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Biomedical subjects

V Bosch

Publications and source records attributed to V Bosch.

At least 19 recordsLinked to original sources

Gestalt perception modulates early visual processing.

We examined whether early visual processing reflects perceptual properties of a stimulus in addition to physical features. We recorded event-related potentials (ERPs) of 13 subjects in a visual classification task. We used four different stimuli which were all composed of four identical elements. One of the stimuli constituted an illusory Kanizsa square, another was composed of the same number of collinear line segments but the elements did not form a Gestalt. In addition, a target and a control stimulus were used which were arranged differently. These stimuli allow us to differentiate the processing of colinear line elements (stimulus features) and illusory figures (perceptual properties). The visual N170 in response to the illusory figure was significantly larger as compared to the other collinear stimulus. This is taken to indicate that the visual N170 reflects cognitive processes of Gestalt perception in addition to attentional processes and physical stimulus properties.

Adult↗

Generation of a flexible cell line with regulatable, high-level expression of HIV Gag/Pol particles capable of packaging HIV-derived vectors.

HIV-derived vectors are of potential clinical relevance due to their ability to transduce nondividing cells in vitro and in vivo. However, the generation of cell lines stably and reproducibly expressing high amounts of defined subviral particles, capable of packaging and transducing HIV-derived vectors, has been hampered by the cytotoxicity of some of the required gene products, in particular of the HIV-1 protease. The successful use of regulatable gene expression systems to overcome this problem requires that the remaining basally expressed gene product activity is below the threshold for cytotoxicity. To try to achieve this, we have consecutively introduced appropriate plasmids, encoding HIV rev and HIV gag/pol gene products, each under the control of separate ecdysone-inducible promoters, into human 293 cells. Using a protocol in which a specific HIV protease inhibitor, Saquinavir, was continuously present in the culture medium during selection, we could generate stable cell lines inducibly expressing high amounts of subviral particles. A cell line, termed 293-Rev/Gag/Pol(i), which has been characterized in more detail, inducibly releases, within 48 h postinduction, high amounts of HIV Gag/Pol particles (about 10 microg CA/ml). These HIV Gag/Pol particles can package and transduce third-generation HIV vectors to high titers. Thus, in addition to other applications, the 293-Rev/Gag/Pol(i) cell line represents a "founder" packaging cell line which, depending on the requirement, can be further modified to include specific transgene-encoding vector and targeting glycoprotein genes.

Cell Line↗

On multivariate spectral analysis of fMRI time series.

Most of functional magnetic resonance imaging (fMRI) time series analysis is based on single voxel data evaluation using parametric statistical tests. The result of such an analysis is a statistical parametric map. Voxels with a high significance value in the parametric test are interpreted as activation regions stimulated by the experimental task. However, for the investigation of functional connectivities it would be interesting to get some detailed information about the temporal dynamics of the blood oxygen level-dependent (BOLD) signal. For investigating that behavior, a method for fMRI data analysis has been developed that is based on Wiener theory of spectral analysis for multivariate time series. Spectral parameters such as coherence measure and phase lead can be estimated. The resulting maps give detailed information on brain regions that belong to a network structure and also show the temporal behavior of the BOLD response function. This paper describes the method and presents a visual fMRI experiment as an example to demonstrate the results.

Adult↗

Slow cortical potentials during retention of object, spatial, and verbal information.

We used event related potentials (ERPs) to examine both the specificity and the timing of slow cortical scalp potentials (SPs) elicited by the retention of object, spatial, and verbal information in working memory (WM). Participants performed a modified delayed matching task in which a task cue presented in the middle of the delay interval indicated what type of information had to be retained for a subsequent comparison with the test stimulus. The first experiment used nameable objects and spatial locations as stimuli. The retrieval mode (visual vs. verbal) was manipulated by presenting either figural information or printed words as test stimuli. Transient ensembles of frontal and parieto-occipital slow waves with different scalp topographies for object and spatial information were evoked as a function of task cues. When words rather than objects were used as test stimuli highly similar, though more pronounced, fronto-parietal slow wave patterns were obtained. The second experiment using unfamiliar objects and non-nameable spatial locations indicated that neither the left frontal negative SP nor the posterior SPs are exclusively related to verbal working memory operations. The results indicate that a parietal negative SP reflects processes of spatial selective attention whereas a parieto-occipital positive SP indexes the retention of visual object information. Left frontal negative SPs are generated by a compound of higher order frontal control processes and vary as a function of information type.

