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Biomedical subjects

F Vega

Publications and source records attributed to F Vega.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Chronic exposure to environmental lead in Chilean infants. II: Effects on the psychomotor development].

BACKGROUND: Lactating children are specially susceptible to lead toxicity due to their underdeveloped nervous system, lower body mass, higher intestinal absorption and lower elimination rates. AIM: To determine the effects of lead exposure, comparing Chilean lactating children residing in rural areas with low lead exposure, and in urban areas with high lead exposure. MATERIAL AND METHODS: Newborns from public maternity hospitals of the rural locality of San Felipe and from Metropolitan Santiago, were recruited for the study. On admission to the study, umbilical cord and maternal blood samples were obtained and an inquiry about perinatal, sociohereditary and lead exposure history was done. Children were followed every 6 months until 24 months of age, measuring blood parameters and neurobehavioral development using Bayley scales. RESULTS: Three hundred twelve children from Santiago and 113 from San Felipe were studied. Maternal and children blood lead levels were higher in Santiago, but lower than those reported in other international studies. At 24 months of age, 4.5% of children from Santiago and 0.7% of children from San Felipe had levels over 10 micrograms/dl. No differences in neurobehavioral development were observed between children of both cities. At 24 months, scores of MDI scales were 91 in Santiago and 97 in San Felipe. The figures for PDI scale were 93 in Santiago and 93 in San Felipe. Main risk factors for a retarded neurobehavioral development were socieconomic level with a mean Odds ratio of 3.5 (0.99-12.4), made sex with an Odds ratio of 2.3 (1.09-5.07) and stimulation at home with an Odds ratio of 0.7 (0.53-0.82). CONCLUSIONS: In this cohort of children, no effect of lead levels on neurobehavioral development was found.

Analysis of Variance↗
PubMed1998

Autocatalytic activation of human legumain at aspartic acid residues.

Human legumain was characterized following overexpression in a murine cell line as the C-terminal Ig-fusion protein. Upon acid treatment, the prolegumain autoproteolyzed distal to two aspartic acid residues to yield a highly active form. The ability of mature legumain to cleave after aspartic acid residues was confirmed with a small peptide substrate. Substitution of alanine for the putative catalytic cysteine, or for either of two strictly conserved histidine residues, partly or wholly eliminated autoactivation but not the ability of wild-type legumain to correctly process the variants to the properly sized proteins.

Amino Acid Sequence↗
PubMed1998

CD40L activation of dendritic cells down-regulates DORA, a novel member of the immunoglobulin superfamily.

Using a cDNA subtraction technique, a novel member of the immunoglobulin superfamily was isolated from human Dendritic cells (DC). This cDNA which we named DORA, for DOwn-Regulated by Activation encodes a protein belonging to the CD8 family of receptors containing a single V type loop domain with an associated J chain region, a transmembrane region containing an atypical tyrosine residue and a cytoplasmic domain containing three putative tyrosine phosphorylation sites. The hDORA gene has been localised to chromosome 16. From database searches a rat cDNA was identified that encoded a polypeptide with 63% identity to hDORA. The expression of the human cDNA was studied in detail. Northern blot analysis revealed 1.0 kb and 2.5 kb mRNAs in peripheral blood lymphocytes, spleen and lymph node, while low levels were observed in thymus, appendix, bone marrow and fetal liver. No signal was noted in non-immune system tissues. By RT-PCR analysis of hDORA revealed expression in cells committed to the myeloid lineage but not in CD34+ precursors or B cells and low expression in T cells. Expression was also observed in DC, purified ex vivo or generated in vitro from either monocytes or CD34+ progenitors. This was down-regulated following activation both by PMA and Ionomycin treatment and also by CD40L engagement. In situ hybridisation performed on tonsil sections showed the presence of hDORA in cells within Germinal Centers. This structure and expression suggests a function as a co-receptor, perhaps in an antigen uptake complex, or in homing or recirculation of DC.

Amino Acid Sequence↗
PubMed1997

Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats.

