Biomedical subjects

A Gomez

Publications and source records attributed to A Gomez.

At least 19 recordsLinked to original sources

PubMed2006

Treatment of Bolivian mucosal leishmaniasis with miltefosine.

BACKGROUND: Although mucosal leishmaniasis is a prominent disease, it has been studied only to a limited extent. It is classically treated with parenteral antimony or, as a last resort, amphotericin B. METHODS: We treated Bolivian mucosal leishmaniasis due to Leishmania braziliensis with the oral agent miltefosine, 2.5 mg/kg/day for 28 days, and followed-up for 12 months. RESULTS: Seventy-two patients were evaluable. The cure rate for the 36 patients who had "mild" disease (i.e., affecting nasal skin and nasal mucosa) was 83%. The cure rate for the 36 patients who had more extensive disease (involving the palate, pharynx, and larynx) was 58%. Patients refused to be randomized to parenteral agents, but the cure rate for an almost contemporary group who was receiving amphotericin B (45 mg/kg over 90 days) was 7 (50%) of 14. CONCLUSIONS: In this unrandomized trial, oral miltefosine was at least as effective as heroic doses of parenteral amphotericin B. The cure rate for miltefosine was approximately equivalent to historical cure rates using parenteral pentavalent antimony for mild and extensive disease in neighboring Peru. Although gastrointestinal side reactions do occur with miltefosine, its toxicity profile is superior to that of antimony and far superior to that of amphotericin B--in part because of the inherent attractiveness of oral versus parenteral agents. Our results suggest that miltefosine should be the treatment of choice for mucosal disease in North and South America.

Adolescent↗

PubMed2006

High polymorphism in Plasmodium vivax merozoite surface protein-5 (MSP5).

A key issue relating to developing multi-component anti-malarial vaccines, lies in studying Plasmodium vivax surface proteins' genetic variation. The present work was aimed at amplifying, cloning and sequencing the gene encoding P. vivax merozoite surface protein 5 (PvMSP5) in samples obtained from infected patients from Colombian areas having varying malaria transmission rates. Nucleotide sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under Accessions numbers DQ341586 to DQ341601. Our results have revealed that PvMSP5 is one of the P. vivax surface proteins having greater polymorphism, this being restricted to specific protein regions. The intron and exon II (which includes the GPI anchor and EGF-like domain) were both highly conserved when compared to exon I; exon I displayed the greatest variation and most of the recombination events occurred within it. No geographical grouping was observed. The Nei-Gojobori test revealed significant positive selection in the samples analysed here, whereas Tajima and Fu and Li tests presented a neutral selection pattern. The results reflected a localized variation pattern, recombination between PvMSP5 alleles and also functional and immune pressures, where stronger selective forces might be acting on exon I than on exon II, suggesting that the latter could be an important region to be included in an anti-malarial vaccine.

Amino Acid Sequence↗

PubMed2006

Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1.

In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 (vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site and reduced its levels in cultured endothelial cells and in mouse models of retinal and choroidal neovascularization (CNV). Compared to injection of an inverted control sequence, quantitative reverse transcriptase-PCR demonstrated statistically significant reductions of 57 and 40% in vegfr1 mRNA after intravitreous or periocular injection of Sirna-027, respectively. Staining showed uptake of 5-bromodeoxyuridine-labeled Sirna-027 in retinal cells that lasted between 3 and 5 days after intravitreous injection and was still present 5 days after periocular injection. In a CNV model, intravitreous or periocular injections of Sirna-027 resulted in significant reductions in the area of NV ranging from 45 to 66%. In mice with ischemic retinopathy, intravitreous injection of 1.0 mug of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0 mug of inverted control siRNA. These data suggest that VEGFR1 plays an important role in the development of retinal and CNV and that targeting vegfr1 mRNA with siRNA has therapeutic potential.

Animals↗

PubMed2006

The RIM101 pathway contributes to yeast cell wall assembly and its function becomes essential in the absence of mitogen-activated protein kinase Slt2p.