Adult↗

Properties of wild-type, C-terminally truncated, and chimeric maedi-visna virus glycoprotein and putative pseudotyping of retroviral vector particles.

We have characterized the properties of the maedi-visna virus (MVV) glycoprotein, which has a long cytoplasmic C-terminal domain, and of a panel of C-terminally truncated and C-terminally chimeric MVV-Env constructs. Cells expressing wild-type MVV glycoprotein form syncytia with target cells from many different species and tissues, demonstrating that the MVV-Env cellular receptor is widely distributed. Similar to the situation with other lentiviral glycoproteins, truncation of the C-terminal domain of MVV-Env significantly increases its membrane fusion capacity. However, despite their presence in a fusogenic form at the cell surface, neither the wild-type nor any of the C-terminally modified MVV-Env constructs, these latter lacking sterically inhibitory C termini, were able to successfully pseudotype murine leukemia virus- or human immunodeficiency virus-derived vector particles.

Amino Acid Sequence↗

[Influential factors in mortality rate from congenital heart disease. Study of 1,216 children in the Autonomous Community of Murcia (1978-1990)].

INTRODUCTION: In the last few years, important progress has taken place in management of congenital heart disease. These changes have had an influence on diagnosis, preoperative management, surgery treatment and postoperative care, giving rise to better results in the treatment of children suffering from congenital heart disease. AIM: To assess the results of congenital heart diseases in a reference hospital by comparing two periods with reference to both diagnosis and therapeutical management. We also intend to investigate the influence that factors such as the existence of extracardiac congenital malformations and heart surgery have on mortality. PATIENTS AND METHODS: Our sample group was made up of 1,216 children suffering from congenital heart disease. Their ages ranged from 1 day to 7 years old. These children were born over a period of thirteen years and studied at the paediatric cardiology unit in a reference hospital in the Autonomous Community of Murcia, a region of Spain. We retrospectively analysed their development by individual heart diseases (and their associated factors), and the global results. Our research was divided into two periods: between 1978 and 1983, and between 1984 and 1990. Differences were found regarding diagnosis and treatment. RESULTS: a) Mortality rate from congenital heart disease decreased in the period between 1984 and 1990 in comparison to the period between 1978 and 1983, from 28 to 21,7% (p < 0.05); b) individually, the mortality rate decreased with statistical significance in two diseases: interventricular communication and patent ductus arteriosus, and c) there is a higher mortality rate of patients with no surgery treatment and/or extracardiac malformations. CONCLUSION: Progress in the management of congenital heart disease has led to a more favourable outcome in the last years.

Child↗

Membrane fusion between retroviral particles: host-range extension and vaccine prospects.

We have analyzed if different populations of retroviral particles carrying the viral and cellular receptors of membrane viruses, respectively, are able to specifically fuse with each other. Using the glycoprotein of human immunodeficiency virus type 1 and its cellular receptor complex, we demonstrate that interviral membrane fusion can, indeed, occur and that the resultant fused viral structures are able to infect cells and transduce a marker gene. On the one hand, these results have relevance for the development of vaccine strategies based on fusion-induced conformational epitopes on the viral glycoprotein. However, in addition to this potential practical application, the results obtained (which were extended to include analyses with the vesicular stomatitis virus G protein and its cellular receptor) have far-reaching implications for in vivo situations in which simultaneous infections with different membrane viruses can occur.

AIDS Vaccines↗

Statistical analysis of multi-subject fMRI data: assessment of focal activations.

A simple procedure for analyzing multi-subject functional magnetic resonance imaging (fMRI) data is proposed. In the first step, a voxel-wise t-test across standardized z-maps is performed to identify areas that are consistently activated across subjects. In the second step, for each area, individual mean z-scores are calculated and subsequently subjected to an analysis of variance. An example is provided.

Analysis of Variance↗

What have Klingon letters and faces in common? An fMRI study on content-specific working memory systems.