Increased apoptosis has been reported in the heart of rats with spontaneous hypertension and cardiac hypertrophy. This study was designed to investigate the relationship between apoptosis and hypertrophy in cardiomyocytes from the left ventricle of spontaneously hypertensive rats (SHR). In addition, we evaluated whether the development of cardiomyocyte apoptosis is related to blood pressure or to the activity of the local angiotensin-converting enzyme (ACE) in SHR. The study was performed in 16-week-old SHR, 30-week-old untreated SHR, and 30-week-old SHR treated with quinapril (10 mg x kg[-1] x d[-1]) during 14 weeks before they were killed. Cardiomyocyte apoptosis was assessed by direct immunoperoxidase detection of digoxigenin-labeled 3'-hydroxyl ends of DNA. Nuclear polyploidization measured by DNA flow cytometry was used to assess cardiomyocyte hypertrophy. Compared with 16-week-old normotensive Wistar-Kyoto rats, 16-week-old SHR exhibited increased blood pressure (P<.001), increased rate of tetraploidy (P<.05), and similar levels of ACE activity and apoptosis. Compared with 30-week-old Wistar-Kyoto rats, 30-week-old SHR showed increased blood pressure (P<.001), increased ACE activity (P<.05), increased rate of tetraploidy (P<.01), and increased apoptosis (P<.01). Untreated 30-week-old SHR exhibited similar values of blood pressure and tetraploidy and higher ACE activity (P<.05) and apoptosis (P<.001) than 16-week-old SHR. A direct correlation (P<.01) was found between ACE activity and the apoptotic index in untreated 30-week-old SHR. The long-term administration of quinapril was associated with the normalization of ACE activity and apoptosis in treated SHR. These results suggest that the timing and mechanisms responsible for apoptosis and hypertrophy of cardiomyocytes are different in SHR. Whereas hypertrophy seems to be an earlier alteration that develops in parallel with hypertension, apoptosis develops later in association with overactivity of the local ACE. Our data suggest that cell death dysregulation may be a novel target for antihypertensive agents that interfere with the renin-angiotensin system in hypertension.

Animals↗
PubMed1997

[Chronic exposure to environmental lead in Chilean infants].

BACKGROUND: In Chile, there are several sources of environmental lead exposure. However, the few studies about lead levels in Chilean infants, do not allow to establish the prevalence of high lead levels in this population. AIM: To measure blood lead levels in nursing infants, living in rural and urban areas, from birth until two years of age. SUBJECTS AND METHODS: Newborns from public maternity hospitals in Santiago and a rural area were selected for the study. An umbilical cord blood sample was obtained at birth and venous blood samples thereafter, every 6 months until the age of 24 months. Lead levels were measured by atomic absorption spectrophotometry. Atmospheric lead was measured simultaneously every week in Santiago and the rural area. RESULTS: Three hundred twelve children from Santiago and 113 from the rural area completed the 24 months follow-up. The mean lead exposure for infants living in Santiago and in the rural area was 1.23 +/- 0.66 and 0.19 +/- 0.15 micrograms/m3 respectively (p < 0.001). Mean blood levels were always higher in infants from Santiago, compared to those from the rural area. At 24 months, 4.5% of children from Santiago and 0.7% of children from the rural area had blood lead levels over 10 micrograms/dl. Significant risk factors for high lead levels were recent painting of the house where the infant lives, eating soil, biting banisters and familiar labor exposure to lead. CONCLUSIONS: Infants living in an urban area and exposed to increased atmospheric lead levels have higher blood lead levels than infants living in a rural area.

Air Pollutants↗
PubMed1996

Primary amyloidosis presenting as renal infarction.

We report a case of primary amyloidosis affecting the kidney and presenting as a renal infarction on computed tomography and ultrasound examination. To our knowledge, it is the first case in the radio-logical literature with these imaging characteristics.

Amyloidosis↗
PubMed1996

Multiple infusions of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (EMD 55,900) in patients with recurrent malignant gliomas.

In a prospective phase I/II trial, EMD 55,900, a murine monoclonal antibody (MAb) directed against EGF receptor, was administered at tumour recurrence to 16 patients previously treated with surgery, radiotherapy and chemotherapy for high grade supratentorial gliomas (11 glioblastomas, five anaplastic astrocytomas). Duration of treatment was planned for at least 4 weeks. The first 10 patients received 40 mg of MAb three times per week (median cumulative dose, 760 mg) and the last 6 patients received 200 mg three times per week (median cumulative dose, 2400 mg). Serum levels of EMD 55,900 were proportional to the injected dose. Repeated infusions of EMD 55,900 were well tolerated. In 13/16 patients, there were no adverse events. Among the 3 others, one had a grade IV neutropenia, one had a clinically asymptomatic hepatitis, and one had a skin rash. This last patient was the only one who had increased human antimouse antibodies (HAMA). After 4 weeks of therapy, 13 patients were evaluable for response. No measurable tumour regression was obtained with either schedule. 6 of the 13 patients (46%) showed evidence of progressive disease, while 7/13 (54%) had stable disease. All patients had progressive disease by 3 months. In this study, repeated infusions of EMD 55,900 were well tolerated but no therapeutic benefit was demonstrated.

Adult↗
PubMed1996

Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR + CD4-CD8-T cells.

