Biomedical subjects

N Lopez

Publications and source records attributed to N Lopez.

At least 19 recordsLinked to original sources

PubMed2002

Are immunoglobulin E levels associated with early wheezing? A prospective study in Brazilian infants.

The relationship between wheezing or asthma and serum immunoglobulin (Ig)E levels in early life is unclear. The aim of this study was to follow-up the IgE immune response in infants that did, or did not, develop recurrent wheezing during their first year of life. One-hundred and two randomised term neonates were included, in which IgE levels were quantified in cord blood samples, at 3, 6, 9 and 12 months of age. Specific IgE levels for food and inhalant allergens and the skin-prick test for inhalant allergens were also assessed at 6 and 12 months. During clinical follow-up, 32 (31%) infants presented with two or more wheezing episodes, while 70 (69%) had no wheezing. Total IgE levels were significantly higher up to 12 months in wheezing infants when compared to nonwheezing group. At 12 months, the specific IgE levels to cow's milk, egg white and mites were higher in infants with recurrent wheezing. There was no influence of family history for atopy on IgE levels. The skin-prick tests were positive in 14% and 23% in wheezing infants at 6 and 12 months, respectively. These results indicate an early allergic sensitisation in wheezing infants, suggesting an altered immunoregulatory T-cell role in immunoglobulin E production.

Allergens↗

PubMed2001

Oxygen vacancies as active sites for water dissociation on rutile TiO(2)(110).

Through an interplay between scanning tunneling microscopy experiments and density functional theory calculations, we determine unambiguously the active surface site responsible for the dissociation of water molecules adsorbed on rutile TiO(2)(110). Oxygen vacancies in the surface layer are shown to dissociate H(2)O through the transfer of one proton to a nearby oxygen atom, forming two hydroxyl groups for every vacancy. The amount of water dissociation is limited by the density of oxygen vacancies present on the clean surface exclusively. The dissociation process sets in as soon as molecular water is able to diffuse to the active site.

Journal Article↗

PubMed2001

The role of Sis1 in the maintenance of the [RNQ+] prion.

Yeast prions are inherited through proteins that exist in alternate, self-perpetuating conformational states. The mechanisms by which these states arise and are maintained are still poorly defined. Here we demonstrate for the first time that Sis1, a member of the Hsp40 chaperone family, plays a critical role in the maintenance of a prion. The prion [RNQ+] is formed by Rnq1, which is present in the same physical complex as Sis1, but only when Rnq1 is in the prion state. The G/F domain of Sis1 is dispensable for rapid growth on rich medium, but is required for [RNQ+] maintenance, distinguishing essential regions of Sis1 from those needed for prion interaction. A specific Sis1 deletion mutant altered the physical aggregation pattern of Rnq1 without curing the prion. This variant state propagated in a heritable fashion after wild-type Sis1 function was restored, indicating that multiple physical states are compatible with prion maintenance and that changes in chaperone activity can create prion variants. Using a prion chimera we demonstrate that the prion-determinant domain of Rnq1 is genetically sufficient for control by Sis1.

Adenosine Triphosphatases↗

PubMed2001

Dipole localization of human induced focal afterdischarge seizure in simultaneous magnetoencephalography and electrocorticography.

Localizations were compared for the same human seizure between simultaneously measured MEG and iEEG, which were both co-registered to MRI. The whole-cortex neuromagnetometer localized a dipole in a sphere phantom, co-registered to the MEG sensor array, with an error of 1.4 mm. A focal afterdischarge seizure was induced in a patient with partial epilepsy, by stimulation at a subdural electrocorticography (ECoG) electrode with a known location, which was co-registered to the MRI and to the MEG sensor array. The simultaneous MEG and ECoG during the 30-second seizure was measured and analyzed using the single, moving dipole model, which is the localization model used clinically. The dipole localizations from simultaneous whole cortex 68-channel MEG and 64-channel ECoG were then compared for the repetitive spiking at six different times during the seizure. There were two main regions of MEG and ECoG activity. The locations of these regions were confirmed by determining the location clusters of 8,000 dipoles on ECoG at consecutive time points during the seizure. The mean distances between the stimulated electrode location versus the dipole location of the MEG and versus the dipole location of the ECoG were each about one (1) centimeter. The mean distance between the dipole locations of the MEG versus the dipole locations of the ECoG was about 2 cm. These errors were compared to errors of MEG and ECoG reported previously for phantoms and for somatosensory evoked responses (SER) in patients. Comparing the findings from the present study to those from prior studies, there appeared to be the expected stepwise increase in mean localization error progressing from the phantom, to the SER, to the seizure.

