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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Increased expression of CD23 (Fc(epsilon) receptor II) by peripheral blood monocytes of aids patients.

Monocytes expressing the Fcepsilon receptor II (CD23) play important roles in inflammatory and allergic immune responses. We found that peripheral blood monocytes of AIDS patients express increased levels of CD23, compared with monocytes of healthy HIV-1-seronegative individuals (controls) (p < 0.05). We compared expression of monocyte CD23 with expression of monocyte Fcgamma receptors (CD16, CD32, CD64), plasma/serum levels of IgE (also IgM, IgG, IgA), and Th1 (IFN-gamma) and Th2 (IL-4, IL-10) cytokines. We found that monocyte CD23 expression directly correlated with monocyte CD16 expression (p < 0.01, R = 0.58), which was also increased in AIDS patients; there was no correlation with CD32 or CD64 or with soluble factors in plasma/serum (i.e., IgE, IL-4, IL-10, and IFN-gamma). Interestingly, despite the known ability of IL-10 to downregulate monocyte CD23 expression, plasma IL-10 levels were increased in these AIDS patients compared with controls (p < 0.05). We thus evaluated the effect of AIDS and control plasma or rhIL-10 to regulate CD23 expression by monocytes in cultures (24 hr) of healthy human cells +/- treatment with anti-IL-10R blocking antibody. We found that anti-IL-10R blocking antibody treatment had no effect on monocyte CD23 expression in cultures containing AIDS plasma, but increased monocyte CD23 expression in cultures containing control plasma (p < 0.05) or rhIL-10. In conclusion, the identification of increased monocyte CD23 expression in AIDS patients may further characterize the aberrant activated phenotype of monocytes during the immunopathogenesis of HIV-1 disease. Further, monocyte CD23 expression does not appear to be suppressed by the IL-10-enriched environment in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: mechanism for removal of apoptotic cells in the inflamed nervous system.

Apoptosis of autoaggressive T cells in the central nervous system (CNS) is an effective, nonphlogistic mechanism for the termination of autoimmune inflammation in experimental autoimmune encephalomyelitis (EAE). The clearance of apoptotic leukocytes by tissue-specific phagocytes is a critical event in the resolution of the inflammatory attack. To investigate the role of microglia in the removal of apoptotic cells and potential regulatory mechanisms of microglial phagocytosis, an in vitro phagocytosis assay was established, using Lewis rat microglia. Microglia exhibited a high capacity for the uptake of apoptotic autologous thymocytes, as well as apoptotic encephalitogenic myelin basic protein (MBP)-specific T cells, in contrast to nonapoptotic target cells. Pretreatment of microglia with interferon-gamma (IFN-gamma) raised the proportion of microglia capable of phagocytosing apoptotic cells to 75% above the untreated controls. The increased phagocytic activity was selective for apoptotic target cells and was not dependent on phosphatidylserine-mediated recognition mechanisms. In contrast, preincubation of microglia with interleukin-4 (IL-4) inhibited the uptake of apoptotic cells, whereas tumor-necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) did not alter phagocytosis. Phagocytic clearance of apoptotic inflammatory cells by microglia may be an important mechanism for the termination of autoimmune inflammation in the CNS. Augmentation of microglial phagocytosis by the Th-1-type cytokine IFN-gamma suggests a feedback mechanism for the accelerated clearance of the inflammatory infiltrate in the CNS.

Animals↗
PubMed2001

Three chromosomal rearrangements in neuroblastoma cluster within a 300-kb region on 1p36.1.

Deletions in the short arm of chromosome 1 (1p36) and MYCN amplification are common in neuroblastoma. Previously we showed evidence of at least two different neuroblastoma tumor-suppressor loci on 1p. One is associated with MYCN single-copy tumors and maps distal on 1p36.3. A second, more proximal locus maps to 1p36.1 and is deleted in about 90% of neuroblastomas with MYCN amplification. The cell line UHG-NP has the smallest 1p36 deletion of all neuroblastoma cell lines with MYCN amplifications. We assume that the more proximal locus maps within this deletion, close to its proximal border. Here we present the exact localization of the 1p deletion breakpoint of UHG-NP. A 600-kb PAC contig spanning the breakpoint was analyzed for genes and aberrations. Two more neuroblastoma-associated aberrations were mapped within 150 kb of the UHG-NP breakpoint. Within the contig, we identified nine genes expressed in neuroblastoma cells. One of these genes, AML2, maps 200 kb distal to the UHG-NP breakpoint but is expressed only rarely in neuroblastoma and showed no mutations.

