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Biomedical subjects

D Vu

Publications and source records attributed to D Vu.

At least 19 recordsLinked to original sources
PubMed2005

Hypofibrinogenaemia caused by a novel FGG missense mutation (W253C) in the gamma chain globular domain impairing fibrinogen secretion.

BACKGROUND: Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating fibrinogen (dysfibrinogenaemia). Extensive allelic heterogeneity has been found for all three disorders: in congenital afibrinogenaemia >30 mutations, the majority in FGA, have been identified in homozygosity or in compound heterozygosity. Several mutations have also been identified in patients with hypofibrinogenaemia; many of these are heterozygous carriers of afibrinogenaemia null mutations. OBJECTIVE: To report the case of a patient from Slovakia diagnosed with hypofibrinogenaemia characterised by fibrinogen concentrations of around 0.7 g/l. RESULTS: The patient was found to be heterozygous for a novel missense mutation W253C (W227C in the mature protein) in the C-terminal globular domain of the fibrinogen gamma chain. Co-expression of the W253C FGG mutant cDNA (fibrinogen Bratislava) in combination with wild-type FGA and FGB cDNAs showed that fibrinogen molecules containing the mutant gamma chain can assemble intracellularly but are not secreted into the media, confirming the causative nature of the identified mutation. CONCLUSIONS: Current analysis of fibrinogen Bratislava indicates that the domains important for the processes of hexamer assembly and hexamer secretion should not be considered as strictly restricted to one or other fibrinogen chain.

Adult↗
PubMed2004

Differential expression of LMO4 protein in Alzheimer's disease.

The molecular bases of late-onset and sporadic Alzheimer's disease (AD) still have to be unraveled. Among putative candidates for molecular variations in AD, we propose LMO4 protein, a transcription regulator, involved in multiple protein complexes. We investigated changes in LMO4 immunoreactivity in vulnerable brain regions of AD cases and controls of comparable age. Immunocytochemical analysis revealed a high level of LMO4 expression in the entorhinal cortex (EC) and in the CA1 hippocampal region of the control brains and a consistent decrease in the AD brains, correlated with the amount of neurofibrillary tangles (NFT) degenerating neurones and the severity of senile plaques deposition. The decrease in LMO4 immunoreactivity resulted both from weaker immunoreactive signals and from a loss of immunoreactive neurones. LMO4 immunocytochemical staining appeared not to be colocalized with NFT in a majority of neurones. Its expression was weak in the dentate gyrus and stronger in CA3-4, two regions with no or low numbers of NFT, but there was no decrease in AD compared to control cases. In the frontal cortex, the ventro-infero-median region (area 12) showed a greater LMO4 expression than the polar one (area 9), but no decrease in AD was observed. As LMO4 has been proposed to inhibit cellular differentiation, it can be hypothesized that a reduced expression is associated in EC and CA1 with attempts of diseased neurones to differentiate (e.g. compensatory neuritogenesis). Taken together, these data indicate that LMO4 protein is involved in the complexity of the disease phenotype, at least as a secondary factor.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier.

PURPOSE: To investigate the influence of astrocytes on P-glycoprotein (Pgp) expression and intracellular accumulation of Pgp substrates, separate from their net transcellular transport across the blood-brain barrier (BBB). METHODS: An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) monolayers or BCEC co-cultured with astrocytes. RESULTS: BCEC+astrocyte co-cultures seemed to express a higher level of Pgp compared to BCEC monolayers. Inhibition of Pgp results in an increased intracellular accumulation of Pgp substrates in both BCEC monolayers and BCEC+astrocyte co-cultures, and increased the sensitivity for vinblastine mediated disruption of the in vitro BBB (called the vinblastine exclusion assay). BCEC monolayers were more sensitive to vinblastine mediated disruption compared to BCEC+astrocyte co-cultures. In the latter, but not in BCEC monolayers, an inhibitable polar transport of Pgp substrates was only found from the brain to the blood side of the filter. CONCLUSIONS: Astrocytes increase the functional expression of Pgp in our in vitro BBB model. These results also illustrate that an important role for Pgp on the BBB is to protect the barrier against intracellular accumulation of cytotoxic BBB disrupting compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Bleomycin-induced pulmonary injury in mice deficient in SPARC.