Neuroimaging studies show that prefrontal, premotor, and parietal cortical regions are part of a working memory network that supports the active retention of information. In two experiments we used fMRI to examine whether prefrontal and posterior cortical areas are organized in a content-specific way for object and spatial working memory. Subjects performed a delayed matching-to-sample task modified to allow the examination of content-specific retention processes, independent of perceptual and decision-related processes. In Experiment 1, either unfamiliar geometrical objects (Klingon letters from an artificial alphabet unknown to the participants) or their spatial locations had to be memorized, whereas in Experiment 2, either unfamiliar faces or biological objects (butterflies) were actively memorized. All tasks activated a similar cortical network including posterior parietal (banks of the intraparietal sulcus), premotor (banks of the inferior precentral sulcus) and prefrontal regions (banks of the inferior frontal sulcus), and the presupplementary motor area (pre-SMA). For geometrical objects and faces for which strategic semantic processing can be assumed, this activation was larger in the left than in the right hemisphere, whereas a bilateral or right dominant distribution was obtained for butterflies and spatial locations. The present results do not support the process-specific or content-specific view of the role of the prefrontal cortex in working memory task. Rather, they suggest that the inferior prefrontal cortex houses nonmemonic strategic processing systems required for response selection and task management that can flexibly be used across a variety of tasks and informational domains.

Adult↗

[Behavior of some anthropometric, clinical and biochemical variables in boys and girls 8 to 12 years of age from the longitudinal study of the metropolitan area].

A longitudinal principal components analysis was used to summarize trends or intraindividual changes in weight, height, blood pressure, serum cholesterol and triglycerides in 32 boys and 28 girls from the Caracas Longitudinal Study (1976-1982), who started follow-up at age 8. A first component was identified for each variable, it represents a measure of position across the whole age period, a "canalization pattern". This component accounted for most of the total variance. The second component represents an unidirectional change in relative position of the values of the variable, a "decanalization pattern", and a third pattern summarized deviations around a position level: "recanalization pattern". The results from the correlation analyses between the components indicate a positive and significant association between the identified trends. These patterns allow predictability of "high and low risk" factors of non-communicable chronic diseases.

Blood Pressure↗

Incorporation of wild-type and C-terminally truncated human epidermal growth factor receptor into human immunodeficiency virus-like particles: insight into the processes governing glycoprotein incorporation into retroviral particles.

Previous results have indicated that incorporation of surface glycoprotein into retroviral particles is not a specific process and that many heterologous viral and cellular glycoproteins can be incorporated as long as they do not have long cytoplasmic C-terminal regions which were presumed to be sterically inhibitory. In this study, this concept has been directly examined by analyzing the incorporation of the wild-type human epidermal growth factor receptor (Wt-EGFR) and of a C-terminally truncated mutant of Wt-EGFR (Tr-EGFR) into human immunodeficiency virus (HIV)-like particles. Incorporation was directly analyzed at the protein level and by immunogold labelling of enriched HIV-like particles. In agreement with the above concept, Tr-EGFR, with only 7 C-terminal amino acids (aa), was efficiently incorporated into HIV-like particles. Incorporation of the Wt-EGFR species, with 542 C-terminal cytoplasmic aa, was reduced by a factor of about 5 in comparison to that of the Tr-EGFR species. However, the Wt-EGFR species was still very significantly present in the HIV-like particles. A series of control experiments verified that this represents genuine incorporation of Wt-EGFR into the membrane of HIV-like particles. These observations allow further speculation as to the processes governing glycoprotein incorporation into retroviral particles and indicate that the internal virus structure of HIV (in particular the matrix layer [MA]) can accommodate much larger heterologous cytoplasmic domains in incorporated glycoproteins than previously assumed.

Cell Line↗

[Tracking of body height, body weight, body mass index, blood lipids and glucose in upper strata girls in Caracas, Venezuela].

In the Caracas Longitudinal Study, the canalization of 24 girls that started follow-up at age 4, 43 at age 8, and 32 at age 12 in: height (H), weight (W), Body Mass Index (BMI), cholesterol (CHOL), triglycerides (TG) and glucose (GL), was studied using Schneiderman n Tracking Index (TI) and age to age correlations. TI presented a gradient H > W > BMI > CHOL and lower in TG and GL. TI of all variables diminished increased with age and in BMI and CHOL. Age to age correlations were significant at all ages in H, W. and BMI and higher in CHOL (p < 0.01) compared to TG and GL. The significant tracking of H, W, BMI and lipids, specially CHOL, is relevant in prevention of non-communicable chronic diseases.

Age Factors↗

Inhibition of cellular glycoprotein incorporation into human immunodeficiency virus-like particles by coexpression of additional cellular interaction partner.

