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Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 55 records · Page 3Linked to original sources

Candida dubliniensis at a cancer center.

Candida dubliniensis, a germ tube-positive yeast first described and identified as a cause of oral candidiasis in patients with acquired immunodeficiency syndrome in Europe in 1995, has an expanding clinical and geographic distribution that appears to be similar to that of the other germ tube-positive yeast, Candida albicans. This study determined the frequency, clinical spectrum, drug susceptibility profile, and suitable methods for identification of this emerging pathogen at a cancer center in 1998 and 1999. Twenty-two isolates were recovered from 16 patients with solid-organ or hematologic malignancies or acquired immunodeficiency syndrome. Two patients with cancer had invasive infection, and 14 were colonized with fungus or had superficial fungal infection. All isolates produced germ tubes and chlamydospores at 37 degrees C, did not grow at 45 degrees C, and gave negative reactions with d-xylose and alpha-methyl-d-glucoside in the API 20 C AUX and ID 32 C yeast identification systems. Phenotypic identification was confirmed by molecular beacon probe technology. All isolates were susceptible to the antifungal drugs amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, and ketoconazole.

Adult↗

p27Kip1 is required for PTEN-induced G1 growth arrest.

The tumor suppressor PTEN is one of the most commonly inactivated genes in human cancer. Glioblastoma multiforme cells harboring mutant PTEN have abnormally high levels of 3' phosphoinositides and elevated protein kinase B activity. Expression of wild-type PTEN in glioma cells, containing endogenous mutant PTEN, reduces 3' phosphoinositides levels, inhibits PKB activity, and induces G1 cell cycle arrest. We investigated the mechanism of the PTEN-induced growth arrest in glioma cell lines. Expression of PTEN is associated with increased expression of p27Kip1, decreased expression of cyclins A and D3, inhibition of cdk2 activity, and dephosphorylation of pRb. Inactivation of p53, by the human papilloma virus E6 oncoprotein, does not prevent PTEN-induced G1 arrest, implying that p53 is not required for G1 arrest. In contrast, p27Kip1 antisense oligonucleotides abrogated the growth arrest induced by PTEN. Furthermore, blocking p27Kip1 expression prevented the PTEN-induced reduction of cyclin-dependent kinase 2 activity, indicating that p27Kip1 functions upstream of cyclin-dependent kinase 2 in the PTEN regulatory cascade. These results implicate p27Kip1 as a critical mediator of PTEN-induced G1 arrest.

CDC2-CDC28 Kinases↗

Rantes activates Jak2 and Jak3 to regulate engagement of multiple signaling pathways in T cells.

The chemokine RANTES (regulated on activation normal T cell expressed and secreted) and its cognate receptor CC chemokine receptor 5 (CCR5) have been implicated in regulating immune cell function. Previously we reported that in T cells, RANTES activation of CCR5 results in Stat1 and Stat3 phosphorylation-activation, leading to Stat1:1 and Stat1:3 dimers that exhibit DNA binding activity and the transcriptional induction of a Stat-inducible gene, c-fos. Given that RANTES and CCR5 have been implicated in T cell activation, we have studied RANTES-induced signaling events in a CCR5-expressing T cell line, PM1. RANTES treatment of PM1 T cells results in the rapid phosphorylation-activation of CCR5, Jak2, and Jak3. RANTES-inducible Jak phosphorylation is insensitive to pertussis toxin inhibition, indicating that RANTES-CCR5-mediated tyrosine phosphorylation events are not coupled directly to Galpha(i) protein-mediated events. In addition to Jaks, several other proteins are rapidly phosphorylated on tyrosine residues in a RANTES-dependent manner, including the Src kinase p56(lck), which associates with Jak3. Additionally our data confirm that the amino-terminally modified RANTES proteins, aminooxypentane-RANTES and Met-RANTES, are agonists for CCR5 and induce early tyrosine phosphorylation events that are indistinguishable from those inducible by RANTES with similar kinetics. Our data also demonstrate that RANTES activates the p38 mitogen-activated protein (MAP) kinase pathway. This is evidenced by the rapid RANTES-dependent phosphorylation and activation of p38 MAP kinase as well as the activation of the downstream effector of p38, MAP kinase-activated protein (MAPKAP) kinase-2. Pharmacological inhibition of RANTES-dependent p38 MAP kinase activation blocks MAPKAP kinase-2 activity. Thus, activation of Jak kinases and p38 MAP kinase by RANTES regulates the engagement of multiple signaling pathways.

