ABSTRACT
OBJECTIVE: We investigated genetic polymorphisms of MBL2 gene, in a cohort of 90 Italian HIV-1 pregnant seropositive women and their children in order to understand whether the MBL2 genotype of HIV-1 positive mothers might be related to their ability to transmit the virus to their children. MATERIALS AND METHODS: DNA was extracted from Iso Code Stix cards, and MBL2 genotyping was performed by Melting Temperature Assay. RESULTS: The frequency of the MBL2 0/0 homozygotes was higher in HIV-1 positive mothers than in healthy controls, the MBL2 0/0 genotype was more frequent in children born from HIV positive mothers than healthy subjects. CONCLUSIONS: We have confirmed the association of polymorphisms involving a gene of the innate immunity with an increased risk of being infected by HIV. These polymorphisms were also evidenced in children born from HIV+ mothers, but the risk of infection was strongly reduced by cesarean delivery and by antiretroviral treatment.
Subject(s)
HIV Infections/transmission , HIV-1 , Immunity, Innate/genetics , Mannose-Binding Lectin/genetics , Adult , Cohort Studies , Female , Genetic Predisposition to Disease , HIV Infections/immunology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Italy , Male , Pilot Projects , Polymorphism, Genetic , PregnancyABSTRACT
Celiac disease is a multifactorial disorder caused, in genetically susceptible patients, by the ingestion of dietary gluten. Very little is known about the genetic factors, but there is a strong association of two HLA haplotypes (DQ2 or alpha1*05, beta1*02 and DQ8 or alpha1*0301, beta1*0302) with the disease. We investigated the relationship between polymorphisms in the first exon of the MBL2 gene, which encodes for mannose binding lectin (MBL) and celiac disease. Moreover we studied the MBL role by immunohistochemistry and TUNEL. Results were confirmed by clinical findings. We enrolled 149 Italian celiac patients; 116 were characterized by the presence of DQ2 or DQ8. The HLA haplotype was established by allelic specific PCR while the MBL2 genotype was resolved by melting temperature assay. Immunohistochemistry and TUNEL assays were performed on serial sections of biopsy specimens from celiac patients and healthy controls. MBL2 allele and genotype frequencies varied significantly between celiac patients and healthy controls. The frequencies of the 0 allele were 28% in DQ2 or DQ8 celiac patients, 36% in HLA atypical celiac patients, and 22% in healthy controls. Interestingly, the MBL2 0/0 genotype was present in 7 of 33 HLA atypical celiac patients (21%) and in 13 of 116 HLA typical celiac patients (13%) but in only 7 of 147 healthy controls (5%). Furthermore, we found that MBL2 genotype is strongly associated with the occurrence of secondary autoimmune diseases. Immunohistochemistry and TUNEL findings support a role of MBL2 in the clearance of apoptotic cells. In conclusion, MBL2 variants, responsible for lower MBL levels, are associated with celiac disease and higher risk of developing autoimmune diseases. Here we propose a role for MBL in the disease which could be easily applied to other autoimmune disorders.
Subject(s)
Celiac Disease/genetics , Mannose-Binding Lectin/genetics , Polymorphism, Genetic , Adolescent , Adult , Apoptosis/genetics , Autoimmune Diseases/genetics , Biopsy , Case-Control Studies , Celiac Disease/pathology , Child , Child, Preschool , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , Haplotypes/genetics , Humans , Infant , Intestines/pathology , Intestines/physiology , Italy , Male , Mannose-Binding Lectin/metabolism , Middle AgedABSTRACT
In this study we show a significant correlation between a single-nucleotide polymorphism in the 5'-untranslated region of the DEFB1 gene, which probably regulates the gene expression of human beta defensin 1 (hBD-1) and the risk of HIV-1 infection in an Italian paediatric population (97 HIV-1 perinatally infected children), pointing to the importance of innate immunity in HIV-1 infection.