The Saccharomyces cerevisiae ynl294cDelta (rim21Delta) mutant was identified in our lab owing to its moderate resistance to calcofluor, although it also displayed all of the phenotypic traits associated with its function as the putative sensor (Rim21p) of the RIM101 pathway. rim21Delta also showed moderate hypersensitivity to sodium dodecyl sulfate, caffeine, and zymolyase, and the cell wall compensatory response in this mutant was very poor, as indicated by the almost complete absence of Slt2 phosphorylation and the modest increase in chitin synthesis after calcofluor treatment. However, the cell integrity pathway appeared functional after caffeine treatment or thermal stress. rim21Delta and rim101Delta mutant strains shared all of the cell-wall-associated phenotypes, which were reverted by the expression of Rim101-531p, the constitutively active form of this transcription factor. Therefore, the absence of a functional RIM101 pathway leads to cell wall defects. rim21Delta, as well as rim101Delta, was synthetic lethal with slt2Delta, a synthetic defect alleviated by osmotic stabilization of the media. The double mutants grown in osmotically stabilized media were extremely hypersensitive to zymolyase and showed thicker cell walls, with poorly defined mannoprotein layers. In contrast, rim21Delta rlm1Delta and rim101Delta rlm1Delta double mutants were fully viable. Taken together, these results show that the RIM101 pathway participates directly in cell wall assembly and that it acts in parallel with the protein kinase C pathway (PKC) in this process independently of the transcriptional effect of the compensatory response mediated by this route. In addition, these results provide new experimental evidence of the direct involvement of the PKC signal transduction pathway through the Sltp2 kinase in the construction of yeast cell walls.

Cell Wall↗

PubMed2006

Beliefs and practices to prevent drowning among Vietnamese-American adolescents and parents.

OBJECTIVE: To determine the beliefs, attitudes and practices regarding water safety among Vietnamese-Americans through focus group interviews. PARTICIPANTS: 15 teenagers (aged 15-19 years) and 20 parents participated, and reported similar attitudes, beliefs and practices regarding water activities. Participants identified a lack of familiarity with water activities and few swimming skills, noting that these activities are not perceived as recreational sports among the Vietnamese. They reported recreating at open water sites because they are free and available, and attributed drowning to fate. Vietnamese youth swim unsupervised, responding to peer pressure despite lack of skills. Participants had negative attitudes toward life jackets using, swimming pools and lessons, because of the costs, but would attend lessons in Vietnamese. They identified schools and Vietnamese media as means of delivering injury-prevention messages. CONCLUSIONS: Decreasing drowning among Vietnamese-Americans requires changing the knowledge, attitudes and safety practices with programs and messages in Vietnamese, as well as targeting the dominant culture.

Adolescent↗

PubMed2005

Ferromagnetic 0-pi junctions as classical spins.

The ground state of highly damped PdNi based 0-pi ferromagnetic Josephson junctions shows a spontaneous half quantum vortex, sustained by a supercurrent of undetermined sign. This supercurrent flows in the electrode of a Josephson junction used as a detector and produces a phi(0)/4 shift in its magnetic diffraction pattern. We have measured the statistics of the positive or the negative sign shift occurring at the superconducting transition of such a junction. The randomness of the shift sign, the reproducibility of its magnitude, and the possibility of achieving exact flux compensation upon field cooling are the features which show that 0-pi junctions behave as classical spins, just as magnetic nanoparticles with uniaxial anisotropy.

Journal Article↗

PubMed2005

The IVS1 +319 t>a of SOD1 gene is not an ALS causing mutation.