A novel cytokine originally designated murine CTLA-8 was described as a cDNA isolated from an activated T cell hybridoma produced by fusing a mouse cytotoxic T cell clone and a rat T lymphoma. This cDNA, which contains mRNA instability sequences characteristic of many cytokines, encoded a putative secreted protein that was homologous to the ORF13 gene of Herpesvirus saimiri. The human homolog to this molecule has recently been identified as the proinflammatory cytokine IL-17. We describe the isolation of a cDNA encoding mouse IL-17 from a cDNA library generated from alpha beta TCR + CD4-CD8- thymocytes using a subtraction technique that enriched for activation specific genes. This cDNA shares 87.3% amino acid identity to the previously described murine CTLA-8. Comparison of murine CTLA-8 to a cDNA we isolated from activated rat splenocytes revealed that murine CTLA-8 is, in fact, the rat homolog of IL-17. Mouse IL-17 mRNA is specifically expressed by activated alpha beta TCR + CD4-CD8- T cells, a small subset with a potentially important role in immune regulation. Mouse, rat, and human IL-17 can induce IL-6 secretion in mouse stromal cells, indicating that all homologs can recognize the mouse receptor.

Animals↗
PubMed1996

Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies.

OBJECTIVE: To evaluate the effect of intravenous high dose human immunoglobulin (IVIg) therapy on the clinical course and autoantibody titres of patients with neurological paraneoplastic syndromes. METHODS: Twenty two patients with paraneoplastic encephalomyelitis and sensory neuronopathy syndrome associated with anti-Hu antibodies (18) or paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies (four), were treated with 1-26 (mean 5.8) cycles of IVIg. The Rankin scale was used to evaluate the response. RESULTS: The only serious toxicity was one case of haemolytic anaemia. Twenty one patients were evaluable for therapeutic response. One patient, with subacute sensory neuronopathy (SSN), improved for at least 15 months, 10 remained stable (eight with anti-Hu and two with anti-Yo antibodies), and 10 deteriorated (eight with anti-Hu and two with anti-Yo antibodies). In seven of the 10 patients who stabilised, the syndrome had already made a plateau when the treatment was started but three patients (one with anti-Hu and two with anti-Yo antibodies) who had still been progressing stabilised for six, eight, and more than 48 months, including one patient with SSN who achieved stabilisation when the neurological dysfunction was only moderate (Rankin scale = 3). Another patient with SSN and initial stable response worsened when IVIg was reduced and improved when it was increased. No significant predictive factors of outcome could be identified but improvement or stabilisation was more frequent in patients with isolated involvement of the peripheral nervous system (62%) than in patients with evidence of CNS damage (37%) at the onset of treatment. Stabilisation in patients with CNS involvement was only achieved when the neurological dysfunction was already severe (Rankin scale > 3). The titres of autoantibodies did not change significantly. CONCLUSION: Treatment with IVIg at the doses given in the present protocol was not effective in paraneoplastic CNS syndromes associated with antineuronal antibodies. The role of this regime in the treatment of SSN should be further evaluated.

Adult↗
PubMed1995

Analysis of the NF2 tumor-suppressor gene and of chromosome 22 deletions in gliomas.

Recurrent deletions of chromosome fragments observed in neoplasms are thought to participate in tumor development through the inactivation of tumor-suppressor genes. In gliomas, the most frequent deletions involve chromosome arms 9p, 10q, 17p, 19q and 22q. We have analysed deletions of chromosome 22 in gliomas by studying loss of heterozygosity (LOH) at 8 microsatellite loci. LOH for this chromosome fragment was observed in 17/70 (24%) cases, most of them encompassing the region which encodes the gene altered in neurofibromatosis 2 (NF2), an inherited disease which predisposes to tumors of the nervous system. To investigate the possible involvement of the NF2 tumor-suppressor gene in the tumorigenesis of gliomas, we searched for alterations in its genomic structure and in its mature transcript. Northern-blot and reverse transcriptase-PCR experiments showed that the NF2 transcript is expressed and does not demonstrate obvious structural alterations. Moreover, analysis, at the genomic level, of the 16 coding exons of the NF2 gene by denaturing gradient gel electrophoresis failed to detect any somatically acquired point mutations. Altogether, these data strongly suggest that, although gliomas demonstrate recurrent chromosome 22 deletions most frequently encompassing the NF2 region, the NF2 gene is not altered in these tumors.

Base Sequence↗
PubMed1995

Treatment of human chronic fascioliasis with triclabendazole: drug efficacy and serologic response.

Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic fascioliasis confirmed by the presence of Fasciola hepatica eggs in feces were treated with a single oral dose of triclabendazole (10 mg/kg of body weight) after an overnight fast. Nineteen (79.2%) of 24 patients were egg-negative two months after treatment. Three of five cases with F. hepatica in feces after the first treatment were retreated and parasitologic cure was achieved. Tolerance to the drug was excellent; none of the patients had either secondary symptoms or important alterations in levels of aspartate and amino transferases, alkaline phosphatase, or bilirubin during or after treatment. Mild eosinophilia, present in 70% of the cases, persisted at least until 60 days after treatment. An enzyme-linked immunosorbent assay (ELISA) was highly effective in diagnosis and post-treatment monitoring. Before treatment, 20 (83.3%) of 24 confirmed cases had positive test results. The test results became negative by the second month of treatment in 40% of the cured cases. This percentage increased progressively, reaching 91.3% at 12 months after therapy. In the five cases in which treatment failed, the ELISA results remained positive until the end of the follow-up period (six months). In three of these cases who accepted a second round of therapy with triclabendazole six months after the first treatment, the ELISA results became negative in all three six months after parasitologic cure and remained negative until the end of the period. Due to its efficacy, excellent tolerance, and ease of administration (a single oral dose), triclabendazole appears to be the drug of choice for chronic human fascioliasis.