SPARC (secreted protein, acidic and rich in cysteine) is a component of the matrix that appears to regulate tissue remodeling. There is evidence that it accumulates in the lung in the setting of pulmonary injury and fibrosis, but direct evidence of its involvement is only now emerging. We therefore investigated the development of pulmonary fibrosis induced by bleomycin administered either intratracheally or intraperitoneally in mice deficient in SPARC. Bleomycin (0.15 U/mouse) given intratracheally induced significantly more pulmonary fibrosis in mice deficient in SPARC compared with that in wild-type control mice, with the mutant mice demonstrating greater neutrophil accumulation in the lung. However, in wild-type and SPARC-deficient mice given intraperitoneal bleomycin (0.8 U/injection x 5 injections over 14 days), the pattern and severity of pulmonary fibrosis, as well as the levels of leukocyte recruitment, were similar in both strains of mice. These findings suggest that the involvement of SPARC in pulmonary injury is likely to be complex, dependent on several factors including the type, duration, and intensity of the insult. Furthermore, increased neutrophil accumulation in the peritoneal cavity was also observed in SPARC-null mice after acute chemical peritonitis. Together, these data suggest a possible role for SPARC in the recruitment of neutrophils to sites of acute inflammation.

Animals↗
PubMed2000

Dietary iron and the integrity of the developing rat brain: a study with the artificially-reared rat pup.

Inadequate iron nutrition is thought to affect many aspects of brain development. Iron is a component of enzyme systems in DNA synthesis, the respiratory chain, neurotransmitter and lipid metabolism. The iron content of the striatum increases post-natally, with neuronal differentiation, myelin lipid and receptor formation: Seventy percent of the iron in the brain is associated with myelin. In an attempt to dissociate the global effects of under-and/or malnutrition and to produce exclusively an iron deficiency, we have used the gastrostomy-reared rat pup fed milk substitutes which vary only in their iron content. To ensure the pups did not have adequate iron reserves at birth, dams were fed a meal diet of low iron content (3 ppm) throughout gestation. The pups were then artificially reared on milk with (43 ppm), and without added iron (2.5 ppm) from 6 up to 21 days after birth. At 21 days of age, body weights of iron deficient pups were about 90% those of control animals. At 21 days of age, the pups were weaned, then fed standard laboratory rat chow. Brain was examined at 42 days of age (for young adults) and up to 6 months of age (180 days as mature adults). Morphometric analysis of sagittal sections of the cerebellum at 21 and 63 days of age revealed a deficit in white matter formation in pups fed low-iron at 21 days of age when compared to controls. This deficit was partially recouped by age 63 days. By contrast, animals fed milk supplemented with iron showed greater definition in white matter formation than controls at 21 days of age; indicative of precocious maturation of the white matter tracts. Our findings indicate that iron deficiency, without under/mal-nutrition and other variables, does not result in extensive growth deficits in body and brain weight. However, the iron status profoundly influences the development of myelination in that the process is delayed in iron deficiency.

Animals↗
PubMed1999

Serotonergic neurons in the brainstem of the wallaby, Macropus eugenii.

The organisation and cytoarchitecture of the serotonergic neurons in a diprotodont marsupial were examined by using serial sections of the brainstem processed for serotonin immunohistochemistry and routine histology. The topographic distribution of serotonergic neurons in the brainstem of the adult wallaby (Macropus eugenii) was similar to that of eutherian mammals. Serotonergic neurons were divided into rostral and caudal groups, separated by an oblique boundary through the pontomedullary junction. Approximately 52% of the serotonergic neurons in the wallaby brainstem were located in the rostral midline nuclei (caudal linear nucleus, dorsal, median, and pontine raphe nuclei and the interpeduncular nucleus), whereas 21% were found in the caudal midline region (nuclei raphe magnus, obscurus, and pallidus). The remaining serotonergic neurons (27%) were located in more lateral regions such as the pedunculopontine tegmental nuclei, the supralemniscal nuclei (B9 group), and the ventrolateral medulla. The largest serotonergic group, the dorsal raphe, contained one-third of the brainstem serotonergic neurons and showed five subdivisions, similar to that described in other species. In contrast, the median raphe did not show clear subdivisions. The internal complexity of the raphe nuclei and the degree of lateralisation of serotonergic neurons suggest that the wallaby serotonergic system is similar in organisation to that described for the cat and rabbit. This study supports the suggestion that the serotonergic system is evolutionally well conserved and provides baseline data for a quantitative study of serotonergic innervation of the developing cortex in the wallaby.