Amyotrophic lateral sclerosis (ALS) is caused by mutations in the gene for Cu/Zn superoxide dismutase (SOD1) in 10% of familial and sporadic cases. During the SOD1 analysis of 9 FALS and 121 SALS, in only one sporadic case we found the exonic mutation N19S; in 15 SALS patients we found a 319t>a variation in IVS1 sequence, at 108 bp upstream from exon 2. This variation has an unusually high frequency of 11% and is always in linkage disequilibrium with a described polymorphism in IVS3, +34a>c. The 319t>a variation is classified in two different public databases, HGMD and The ALS Online Database, as a splicing mutation and not as a polymorphism. The unusually high frequency of this mutation in our patients prompted us to determinate its frequency in 130 age- and gender- matched healthy controls and in 54 patients with Alzheimer's disease. We found again linkage disequilibrium with the polymorphism in intron 3, and the frequency of 11% and 7.8%, respectively. These results strongly support the idea that the IVS1 +319 t>a alone is not an ALS causing mutation, and that special care must be taken in the interpretation of data from mutations databases for correct genetic counselling.

Aged↗

PubMed2004

Diagnosis of orthopedic infection in clinical practice using Tc-99m sulesomab (antigranulocyte monoclonal antibody fragment Fab'2).

OBJECTIVE: The aim of the study was to analyze the use of Tc-99m-labeled antigranulocyte monoclonal antibody fragment Fab'2 (SMab, Leukoscan) in the diagnosis of acute osteomyelitis and articular prosthesis infection. One hundred seventeen patients (118 studies) have been included, 92 women and 25 men. Thirty-seven had a suspicion of osteomyelitis and 81 with suspicion of infection of a hip (35 patients) or a knee (45 patients) prosthesis. The mean age was 64 years. A 3-phase bone scan and a SMab scan were obtained in all patients. Antigranulocyte scans were obtained within 3 and 8 hours postinjection of 20 mCi (740 MBq) of Tc-99m-labeled antibody. Diagnosis of infection was based on bone biopsy in 8 cases and on at least 2 positive cultures in the remaining cases. Infection was ruled out with negative cultures or 1-year patient follow up with negative C-reactive protein and normal erythrocyte sedimentation rate. RESULTS: Sensitivity, specificity, accuracy, and negative predictive value of Tc 99m-SMab scintigraphy were: 75%, 95%, 87%, and 92% for long bone osteomyelitis and 80%, 89%, 87%, and 91% for articular prosthesis infection, respectively. Positive predictive values were 83% and 63%, respectively. CONCLUSION: Tc-99m-antigranulocyte monoclonal antibody fragment Fab'2 scintigraphy seems to be a useful method in the diagnosis of osteoarticular infection.

Acute Disease↗

PubMed2003

Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis?

OBJECTIVE: To analyse the prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA) in patients with palindromic rheumatism (PR). METHOD: Sixty-three patients with PR were included: 33 were defined as pure or persistent PR at the time of serum test measurement, and 30 as associated PR, defined as patients with past history of PR who had developed persistent arthritis at the time of serum test: [21 with rheumatoid arthritis (RA)]. Sixty patients with early RA, and 80 with seronegative spondyloarthropathy were included as control groups. Anti-CCP were determined by a standardized ELISA test and AKA by indirect immunofluorescence in rat oesophagus. Clinical characteristics of these pure PR patients were compared according to the presence or absence of anti-CCP antibodies. A follow-up study was also performed. RESULTS: Anti-CCP were detected in 18 out of 32 (56.3%) patients with pure PR and 10 out of 30 (33.3%) with associated PR (38.1% in RA-associated PR patients). AKA were detected in 12 patients out of 33, with pure PR (36.4%), and in 9 out of 30 with associated PR (30%) (33.3% in RA-associated PR patients). The prevalence of anti-CCP and AKA in the RA control group was 55% (not significantly different from the pure PR group) and 61.7% (with respect to pure PR patients, P=0.02), respectively. In the spondyloarthropathy group, the prevalence of anti-CCP and AKA was 2.5 and 3.8%, respectively (P<0.001 compared with pure PR patients). No significant clinical differences were observed between pure PR patients with and without CCP antibodies. CONCLUSIONS: Anti-CCP and, to a lesser extent, AKA, were found in a high proportion of patients with PR, suggesting that this syndrome is an abortive form of RA. The predictive value of these antibodies in PR, as markers of progression to an established RA, remains uncertain.

Adult↗

PubMed2003

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting.

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.