Adolescent↗

PubMed1999

Asian-american variants of human papillomavirus type 16 have extensive mutations in the E2 gene and are highly amplified in cervical carcinomas.

Human-papillomavirus (HPV)-E2 protein is involved in gene-expression regulation and replication of HPV genome. Disruption of the E2 gene during viral integration has been proposed as a mechanism of tumoral progression, since the expression of E6/E7 viral oncogenes is allowed. However, retention of E1/E2 genes and high viral amplification are frequently found in HPV16-positive carcinomas of some populations. In this study, we investigated whether retention of E1/E2 and viral amplification are associated with particular HPV16 E2 variants in cervical carcinomas. HPV16 detection, E1/E2 integrity and viral amplification were explored by Southern blot in 123 cervical carcinomas. HPV16 variants were identified by Southern blot and by sequencing E6, L1/MY and E2 regions. Of 46 HPV16-positive tumors, 34 were positive for E1/E2 and 14 of them showed a variant restriction pattern by mutations in E2. All 14 were Asian-American (AA) variants and, of 11 sub-classified, 6 were AA-a and 5 AA-c. Two E1/E2-negative tumors also contained the AA-c variant, while the remaining HPV16-positive tumors contained only European variants. The E2 gene of AA variants showed 24 mutations, 19 identical in both sub-classes. The 24 mutations were distributed throughout the entire gene and 19 result in 18 amino-acid changes. The AA variants were associated with E1/E2-positive carcinomas with more than 50 viral copies/cell (p = 0.035). The association of Asian-American E2 variants with retention of E1/E2 suggests that E2 variation may be an alternative mechanism de-regulating the expression of viral oncogenes.

Amino Acid Substitution↗

PubMed1999

Haematopoietic damage persists 1 year after autologous peripheral blood stem cell transplantation.

In the present study we have used cell culture assays in order to assess the damage in the haematopoietic system 1 year after peripheral blood stem cell transplantation (PBSCT), and to establish at what level, haematopoietic progenitor cells (HPC) or stroma, this damage occurs. Thirty-one patients, nine breast cancer (BC), 17 non-Hodgkin lymphoma (NHL) and five Hodgkin disease (HD), who had received autologous PBSCT were included. Forty-eight normal subjects who had given informed consent were used as controls. Results were also compared with a matched group of patients (25 cases) prior to PBSCT. Progenitor cells were analysed using CFU-GM and plastic adherent delta (Pdelta) assays. Long-term bone marrow cultures (LTBMC) in one and two stages were established. One year after transplant both the number of committed progenitor cells and the CFU-GM production in LTBMC were significantly reduced in the three groups of patients when compared with controls (P < 0.05 or P < 0.01). Two-stage LTBMC experiments showed that the impairment in CFU-GM production was due to damage in both patients' stroma and haematopoietic progenitor cells (HPC). All patients, except those with HD, showed a decreased stromal layer confluence (P < 0.05), with significant differences in cell composition as compared to normal bone marrow (P = 0.001). When all these variables were compared with pretransplant results, we observed that stroma formation was significantly lower after PBSCT (P < 0.05), while the number of progenitor cells analysed by the Pdelta assay was significantly increased (P < 0.05). We can conclude that even 1 year after PBSCT, both the committed HPC and BM stroma remain damaged.

Adolescent↗

PubMed1999

SSB, encoding a ribosome-associated chaperone, is coordinately regulated with ribosomal protein genes.