Animals↗
PubMed1999

Comparison of high-calorie, low-nutrient-dense food consumption among obese and non-obese adolescents.

OBJECTIVE: The purpose of this study was to determine whether obese adolescents eat more high-calorie low-nutrient-dense foods than non-obese adolescents. RESEARCH METHODS AND PROCEDURES: Using a cross-sectional design, 22 non-obese and 21 obese adolescents kept 14-day food records. Records provided estimates of total daily energy intake and caloric intake from five categories of high-calorie, low-nutrient-dense (HC) foods: candy, chips, soda, baked goods, and ice cream. Body composition was determined by 18O dilution and daily energy expenditure by doubly labeled water. Percentage of energy intake reported (%report) was calculated as the ratio of reported energy intake to measured energy expenditure (x 100%). RESULTS: Both groups underreported energy intake, but the percentage reported was significantly greater in the non-obese group (78.2+/-20.5% non-obese vs. 55.5+/-21.8% obese, p<0.001). Consumption of calories from chips and soda was similar among non-obese and obese adolescents. However, total energy intake from all HC foods was higher in the non-obese group than among the obese (617+/-356 kcal/day vs. 362+/-223 kcal/day; p<0.01) and represented 27.2+/-10.5% and 19.9+/-9.6% of reported energy intake in the non-obese and obese groups, respectively. After adjustment for under-reporting, the percentage of calories provided by each of the HC foods was similar in the obese and non-obese groups except for ice cream, which remained significantly greater in the non-obese group (p<0.05). DISCUSSION: Our findings suggest that both non-obese and obese adolescents consume a substantial portion of reported calories from HC foods and that obese adolescents do not consume more calories from these foods than non-obese adolescents. These data offer no evidence to support the widespread notion that obese adolescents eat more "junk food" than non-obese adolescents. Health professionals who treat obese adolescents must be aware that the excess calories in their diets may come from a variety of food sources and not solely from high-calorie snack foods.

Adipose Tissue↗
PubMed1999

Isolation of feline parvovirus from peripheral blood mononuclear cells of cats in northern Vietnam.

Feline parvovirus (FPV) was isolated rather frequently from the peripheral blood mononuclear cells (PBMCs) of cats in northern Vietnam by coculturing with MYA-1 cells (an interleukin-2-dependent feline T lymphoblastoid cell line) or Crandell feline kidney (CRFK) cells (a feline renal cell line). Efficiency of virus isolation was higher in MYA-1 cells than in CRFK cells. Interestingly, among the 17 cats from which FPV was isolated, 9 cats were positive for virus neutralizing (VN) antibody against FPV, indicating that FPV infected PBMCs and was not eliminated from PBMCs even in the presence of VN antibodies in the cats.

Animals↗
PubMed1998

Seroepidemiological survey of feline retrovirus infections in domestic and leopard cats in northern Vietnam in 1997.

The prevalence of infections with three feline retroviruses (feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and feline syncytial virus (FSV)) was examined in northern Vietnam in 1997. We collected a total of 77 blood samples from 69 domestic and 8 leopard cats, and examined the presence of anti-FIV and FSV antibodies and FeLV p27 antigen in the plasma samples by the indirect immunofluorescence and/or two commercial kits. None of the samples was positive for FIV and FeLV. The overall positive rate of FSV was 31% and the positive rates among the domestic and leopard cats were 29 and 50%, respectively. We isolated FSV from peripheral blood mononuclear cells of 6 domestic and one leopard cats.

Animals↗
PubMed1997

Translational regulation of lipoprotein lipase by epinephrine involves a trans-acting binding protein interacting with the 3' untranslated region.