Administration, Oral↗
PubMed1994

A cytogenetic study of 19 recurrent gliomas.

A cytogenetic analysis was performed on 19 recurrent gliomas all of which had been treated by radiotherapy. All cases exhibited clonal chromosomal anomalies, the tumors were classified into four categories in relation to their mono- or polyclonality and to the presence or absence of a clonal evolution. Polyclonal tumors without clonal evolution had a delay of recurrence significantly longer than monoclonal or polyclonal tumors with clonal evolution. This difference could be related to the presence of clones with different malignant potential, which could be differentiated by their pattern of chromosomal aberrations. The malignant potential of "highly malignant" clones resulted from the juxtaposition of imbalances, such as monosomy 10, as in high-grade primary gliomas, and presumably radiation-induced structural rearrangements. That of clones of low malignancy was almost limited to the presence of multiple balanced structural rearrangements, probably induced by radiation.

Adolescent↗
PubMed1994

Purine and pyrimidine metabolism in human gliomas: relation to chromosomal aberrations.

Chromosomal aberrations in human gliomas are principally numerical. In tumours of low malignancy, karyotypes are frequently normal, but occasionally an excess of chromosome 7 and a loss of sex chromosome are observed. In highly malignant tumours, the most frequent aberrations are gain of chromosome 7, loss of chromosome 10 and less frequently losses or deletions of chromosomes 9, 22, 6, 13 and 14 or gains of chromosomes 19 and 20. To understand the meaning of these chromosome imbalances, the relationships between chromosome abnormalities and metabolic disturbances were studied. The losses or deletions observed affected principally chromosomes carrying genes encoding enzymes involved in purine metabolism. The activities of ten enzymes were measured: adenosine kinase, adenine phosphoribosyltransferase, adenylate kinase, methylthioadenosine phosphorylase, hypoxanthine phosphoribosyltransferase, adenylosuccinate lyase, inosine monophosphate dehydrogenase, adenosine deaminase, nucleoside phosphorylase and adenosine monophosphate deaminase. In parallel, two enzymes involved in pyrimidine metabolism, thymidine kinase and thymidylate synthase (TS), were studied. The activities of all these enzymes were measured on samples from 30 human primary glial tumours with low or high malignancy, six xenografted tumours at different passages, four portions of normal brain tissue and four non-glial brain neoplasms. As suggested by cytogenetic data, the enzymatic results showed a relatively low activity of purine metabolism in glial tumours when compared with normal brain and non-glial brain neoplasms. Considering the two enzymes involved in pyrimidine metabolism, only TS had higher activity in glial tumours of high malignancy than in normal brain. In comparison with normal brain, the balance between salvage and de novo pathways changes in gliomas, and even more in grafted tumours, in favour of de novo synthesis. The relation between chromosomes and metabolic imbalances does not correspond to a simple gene dosage effect in these tumours. These data suggest that the decrease of adenosine metabolism occurs before chromosomal aberrations appear, since it is observed in tumours of low malignancy when most karyotypes are still normal, and that the de novo pathway increases with tumour progression.

Adolescent↗
PubMed1994

Intrathecal synthesis of the anti-Hu antibody in patients with paraneoplastic encephalomyelitis or sensory neuronopathy: clinical-immunologic correlation.

We studied the intrathecal synthesis of the anti-Hu antibody (also called type 1 antineuronal nuclear autoantibody) in 14 patients with isolated paraneoplastic subacute sensory neuronopathy (SSN) and 16 with paraneoplastic encephalomyelitis (PEM). Patients with PEM had higher anti-Hu titers in the CSF (p = 0.003) but not in the serum than those with SSN. Only one patient (7%) with SSN had a positive intrathecal anti-Hu antibody synthesis whereas this was present in 14 (88%) of the 16 patients with PEM (p < 0.0001). The correlation between the intrathecal production of anti-Hu antibodies and PEM supports the role of autoimmune mechanisms in the pathogenesis of PEM. The absent intrathecal synthesis of anti-Hu antibodies in patients with SSN suggests easier accessibility of the systemic immune reaction to the sensory neurons probably due to the partial absence of blood-nerve barrier in the dorsal root ganglia.

Aged↗