Genes encoding ribosomal proteins and other components of the translational apparatus are coregulated to efficiently adjust the protein synthetic capacity of the cell. Ssb, a Saccharomyces cerevisiae Hsp70 cytosolic molecular chaperone, is associated with the ribosome-nascent chain complex. To determine whether this chaperone is coregulated with ribosomal proteins, we studied the mRNA regulation of SSB under several environmental conditions. Ssb and the ribosomal protein rpL5 mRNAs were up-regulated upon carbon upshift and down-regulated upon amino acid limitation, unlike the mRNA of another cytosolic Hsp70, Ssa. Ribosomal protein and Ssb mRNAs, like many mRNAs, are down-regulated upon a rapid temperature upshift. The mRNA reduction of several ribosomal protein genes and Ssb was delayed by the presence of an allele, EXA3-1, of the gene encoding the heat shock factor (HSF). However, upon a heat shock the EXA3-1 mutation did not significantly alter the reduction in the mRNA levels of two genes encoding proteins unrelated to the translational apparatus. Analysis of gene fusions indicated that the transcribed region, but not the promoter of SSB, is sufficient for this HSF-dependent regulation. Our studies suggest that Ssb is regulated like a core component of the ribosome and that HSF is required for proper regulation of SSB and ribosomal mRNA after a temperature upshift.

Alleles↗

PubMed1999

Illegal drug-using trends among students in a Spanish university in the last decade (1984-1994).

A sample of 2,086 university students in Valladolid (Spain) were surveyed in 1994 to assess their current use of illicit drugs. That information was used as a baseline to show the trends in the last decade in order to compare two other studies carried out on a similar target population in 1984 and 1990. Of those surveyed, 28.3% had taken some illicit drug within their lifetime, 16.7% in the previous year, and 7.2% in the previous month. Cannabis was the most common illicit drug used in the three levels among these students. 14.2 is the average starting age at which inhalants are used and 19.3 for opiates. 49.8% were opposed to any drug legalization. More than a quarter of the students (28.7%) could be considered as a mental disorder case-finding as measured by Golberg's General Health Questionnaire (GHQ), which was much more relevant among illicit drug users than among nonusers. A decrease in illegal drug use frequency among university students has been observed in the last 10 years.

Adolescent↗

PubMed1999

Hematopoietic damage prior to PBSCT and its influence on hematopoietic recovery.

BACKGROUND AND OBJECTIVE: Patients with malignancies receive chemotherapy to induce tumor remission which could damage hematopoiesis and adversely influence hematopoietic reconstitution after transplantation. In the present study we used a long-term culture (LTBMC) system and clonogenic assays to evaluate the marrow damage in patients selected to receive peripheral blood stem cell transplantation (PBSCT). DESIGN AND METHODS: Thirty-five patients - 20 with breast cancer (BC), 9 with non-Hodgkin's lymphoma (NHL) and 6 with Hodgkin's disease (HD) - were included. Bone marrow aspiration was performed one day prior to the initiation of the conditioning therapy. CFU-GM were cultured in methylcellulose with PHA-LCM. Delta assays of plastic adherent progenitor cells (PD) were performed according to Gordon's method. LTBMC were established for 5 weeks. RESULTS: There were fewer CFU-GM from all patient groups than from normal BM (p<0.05). In contrast, the number of immature progenitor cells (PD) was not decreased. The total number of CFU-GM produced by LTBMC patients was significantly reduced (p<0.05). The adherent layer from patients was often qualitatively different. In order to know whether the hematopoietic damage could affect hematopoietic reconstitution, we correlated culture data with time taken to reach peripheral cell counts. A negative correlation (r= - 0.71) was found between percentage of stromal layer and time taken to reach 20x10(9) platelets/L (tplat= 20x3-0.08% stromal layer). INTERPRETATION AND CONCLUSIONS: We can conclude that prior to PBSCT, hematopoietic function is impaired at both the level of committed progenitor cells and that of BM stroma. This damage could influence platelet recovery.

Adolescent↗

PubMed1998

Reduced mitochondrial DNA transcription in senescent rat heart.