Chemokine CCL5↗

Intervention and policy issues related to children's exposure to environmental tobacco smoke.

BACKGROUND: Children's exposure to environmental tobacco smoke (ETS) is unacceptably high; almost 40% of children in the United States are regularly exposed to ETS. METHODS: This paper presents a review of the literature that evaluates interventions designed to reduce ETS exposure among young children. In addition, it presents the study design for Project KISS (Keeping Infants Safe from Smoke), an intervention designed to utilize exposure-related feedback to increase parents' motivation for ETS reduction and to reduce household ETS levels. Baseline data are presented to illustrate factors that should be addressed in ETS interventions. RESULTS: The literature review demonstrates the dearth of studies in the literature targeting ETS reduction among children. Participants in Project KISS believed that smoking had affected their children's health and were in later stages of motivational readiness to quit smoking than is typically observed. However, they face a number of challenges to smoking, such as high prevalence of nicotine dependence, high prevalence of living with other smokers, and socioeconomic and stress-related barriers. CONCLUSIONS: The policy implications of this research are discussed, and recommendations are made for future research.

Adult↗

Preclinical evaluation of docusate as protective agent from herpes simplex viruses.

Prevention of sexually transmitted infections (STIs) is key to public health efforts to control these diseases. An effective vaginal microbicide could provide topical, broad-spectrum prevention against the transmission of several STI pathogens. Docusate is a sulfated surfactant and, as such, may inactivate viral pathogens by disrupting viral envelopes and/or denaturing/disassociating proteins. Accordingly, the in vitro efficacy and toxicity of docusate (dioctyl sodium sulfosuccinate; Zorex; Meditech Pharmaceuticals, Inc., Scottsdale, Arizona) against herpes simplex viruses (HSV) were evaluated. Docusate was effective in vitro against wild type and drug-resistant strains of HSV type 1 and 2 with EC(90-100) (effective concentration giving 90-100% virus yield reduction) of approximately 0.005% (w/v). Sodium dodecyl sulfate (SDS) was equipotent, however, docusate was somewhat less toxic to uninfected Vero cells compared with SDS after 2 days incubation (docusate CC(50) approximately 0.01% vs. SDS approximately 0.005%). The cytotoxicity profiles of docusate were time- and dose-dependent and thus associated with the frequency of use. Kinetics of inactivation examined by pre-mixing virus and drug in a time-course experiment demonstrated that docusate could reach its EC(90-100) within 30 min. Docusate pretreatment of cells was associated with a 45% reduction in infectivity of those cells, despite a triple washing procedure. Once infected, an approximate 30% plaque reduction was observed with treatment.

Animals↗

Dementia-related behavioral changes - a physician's office-based study.

This is a physician's office-based retrospective study of 161 dementia patients with (94) and without (67) behavioral symptoms. Those with disturbed behavior were subdivided into patients with behavior changes at initial evaluation and those encountered in existing dementia. The two main groups and the subgroups were studied in relation to individual and disease characteristics. The targeted behaviors (aggression, psychosis, aberrant motor behavior and miscellaneous) were analyzed in relation to four dementia-related domains namely cognitive impairment, language impairment, stage of illness (CDR) and functional disability (Rankin grades). No differences were observed between the two main groups in relation to age and gender and to cognitive impairment, language impairment and disability except for stage of illness (P=0.01). There were no significant differences in terms of age and gender in the two subgroups and in the frequency of single targeted behaviors but for psychosis which was the most commonly recorded disturbed behavior. There was no correlation between the single targeted behaviors and the different domains examined but for aberrant motor behavior and stage of illness (P=0.04) in the subgroups.

Journal Article↗

Development of mechanically stable alginate/chondrocyte constructs: effects of guluronic acid content and matrix synthesis.

The purpose of this study was to investigate factors which enhanced the compressive properties of alginate/chondrocyte constructs. Firstly, we studied the effect of biochemical composition (high, mid and low guluronic acid content) and sterilization method on alginate properties. Secondly, we studied the biosynthetic characteristics of chondrocytes in three different alginate compositions and performed mechanical tests to determine whether the synthesis of cartilage matrix components could significantly enhance the compressive properties. 2% alginate solutions containing an initial cell density of 4 x 10(6) cells/ml were cast into cylinders and cultured for seven weeks. Compression tests, biochemistry, immunohistochemistry and electron microscopy were performed at fixed intervals during the seven-week culture period. The dynamic modulus, peak strain, and peak stress were maximum for alginate with the highest guluronic acid content. The presence of cells and their respective matrix components enhanced the equilibrium modulus of the constructs for all types of alginate, though this effect was small. Alginate containing the middle amount of guluronic acid resulted in constructs which were both mechanically stable and which promoted synthesis of cartilage matrix proteins. In experiments and applications in which the mechanical integrity of the alginate is important, the composition and purity of the alginate and its method of sterilization should be selected with care.