To better characterize the translational regulation of lipoprotein lipase (LPL) by epinephrine, cytoplasmic extracts were prepared from 3T3-L1 adipocytes, 3T3-F442A adipocytes, and other nonadipocyte cell lines (C2 cells, 3T3 fibroblasts, and Chinese hamster ovary cells). After treatment with epinephrine, cell extracts from the adipocytes inhibited LPL translation in an in vitro translation assay, whereas extracts from the C2 cells and 3T3 fibroblasts did not affect LPL translation. To identify the region on the LPL mRNA that controlled translation, in vitro translation was carried out using constructs containing different LPL sequences. Specific deletion of the first 50 (1601-1650) nucleotides of the 3' untranslated region (UTR) resulted in a loss of translation inhibition. The addition of LPL 3' UTR to a heterologous reporter gene construct resulted in an inhibition of translation. Inhibition of the reporter LPL 3' UTR translation was demonstrated by the addition of epinephrine-treated cell extracts to an in vitro translation assay, as well as by transfection of this construct into 3T3-F442A cells, followed by treatment of the cells with epinephrine. Competition for a trans-acting binding protein was demonstrated by the addition of sense mRNA strands corresponding to the proximal 135 nucleotides of the 3' UTR of LPL. To identify a RNA-binding protein, adipocyte extracts were incubated with 32P-labeled RNA sequences followed by RNase treatment. The epinephrine-treated cell extract protected a fragment of RNA when the RNA included sequences on the proximal 3' UTR of LPL. Cross-linking of this protected fragment and analysis by SDS-polyacrylamide gel electrophoresis revealed a protein that migrated at about 30 kDa. Thus, the addition of epinephrine to 3T3 adipocytes results in an inhibition of translation through the production of a RNA-binding protein that binds to a region on the proximal 3' UTR of the LPL mRNA.

3T3 Cells↗
PubMed1997

Virtual reality: teaching tool of the twenty-first century?

Virtual reality (VR) is gaining recognition for its enormous educational potential. While not yet in the mainstream of academic medical training, many prototype and first-generation VR applications are emerging, with target audiences ranging from first- and second-year medical students to residents in advanced clinical training. Visualization tools that take advantage of VR technologies are being designed to provide engaging and intuitive environments for learning visually and spatially complex topics such as human anatomy, biochemistry, and molecular biology. These applications present dynamic, three-dimensional views of structures and their spatial relationships, enabling users to move beyond "real-world" experiences by interacting with or altering virtual objects in ways that would otherwise be difficult or impossible. VR-based procedural and surgical simulations, often compared with flight simulators in aviation, hold significant promise for revolutionizing medical training. Already a wide range of simulations, representing diverse content areas and utilizing a variety of implementation strategies, are either under development or in their early implementation stages. These new systems promise to make broad-based training experiences available for students at all levels, without the risks and ethical concerns typically associated with using animal and human subjects. Medical students could acquire proficiency and gain confidence in the ability to perform a wide variety of techniques long before they need to use them clinically. Surgical residents could rehearse and refine operative procedures, using an unlimited pool of virtual patients manifesting a wide range of anatomic variations, traumatic wounds, and disease states. Those simulated encounters, in combination with existing opportunities to work with real patients, could increase the depth and breadth of learners' exposure to medical problems, ensure uniformity of training experiences, and enhance the acquisition of clinical skills.

Anatomy↗
PubMed1997

A flexible and extensible object-oriented 3D architecture: application in the development of virtual anatomy lessons.

"Anatomic VisualizeR" represents the first application to be developed using a 3D architectural framework created at the University of California, San Diego, School of Medicine. This application combines 3D anatomic models (based on the Visible Human dataset) with supporting 2D media (e.g., diagnostic imagery, surgical videos, etc.) to establish a comprehensive learning environment for anatomy. "Guided lessons" are being created to address complex curricular and learning objectives. Faculty expertise is represented in these preconfigured lessons, in part through the specification of appropriate content and the incorporation of activities to enhance visualization. These lessons are an intellectual framework which ensures that clinically-relevant issues and ancillary learning opportunities are available. The curricular exercises are non-sequential and can be interrupted at any time; users are encouraged to freely explore the environment. At the core of Anatomic VisualizeR's object-oriented architecture is the ability to identify, access, view, and manipulate heterogeneous content. The capacity to query a database gateway to retrieve specified resources has been built into the application. Encapsulation of individual elements to form 3D display objects ("blocks") enables Anatomic VisualizeR to efficiently manage 3D models, 2D images, text, sound, and video. The "block" paradigm also allows Anatomic VisualizeR to associate contextually appropriate display characteristics and behaviors with the various content elements. For example, the anatomic model block provides the capability to "link" and "unlink" the anatomic models and to alter their transparencies. The anatomic models can be displayed concurrently with other blocks to facilitate structural comparisons. Anatomic VisualizeR marks a major milestone in our developmental efforts. While lessons and database content are still not complete, we are confident that it will become the first tangible realization of our vision.