We studied the effect of senescence on mitochondrial DNA (mtDNA) transcription with an in organello system using intact isolated rat heart mitochondria. A comparison of the electrophoretic patterns of mtDNA transcription products in young, adult and senescent rats showed an age-related reduction in newly-synthesized mitochondrial RNAs that reflects a decrease in the synthesis rate. These results correlate with the enzyme activities of the oxidative phosphorylation complexes I and IV, that are partially encoded by the mitochondrial genome. In addition, an age-related increase in the protein carbonyl content of the mitochondrial membranes was observed in senescent mitochondria suggesting an accumulation of mitochondrial oxidative damage. This reduction in the mtDNA transcriptional rate in the heart of senescent animals suggests that this could be one of the molecular bases underlying senescence of the myocardium.

Aging↗

PubMed1998

Social anxiety among adolescents: linkages with peer relations and friendships.

This study examined the utility of modifying the Social Anxiety Scale for Children-Revised (SASC-R) for use with adolescents, and examined associations between adolescents' social anxiety (SA) and their peer relations, friendships, and social functioning. Boys (n = 101) and girls (n = 149) in the 10th through 12th grades completed the Social Anxiety Scale for Adolescents (SAS-A) and measures of social support, perceived competence, and number and quality of their best friendships. Factor analysis of the SAS-A confirmed a three-factor structure: Fear of Negative Evaluation, Social Avoidance and Distress in General, and Social Avoidance Specific to New Situations or Unfamiliar Peers. Girls reported more SA than boys, and SA was more strongly linked to girls' social functioning than boys'. Specifically, adolescents with higher levels of SA reported poorer social functioning (less support from classmates, less social acceptance), and girls with higher levels of SA reported fewer friendships, and less intimacy, companionship, and support in their close friendships. These findings extend work on the SASC-R to adolescents, and suggest the importance of SA for understanding the social functioning and close friendships of adolescents, especially girls.

Adolescent↗

PubMed1998

Homology modeling, model and software evaluation: three related resources.

MOTIVATION: Homology modeling is rapidly becoming the method of choice for obtaining three-dimensional coordinates for proteins because genome projects produce sequences at a much higher rate than NMR and X-ray laboratories can solve the three-dimensional structures. The quality of protein models will not be immediately clear to novices and support with the evaluation seems to be needed. Expert users are sometimes interested in evaluating the quality of modeling programs rather than the quality of the models themselves. RESULTS: Three servers have been made available to the scientific community: a homology modeling server, a model quality evaluation server and a server that evaluates models built of proteins for which the structure is already known, thereby implicitly evaluating the quality of the modeling program. AVAILABILITY: The modeling-related servers and several structure analysis servers are freely available at http://swift.embl-heidelberg.de/servers/ CONTACT: gert.vriend@embl-heidelberg.de

Computational Biology↗

PubMed1998

Providing care in an infectious disease clinic. Why students volunteer.

This qualitative study explores the motivations of dental students who volunteered as care providers for patients identified as carriers of infectious diseases. The study involved 12 students, seven 4th year and five 3rd year students who worked 1-2.5 days per week in an infectious disease clinic in a dental school in the northeastern United States. 4 faculty members who also volunteered their time in the clinic supervised the students. Personal interviews were conducted with each student to determine their reasons for volunteering and to explore the perceived significance of their experiences in the clinic. Internal validity was established through group interviews wherein responses during the personal interviews were discussed with the students. All 12 students were interested in Oral Medicine and all 4th year students had completed a course on HIV-AIDS for their selective requirement. Students expressed willingness to care for patients who are medically compromised in anticipation of an increase of this type of patients in their future practice. Previous exposure to a family member or friend or patients (non-dental) who were terminally ill or to patients with HIV was another common reason. All 12 students preferred to work in the infectious disease clinic more than in other school clinics. They felt that there was more faculty-student interaction and a more stimulating learning atmosphere that the faculty created. The students felt that the patients treated in the clinic were more appreciative. Students also claim they experienced more team spirit among their fellow students and staff and that the clinic atmosphere was more relaxed and less competitive. Students got the most satisfaction from helping patients who were perceived to have had problems in accessing care prior to their visit to the clinic. Results of the study show that the students volunteered to treat patients who are known to have infectious diseases such as HIV/AIDS because they find personal and academic satisfaction from working in a clinic which provides care to individuals with specific medical needs.

