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Biomedical subjects

A S Chan

Publications and source records attributed to A S Chan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Regulation of beta 1-integrin-mediated cell adhesion by the Cbl adaptor protein.

BACKGROUND: Leukocyte activation results in a rapid increase in adhesion to the extracellular matrix due to the activation of beta 1 integrin receptors. A role for phosphatidylinositol (PI) 3-kinase in integrin activation has been proposed, as activation of integrins by many receptors can be blocked by PI 3-kinase inhibitors. One receptor that regulates integrins is the CD28 surface antigen; here, we investigated the mechanisms responsible for CD28-mediated integrin activation. RESULTS: CD28-mediated integrin activation was blocked by mutation of the binding site for the p85 catalytic subunit of PI 3-kinase in the CD28 cytoplasmic domain, and by expression of a dominant-negative form of the p85 subunit. Substitution of the Src homology 2 (SH2)-binding motif in the CD28 cytoplasmic domain for the corresponding motif in the CD28-related CTLA-4 surface antigen also blocked integrin activation but did not affect the recruitment and activation of PI 3-kinase. Mutations of the CD28 cytoplasmic domain that blocked integrin activation also impaired the tyrosine phosphorylation of the Cbl adaptor protein and the activation of the PI 3-kinase that was associated with Cbl. This Cbl-associated PI 3-kinase was distinct from the PI 3-kinase that coprecipitated with the CD28 cytoplasmic domain. CD28-mediated activation of beta 1 integrins was inhibited by expression of a mutant Cbl protein that shows reduced association with PI 3-kinase. CONCLUSIONS: Cbl is required for PI-3-kinase-dependent regulation of integrin receptors by CD28. Furthermore, CD28 is coupled to two distinct pools of PI 3-kinase, one directly associated with the CD28 cytoplasmic tail and the other associated with Cbl.

Amino Acid Substitution↗
PubMed1998

Trial of a community-based intervention to decrease infestation of Aedes aegypti mosquitoes in cement washbasins in El Progreso, Honduras.

Washbasins and metal drums are important sources of Aedes aegypti mosquitoes in much of Latin America. When manual cleaning was found to be ineffective in eliminating mosquito larvae in a community-based control programme in El Progreso, Honduras, it was decided to develop and evaluate an improved method of removing mosquito eggs based on commonly-available materials. The method, named La Untadita ('The Little Dab', in English), consists of five steps: mixing chlorine bleach and detergent to make a paste, applying the mixture to the walls of the container, waiting 10 min, scrubbing with a brush, and finally rinsing with water. A field trial of the Untadita was conducted in 13 peri-urban neighbourhoods. At the first post-intervention survey, in spite of high levels of exposure to the community-based intervention, high levels of knowledge regarding the Untadita and high levels of its reported use, little or no impact was discernable on mosquito larvae and pupae. The method was then modified by increasing the recommended quantities of bleach and detergent and simplifying the instructions. In the second post-intervention survey, knowledge of the steps and their order increased further; the intervention neighbourhoods had significantly fewer algae on washbasin walls, an indicator of more effective cleaning; and numbers of pupae and 3rd and 4th instar larvae were significantly lower than in untreated neighbourhoods. Effective promotion of the Untadita should be able to control mosquito infestation in many washbasins, especially those in frequent use, thus reducing the need for chemical and biological larvicides that may be either more costly or less acceptable to householders.

Aedes↗
PubMed1998

Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung.

Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized primary non-small cell lung carcinoma with distinct clinicopathological features and an aetiological association with Epstein-Barr virus (EBV) infection. The tumour consists of clusters and sheets of poorly or undifferentiated tumour cells in close association with numerous mononuclear inflammatory cells, including a rich component of tumour-associated macrophages (TAMs). To investigate the molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte-specific chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), and the presence of TAMs was demonstrated by immunohistochemistry in nine LELCs. The results were compared with those found in 17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1 amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and extensive expression of MCP-1 transcripts by the tumour cells of LELCs only, while TAMs, stromal fibroblasts, and endothelial cells formed the major source of MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close topographical relationship with the MCP-1-expressing tumour cells. The results indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism contributing to their distinctive morphological features. This is the first study that demonstrates the in vivo upregulation of a monocyte-specific chemokine by EBV-related carcinomas, illustrating an interesting aspect of tumour biology in EBV-related neoplasms.

Adult↗
PubMed1998

Ontogeny of NADPH-d expression in the thymic microenvironment of the chick embryo.

Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry was used to demonstrate the presence of nitric oxide in the developing chicken thymus. NADPH-d was first expressed in the epithelial cells located at the corticomedullary junction of the thymic rudiment on day 13 of incubation. The number of labelled cells gradually increased from day 13 to day 21. Ultrastructural evidence showed that the labelling was localized in a heterogeneous population of cells in the medulla near the corticomedullary junction, comprising the cystic, undifferentiated, myoid, lymphoid and epithelial reticular cells. At this age, the vascular endothelium was NADPH-d positive. Labelling was also detected in some macrophages. The reaction product primarily labelled profiles of rough endoplasmic reticulum and to a lesser extent the outer membranes of mitochondria, portions of the nuclear envelope and the Golgi apparatus. By day 18/19, NADPH-d-labelled nerve fibres were occasionally observed in the interlobular connective tissue. By day 21, these fibres formed perivascular plexuses. Labelled nerve fibres were occasionally observed in the medullary parenchyma. Possible functions of nitric oxide in the embryonic thymus are discussed.

Animals↗
PubMed1998

Microsatellite instability and mutation of DNA mismatch repair genes in gliomas.

Microsatellite instability (MSI) has been identified in various human cancers, particularly those associated with the hereditary nonpolyposis colorectal cancer syndrome. Although gliomas have been reported in a few hereditary nonpolyposis colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are conflicting, and the nature of the mismatch repair (MMR) defect is not known. We established the incidence of MSI and the underlying MMR gene mutation in 22 patients ages 45 years or less with sporadic high-grade gliomas (17 glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). Using five microsatellite loci, four patients (18%) had high level MSI, with at least 40% unstable loci. Germline MMR gene mutation was detected in all four patients, with inactivation of the second allele of the corresponding MMR gene or loss of protein expression in the tumor tissue. Frameshift mutation in the mononucleotide tract of insulin-like growth factor type II receptor was found in one high-level MSI glioma, but none was found in the transforming growth factor beta type II receptor and the Bax genes. There was no family history of cancer in three of the patients, and although one patient did have a family history of colorectal carcinoma, the case did not satisfy the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome. Three patients developed metachronous colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas. These results have important implications in the genetic testing and management of young patients with glioma and their families.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Expression of vascular endothelial growth factor in von Hippel-Lindau syndrome-associated papillary cystadenoma of the epididymis.

Vascular endothelial growth factor (VEGF) is a hypoxia inducible angiogenic and vascular permeability factor. Although VEGF expression in glioblastoma is induced by hypoxia, its expression in renal cell carcinoma and hemangioblastoma is thought to be related to mutation of the von Hippel-Lindau (VHL) gene. It is not certain whether other lesions in VHL syndrome are associated with an elevated VEGF level. We report a VHL syndrome patient with multiple hemangioblastomas and bilateral epididymal clear cell papillary cystadenomas. In situ hybridization revealed high levels of VEGF mRNA in the clear cells of the epididymal tumor and the stromal cells of the hemangioblastoma. This lends support to the notion that upregulation of VEGF is caused by loss of the wild-type VHL protein. We postulate that the elevated VEGF levels may account for the cyst formation and vascularized stroma present in these VHL-associated tumors.

Adult↗
PubMed1998

Pregnancies complicated by retained placenta: sex ratio and relation to pre-eclampsia.

Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's Hospital, covering 8549 births between 1993 and 1995, were used to ascertain the sex ratios in singleton pregnancies and the sex ratios in those pregnancies in which there was retained placenta, hypertension in pregnancy, or pre-eclampsia. The likelihood of independence of occurrence or mutual exclusivity of retained placenta and hypertension in pregnancy or pre-eclampsia were also examined. The male:female sex ratio in the South Australian population was 1.077. In pregnancies with hypertension in pregnancy it was 1.165 (P<0.001) and in pregnancies with retained placenta it was 0.883 (P<0.0001). There was a trend to an increased sex ratio in pre-eclamptic pregnancy (1.248 in primigravid and 1.092 in multigravid women) but there was insufficient power to detect significance (P=0.207 and 0.470, respectively). Neither hypertension in pregnancy nor pre-eclampsia were mutually exclusive of placenta accreta: hypertensive disorders of pregnancy and placenta accreta occurred independently of each other. Our findings suggest that sex-linked antigens are unlikely to influence maternofetal interactions consistently to give rise to one but not the other pregnancy complication.

Adult↗
PubMed1998

Repetition priming with nonverbal stimuli in patients with dementia of the Alzheimer type.