Alginates↗

Infantile spasms.

Infantile spasms constitute both a distinctive seizure type and an age-specific epilepsy syndrome that have been extensively described for over a century. Standardization of the classification of infantile spasms has evolved, culminating in recent recommendations for separately recognizing and distinguishing the seizure type (spasms or epileptic spasms) and the epilepsy syndrome of infantile spasms (West syndrome). More-detailed descriptions of the clinical and electrographic features of epileptic spasms and hypsarrhythmia have emerged. Advances in neuroimaging techniques have revealed clues about pathophysiology and increased the etiologic yield of the diagnostic evaluation of patients with infantile spasms. Adrenocorticotrophic hormone remains the treatment of choice for many neurologists. Recent controlled studies support vigabatrin as first-line therapy, and open-label studies suggest that topiramate, lamotrigine, and zonisamide may be useful in treating spasms. Recent reports of visual-field constriction with vigabatrin may limit its use. Surgical treatment has been used successfully in a select subgroup of patients with secondarily generalized spasms from a single epileptogenic zone. Although the prognosis for most patients with infantile spasms remains poor, further studies identifying predictors of favorable prognosis and recent advances in understanding the pathophysiology of infantile spasms offer hope of safer and more-effective therapies that improve long-term outcome.

Adrenocorticotropic Hormone↗

The role of selective estrogen receptor modulators in the prevention and treatment of osteoporosis.

Osteoporosis can affect almost everyone in the population, and although clinical outcome of fracture is manifested in late life, the disease process begins in the early postmenopausal years in women. The pharmacologic agents currently available for osteoporosis prevention and treatment act by inhibiting bone resorption, and include estrogen or hormone replacement therapy (estrogen with progestin), bisphosphonates, salmon calcitonin nasal spray, and selective estrogen receptor modulators (SERMs). Raloxifene is a benzothiophene SERM that has estrogen against effects in bone and on serum lipid metabolism and estrogen antagonist effects on breast and uterine tissue. This article summarizes the effects of these antiresorptive agents, as measured by changes in bone mineral density, biochemical markers of bone turnover, and incident fractures in postmenopausal osteoporosis.

Aged↗

Postictal cerebrospinal fluid abnormalities in children.

OBJECTIVES: To determine the frequency and characteristics of seizure-induced cerebrospinal fluid (CSF) abnormalities in children and to identify potential alternative causes of these findings. METHODS: Consecutive patients (n = 80) who underwent lumbar puncture within 24 hours after a seizure were studied retrospectively. The presence of CSF abnormalities in total leukocytes, polymorphonuclear cells, and protein was determined by using age-specific reference values. Coexisting conditions that could affect CSF findings, such as traumatic lumbar puncture, concurrent neurologic disease, and undiagnosed meningitis, were identified. RESULTS: Eighteen of the 80 patients were excluded from the final study group because of the presence of another condition that could alter the CSF. More than 50% of the excluded patients had an abnormal CSF leukocyte count or protein level, including 2 patients with initially undiagnosed meningitis, which was subsequently detected by post-hoc polymerase chain reaction testing. In the remaining 62 patients, postictal pleocytosis was detected in only 3 (5%), and increased protein was detected in only 6 (10%). The maximal postictal pleocytosis and protein level were 8 x 10(6) leukocytes/L (8 leukocytes/mm(3)) and 0.52 g/L (52 mg/dL), respectively. CONCLUSIONS: Seizure-induced CSF abnormalities are rare in children, and alternative, often unidentified, disease processes may account for many observed postictal abnormalities. All patients with abnormal CSF after a seizure should be thoroughly evaluated for other causes of the abnormality.

Adolescent↗

Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium.

