepines. The overall data suggest that the features contributing to the observed high potency in this series are the orientation of the 3-4 amide and the conformational constraint imposed by the seven-membered ring, both of which position the key acidic and basic groups in the proper spatial relationship.

Benzodiazepines

Rabbit sex hormone binding globulin: primary structure, tissue expression, and structure/function analyses by expression in Escherichia coli.

Sex hormone binding globulin (SHBG) is a homodimeric plasma protein found in mammals that binds sex steroids with high affinity and regulates their bioavailability. The protein is identical in structure and properties to the androgen binding protein (ABP) found in the male reproductive tract. We have isolated a 1245-base pair rabbit SHBG cDNA encoding a reading frame for a signal peptide followed by a protein of 367 amino acids, which shares 79.0, 68.1 and 63.2% amino acid identity with the corresponding human, rat and mouse proteins respectively. Northern blot and hot-nested PCR analyses indicated that rabbit SHBG is produced from a 1.6 kilobase mRNA in the liver of both sexes and in the testis. The rabbit SHBG cDNA was inserted into pGEX-1 lambda T for expression of a glutathione S-transferase/SHBG fusion protein in Escherichia coli. The bacterial product bound 5 alpha-dihydrotestosterone (DHT) in the same manner as the corresponding protein in serum. The dissociation constants (Kd) for rabbit and human SHBGs produced in E. coli were 11.1 +/- 1.1 nM and 2.1 +/- 0.6 nM respectively, and rabbit SHBG formed a less stable protein-steroid complex (t1/2 = 5 min) than human SHBG (t1/2 > 60 min). Unlike human SHBG, rabbit SHBG does not bind estradiol with high affinity. To aid in the identification of differences in the sequences of rabbit and human SHBG, which determine species differences in steroid-binding affinity and specificity, chimeras containing the 5'-terminal half of SHBG from one species and 3'-terminal half of SHBG from the other species were constructed and expressed. It was found that the chimeric proteins assumed similar steroid-binding affinity and specificity as the wild-type proteins when the amino (N)-terminal half of SHBG was derived from the same species. Replacement of the carboxyl (C)-terminal half of rabbit SHBG by the corresponding region of the human molecule increased the integrity of its steroid-protein complex. This supports the concept that amino acids within the N-terminal half of SHBG constitute the steroid-binding domain while the C-terminal half of the molecule may provide structural stability to the protein and its steroid-binding site.

Amino Acid Sequence

Neurocysticercosis--case report and literature review.

A 30-year-old Indian migrant worker presented with seizures at the National University Hospital. A CT-scan of the brain showed multiple calcifications and cysts consistent with neurocysticercosis. Plain radiographs of the humeri and femora also revealed multiple soft tissue calcifications. He was given a course of anti-helminthic therapy and started on anti-epileptics. Neurocysticercosis is a common cause of seizures in endemic areas and must be considered in the differential diagnosis of epilepsy involving the members of the large community of migrant workers in Singapore.

Adult

Sport specific fitness testing of elite badminton players.

There is a scarcity of descriptive data on the performance capacity of elite badminton players, whose fitness requirements are quite specific. The purpose of this paper is to investigate the physiological response of elite badminton players in a sport-specific fitness test. Twelve Hong Kong national badminton team players performed a field test on a badminton court. Six light bulbs were connected to a programming device causing individual bulbs to light up in a given sequence. The players were instructed to react to the flashes by running towards them, and striking shuttles mounted in the vicinity of the bulbs. Exercise intensity was controlled by altering the interval between successive lightings. A low correlation (r = 0.65) was found between the results of the field test and the rank-order list of subjects, based on an objective on-field physiological assessment and subjective ranking. This may be explained by the requirements of other factors besides physical fitness which contribute to success in elite level badminton competition. These factors may include, for example, technical skill, mental power, and aesthetic judgements on the court. Maximum mean (s.d.) heart rate data (187(8) beats.min-1) and blood lactate values (10.4(2.9) mmol.l-1) in this study showed that players were under maximal load during the field test. From the testing data, it seems reasonable to speculate that the intensity of level 3 (20 light pulses.min-1; 3.0 s.pulse-1) and level 4 (22 light pulses.min-1; 2.7 s.pulse-1) simulates the requirement of actual games energy expenditure of the Hong Kong badminton players exercising at close to their anaerobic threshold. The results also show that an estimate of fitness can be derived from measurements involving exercise closely resembling that which is specific for the sports activity in question. Improved training advice and guidance may result from such studies.

