RESUMEN
Viruses share antigenic sites with normal host cell components, a phenomenon known as molecular mimicry. It has long been suggested that viral infections might trigger an autoimmune response by several mechanisms including molecular mimicry. More than 600 antiviral monoclonal antibodies generated against 11 different viruses have been reported to react with 3.5% of cells specific for uninfected mouse organs. The main pathological feature of tropical spastic paraparesis/human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. We detected the presence of autoantibodies against a 98- to 100-kDa protein of in vitro cultured human astrocytes and a 33- to 35-kDa protein from normal human brain in the serum of HTLV-I-seropositive individuals. The two cell proteins exhibited molecular mimicry with HTLV-I gag and tax proteins in TSP/HAM patients, respectively. Furthermore, the location of 33- to 35-kDa protein cross-reaction correlated with the anatomical spinal cord areas (in the rat model) in which axonal damage has been reported in several cases of TSP/HAM patients. Our experimental evidence strongly suggests that the demyelinating process occurring in TSP/HAM may be mediated by molecular mimicry between domains of some viral proteins and normal cellular targets of the spinal cord sections involved in the neurodegeneration.
Asunto(s)
Astrocitos/virología , Autoinmunidad/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Imitación Molecular/inmunología , Paraparesia Espástica Tropical/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Astrocitos/inmunología , Autoanticuerpos/inmunología , Western Blotting , Reacciones Cruzadas , Humanos , Inmunohistoquímica , Paraparesia Espástica Tropical/patología , Ratas , Ratas WistarRESUMEN
Viruses share antigenic sites with normal host cell components, a phenomenon known as molecular mimicry. It has long been suggested that viral infections might trigger an autoimmune response by several mechanisms including molecular mimicry. More than 600 antiviral monoclonal antibodies generated against 11 different viruses have been reported to react with 3.5 percent of cells specific for uninfected mouse organs. The main pathological feature of tropical spastic paraparesis/human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. We detected the presence of autoantibodies against a 98- to 100-kDa protein of in vitro cultured human astrocytes and a 33- to 35-kDa protein from normal human brain in the serum of HTLV-I-seropositive individuals. The two cell proteins exhibited molecular mimicry with HTLV-I gag and tax proteins in TSP/HAM patients, respectively. Furthermore, the location of 33- to 35-kDa protein cross-reaction correlated with the anatomical spinal cord areas (in the rat model) in which axonal damage has been reported in several cases of TSP/HAM patients. Our experimental evidence strongly suggests that the demyelinating process occurring in TSP/HAM may be mediated by molecular mimicry between domains of some viral proteins and normal cellular targets of the spinal cord sections involved in the neurodegeneration.
Asunto(s)
Humanos , Animales , Ratas , Astrocitos/virología , Autoinmunidad/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Imitación Molecular/inmunología , Paraparesia Espástica Tropical/inmunología , Anticuerpos Monoclonales/inmunología , Astrocitos/inmunología , Autoanticuerpos/inmunología , Western Blotting , Reacciones Cruzadas , Inmunohistoquímica , Paraparesia Espástica Tropical/patología , Ratas WistarRESUMEN
The Amazon river dolphin, genus Inia, is endemic to the major river basins of northern South America. No previous studies have focused on the genetic structure of this genus. In this work, 96 DNA samples from specimens of this genus were collected in the Orinoco basin (four rivers), the Putumayo River, a tributary of the Colombian Amazon and the Mamoré, and the Tijamuchí and Ipurupuru rivers in theBolivian Amazon. These samples were used to amplify a fragment of 400 bp of the mitochondrial DNA (mtDNA) control region. In addition, 38 of these samples were also used to sequence 600 bp of the mitochondrial cytochrome b gene. The analysis of the population structure subdivision with an analysis of molecular variance (AMOVA) revealed important aspects about the genetic structure of Inia groups fromthese three geographically separate regions. By comparing the control region DNA and cytochrome b sequences, distinct types of nonshared haplotypes were observed. The net genetic divergence of control region sequences was 6.53% between the Orinoco and Bolivian rivers, 5.32% between the Putumayo and Bolivian rivers, and 2.50% between the Orinoco and Putumayo rivers. For the cytochrome b gene, these values were 2.48%, 2.98%, and 0.06%, respectively. The nucleotide sequences were analyzed phylogenetically using several genetic distance matrices and applying neighbor-joining, maximum likelihood, and maximum parsimony procedures. The results support the proposal to subdivide the Inia genus into at least two evolutionarily significant units: one confined to the Bolivian river basin and the other widely distributed across the Amazon and Orinoco basins.
Asunto(s)
Delfines/genética , Evolución Molecular , Animales , Bolivia , Grupo Citocromo b/genética , ADN Mitocondrial , Delfines/clasificación , Variación Genética , Haplotipos , Filogenia , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
Normal pregnant women in the second and third trimester were screened to detect gestational diabetes. Using the protocol proposed by the World Health Organization, we identified 33 women whose two hr glucose levels was > 200 mg/dl. Only sixteen women had less than 34 weeks of pregnancy when were seen for the first time at the diabetes clinic, the other seventeen women had more than 34 weeks when they presented to the diabetes clinic. The first group, was called the treated group and the second group was the non-treated group. The main clinical characteristics of these patients, treated vs non-treated, were (X +/- SD): age (years) 33.2 +/- 5.2 (20-40) vs 30.2 +/- 6.5 (20-39), p < 0.05; weeks of pregnancy at diagnosis: 27.9 +/- 4.1 (19-33) vs 36.1 +/- 2.3 (34-40), p < 0.05; weight (Kg): 79.9 +/- 13.1 (61.8-108) vs 87.4 +/- 16.8 (60.8-118), p = NS; length of pregnancy (weeks) 38 +/- 1.3 (36-40) vs 38.4 +/- 1.4 (35-40), p = NS; newborns weight (g): 3,654 +/- 650 (2,475-5,100) vs 3,221 +/- 529 (2,650-4,650), p = NS. There was an intrauterine death of a macrosomic fetus in the non-treated group. There were three macrosomic newborns in the treated group and one in the non-treated group, p = NS. Also, there was a premature newborn of 1,975 g, whose pregnancy was interrupted for acute fetal distress. Delivery by cesarean section occurred in 29 women (87.8%), and it was mainly related to the diabetes diagnosis. The prevalence of macrosomia in the treated group supports the idea that treatment has to be established at least at 24 weeks of pregnancy, to reduce this rate. It is concluded that gestational diabetes is associated to an increase in maternal and fetal morbidity, requiring strict supervision to detect and treat fetal distress and a tight glucose control to decrease the macrosomia rate.