BACKGROUND: Validation studies of dietary instruments developed for epidemiological studies have typically used some form of diet record as the standard for comparison. Recent work suggests that comparison with diet record may overestimate the ability of the epidemiological instrument to measure habitual dietary intake, due to lack of independence of the measurement errors. The degree of regression dilution in estimating diet-disease association may therefore have been correspondingly underestimated. Use of biochemical measures of intake may mitigate the problem. In this paper, we report on the use of urinary measures of intakes of nitrogen, potassium and sodium to compare the performance of a semi-quantitative food frequency questionnaire (FFQ) and a 7-day diet diary (7DD) to estimate average intake of these nutrients over one year. METHODS: In all, 179 individuals were asked to complete an FFQ and a 7DD on two occasions separated by approximately 12 months. The individuals were also asked to provide 24-hour urine samples on six occasions over a 6-9-month period, covering the time at which the record FFQ and 7DD were completed. The urine was assayed for nitrogen, potassium and sodium. The protocol was completed by 123 individuals. The data from these individuals were analysed to estimate the covariance structure of the measurement errors of the FFQ, the 7DD and a single 24-hour urine measurement, and to estimate the degree of regression dilution associated with the FFQ and 7DD. RESULTS: The results demonstrated that: (1) the error variances for each of the three nutrients was more than twice as great with the FFQ than the 7DD; (2) there was substantial correlation (0.46-0.58) between the error of both the FFQ and the 7DD completed on different occasions; (3) there was moderate correlation (0.24- 0.29) between the error in the FFQ and the error in the 7DD for each nutrient; (4) the correlation between errors in different nutrients was higher for the FFQ (0.77-0.80) than for the 7DD (0.52-0.70). CONCLUSIONS: The regression dilution with the FFQ is considerably greater than with the 7DD and also, for the nutrients considered, greater than would be inferred if validation studies were based solely on record or diary type instruments.

Adult↗

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: I--Simultaneous prediction of reaction force and lateral displacement.

This study investigated the ability of the linear biphasic poroelastic (BPE) model and the linear biphasic poroviscoelastic (BPVE) model to simultaneously predict the reaction force and lateral displacement exhibited by articular cartilage during stress relaxation in unconfined compression. Both models consider articular cartilage as a binary mixture of a porous incompressible solid phase and an incompressible inviscid fluid phase. The BPE model assumes the solid phase is elastic, while the BPVE model assumes the solid phase is viscoelastic. In addition, the efficacy of two additional models was also examined, i.e., the transversely isotropic BPE (TIBPE) model, which considers transverse isotropy of the solid matrix within the framework of the linear BPE model assumptions, and a linear viscoelastic solid (LVE) model, which assumes that the viscoelastic behavior of articular cartilage is solely governed by the intrinsic viscoelastic nature of the solid matrix, independent of the interstitial fluid flow. It was found that the BPE model was able to accurately account for the lateral displacement, but unable to fit the short-term reaction force data of all specimens tested. The TIBPE model was able to account for either the lateral displacement or the reaction force, but not both simultaneously. The LVE model was able to account for the complete reaction force, but unable to fit the lateral displacement measured experimentally. The BPVE model was able to completely account for both lateral displacement and reaction force for all specimens tested. These results suggest that both the fluid flow-dependent and fluid flow-independent viscoelastic mechanisms are essential for a complete simulation of the viscoelastic phenomena of articular cartilage.

Animals↗

Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6.

Adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5' AMP. Using intestinal epithelial cell line T84, we studied the effect of adenosine on the secretion of IL-6, a proinflammatory cytokine involved in neutrophil degranulation and lymphocyte differentiation. Stimulation of T84 monolayers with either apical or basolateral adenosine induces A2b receptor-mediated increase in IL-6 secretion, which is polarized to the apical (luminal) compartment. In addition, Salmonella typhimurium, TNF-alpha, and forskolin, known inducers of IL-6 secretion in intestinal epithelial cells, also stimulate IL-6 secretion into the apical compartment. We show that IL6 promoter induction by adenosine occurs through cAMP-mediated activation of nuclear cAMP-responsive element-binding protein (CREB). We also show that IL-6 released in the luminal (apical) compartment achieves a sufficient concentration to activate neutrophils (from which the adenosine signal originates), since such IL-6 is found to induce an intracellular [Ca(++)] flux in neutrophils. We conclude that adenosine released in the intestinal lumen during active inflammation may induce IL-6 secretion, which is mediated by cAMP/CREB activation and occurs in an apically polarized fashion. This would allow sequential activation of neutrophil degranulation in the lumen -- a flow of events that would, in an epithelium-dependent fashion, enhance microbicidal activity of neutrophils as they arrive in the intestinal lumen.

Activating Transcription Factors↗

Monitoring signal transduction in cancer: tyrosine kinase gene expression profiling.

