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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
PubMed2005

Effect of bone material properties on the initial stability of a cementless hip stem: a finite element study.

In previous finite element studies of cementless hip stems reported in the literature, the effect of bone quality on the initial micromotion and interface bone strain has been rarely reported. In this study, the effect of varying cortical and cancellous bone modulus on initial stem micromotion and interface bone strain was examined and the potential consequence of these changes on bone ingrowth and implant migration was reported. A finite element (FE) model of a total hip replacement (THR) was created and the Young's moduli of cortical and cancellous bone were systematically varied to study the relative effect of the quality of both types of bone on the initial stability of a cementless THR. It was found that the initial micromotion and interface bone strain in a THR was significantly affected by the overall stiffness of the femur. In other words, both the reduction of the modulus of cortical and cancellous bone caused an increase in the initial micromotion and interface bone strain. This suggests that for FE studies to be truly predictive, a range of bone quality must be examined to study the performance envelope of a particular stem and to allow comparison with clinical results.

Arthroplasty, Replacement, Hip↗
PubMed2001

Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis?

Since autocrine regulation of HGF-Met is implicated in many forms of human cancer, we investigated whether the predisposition to develop ovarian cancer in women with hereditary ovarian cancer syndromes involves changes in the expression of HGF-Met by the tissue of origin of epithelial ovarian cancers, the ovarian surface epithelium (OSE). We compared cultures of normal OSE from women with (FH-OSE) (n=20) and with no (NFH-OSE) (n=48) family histories of ovarian cancer, SV40 Tag immortalized OSE lines (IOSE, n=5) and ovarian cancer cell lines (n=3). Cultures derived from 21/22 women with NFH-OSE and 13/13 women with FH-OSE expressed Met mRNA initially. After two to three passages, Met was downregulated in 37% of NFH-OSE cultures but persisted in 100% of FH-OSE cultures and ovarian cancer lines, like other epithelial differentiation markers that are stabilized in FH-OSE and neoplasia. HGF and Met mRNA were concomitantly expressed by NFH-OSE from only three of 32 women but in FH-OSE from eight of 13 women, and also in five of five IOSE and two of three ovarian cancer lines. Conditioned media from FH-OSE, but not NFH-OSE, contained immunoreactive HGF and induced cohort migration which was inhibited by neutralizing HGF antibody. Several signaling molecules of the PI3K pathway, including Akt2 and p70 S6K, were constitutively activated in FH-OSE from six of six women but in NFH-OSE from only four of eight women. Exogenous HGF was mitogenic in OSE, and that effect was regulated through the MAP kinase (ERK1/ERK2) and FRAP/p70 S6K pathways. The proliferative response to HGF was greater in NFH-OSE than in FH-OSE cultures. The results show that FH-OSE cultures differ from NFH-OSE by increased stability of Met expression and by HGF secretion. Constitutive phosphorylation of kinases and a diminished growth response to HGF suggest the presence of autocrine regulation in FH-OSE. In analogy with other cell types where an autocrine HGF-Met loop has been implicated in tumorigenic transformation, this change in FH-OSE may play a role in the enhanced susceptibility to ovarian carcinogenesis in women with hereditary ovarian cancer syndromes.

Autocrine Communication↗
PubMed2001

Profiling of protein kinases in the neoplastic transformation of human ovarian surface epithelium.