Base Composition↗
PubMed2001

Mast cells in the rat liver are phenotypically heterogeneous and exhibit features of immaturity.

Gastrointestinal hypersensitivity to food allergens is a significant but relatively poorly understood allergic disease. Recent evidence from a rat model of IgE-mediated gastrointestinal hypersensitivity has suggested that hepatic mast cells (HMC) may play an important role in such reactions. The present study was undertaken to better define their phenotype. Livers from Australian albino Wistar (AaW), Brown Norway (BN) and PVG/c rats were examined using traditional histological techniques and reverse transcription-polymerase chain reaction (RT-PCR). Hepatic mast cells were overwhelmingly Alcian blue positive, sensitive to formalin fixation and predominantly rat mast cell protease (RMCP) 1+/2- (AaW 57%; BN 53%). Such a phenotype has previously been associated with an immature mast cell phenotype. A significant number of HMC also stained RMCP 1-/2+ (AaW 15%; BN 19%) or were RMCP 1+/2+ (AaW 24%; BN 26%). In contrast to previous reports, RT-PCR showed that the liver expressed mRNA of other mast cell proteases, including the chymase RMCP 5 as well as two tryptases, RMCP 6 and RMCP 7. These results suggest that HMC are a heterogeneous population of mast cells with some characteristics previously associated with immature cells.

Animals↗
PubMed2001

Comparison of Dinamap 8100 with sphygmomanometer blood pressure measurement in a prepubertal diabetes cohort.

OBJECTIVE: To compare the conventional sphygmomanometer with the semiautomated Dinamap 8100 (Critikon, Tampa, FL, USA) for the measurement of blood pressure in prepubertal children with insulin-dependent diabetes mellitus. METHODOLOGY: Blood pressure was measured using both methods in 61 prepubertal children (aged 8-13 years) on 189 occasions over 4 years. The measurements were compared using the Bland-Altman plot. Tracking correlations of blood pressure centiles over time were analyzed by the general estimating equation. RESULTS: Accuracy criteria of the Association for the Advancement of Medical Instrumentation were met and a British Hypertensive Society 'B' grading was reached. Differences in systolic and diastolic blood pressure were found between the two methods (P < 0.01). For systolic blood pressure, common correlations were 0.54 (Dinamap) and 0.51 (sphygmomanometer) and for diastolic blood pressure were 0.33 and 0.42, respectively. CONCLUSION: The Dinamap 8100 is an acceptable alternative in clinic practice and research for prepubertal children.

Australia↗
PubMed2001

Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus.

Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated esterase, which may prevent the transformation of low-density lipoproteins (LDL) into biologically active, atherogenic particles. PON concentration and activity are affected by PON1 gene polymorphisms and found to be altered in type 2 diabetes patients with retinopathy. We investigated serum PON concentration, in vitro activity and polymorphism at position 54 (L/M, Leu-Met54) in 193 Caucasian adolescents and young adults (88 males, 105 females) with type 1 diabetes mellitus, as well as its relationship to the presence of retinopathy. An inverse linear correlation was found between blood glucose levels and both serum PON concentration (r = -.20, P =.017) and its activity (r = -0.17, P =.037). Patients with elevated blood glucose values (> or =10 mmol/L) had significantly lower levels of both PON concentration (P =.003) and activity (P =.028) than those with lower glucose levels. After adjusting for blood glucose and diabetes duration, PON activity was significantly higher in patients with different stages of retinopathy compared with those without retinopathy (P =.003). The L/L genotype was closely associated with the presence of retinopathy (P <.0001). These data show that young people with type 1 diabetes and the L/L polymorphism at position 54 of PON1 gene are more susceptible to retinal complications. However, the role of serum PON concentration and activity as a possible marker for monitoring late microvascular complications in these patients has to be established.

Adolescent↗
PubMed2001

Accuracy and bias of licensed practical nurse and nursing assistant ratings of nursing home residents' pain.