Attitude of Health Personnel↗

PubMed1998

Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism.

With persistent foot-and-mouth disease virus (FMDV) in BHK-21 cells, there is coevolution of the cells and the resident virus; the virulence of the virus for the parental BHK-21 cells is gradually increased, and the cells become partially resistant to FMDV. Here we report that variants of FMDV C3Arg/85 were selected in a single infection of partially resistant BHK-21 cells (termed BHK-Rb cells). Indirect immunofluorescence showed that the BHK-Rb cell population was heterogeneous with regard to susceptibility to C3Arg/85 infection. Infection of BHK-Rb cells with C3Arg/85 resulted in an early phase of partial cytopathology which was followed at 6 to 10 days postinfection by the shedding of mutant FMDVs, termed C3-Rb. The selected C3-Rb variants showed increased virulence for BHK-21 cells, were able to overcome the resistance of modified BHK-21 cells to infection, and had acquired the ability to bind heparin and to infect wild-type Chinese hamster ovary (CHO) cells. A comparison of the genomic sequences of the parental and modified viruses revealed only two amino acid differences, located at the surface of the particle, at the fivefold axis of the viral capsid (Asp-9-->Ala in VP3 and either Gly-110-->Arg or His-108-->Arg in VP1). The same phenotypic and genotypic modifications occurred in a highly reproducible manner; they were seen in a number of independent infections of BHK-Rb cells with viral preparation C3Arg/85 or with clones derived from it. Neither amino acid substitutions in other structural or nonstructural proteins nor nucleotide substitutions in regulatory regions were found. These results prove that infection of partially permissive cells can promote the rapid selection of virus variants that show alterations in cell tropism and are highly virulent for the same cells.

Amino Acid Substitution↗

PubMed1998

The value of cell cultures for the diagnosis of mixed myelodysplastic/myeloproliferative disorders.

BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are a group of disorders characterized by dyshematopolesis in bone marrow (BM) and peripheral blood (PB) cytopenias. In recent years particular attention has been paid to myeloproliferative disorders with dysplastic features or myelodysplastic syndromes that evolve into a myeloproliferative disorder. The present study was designed to analyze patients with MDS but with a normal or increased colony forming capacity, in order to see whether or not cell cultures could contribute to the diagnosis of intermediate MDS-MPD conditions. DESIGN AND METHODS: A total of 80 patients diagnosed as having MDS were included in the study. CFU-GM assay was performed by plating 1 x 10(5) mononuclear cells/mL in IMDM and 0.9% methyl-cellulose containing 10% PHA-LCM. In all cases cultures were run in parallel without PHA-LCM to assess autonomous growth. Cultures were incubated at 37 degrees C in a fully humidified atmosphere with 5% CO2 and scored at day 14. Cytogenetic analysis was performed according to standard procedures. Short-term cultures of 24 and/or 48 hours were used. RESULTS: Twenty-two patients out of the 80 MDS cases included in the study showed a normal or increased cell growth pattern. Among these 22 patients, eight were diagnosed as suffering from chronic myelomonocytic leukemia (CMML) according to the FAB criteria and were excluded from the present analysis. The remaining 14 cases, which constitute the body of this study, displayed an increased number of clusters and/or colonies, with an altered cluster/colony ratio (anomalous growth) in 10 cases. Autonomous colony formation was present in five of these 14 cases and autonomous cluster growth was seen in all but three of them. In addition, one patient showed endogenous BFU-E growth. Morphological diagnoses were then revised due to this aberrant colony growth pattern: based on actual criteria, 3 patients could have been considered as having a-CML (atypical chronic myeloid leukemia). Another 6 cases evolved to a more proliferative disorder: 5 to CMML, and one to a-CML. Interestingly, in 3 of these 6 patients the evolution took place concomitantly with an infectious episode. In one additional patient the platelet count increased up to 1000 x 10(9)/L and required treatment with hydroxyurea. INTERPRETATION AND CONCLUSIONS: Our results show that intermediate MDS-MPD cases are relatively common and that in vitro characteristics, i.e. high clonogenic capacity with a high cluster/colony ratio and scanty autonomous growth, in patients showing myelodysplastic features could contribute to an early diagnosis in these cases. It is possible that in some cases an infectious episode, through higher cytokine secretion, contributes to the development of these disorders.