Adult

Physiological profiles and sport specific fitness of Asian elite squash players.

There is a scarcity of descriptive data on the physiological characteristics of elite Asian squash players. The purpose of this study was to evaluate the physiological profile and sports specific fitness of Hong Kong elite squash players. It was conducted before the selection of the Hong Kong national squash team for the 1992 Asian Squash Championship. Ten elite squash players were selected as subjects for the study. Maximum oxygen uptake was measured using a continuous treadmill running test. A sports specific field test was performed in a squash court. The following means (s.d.) were observed: height 172.6(4.3) cm; weight 67.7(6.9) kg; body fat 7.4(3.4)%; forced vital capacity (FVC) 5.13(0.26) litres; maximum oxygen uptake (VO2max) 61.7(3.4) ml.kg-1.min-1; anaerobic threshold (AT) 80.2(3.3)% of VO2max; alactic power index 15.5(1.8) W.kg-1; lactic work index 323.5(29.4) J.kg-1, peak isokinetic dominant knee extensor and flexor strengths 3.11(0.29) Nm.kg-1 and 1.87(0.18) Nm.kg-1. The results show that the Hong Kong squash players have relatively high cardiorespiratory sports specific fitness and muscle strength which may be one of the key factors that contributed to the success of the Hong Kong team in the Asian Championship.

Adipose Tissue

Cardiorespiratory fitness and isokinetic muscle strength of elite Asian junior soccer players.

There is a scarcity of descriptive data on the physiological characteristics of elite Asian junior soccer players. The purpose of this study was to evaluate the cardiorespiratory fitness and isokinetic muscle strength of elite junior soccer players in Hong Kong. It was conducted in conjunction with the selection of the Hong Kong team to the 1989 Gothia Cup held in Sweden. Twenty-one top junior soccer players were selected as subjects for the study. The following means (+/- SD) were observed: age 17.3 +/- 1.1 years; height 172.5 +/- 6.2 cm; weight 62.8 +/- 7.0 kg; body fat 5.2 +/- 1.8%; forced vital capacity (FVC) 4.6 +/- 0.6 L; maximum oxygen uptake (VO2max) 58.6 +/- 2.9 ml.kg-1.min-1; anaerobic threshold (AT) 76.7 +/- 10.2% of VO2max; peak isokinetic dominant knee extensor and flexor strengths 3.28 +/- 0.37 Nm.kg-1 and 1.84 +/- 0.24 Nm.kg-1; hamstring to quadriceps peak torque ratio (H/Q) 56 +/- 0.6% measured at 60 degrees s-1. Hong Kong players appeared to have comparable aerobic power, light body weight, poor flexibility and above average isokinetic muscle strength compared to other international junior soccer players. Training programs to improve the contralateral knee muscle imbalance and to increase the fast speed movement capability of the non-dominant knee flexors are recommended.

Adipose Tissue

Aqueous flare measurement with laser flare-cell meter.

The laser flare-cell meter is a newly developed instrument designed to measure anterior chamber protein concentration in vivo. There was a linear relationship between photon count measured with this instrument and the concentration of bovine serum albumin. Measurements were taken in 29 eyes of normal subjects divided into two groups. Group 1 (15 eyes) had brown or dark irises and Group 2 (14 eyes) had blue or green irises. Photon counts obtained from Groups 1 and 2 were not significantly different. Aqueous protein concentrations estimated from standard curves were 15.7 and 18.6 mg/100 ml for Groups 1 and 2, respectively. On the other hand, the background value obtained from Group 2 was about twice the value from Group 1. These results indicate that background scattering has little effect on photon count. There was a good correlation between photon counts measured with the laser flare-cell meter and the evaluation of flare made by conventional microscopic observations. It was concluded that this instrument will be useful for clinical research studies.

Adult

Altruistic behaviour of young rats in a conflict situation.

An intraperitoneal injection of d-amphetamine (1 mg/kg) impaired the altruistic behaviour of young rats, characterized by pulling their littermates to a safe part of a two-compartment apparatus. The direction of the pulling behaviour could be changed by passive avoidance training.

Altruism

Environmental degradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Herbicide formulations containing known amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and exposed to natural sunlight on leaves, soil, or glass plates lost most or all of the TCDD during a single day, due principally to photochemical dechlorination. Despite the known persistence of pure TCDD, it is not stable as a contaminant in thin herbicide films exposed to outdoor light.

Dioxins