OBJECTIVE: The aim of this study was to study the pattern of protein kinase expression in a culture model of epithelial ovarian carcinogenesis. METHODS: Cultures of normal human ovarian surface epithelium (OSE), OSE from women with BRCA1 mutations, a cell culture model of preneoplastic (SV40 T-antigen-immortalized, nontumorigenic) and neoplastic (SV40-E-cadherin transfected, tumorigenic) OSE, and three ovarian cancer cell lines were used to represent OSE phenotypes of different genetic backgrounds and at different, progressive stages of neoplastic transformation. The protein kinase network signaling was studied by Western blotting, simultaneously using multiple antibodies for specific protein kinases. RESULTS: High levels of cGMP-dependent protein kinase were found in normal and preneoplastic OSE, but were absent in neoplastic OSE. In contrast, expression of MEK6 was detected exclusively in neoplastic OSE. The expressions of casein kinase II (CK2), p38 mitogen-activated protein kinase (MAPK), cyclin-dependent kinase, and the phosphatidylinositol 3-kinase (PI3K) effectors Akt2 and p70 S6 kinase (S6K) were several-fold higher in neoplastic OSE than in normal OSE, whereas the expressions of the MAPKs extracellular signal-regulated kinases ERK1 and -2 were unchanged. Importantly, constitutive phosphorylation of Akt2 and p70 S6K, as found in neoplastic OSE, was also observed in overtly normal OSE from women with predisposing BRCA1 gene mutations. CONCLUSIONS: These data demonstrate that different repertoires of downstream signaling proteins, particularly those of the MEK6-p38 MAPK-CK2 pathway and the PI3K pathway, are correlated with phenotypic manifestations of a cell culture model of OSE at progressive stages in the development of ovarian cancer. Changes in PI3K effectors are already found in overtly normal OSE from women with BRCA1 mutations.

Animals↗
PubMed2001

Rabbit sex hormone-binding globulin: expression in the liver and testis during postnatal development and structural characterization by truncated proteins.

Although sex hormone binding globulin (SHBG) is found in the blood plasma of adult humans and rabbits and the gene is expressed in their livers, it is not detected in the plasma of adult rodents nor is it expressed in adult rodent livers. Thus the rabbit represents a good model to study the metabolism and function of SHBG in the blood. We have used a cloned rabbit SHBG cDNA to detect mRNA expression in rabbits during the postnatal period, and to construct truncated SHBG proteins for structure/function analysis. The SHBG mRNA appeared in the testis as early as 3 days after birth. The level increased gradually in abundance throughout postnatal development, and attained a maximum at 12 weeks of age when the gonads were fully matured. In contrast, SHBG mRNA in the livers of male and female animals increased to a maximum by 4 weeks of age, and were maintained at this level until 12 weeks before subsiding to the initial levels. The increase and decrease in SHBG mRNA levels in the liver were accompanied by similar changes in serum SHBG. This suggests that SHBG in the blood circulation comes from the liver and this might also provide a source of SHBG for the male reproductive tract before formation of the blood-testis barrier. To elucidate the minimal sequence of rabbit SHBG responsible for steroid-binding, a panel of 13 truncated SHBG proteins was constructed, expressed in Escherichia coli, and biochemically purified for study. It was shown that the complete protein sequence of rabbit SHBG was important for maintaining a stable steroid-protein complex. Unlike human SHBG for which a truncated protein of the first 206 residues of the 373 amino acid protein can still bind steroid, removal of 43 or more residues from the C-terminus of rabbit SHBG completely abolished steroid-binding.

Age Factors↗
PubMed2001

Ovarian surface epithelium: biology, endocrinology, and pathology.

The epithelial ovarian carcinomas, which make up more than 85% of human ovarian cancer, arise in the ovarian surface epithelium (OSE). The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies because there are no appropriate animal models, and because methods to culture OSE have become available only recently. The objective of this article is to review the cellular and molecular mechanisms that underlie the control of normal and neoplastic OSE cell growth, differentiation, and expression of indicators of neoplastic progression. We begin with a brief discussion of the development of OSE, from embryonic to the adult. The pathological and genetic changes of OSE during neoplastic progression are next summarized. The histological characteristics of OSE cells in culture are also described. Finally, the potential involvement of hormones, growth factors, and cytokines is discussed in terms of their contribution to our understanding of the physiology of normal OSE and ovarian cancer development.

Adult↗
PubMed2001

Fatal chemotherapy associated Clostridium difficile infection--a case report.

Clostridium difficile associated diarrhoea or Pseudomembranous colitis occasionally occurs without prior antibiotic usage. While the association of chemotherapy and Clostridium difficile infection has previously been well recorded, the true incidence is unknown. We report a case of Clostridium difficile associated diarrhoea after chemotherapy for lung cancer. The fatal outcome in this case and the increasing use of chemotherapy in this country highlights the need to have a high index of suspicion in any case of unexplained diarrhoea post chemotherapy. A review of the literature is presented.