Anatomy↗
PubMed1996

A novel sea urchin nuclear receptor encoded by alternatively spliced maternal RNAs.

Screening of a genomic library from the sea urchin Strongylocentrotus purpuratus with a human COUP-TF I cDNA probe revealed the presence of a novel gene member of the steroid-thyroid-retinoic acid receptor superfamily, which was named SpSHR2 (S. purpuratus Steroid Hormone Receptor 2). Sequence analysis of the isolated genomic clone revealed that the DNA binding domain of this orphan receptor is most homologous to the human TR2 receptor. Using this sea urchin genomic fragment as probe, a S. purpuratus embryonic cDNA library was screened and two distinct but homologous cDNA clones were isolated. The two cDNAs encode the same DNA binding domain as the SpSHR2 gene and carry an almost identical 3'-untranslated sequence. One of the clones, however, is missing an entire region of about 1100 nt which includes the putative ligand binding domain. Genomic DNA hybridization suggests that SpSHR2 is a single-copy gene in the S. purpuratus genome. Exon skipping during splicing of a single primary transcript appears to be the reason for the differently sized mRNAs. RNA blot hybridization results suggest that SpSHR2 transcripts are stored as maternal RNA in the egg and are not detected beyond the blastula stage. In vitro transcription and translation of the full-length cDNA produced a polypeptide which specifically binds to the hormone response element in the 5'-flanking region of the sea urchin actin CyIIIb gene. In vivo labeling of proteins synthesized by cleavage stage embryos followed by immune precipitation of the SpSHR2 protein using specific antibodies reveals that the maternal SpSHR2 mRNA is being translated during early embryonic development.

Alternative Splicing↗
PubMed1996

Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage.

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

Acetylglucosaminidase↗
PubMed1996

1,25-Dihydroxyvitamin D induces lipoprotein lipase expression in 3T3-L1 cells in association with adipocyte differentiation.

1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is known to modulate the development of bone and other mesenchymal cell types. Since osteoblasts and adipocytes are thought to arise in bone marrow from a common progenitor, this work examined the effects of 1,25-(OH)2D3 on adipocyte development, and in particular on the expression of lipoprotein lipase (LPL), which is an early marker for the differentiated adipocyte. 3T3-L1 preadipocytes were cultured in the presence of 1,25-(OH)2D3 (10(-9) to 10(-7) M) for up to 7 days. LPL activity was measured in the medium and cell extracts, and LPL messenger RNA levels were measured by Northern blotting. When compared to control cells, 10(-7) M 1,25-(OH)2D3 increased medium LPL activity by 2- to 3-fold and cellular LPL by 1.5-fold. Significant increases in medium and cellular LPL were observed at 10(-9) M and were maximal at 10(-7) M. Along with the increase in LPL activity, there was an increase in LPL messenger RNA by 2-fold at 5 days, and by 5-fold at 7 days. In addition to an increase in LPL, 1,25-(OH)2D3 increased expression of aP2, an adipocyte-specific marker associated with differentiation. After the addition of 1,25-(OH)2D3, there was a decrease in 3T3-L1 cell number, which is consistent with differentiation, and a decrease in vitamin D receptors. Finally, these cells developed a different morphology. 1,25-(OH)2D3-treated cells assumed a rounded appearance, although without detachment from the dish and without the degree of lipid accumulation usually associated with the addition of insulin, isbutylmethylxanthine, and dexamethasone. It is concluded that 1,25-(OH)2D3 induced LPL expression in 3T3-L1 cells through an induction of differentiation-dependent mechanism(s). These findings suggest an important role for 1,25-(OH)2D3 in normal adipocyte differentiation.

1-Methyl-3-isobutylxanthine↗