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Biomedical subjects

A Lu

Publications and source records attributed to A Lu.

At least 19 recordsLinked to original sources
PubMed2006

Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study.

Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.

Aged↗
PubMed2006

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

Journal Article↗
PubMed2004

First results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.

We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

Journal Article↗
PubMed2003

Neurons derived from embryonic stem (ES) cells resemble normal neurons in their vulnerability to excitotoxic death.

We determined whether embryonic stem (ES) cells could provide a model system for examining neuronal death mediated by glutamate receptors. Although limited evidence indicates that normal neurons can be derived from mouse ES cells, there have been no studies examining pathophysiological responses in mouse ES cell systems. Mouse ES cells, induced down a neural lineage by retinoic acid (RA), were found to have enhanced long-term survival when plated onto a layer of cultured mouse cortical glial cells. In these conditions, the ES cells differentiated into neural cells that appeared normal morphologically and displayed normal features of immunoreactivity when tested for neuron-specific elements. Varying the culture medium generated cultures of mixed neuronal/glial cells or enriched in oligodendrocytes. These cultures were viable for at least four weeks. Real-time PCR analysis of N-methyl-D-aspartate (NMDA) receptor subunits revealed an appropriate age-in-vitro dependent pattern of expression. Neurons derived from ES cells were vulnerable to death induced by a 24-h exposure to the selective glutamate receptor agonists NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). This vulnerability to agonist-induced death increased with age in vitro, and related closely to expression of receptor subunits, as it does in cultured primary neurons. Experiments with selective receptor antagonists showed that glutamate receptors mediated the NMDA- and kainate-induced death. Neuronal differentiated ES cells therefore exhibited an excitotoxic response resembling that displayed by central nervous system (CNS) neurons. Thus, ES cells, which are very amenable to genetic manipulation, provide a valid system for studying glutamate receptor-mediated toxicity at the molecular level.

Animals↗
PubMed2002

Hartnup disorder: polymorphisms identified in the neutral amino acid transporter SLC1A5.

Hartnup disorder is an inborn error of renal and gastrointestinal neutral amino acid transport. The cloning and functional characterization of the 'system B0' neutral amino acid transporter SLC1A5 led to it being proposed as a candidate gene for Hartnup disorder. Linkage analysis performed at 19q13.3, the chromosomal position of SLC1A5, was suggestive of an association with the Hartnup phenotype in some families. However, SLC1A5 was not linked to the Hartnup phenotype in other families. Linkage analysis also excluded an alternative candidate region at 11q13 implicated by a putative mouse model for Hartnup disorder. Sequencing of the coding region of SLC1A5 in Hartnup patients revealed two coding region polymorphisms. These mutations did not alter the predicted amino acid sequence of SLC1A5 and were considered unlikely to play a role in Hartnup disorder. There were no mutations in splice sites flanking each exon. Quantitative RT-PCR of SLC1A5 messenger RNA in affected and unaffected subjects did not support systemic differences in expression as an explanation for Hartnup disorder. In the six unrelated Hartnup pedigrees studied, examination of linkage at 19q13.3, polymorphisms in the coding sequence and quantitation of expression of SLC1A5 did not suffice to explain the defect in neutral amino acid transport.

Amino Acid Transport System ASC↗
PubMed2002

Humans and great apes share a large frontal cortex.

Some of the outstanding cognitive capabilities of humans are commonly attributed to a disproportionate enlargement of the human frontal lobe during evolution. This claim is based primarily on comparisons between the brains of humans and of other primates, to the exclusion of most great apes. We compared the relative size of the frontal cortices in living specimens of several primate species, including all extant hominoids, using magnetic resonance imaging. Human frontal cortices were not disproportionately large in comparison to those of the great apes. We suggest that the special cognitive abilities attributed to a frontal advantage may be due to differences in individual cortical areas and to a richer interconnectivity, none of which required an increase in the overall relative size of the frontal lobe during hominid evolution.

Animals↗
PubMed2002

Comparative analysis of the complete genome sequences of Helicoverpa zea and Helicoverpa armigera single-nucleocapsid nucleopolyhedroviruses.