BACKGROUND: This study evaluated the accuracy of licensed practical nurses' (LPN) and nursing assistants' (NA) Minimum Data Set (MDS) pain ratings of nursing home residents and evaluated the bias in pain ratings associated with residents' race, gender, mental status, function, depression, or disruptive behavior. METHODS: Data were obtained on the same day directly from residents, LPNs, and NAs by trained interviewers in two safety-net nursing homes. A total of 252 residents were included in this study: 79% were Black, and 60% were men. MDS items J2a and J2b evaluated pain frequency and pain intensity during the last 7 days (weekly pain frequency and weekly pain intensity). A parallel question evaluated pain intensity on the day of the interview (daily pain intensity). MDS data were obtained for the MDS Cognition Scale, the MDS Activities of Daily Living-Long Form Scale, the MDS Depression Rating Scale, and the MDS Disruptive Behavior Scale. RESULTS: Kappa coefficients documented fair to good resident-LPN (K =.70,.56, and.50) and resident-NA (K =.72,.58, and.60) agreement for weekly pain frequency, weekly pain intensity, and daily pain intensity ratings. LPNs and NAs underestimated residents' weekly pain frequency (p <.001 for LPNs, and p <.001 for NAs), weekly pain intensity (p <.001 for LPNs, and p <.001 for NAs), and daily pain intensity (p <.001 for LPNs, and p =.002 for NAs). LPNs underestimated weekly and daily pain intensity more than NAs did (p =.016 for weekly pain intensity, and p =.035 for daily pain intensity). LPN and NA pain ratings were not biased by resident race, gender, mental status, function, depression, or disruptive behavior. CONCLUSIONS: Results documented that (i) LPNs and NAs underestimated residents' pain frequency and pain intensity, (ii) NAs were more accurate than LPNs for pain intensity, and (iii) resident characteristics did not bias LPN or NA pain ratings.

Activities of Daily Living↗
PubMed2001

Subsequent birth outcomes after an unexplained stillbirth: preliminary population-based retrospective cohort study.

The objective of this study was to determine whether women who have experienced an unexplained stillbirth have a higher risk of adverse perinatal outcomes in subsequent births. We compared 316 subsequent births to women with a previous unexplained stillbirth, with 3160 births to women with no previous history of stillbirth, matched by year of birth, in the period 1987-1997, from the South Australian perinatal database, using logistic regression analysis. There was no increase in the rate of stillbirth and no statistically significant increase in the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death, although larger studies are needed to confirm this. However, after adjusting for age, parity, and hospital category of birth, women who had a previous stillbirth had increased incidences in subsequent births of abnormal glucose tolerance or gestational diabetes (a fourfold increase); induction of labour and elective Caesarean section; fetal distress and postpartum haemorrhage; and forceps and emergency Caesarean delivery and preterm birth, which were independent of induction of labour. Gestational age at birth and birthweight were also significantly reduced, suggesting a need for close monitoring of their future pregnancies.

Adult↗
PubMed2001

Ganglioneurocytoma mimicking a malignant tumor: case report with a literature review of the MRI appearance of neurocytomas and gangliogliomas.

A 14-year-old girl presented with symptoms of increased intracranial pressure after her head was squeezed at a party. MRI demonstrated a mass that was hypointense to brain on T1WI and heterogeneous in signal on PD and T2WI; compression of the ventricle, midline shift, and mild ventriculomegaly also were present. Contrast enhancement was extensive and heterogeneous, mimicking a malignant tumor. Neuropathology revealed a ganglioneurocytoma.