Perceptual repetition priming was examined in patients with dementia of the Alzheimer type (DAT) and normal control (NC) participants using a task involving the discrimination of geometric designs that had either a continuous ("closed") or discontinuous ("open") perimeter. With the open stimuli, the groups displayed significant and equivalent levels of priming after immediate repetition of the stimuli, whereas only the NC group primed significantly over a delay of three intervening items. Neither group demonstrated significant priming with the closed stimuli. Results indicate that under some conditions DAT patients can exhibit normal repetition priming with stimuli that do not have preexisting representations but that (due possibly to a deficiency in the level of steady-state cortical activation) this priming dissipates more rapidly in DAT patients than in NC participants.

Aged↗
PubMed1998

Development of an indicator to evaluate the impact, on a community-based Aedes aegypti control intervention, of improved cleaning of water-storage containers by householders.

Householders in a community-based programme to control dengue in El Progreso, Honduras, are being encouraged to improve the cleaning of the water-storage containers in which many of the vectors thrive. The objective of the present study was to develop an indicator of the change occurring in human behaviour. Traditional Aedes aegypti larval indices do not differentiate between containers in which all the immature stages are present and those which hold only first- and second-instar larvae. However, it is not essential to prevent all larval development to limit transmission of pathogens by the adults; if the Ae. aegypti in the containers only manage to develop to young larvae before the containers are cleaned, then control of the vector in these containers will be effective. In field trials, sampling of third- and fourth-instar larvae in washbasins by taking five dips (quick immersions to a standard depth) with a hand-held net was found to be sufficient for estimating the true population size of that same cohort. This sampling method was then included in a large-scale survey of households, conducted for programme monitoring. An index was then developed as a summary measure of the degree of infestation of a washbasin by Ae. aegypti. This index was the sum of four variables assessed in the survey: presence of any immature stages (larvae and/or pupae); presence of pupae; detection of third-fourth-instar larvae in a five-dip sample; and a log-transformation of the number of larvae recovered. Based on this new index, the 884 washbasins encountered in the survey were classified as infestation-free (76.2%), or with low-(6.7%), medium-(14.9%) or high-level (2.2%) infestation. Application of the same procedure to 240 drums encountered in the survey showed that 66.3% were infestation-free and 9.2%, 17.1% and 7.4% had low-, medium- and high-level infestations, respectively. Compared with the traditional indices, this new index should be more sensitive to changes in human behaviour resulting from a control programme exposure than a simple, dichotomous variable (i.e. positive/negative for presence of immature stages). The use of such an index could make the control programme more efficient, allowing the greatest efforts to be targeted at households that have medium-high levels of infestation.

Aedes↗
PubMed1998

Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic factor, which is known to be upregulated in most cases of glioblastoma multiforme (GBM). The expression of VEGF and its receptors in ependymomas, oligodendrogliomas, and particularly the expression during anaplastic progression of these three types of gliomas has not been studied extensively. Fifty-six gliomas, consisting of 10 ependymomas, 12 oligodendrogliomas, 3 anaplastic oligodendrogliomas, 6 astrocytomas grade II, 5 anaplastic astrocytomas, and 20 glioblastoma multiformes, were investigated for VEGF and receptor expression using in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR). Results showed that VEGF was moderately to strongly expressed in 8 of 10 ependymomas and in all anaplastic oligodendrogliomas and glioblastoma multiforme cases. These tumors displayed similar degrees of extensive necrosis and vascular proliferation, with VEGF expression consistently seen in tumor cells around necrotic areas. The VEGF expression, although present at a lower level, also was shown in 4 of 12 oligodendrogliomas, in 3 of 6 astrocytomas grade II, and in 2 of 5 anaplastic astrocytomas, with a regional rather than diffuse pattern of positive result. The findings from the in situ hybridization study correlated with the expression index, as determined by reverse transcription polymerase chain reaction. Expression of VEGF was correlated significantly with vascular proliferation (p < 10(-5)) and necrosis (p < 10(-5)), as well as with microvessel density (p = 0.002, rs = 0.41). The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis, whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal. Anaplastic progression in all three types of gliomas is heralded by the occurrence of small zones of VEGF-expressing cells and early vascular proliferation, followed by an accelerated phase of angiogenesis closely associated with VEGF induction around areas of necrosis and with the expression of VEGF receptors in the tumor vasculature.

Astrocytoma↗
PubMed1998

La Untadita: a procedure for maintaining washbasins and drums free of Aedes aegypti based on modification of existing practices.