The complete nucleotide sequence of Helicoverpa zea single-nucleocapsid nucleopolyhedrovirus (HzSNPV) has been determined (130869 bp) and compared to the nucleotide sequence of Helicoverpa armigera (Ha) SNPV. These two genomes are very similar in their nucleotide (97% identity) and amino acid (99% identity) sequences. The coding regions are much more conserved than the non-coding regions. In HzSNPV/HaSNPV, the 63 open reading frames (ORFs) present in all baculoviruses sequenced so far are much more conserved than other ORFs. HzSNPV has four additional small ORFs compared with HaSNPV, one of these (Hz42) being in a correct transcriptional context. The major differences between HzSNPV and HaSNPV are found in the sequence and organization of the homologous regions (hrs) and the baculovirus repeat ORFs (bro genes). The sequence identity between the HzSNPV and HaSNPV hrs ranges from 90% (hr1) to almost 100% (hr5) and the hrs differ in the presence/absence of one or more type A and/or B repeats. The three HzSNPV bro genes differ significantly from those in HaSNPV and may have been acquired independently in the ancestral past. The sequence data suggest strongly that HzSNPV and HaSNPV are variants of the same virus species, a conclusion that is supported by the physical and biological data.

Animals↗
PubMed2001

Molecular mechanisms for aberrant expression of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences.

Breast cancer specific gene 1 (BCSG1), also referred as synuclein gamma, is the third member of a neuronal protein family synuclein. BCSG1 is not expressed in normal breast tissues but highly expressed in advanced infiltrating breast carcinomas. When over expressed, BCSG1 significantly stimulates breast cancer metastasis. To elucidate the molecular mechanisms underlying the abnormal transcription of BCSG1 in breast cancer cells, in this study, we isolated a 2195 base pair fragment of human BCSG1 gene. This fragment includes 1 kb 5'-flanking region, exon 1, and intron 1. By analysing the promoter activity and the methylation status of the exon 1 region, we show that (1) Intron 1 plays critical roles in the control of BCSG1 gene transcription through cis-regulatory sequences that affect BCSG1 transcription in cell type-specific and cell type-nonspecific manners. (2) The activator protein-1 (AP-1) is functionally involved in BCSG1 transcription in breast cancer cells through its binding to an AP-1 motif located in the intron 1. (3) The exon 1 region of BCSG1 gene contains a CpG island that is unmethylated in BCSG1-positive SKBR-3 and T47D cells but densely methylated in BCSG1-negative MCF-7 cells. (4) Treating MCF-7 cells with a demethylating agent 5-Aza-2'-deoxycytidine specifically activated BCSG1 transcription. Thus, our results suggest that while the cellular content of transcription activators and repressors that interact with the cis-regulatory sequences present in the intron 1 contribute prominently to the tissue-specific expression of BCSG1, demethylation of exon 1 is an important factor responsible for the aberrant expression of BCSG1 in breast carcinomas.

Amino Acid Motifs↗
PubMed2001

Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease.

Using microarray technology, we investigated whether the gene expression profile in white blood cells could be used as a fingerprint of different disease states. Adult rats were subjected to ischemic strokes, hemorrhagic strokes, sham surgeries, kainate-induced seizures, hypoxia, or insulin-induced hypoglycemia, and compared with controls. The white blood cell RNA expression patterns were assessed 24 hours later using oligonucleotide microarrays. Results showed that many genes were upregulated or downregulated at least twofold in white blood cells after each experimental condition. Blood genomic response patterns were different for each condition. These results demonstrate the potential of blood gene expression profiling for diagnostic, mechanistic, and therapeutic assessment of a wide variety of disease states.

Animals↗
PubMed2001

Evaluating the impact of peer, nurse case-managed, and standard HIV risk-reduction programs on psychosocial and health-promoting behavioral outcomes among homeless women.

Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors (substance use and sexual risk behaviors) and cognitive and psychological resources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners. Participants were randomized by shelter to a peer-mentored, a nurse case-managed, or a standard care HIV risk-reduction program. Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological resources except for self-esteem. Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the standard group in self-esteem, life satisfaction, psychological well-being, use of noninjection drugs, sex with multiple partners, and unprotected sex at 6 months (n = 633). It was concluded that a standard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implications. Further, the impact of short-term programs that address psychological vulnerabilities of impoverished populations needs to be studied further.