Aged↗
PubMed2000

Hepatocyte growth factor promotes in vitro scattering and morphogenesis of human cervical carcinoma cells.

OBJECTIVE: Hepatocyte growth factor (HGF) enhances cell dissociation and morphogenesis in many forms of carcinomas including some, but not all, cervical carcinomas. In this study, we examined the effects of HGF on two cervical cancer cell lines, derived from the same tumor, with different growth patterns in vivo and in vitro. METHODS: Two cell lines, derived from the same cervical carcinoma, express spinous (C-4I) and basal (C4-II) squamous cell differentiation, respectively. A cell scattering assay was used to determine whether HGF would stimulate cell dissociation and motility. The morphogenetic capacity of HGF was assessed in collagen gel cultures, expression of the HGF receptor c-Met by Western blot analysis, and cadherin expression by immunofluorescence microscopy. RESULTS: HGF-induced cell scattering was intense in C-4II, but limited in C-4I cultures. In collagen gels, C-4I cells formed large, spherical compact colonies with necrotic centers while C-4II cells formed small, irregular colonies with no necrosis. HGF induced proliferation and branching morphogenesis in both lines, but more prominently in C-4II cultures. There was no difference in c-Met or E- and P-cadherin expression between C-4I and C-4II cultures, but the lines differed in their signal transduction responses to HGF. The scatter response was mediated primarily by phosphatidylinositol 3-kinase in line C-4I, but by mitogen-activated protein kinase in line C-4II. HGF induced collagen gel contraction by C-4 cells, demonstrating for the first time that HGF has the capacity to induce this function. CONCLUSIONS: The HGF-induced cell dispersion, morphogenesis, and collagen gel contraction in two cervical carcinoma cell lines were greatly influenced by differences between the lines in differentiation-associated properties. These properties, which include variations in extracellular matrix, junctional proteins, and signal transduction, may also modulate HGF action in vivo and thus determine patterns of invasiveness and growth of cervical carcinomas.

Animals↗
PubMed2000

The sedative and electroencephalographic effects of regional anaesthesia.

We studied sedation scores, the processed electroencephalogram and mean arterial pressure pre-operatively in patients before and after spinal (n = 15) and lumbar epidural (n = 15) anaesthesia. We compared them with changes occurring over time in a control group (n = 15), using the responsiveness component of the Observer Assessment of Alertness and Sedation rating scale. The electroencephalographic variables studied were bispectral index, 95% spectral edge frequency, median frequency and the power distribution between frequency bands alpha, beta, theta and delta. No differences were detected within groups in sedation scores before and after intervention, or between groups at either stage. No between-group differences were detected in electroencephalographic variables. In the spinal group, spinal anaesthesia caused an increase in bispectral index, 95% spectral edge frequency, median frequency and beta frequencies, and a decrease in delta frequencies and mean arterial pressure. The increase in beta frequencies is similar to that seen in patients with low plasma concentrations of midazolam and may represent subclinical sedation.

Adult↗
PubMed2000

Effects of load carriage on heart rate, blood pressure and energy expenditure in children.

Fifteen male primary school children, aged 10 years, were selected to carry school bags of 10, 15 and 20% of their own body weights, where 0% body weight was used as a control. Maximum oxygen uptake (VO2max) tests were conducted on a motorized treadmill using a continuous incremental protocol. During the load carrying test, subjects walked on a treadmill at 1.1 m s(-1) for 20 min at each load condition. Blood pressures were measured before, immediately following, and at 3 and 5 min after every trial. Heart rate and expired VO2 were recorded before, during and 5 min after walking using a cardiopulmonary function system. The results showed a significant difference in oxygen uptake, energy expenditure and the recovery of blood pressure rise for between 10 and 20% body weight load conditions. The carrying weight of a school bag for children could be recommended as 10% of body weight because it was not significantly different from 0% load in the metabolic cost.

Biomechanical Phenomena↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1995

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↗
PubMed1995

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↗