Abnormal expression of tyrosine kinase (TK) genes is common in tumors, in which it is believed to alter cell growth and response to external stimuli such as growth factors and hormones. Although the etiology and pathogenesis of carcinomas of the thyroid or breast remain unclear, there is evidence that the expression of TK genes, such as receptor tyrosine kinases, or mitogen-activated protein kinases, is dysregulated in these tumors, and that overexpression of particular TK genes due to gene amplification, changes in gene regulation, or structural alterations leads to oncogenic transformation of epithelial cells. We developed a rapid scheme to measure semiquantitatively the expression levels of 50-100 TK genes. Our assay is based on RT-PCR with mixed based primers that anneal to conserved regions in the catalytic domain of TK genes to generate gene-specific fragments. PCR products are then labeled by random priming and hybridized to DNA microarrays carrying known TK gene targets. Inclusion of differently labeled fragments from reference or normal cells allows identification of TK genes that show altered expression levels during malignant transformation or tumor progression. Examples demonstrate how this innovative assay might help to define new markers for tumor progression and potential targets for disease intervention. (J Histochem Cytochem 49:673-674, 2001)

Breast Neoplasms↗

Monitoring signal transduction in cancer: cDNA microarray for semiquantitative analysis.

This study targeted the development of a novel microarray tool to allow rapid determination of the expression levels of 58 different tyrosine kinase (tk) genes in small tumor samples. The goals were to define a reference probe for multi-sample comparison and to investigate the variability and reproducibility of the image acquisition and RT-PCR procedures. The small number of tk genes on our arrays enabled us to define a reference probe by artificially mixing all genes on the arrays. Such a probe provided contrast reference for comparative hybridization of control and sample DNA and enabled cross-comparison of more than two samples against one another. Comparison of signals generated from multiple scanning eliminated the concern of photo bleaching and scanner intrinsic noise. Tests performed with breast, thyroid, and prostate cancer samples yielded distinctive patterns and suggest the feasibility of our approach. Repeated experiments indicated reproducibility of such arrays. Up- or downregulated genes identified by this rapid screening are now being investigated with techniques such as in situ hybridization.

Breast Neoplasms↗

Attitudes about organ and tissue donation among the general public and blood donors in Hong Kong.

CONTEXT: The cadaveric organ and tissue donation rate in Hong Kong is not satisfactory; 1 million blood donors are registered and more than 300,000 are active. However, the current attitudes toward organ and tissue donation in the general public and blood donors of Hong Kong are unknown. METHODS: Random general public (n = 1018) and blood donors (n = 1227) of Chinese origin, with age ranging from 16 to 60 years, were interviewed using a standard verified questionnaire that examines attitudes and knowledge of organ and tissue donation. RESULTS: The mean age of the general public and blood donors were 32.6 and 28.9 years, respectively. Of the general public, 44.4% were men and among blood donors, 60% were men. About 56% of both groups thought that organ donation is an obligation of citizens. Blood donors were more aware than the general public about the types of organs that can be donated. When compared with the general public, a significantly higher percentage of blood donors were willing to donate their organs (81% vs 53%), had heard about organ donation cards (98.3% vs 89.5%), and had signed the cards (49.9% vs 22.6%). About 70% of both groups who had signed a card were carrying it. Thirty-nine percent of the general public and 17% of blood donors had not decided whether they would donate. For blood donors, 49.7% were willing to donate their relatives' organs, compared with 41.8% of the general public. Most individuals in both groups would not object to their relatives' decision to donate. About two thirds of individuals in both groups disagreed with the concept of an opt-out law, though only 20% of the general public and 14.4% of blood donors would refuse donation if an opt-out law were in practice. CONCLUSIONS: This study shows that blood donors have better knowledge of organ donation and are more willing to donate their organs and sign an organ donation card than the general public. However, a substantial proportion of blood donors have not signed a donor card. It would be useful to design promotion programs to facilitate blood donors' participation in organ donation.

Adolescent↗

Ren and Yuan: a cultural interpretation of Chinese women's responses to battering.

The purpose of the study was to examine women's responses to battering within the context of Chinese culture. The stories of 11 Chinese women living in Hong Kong formed the basis of the inquiry. Analysis of the women's accounts revealed Chinese values in their responses to battering: they adopted ren, or endurance, as a coping mechanism and used Yuan, or predestination, as an explanation for their failed relationship. The resilience and resourcefulness of the women are clearly demonstrated in the strategies they employed to cope with the abuse. Their responses to battering were purposeful and varied according to the status of their relationship.

Adaptation, Psychological↗