Adult↗

PubMed2003

Effectiveness of low-dose intramuscular anti-VHB immune globulin in the prophylaxis of viral B hepatitis reinfection after liver transplantation: preliminary report.

INTRODUCTION: Prophylaxis using high-dose intravenous anti-HBV immune globulin (HBIG) is effective to prevent reinfection due to hepatitis B virus (HBV) after orthotopic liver transplantation (OLT). However, this treatment is expensive and intravenous administration is difficult during outpatient care. Our aim was to assess the effectiveness of low-dose intramuscular HBIG to prevent HBV reinfection after OLT. PATIENTS: Six patients (all men, mean age 41 years, negative HBV DNA without hepatotropic virus coinfection) were transplanted in our institution due to HBV cirrhosis and included in a prospective noncomparative study. Intramuscular HBIG (2000 IU) was administered during the anhepatic phase of OLT, followed by daily 2000 IU doses for 7 days and then monthly. HBV antibody titers were measured every month. Reinfection was defined as the recurrence of surface HBV antigen in serum after transplantation. RESULTS: After 1 year follow-up, none of the six patients had detectable HBV surface antigen and the liver biopsies were normal in all cases. Using 2000 IU, anti-HBs levels were: 880+/-356 IU/L at 1 month, 191+/-123 at 6 months, and 225+/-49 after 1 year. In all cases anti-HBs titers were above 100 IU/L during the follow-up. CONCLUSIONS: Monthly administration of low-dose (2000 IU) intramuscular HBIG effectively prevents recurrence of HBV infection as well as attains a protective level of anti-HBs antibodies (over 100 IU/L) for at least the first year after transplantation.

Adult↗

PubMed2003

The association of intestinal parasitosis and H. pylori infection in children and adults from a Mexican community with high prevalence of parasitosis.

BACKGROUND: Experimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. MATERIALS AND METHODS: The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. RESULTS: In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). CONCLUSIONS: Intestinal parasitic infections and serum IgE levels showed an age-dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence.

Adolescent↗

PubMed2002

Distribution of genes encoding the trypsin-dependent lantibiotic ruminococcin A among bacteria isolated from human fecal microbiota.

Fourteen bacterial strains capable of producing a trypsin-dependent antimicrobial substance active against Clostridium perfringens were isolated from human fecal samples of various origins (from healthy adults and children, as well as from adults with chronic pouchitis). Identification of these strains showed that they belonged to Ruminococcus gnavus, Clostridium nexile, and Ruminococcus hansenii species or to new operational taxonomic units, all from the Clostridium coccoides phylogenetic group. In hybridization experiments with a probe specific for the structural gene encoding the trypsin-dependent lantibiotic ruminococcin A (RumA) produced by R. gnavus, seven strains gave a positive response. All of them harbored three highly conserved copies of rumA-like genes. The deduced peptide sequence was identical to or showed one amino acid difference from the hypothetical precursor of RumA. Our results indicate that the rumA-like genes have been disseminated among R. gnavus and phylogenetically related strains that can make up a significant part of the human fecal microbiota.

Bacteria↗

PubMed2001

Lack of association of apolipoprotein E polymorphism in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) could be considered a neurodevelopmental disorder, from several lines of evidence. One of the most widely studied genes in these disorders is the apolipoprotein E gene, particularly allele 4. We analyzed for association among patients with OCD versus normal controls and cognitively impaired patients. There were no significant differences between OCD probands compared with population controls. However, the cognitively impaired group showed a higher frequency of allele apolipoprotein E gene compared with normal controls and patients with OCD.

Journal Article↗

PubMed2001

A new organic-rich soil reference material certified for its EDTA- and acetic acid- extractable contents of Cd, Cr, Cu, Ni, Pb and Zn, following collaboratively tested and harmonised procedures.