Adolescent↗
PubMed2001

Chickenpox and stroke in childhood: a study of frequency and causation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether infection with varicella is causal for arterial ischemic stroke (AIS) in children. METHODS: First, a prospective cohort study was conducted in young children (aged 6 months to 10 years) with AIS at 2 institutions (cohort study). The presence of varicella infection <12 months before AIS was determined and compared with the published frequency of varicella infection in the healthy pediatric population. The clinical and radiographic features of AIS were compared between the varicella and nonvaricella study cohorts. Second, a literature search of varicella-associated AIS was conducted, and the clinical and radiographic features were compared with the study nonvaricella cohort. RESULTS: In the cohort study, 22 (31%) of 70 consecutive children with AIS had a varicella infection in the preceding year compared with 9% in the healthy population. Children in the varicella cohort were more likely to have basal ganglia infarcts (P<0.001), abnormal cerebral vascular imaging (P<0.05), and recurrent AIS or transient ischemic attacks (P<0.05) than those in the nonvaricella cohort. The pooled literature analysis of 51 cases of varicella-associated AIS showed similar findings to the varicella cohort. CONCLUSION: In young children with AIS, there is a 3-fold increase in preceding varicella infection compared with published population rates, and varicella-associated AIS accounts for nearly one third of childhood AIS. Varicella-associated AIS has characteristic features, including a 2-fold increase in recurrent AIS and transient ischemic attacks. Varicella is an important risk factor for childhood AIS.

Age Distribution↗
PubMed2001

Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.

BACKGROUND: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulated diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis; however, a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed. MATERIALS AND METHODS: We generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed similar levels of dominant inhibitory mutants of Cdc42-, Rac- and Rho-dependent signaling, to examine the contribution of these GTPases to cell spreading, guided chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate intravasation into the peripheral blood was determined by implanting MTLn3 cell stable dominant negative lines in nude mice and measuring the formation of breast cancer cell colonies grown from the peripheral blood. Serial sectioning of the lungs was performed to determine the presence of metastasis in mice in which mammary tumors expressing the dominant negative Rho family proteins had grown to a similar size. RESULTS: Cell spreading of MTLn3 cells was selectively abrogated by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and disrupted the co-localization of vinculin with phosphotyrosine at FCs. While N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all three GTPases affected cell growth in vivo. To distinguish effects on tumorigenicity from intravasation into the bloodstream, implanted tumors were grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also abrogated by the dominant inhibitory Rho proteins, despite the presence of residual CFU. CONCLUSIONS: These studies demonstrate for the first time a critical role for the Rho GTPases involving independent signaling pathways to limit mammary tumor cellular growth and metastasis in vivo.

Adenocarcinoma↗
PubMed2000

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗
PubMed2000

Enhanced Tn10 and mini-Tn10 precise excision in DNA replication mutants of Escherichia coli K12.

The precise excision of transposon Tn10 and a mini-Tn10 derivative, inserted in the gal or lac operons, was studied in dnaB252 and dnaE486 temperature-sensitive mutants of Escherichia coli. dnaB codes for a DNA replication helicase and dnaE for the alpha subunit of DNA polymerase III. Mutations in these genes were found to enhance, at the permissive temperature, the precise excision of both genetic elements. The increase factor was much more pronounced for the dnaB252 mutant with the transposons inserted in gal. The stimulated excision was only partially affected by a recA null mutation but was significantly reduced by introduction of recF null or ruvA mutations. A model involving template switching of the polymerase between the direct repeats flanking the transposons, on the same strand or between sister strands, could account for the observed results.

Bacterial Proteins↗
PubMed2000

Bimodal activation of acetyl-CoA carboxylase by glutamate.

Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, an essential substrate for fatty acid biosynthesis and a potent inhibitor of fatty acid oxidation. Here, we provide evidence that glutamate may be a physiologically relevant activator of ACC. Glutamate induced the activation of both major isoforms of ACC, prepared from rat liver, heart, or white adipose tissue. In agreement with previous studies, a type 2A protein phosphatase contributed to the effects of glutamate on ACC. However, the protein phosphatase inhibitor microcystin LR did not abolish the effects of glutamate on ACC activity. Moreover, glutamate directly activated purified preparations of ACC when protein phosphatase activity was excluded. Phosphatase-independent ACC activation by glutamate was also reflected by polymerization of the enzyme as judged by size-exclusion chromatography. The sensitivity of ACC to direct activation by glutamate was diminished by treatment in vitro with AMP-activated protein kinase or cAMP-dependent protein kinase or by beta-adrenergic stimulation of intact adipose tissue. We conclude that glutamate, an abundant intracellular amino acid, induces ACC activation through complementary actions as a phosphatase activator and as a direct allosteric ligand for dephosphorylated ACC. This study supports the general hypothesis that amino acids fulfill important roles as signal molecules as well as intermediates in carbon and nitrogen metabolism.

Acetyl-CoA Carboxylase↗