Adolescent↗
PubMed2001

Antithrombotic and fibrinolytic system of human endothelial cells seeded on PTFE: the effects of surface modification of PTFE by ammonia plasma treatment and ECM protein coatings.

The aim of this study was to determine the effects of ECM protein coatings and surface modification of PTFE on the ability of seeded human endothelial cells (EC) to secrete prostacyclin (PGI2), plasminogen inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA). PTFE surfaces were modified by a novel surface modification technique based on ammonia plasma. Fibronectin, collagen type-1 and gelatin-coated ammonia plasma modified PTFE and unmodified PTFE surfaces were employed and compared in this study. All ammonia plasma modified surfaces showed similar secretions of PGI2 compared to non-modified PTFE surfaces. With the exception of gelatin-coated modified PTFE, seeded EC seeded on all modified PTFE showed lower levels of PAI-1 secretion compared to those seeded on unmodified PTFE. The specific activity of t-PA secreted by EC seeded on ammonia plasma modified and fibronectin coated modified PTFE showed increases of 100 and 30%, respectively, when compared to their unmodified counterparts. Our studies show that EC seeded on modified PTFE have ability to secrete PGI2 that modulates the early phase of thrombus formation. Furthermore, superior t-PA profile, along with lower levels of PAl-1 suggest that ammonia plasma modification and use of appropriate ECM proteins can modulate antithrombotic and fibrinolytic properties of in vitro endothelialized vascular prostheses. Accordingly, these surfaces may be suitable to further develop protocols and other strategies for arterial and venous reconstruction.

Ammonia↗
PubMed2001

Microglia/macrophages proliferate in striatum and neocortex but not in hippocampus after brief global ischemia that produces ischemic tolerance in gerbil brain.

The current study determined whether short durations of ischemia that produce ischemia-induced tolerance stimulate glial proliferation in brain. Adult male gerbils were injected with BrdU (50 mg/kg) and dividing cells were detected using immunocytochemistry after sham operations, 2.5 or 5 minutes of global ischemia, or ischemia-induced tolerance. The 2.5-minute ischemia and the ischemia-induced tolerance did not kill hippocampal CA1 pyramidal neurons, whereas the 5-minute ischemia did kill the neurons. At 4 days after 2.5-minute global ischemia, when cell proliferation was maximal, BrdU-labeled cells increased in striatum and in neocortex, but not in hippocampus. The majority of the BrdU-labeled cells were double-labeled with isolectin B4, showing that these dividing cells were primarily microglia or macrophages, or both. Similarly, BrdU-labeled microglia/macrophages were found in striatum and neocortex but not in hippocampus of most animals 4 days after ischemia-induced tolerance (2.5 minutes of global ischemia followed 3 days later by 5 minutes of global ischemia). No detectable neuronal cell death existed in striatal and cortical regions where the microglia/macrophage proliferation occurred. Though 3 of 7 animals subjected to 2.5 minutes of ischemia showed decreased myelin-associated glycoprotein (MAG) immunostaining and increased numbers of adenomatous polyposis coli-stained oligodendrocytes in lateral striatum, this did not explain the microglia/macrophage proliferation. Data show that ischemia-induced tolerance in the gerbil is associated with proliferation of microglia/macrophages in striatum and cortex but not in hippocampus. Because there is no apparent neuronal death, it is postulated that the microglia/macrophage proliferation occurs in response to an unknown nonlethal injury to neurons or glia and may be beneficial.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Enhanced susceptibility to pulmonary infection with Burkholderia cepacia in Cftr(-/-) mice.

Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs of Cftr (m1unc-/-) (Cftr(-/-)) and congenic Cftr(+/+) controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptible Cftr(-/-) mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from the Cftr(-/-) mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages from Cftr(-/-) mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF.

Animals↗
PubMed2001

In vivo evaluation of ammonia plasma modified ePTFE grafts for small diameter blood vessels replacement. A preliminary report.