There is an increasing requirement for assessment of the bioavailable metal fraction and the mobility of trace elements in soils upon disposal. One of the approaches is the use of leaching procedures, but the results obtained are operationally defined; therefore, their significance is highly dependent on the extraction protocol performed. So, for this type of study, there is a need for reference materials that allow the quality of measurements to be controlled. This paper describes the steps involved in the certification of an organic-rich soil reference material, BCR-700, for the EDTA- and acetic acid-extractable contents of some trace elements, following collaboratively tested and harmonised extraction procedures. Details are given for the preparation of the soil, homogeneity and stability testing, analytical procedures and the statistical selection of data to be included in the certification.

Acetic Acid↗

PubMed2001

Ruminococcin A, a new lantibiotic produced by a Ruminococcus gnavus strain isolated from human feces.

When cultivated in the presence of trypsin, the Ruminococcus gnavus E1 strain, isolated from a human fecal sample, was able to produce an antibacterial substance that accumulated in the supernatant. This substance, called ruminococcin A, was purified to homogeneity by reverse-phase chromatography. It was shown to be a 2,675-Da bacteriocin harboring a lanthionine structure. The utilization of Edman degradation and tandem mass spectrometry techniques, followed by DNA sequencing of part of the structural gene, allowed the identification of 21 amino acid residues. Similarity to other bacteriocins present in sequence libraries strongly suggested that ruminococcin A belonged to class IIA of the lantibiotics. The purified ruminococcin A was active against various pathogenic clostridia and bacteria phylogenetically related to R. gnavus. This is the first report on the characterization of a bacteriocin produced by a strictly anaerobic bacterium from human fecal microbiota.

Amino Acid Sequence↗

PubMed2001

Detection of phospholipase C in nontuberculous mycobacteria and its possible role in hemolytic activity.

Phospholipase C plays a key role in the pathogenesis of several bacterial infections, for example, those caused by Clostridium perfringens and Listeria monocytogenes. Previous studies have reported multiple copies of plc genes homologous to Pseudomonas aeruginosa plcH and plcN genes encoding the hemolytic and nonhemolytic phospholipase C enzymes in the genomes of Mycobacterium tuberculosis, M. marinum, M. bovis, and M. ulcerans. In this study we analyzed the possible relationship between phospholipase C and hemolytic activity in 21 strains of nontuberculous mycobacteria representing nine different species. Detection of phospholipase C enzymatic activity was carried out using thin-layer chromatography to detect diglycerides in the hydrolysates of radiolabeled phosphatidylcholine. DNA sequences of M. kansasii and M. marinum homologous to the genes encoding phospholipase C from M. tuberculosis and M. ulcerans were identified by DNA-DNA hybridization and sequencing. Finally, we developed a direct and simple assay to detect mycobacterial hemolytic activity. This assay is based on a modified blood agar medium that allows the growth and expression of hemolysis of slow-growing mycobacteria. Hemolytic activity was detected in M. avium, M. intracellulare, M. ulcerans, M. marinum, M. tuberculosis, and M. kansasii mycobacteria with phospholipase C activity, but not in M. fortuitum. No hemolytic activity was detected in M. smegmatis, M. gordonae, and M. vaccae. Whether or not phospholipase C enzyme plays a role in the pathogenesis of nontuberculous mycobacterial diseases needs further investigation.

Culture Media↗

PubMed2001

Perceived maternal control and support: effects on hostile biased social information processing and aggression among clinic-referred children with high aggression.

Based on a sample of 89 aggressive clinic-referred children, aged between 9 and 11 years, a longitudinal study of 1-year duration was conducted to examine (a) whether the children's perception of control and support of their mothers' to them predicted their hostile attribution of intent and hostile response selection, and (b) whether these hostile biased social cognitions mediated the relationships between their perceived maternal behaviours and their aggression. Participants completed a questionnaire covering both the perceived maternal control and support. One year later, their hostile attribution of intent and response selection, and aggression, were measured. Results showed that perceived maternal control and perceived maternal support were associated positively and negatively, respectively, with both the social cognition measures. Also, the social cognition measures mediated the relationships of the perceived maternal measures with aggression. The findings are discussed in terms of how children's hostile biased relational schemas and scripts, developed from negative parenting and insecure attachment, favour more hostile social cognitions, and how these in turn mediate children's current hostile biased social behaviours.

Adult↗