Chlorine bleach and detergent are routinely used by householders in El Progreso, Honduras in the process of cleaning washbasins and drums, the two most important larval habitats of Aedes aegypti in the city. The efficacy of these materials in eliminating eggs, larvae, and pupae of Ae. aegypti was assessed under controlled conditions. The promising results obtained led to trials using a combination of chlorine bleach and detergent to apply to the walls of washbasins and drums as a method for eliminating eggs. The bleach maintained its ovicidal properties when mixed with detergent, and the detergent gave the mixture consistency so that it could be applied as a thin film to the walls. This new procedure was named the little dab (Untadita in Spanish) and allows households to direct their efforts against a stage of the mosquito life cycle that has been ignored in the past: the egg.

Aedes↗
PubMed1997

Prevalence of mutations and 30-bp deletion in the C-terminal region of Epstein-Barr virus latent membrane protein-1 oncogene in reactive lymphoid tissue and non-nasopharyngeal EBV-associated carcinomas in Hong Kong Chinese.

A specific variant of Epstein-Barr virus (EBV) with a 30-bp deletion in the C-terminal region of the LMP1 gene has been found in some EBV-associated malignancies. To better understand the tumorigenic role of this LMP1 variant, we used PCR and sequencing to examine the LMP1 gene in 38 EBV-associated carcinomas (EBV-CAs) occurring in various organs (6 lung, 10 salivary gland, 5 sino-nasal, 16 gastric and 1 metastatic NPC), 55 reactive lymphoid tissues from tonsils (TON) and 67 EBV-negative tumours in various organs (22 adenolymphoma of salivary gland, 14 gastric and 31 colonic adenocarcinomas), where the virus was demonstrated in lymphocytes. The TON showed prevalence of both deleted and non-deleted variants of LMP1, with dual infection being common. Significantly more of the LMP1 variant was deleted in EBV-CA and in EBV-negative tumours. Sequencing showed that the deleted and non-deleted variants have different sets of amino acid mutation. Mutations in codon 344 and 355 in the non-deleted variant disrupted the 9 nucleotide repeat flanking the deletion and thus may have conferred resistance to the deletion. The prevalence of both variants in the TON, with enrichment for the deleted variant in various organs, argues for the existence of an immune selection pressure in our population. The deleted variant, which may have a higher tumorigenic potential, may contribute to the high incidence of NPC, as well as the occurrence of EBV-CA in organs outside the nasopharynx in our locality.

Adolescent↗
PubMed1997

CD7-mediated regulation of integrin adhesiveness on human T cells involves tyrosine phosphorylation-dependent activation of phosphatidylinositol 3-kinase.

The functional activity of integrin receptors on T cells is dynamically regulated so that T cells can alternate rapidly between adhesive and nonadhesive states. The CD7 Ag is one of several molecules on T cells that can transduce intracellular signals that rapidly up-regulate integrin-mediated adhesion. We demonstrate in this report that the signaling pathway that CD7 utilizes to regulate integrin activity involves the lipid kinase phosphatidylinositol 3-kinase (PI 3-K). CD7 stimulation of both Jurkat T cells and resting human peripheral blood CD4+ T cells results in rapid association and activation of PI 3-K with CD7. Phosphopeptide competition assays demonstrate that the association of CD7 with PI 3-K is dependent on tyrosine phosphorylation of the SH2 binding motif Tyr-Glu-Asp-Met (YEDM) in the CD7 cytoplasmic domain. A role for PI 3-K in the regulation of integrin function by CD7 is demonstrated by: 1) the ability of two structurally distinct PI 3-K inhibitors, wortmannin and LY294002, to inhibit CD7-mediated increases in beta1 integrin function of human T cells; and 2) inhibition of CD7-mediated activation of beta3 integrin function in human T cells by expression of a dominant negative form of the p85 subunit of PI 3-K. These results demonstrate that the CD7 Ag on human T cells is coupled to PI 3-K and that this association is relevant to CD7-mediated signaling events, specifically CD7-induced increases in integrin adhesiveness. Furthermore, these studies provide important new evidence implicating PI 3-K in the regulation of integrin adhesiveness by multiple cell surface signaling receptors.

Antigens, CD7↗
PubMed1997

Conscious sedation for interventional neuroradiology: a comparison of midazolam and propofol infusion.