BACKGROUND: Today, saphenous veins are most frequently used to reconstruct occluded or diseased small diameter vessels (< or =6 mm in diameter). However, these veins are unavailable in 30-40% of patients. In such a situation, prosthetic grafts provide the only alternative. Since an endothelial cell (EC) lining, important for maintaining a haemostatic-thrombotic balance, does not develop onto the intima of implanted grafts in humans, these grafts occlude within a short period of time. The failure of vascular grafts is attributed to their characteristics which are nonconducive towards endothelial cell adhesion, spreading and growth. In order to examine whether the patency of vascular grafts can be improved by the surface modification of grafts' intima, small diameter grafts were modified by a novel ammonia plasma treatment to enhance their interactions with EC. METHODS: Through laparotomy, ammonia plasma treated ePTFE (4 mm in diameter) grafts (n=3) and control untreated grafts (n=6) were implanted into the distal infrarenal aorta of rabbits. At appropriate time, grafts and adherent tissue were removed, fixed, stained and embedded in Poly/Bed 812. Light microscopic examination of thin sections cut from the proximal and distal anastomatic and midportion segments of explanted grafts was carried out. RESULTS: In control group studies, all animals developed lower limb paraplegia within seven days of implantation. Light microscopic examination of explanted control grafts showed that control grafts were obstructed by thrombosis/intimal hyperplasia. However, ammonia plasma modified explanted grafts, after one month of transplantation, revealed an endothelial cell-like lining that covered the grafts' inner surfaces. Accordingly, these grafts remained patent in animals. CONCLUSIONS: The grafts' surfaces that are made conducive to EC adhesion and proliferation and host response may influence endothelial regeneration. It is hoped that the combination of angiogenic molecules (i.e. endothelial cell specific growth factors such as VEGF) with ammonia plasma modified grafts may provide further insight into the development of ideal small diameter prosthesis.

Ammonia↗
PubMed2001

The effect of magnetic stent on coronary restenosis after percutaneous transluminal coronary angioplasty in dogs.

OBJECTIVE: To investigate the effects of magnetic stents on coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Twenty dogs were randomly divided into the control and experimental groups, each with 10 dogs. The control group was given common Palmaz-stents in the 6-8 segment of left anterior descending coronary artery or in the 11-14 segment of the left circumflexus. The experimental group was given magnetic stents in the same parts of the coronary arteries. The dogs were not given antiplatelet or anticoagulant drugs before or after the operation. Six months later, the 20 dogs were subjected to coronary angiographies, and then were sacrificed. Three centimeter long segments of the target vessels were cut for pathological examination. RESULTS: The degree of restenosis in 3 dogs of the control group was more than 50%, but none in the experimental group experienced restenosis. The average thickness of the tunica intima of the target artery was 2.98 +/- 0.56 mm in the control and 1.13 +/- 0.41 mm in the experimental group (P < 0.05). CONCLUSION: Magnetic stents could have a significant preventive effect on coronary restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2000

Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK activation. Role of cholesterol and actin cytoskeleton.

The endocytic compartment of eukaryotic cells is a complex intracellular structure involved in sorting, processing, and degradation of a great variety of internalized molecules. Recently, the uptake through caveolae has emerged as an alternative internalization pathway, which seems to be directly related with some signal transduction pathways. However, the mechanisms, molecules, and structures regulating the transport of caveolin from the cell surface into the endocytic compartment are largely unknown. In this study, normal quiescent fibroblasts (normal rat kidney (NRK)) were used to demonstrate that epidermal growth factor causes partial redistribution of caveolin from the cell surface into a cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin D or latrunculin A inhibits this pathway and the concomitant activation of Mek and mitotic-activated protein (MAP) kinase; however, if cells were pre-treated with filipin, cytochalasin D does not inhibit the phosphorylation of MAP kinase induced by epidermal growth factor. From these results we conclude that in NRK cells the intact actin cytoskeleton is necessary for the EGF-mediated transport of caveolin from the cell surface into the early endocytic compartment and the activation of MAP kinase pathway.

Actins↗
PubMed2000

Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.

The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment.

Journal Article↗