Adult↗

PubMed1997

Analysis of the 3' terminal sequence recognized by the Rift Valley fever virus transcription complex in its ambisense S segment.

A reconstituted transcription system composed of the Rift Valley fever phlebovirus (Bunyaviridae family) proteins L and N expressed via recombinant vaccinia viruses and an S-like model RNA containing the CAT gene in the antisense orientation, has been described previously by Lopez et al. (J. Virol., 1995, 69, 3972-3979). We extended the use of this in vivo system to determine the sequence at the 3' end of the ambisense S segment recognized by the transcription complex. A mutational analysis of the sequences at the 3' end of the S-like genomic or antigenomic RNA was undertaken. The data indicated that the minimal sequence required for transcription resides in the 13 first 3' nucleotides of the genomic or antigenomic RNA. In these sequences, two regions appeared crucial: the bases at positions 3 to 8 and the purine at position 13. In addition, the terminal repeat ...GU could be deleted without affecting significantly the template activity of the RNA. These data support the prime and realign mechanism proposed recently for Bunya- and Arenaviruses

Chloramphenicol O-Acetyltransferase↗

PubMed1997

The Journal of Abnormal Child Psychology at 25.

This issue, redesigned in a new format, marks the beginning of Volume 25, the beginning of the "silver anniversary" year of the Journal of Abnormal Child Psychology. Data were compiled from the first 24 volumes to study changes over time, and Pearson correlations were calculated to determine linear trends in the journal's development. The number of articles per volume has doubled, from about 25 to 50. In recent years the first authors of articles were more likely to be located outside the U.S. (up from about 5% to about 25%). Also, in recent years the first authors of articles were less likely to be affiliated with nonmedical school university departments and more likely to be affiliated with medical schools or research institutes. An introduction to this special 25th anniversary issue is provided.

Child↗

PubMed1996

Multiparametric cell-cycle analysis of peripheral blood-activated lymphocyte subsets using staining based on the TdT method for incorporated BrdUrd.

This study describes a new method for the simultaneous assessment of the distribution of a cell population in the G0/G1, S, and G2/M cell-cycle phases by using multiparameter flow cytometry and single staining based on BrdUrd incorporation. Both the K562 cell line and PHA-stimulated peripheral blood lymphocytes (PBL) were analyzed. Cells were cultured in the presence of BrdUrd for 30 min prior to cell harvesting. Once collected, cells were exposed to ultraviolet light for 5 min and then fixed immediately in 70% ethanol (-20 degrees C) for at least 30 min. Once fixed, the cells were placed for 30 min at 37 degrees C in the presence of terminal deoxynucleotidyl transferase (TdT) and dUTP labeled with digoxigenin; they were then stained with FITC-labeled anti-digoxigenin. Our results show that G0/G1, s, and G2/M cell populations can be clearly discriminated according to FITC fluorescence and light-scatter parameters. In this way, S-phase cells can be identified by their FITC staining. From the cells which were negative for anti-digoxigenin-FITC antibody, two clear populations could be resolved in a forward scatter, side scatter, and fluorescence pulse-width three-dimensional plot; the values obtained for G0/G1 cells were lower than those obtained for G2/M cells in all three parameters. Multiparameter analysis of PBL stained for two surface antigens (CD3 and CD8) and for BrdUrd by direct or indirect TdT method permitted cell-cycle analysis of different subpopulations, including CD3+/CD8+, CD3+/CD8-, CD3-/CD8+, and CD3-/CD8-.

Bromodeoxyuridine↗