We examined the concepts of whether cellular surface glycoprotein overexpressed in heterologous cells can be efficiently incorporated into lentiviral particles and whether incorporation is blocked when a natural interaction partner is coexpressed. Human CD4 and a truncated version lacking the cytoplasmic C terminus, expressed in 293T cells, were efficiently incorporated into Env-defective human immunodeficiency virus type 1 virus-like particles. However, on coexpression of p56(lck), the natural binding partner of the CD4 C-terminal domain in T lymphocytes, incorporation of the wild-type CD4 was completely abolished, whereas incorporation of the C-terminally truncated mutant remained unaffected. Confocal microscopy and detergent solubility assays did not reveal any significant difference in the distribution of wild-type CD4 at the plasma membrane in the presence or absence of p56(lck). These results give some insight into the processes governing protein incorporation into the lipid bilayer of lentiviruses.

Alkaline Phosphatase↗

[The liver as a source of essential long chain polyunsaturated fatty acids for postnatal brain development in the rat].

We address here the issue concerning the origin of essential long chain polyunsaturated fatty acids (LC-PUFA) needed for early postnatal brain development. Normal newborn rats 1, 5, 10 and 20 day-old were decapitated, immediately after, the livers were processed to obtain the microsomal fraction and its delta 6 fatty acid desaturase activity and fatty acid composition were determined. Samples of plasma, whole homogenized brain hemispheres and milk contained in the gastric cavity of the suckling rats, were analyzed to obtained their fatty acid composition. We fond that the rat neonate has a very low delta 6 desaturase activity in liver microsomes as compared with the adult. In contrast, there is a considerable quantity of DHA an AA in the milk, liver microsomes, plasma lipids and brain. In conclusion, we propose that brain DHA and AA cannot be derived substantially through liver synthesis, but through the availability of these preformed fatty acids in the milk. These fatty acids are concentrated in liver microsomes and then secreted into plasma lipid pool to reach finally to brain structures.

Animals↗

Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV generates a retroviral vector with specificity of infection for CD4-expressing cells.

CD4-expressing T cells in lymphoid organs are infected by the primary strains of HIV and represent one of the main sources of virus replication. Gene therapy strategies are being developed that allow the transfer of exogenous genes into CD4(+) T lymphocytes whose expression might prevent viral infection or replication. Insights into the mechanisms that govern virus entry into the target cells can be exploited for this purpose. Major determinants of the tropism of infection are the CD4 molecules on the surface of the target cells and the viral envelope glycoproteins at the viral surface. The best characterized and most widely used gene transfer vectors are derived from Moloney murine leukemia virus (MuLV). To generate MuLV-based retroviral gene transfer vector particles with specificity of infection for CD4-expressing cells, we attempted to produce viral pseudotypes, consisting of MuLV capsid particles and the surface (SU) and transmembrane (TM) envelope glycoproteins gp120-SU and gp41-TM of HIV type 1 (HIV-1). Full-length HIV-1 envelope glycoproteins were expressed in the MuLV env-negative packaging cell line TELCeB6. Formation of infectious pseudotype particles was not observed. However, using a truncated variant of the transmembrane protein, lacking sequences of the carboxyl-terminal cytoplasmic domain, pseudotyped retroviruses were generated. Removal of the carboxyl-terminal domain of the transmembrane envelope protein of HIV-1 was therefore absolutely required for the generation of the viral pseudotypes. The virus was shown to infect CD4-expressing cell lines, and infection was prevented by antisera specific for gp120-SU. This retroviral vector should prove useful for the study of HIV infection events mediated by HIV-1 envelope glycoproteins, and for the targeting of CD4(+) cells during gene therapy of AIDS.

CD4 Antigens↗

Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41.

To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.

Animals↗

Analysis of vif-defective human immunodeficiency virus type 1 (HIV-1) virions synthesized in 'non-permissive' T lymphoid cells stably infected with selectable HIV-1.

In order to facilitate analyses of the molecular function of the human immunodeficiency virus type 1 (HIV-1) Vif protein, we have developed a cell culture model-system which allows permanent production of genotypically and phenotypically vif-defective HIV-1 virions in 'non-permissive' H9 cells. Using recombinant, replication-competent HIV-1 proviruses coding for a selectable marker gene (gpt) instead of nef, two stably infected H9 subclones named M2 (vif-mutant) and WX (wild-type), respectively, were generated. Virions released from cell line M2--displaying the expected vif-defective phenotype--are produced permanently, and in an at least 50 times higher amount than virus particles from acutely vif-negative HIV-1-infected H9 cells. Analysis of viral protein composition and the electron-microscopic morphology of vif-mutant virions did not reveal any detectable differences in comparison to wild-type virions.

Animals↗