PURPOSE: The aim of this study was to compare two conscious sedation techniques, midazolam (M) and propofol (P), for interventional neuroradiology by assessment of the incidence of complications and satisfaction scores. METHODS: Forty patients were randomized to receive 0.75 micrograms.kg-1 fentanyl and a M or P bolus followed by an infusion (M 15 micrograms.kg-1 + 0.5 micrograms.kg-1.min-1; P 0.5 mg.kg-1 + 25 micrograms.kg-1 min-1). The incidences of complications and untoward events requiring intervention were documented. These included respiratory depression, excessive pain, inappropriate movements and the inability to examine the patient. The satisfaction of the anaesthetic technique from the perspective of both the neuroradiologist and the patient was scored. RESULTS: The incidence and types of complications were no different between the two groups. Pain occurred in 12 patients (6M, 6P), inappropriate movements in 17 (7M, 10P) and respiratory changes in 10 patients (2M, 8P). CONCLUSIONS: Both techniques were satisfactory and the incidence of complications was similar for both groups.

Adult↗
PubMed1997

Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas.

While the number of reports on macrophage infiltration of gliomas is increasing, the extent and mechanisms of macrophage recruitment remain unclear. To investigate whether monocyte chemoattractant protein-1 (MCP-1) plays a role in this process, in situ hybridisation (ISH) was performed for 22 glioblastomas (GBM), 1 anaplastic astrocytoma (AA) and 4 grade II fibrillary astrocytomas (AII) and reverse transcription-polymerase chain reaction was performed in 13 GBM, 1 AA and 3 AII. High levels of MCP-1 mRNA were detectable in most GBM, while a lower level was detected in AII. Many tumour-associated macrophages (TAM) could be demonstrated by immunohistochemistry (IHC) in most GBM, while the AII contained a lower number of TAM. The positive correlation between the MCP-1 level and abundance of TAM suggested that MCP-1 has a role in TAM recruitment. By combining ISH and IHC, high levels of MCP-1 mRNA were shown both in tumour cells and TAM. Along tumour borders, reactive astrocytes and microglia also expressed MCP-1. In areas with T lymphocyte infiltration, larger numbers of MCP-1-positive cells with an enhanced level of expression could be identified. We propose that the mechanism of macrophage recruitment is, at least partly, effected by constitutive expression and T cell-mediated up-regulation of MCP-1 in tumour cells and TAM. The production of MCP-1 by TAM establishes a positive amplification circuit for macrophage recruitment in gliomas.

Astrocytoma↗
PubMed1997

The deterioration of semantic networks in patients with Alzheimer's disease: a cross-sectional study.

Previous studies showed that the semantic networks of Alzheimer's disease (AD) patients are disrupted in the early stages of the disease. The present study examined the semantic networks of 33 AD patients in different stages of disease severity to compare the quantitative and qualitative changes in their networks as the disease progresses. The properties of the semantic networks (e.g. the dimensionality and strength of the connections) were examined with multidimensional scaling and Pathfinder analyses. The results showed that, as AD patients became more demented, they focused less on abstract attributes in categorizing concepts, and have an alteration in the relative strength of associations between concepts. These findings indicate that the structure of semantic knowledge deteriorates in a systematic manner throughout the course of AD.

Aged↗
PubMed1997

Expression of vascular endothelial growth factor and its receptors in pilocytic astrocytoma.

Vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, is important in the angiogenesis of glioblastoma. A major difference between pilocytic astrocytoma, a grade I tumor, and the grade II fibrillary astrocytoma is the vascular proliferation, highly vascularized stroma, and great propensity for cyst formation in the former. In order to explore factors regulating such angiogenesis and cyst formation in pilocytic astrocytoma, we examined expression of VEGF and its receptors (KDR and Flt-1) using in situ hybridization. In all 14 cases a high level of VEGF transcripts could be demonstrated. These were found in specific regions, namely, in the tumor cyst wall, in areas of hyaline cystic degeneration, in stellate reticulated astrocytes around microcysts in the biphasic compact and loose areas, and in tumor cells with degenerative pleomorphic multicoated nuclei. KDR and Flt-1 were expressed in the tumor vasculature, with particularly high levels seen in coiled young proliferating vessels, especially those in the cyst wall. Given the known angiogenic and vascular permeability activities of VEGF, we propose that VEGF plays an important role in molding the characteristic morphologic features of this tumor, namely, the formation of cysts, microcystic pattern, hyaline cystic degeneration, hyaline vessels, and vascular proliferation. Mechanisms that block the VEGF pathway could constitute a potential therapeutic strategy for the treatment of this tumor.

Adolescent↗