Subject(s)
HIV Infections/genetics , HIV-1 , Polymorphism, Single Nucleotide/genetics , beta-Defensins/genetics , Child , Gene Frequency , Humans , Risk FactorsABSTRACT
We have investigated the molecular evolution of the gene coding for beta-defensin 3 (DEFB103) in 17 primate species including humans. Unlike the DEFB4 genes (coding for beta-defensin 2) [Boniotto, Tossi, Del Pero, Sgubin, Antcheva, Santon and Masters (2003) Genes Immun. 4, 251-257], DEFB103 shows a marked degree of conservation in humans, Great Apes and New and Old World monkeys. Only the Hylobates concolor defensin hcBD3 showed an amino acid variation Arg17-->Trp17 that could have a functional implication, as it disrupts an intramolecular salt bridge with Glu27, which locally decreases the charge and may favour dimerization in the human congener hBD3. This is thought to involve the formation of an intermolecular salt bridge between Glu28 and Lys32 on another monomer [Schibli, Hunter, Aseyev, Starner, Wiencek, McCray, Tack and Vogel (2002) J. Biol. Chem. 277, 8279-8289]. To test the role of dimerization in mediating biological activity, we synthesized hBD3, hcBD3 and an artificial peptide in which the Lys26-Glu27-Glu28 stretch was replaced by the equivalent Phe-Thr-Lys stretch from human beta-defensin 1 and we characterized their structure and anti-microbial activity. Although the structuring and dimerization of these peptides were found to differ significantly, this did not appear to affect markedly the anti-microbial potency, the broad spectrum of activity or the insensitivity of the anti-microbial action to the salinity of the medium.
Subject(s)
Primates , beta-Defensins/chemistry , Amino Acid Sequence , Amino Acid Substitution/genetics , Animals , Base Sequence , Cercopithecidae , Genetic Variation , Gorilla gorilla , Humans , Hylobatidae , Molecular Sequence Data , Pan troglodytes , Pongo pygmaeus , Saguinus , beta-Defensins/genetics , beta-Defensins/metabolismABSTRACT
In this study, we investigated the role of mannose-binding lectin (MBL) in celiac disease, by performing genotype analysis for the three point mutations in the first exon of the gene in 117 Italian celiac patients (characterized by flat biopsy and positive for anti-endomysium antibody and human transglutaminase antibodies) and 130 pan-ethnic healthy controls. The frequency of homozygous mutant 0/ 0 was significantly higher in the 117 Italian celiac patients (0.13) than in the 130 pan-ethnic healthy controls (0.05; P=0.0405). An increased frequency of homozygous 0/0 allele was found among patients with celiac disease compared with controls. These results suggest an involvement of MBL in the pathophysiology of celiac disease.
Subject(s)
Celiac Disease/genetics , Genetic Predisposition to Disease , Mannose-Binding Lectin/analogs & derivatives , Mannose-Binding Lectin/genetics , Point Mutation , Alleles , Gene Frequency , Genotype , HumansABSTRACT
Se presenta un trabajo retrospectivo de 100 pacientes de la emergencia del Hospital Pasteur, colecistectomizados con diagnóstico clínico-ecográfico y/o anátomo patológico de colecistitis aguda, entre enero de 1996 y julio de 1998. El objetivo del mismo es valorar la sensibilidad y especificidad de la ecografía como método diagnóstico en la emergencia comparándola con los informes de la anatomía patológica. De los resultados se destaca que el 59 por ciento de las ecografías se hicieron en el Hospital Pasteur, encontrando en el 80 por ciento engrosamiento parietal. En cuanto a la litiasis en un 10 por ciento no consta el número de las mismas y en el 30 por ciento su tamaño. El diagnóstico ecográfico fue en 49 casos de colecistitis aguda, en 36 de litiasis vesicular y sin diagnóstico en 15. Sin embargo si se los compara con los hallazgos histopatológicos, existe un error diagnóstico global del 43.52 por ciento, con un 18.36 por ciento de falsos positivos y un 77 por ciento de falsos negativos. Con respecto a la relación existente entre engrosamiento parietal por ecografía y anatomía patológica es del 83.75 por ciento. En lo referente al número y tamaño de las litiasis el acierto diagnóstico es mayor del 90 por ciento. Como conclusión del trabajo se señala que la sensibilidad de la ecografía como estudio diagnóstico de las colecistitis agudas, es inferior a lo señalado en la literatura mundial, observándose además una relativa alta frecuencia de informes incompletos
Subject(s)
Humans , Male , Adult , Female , Middle Aged , CholecystitisABSTRACT
Se usaron 24 ratas sometidas a estrés por restricción como modelo para producir injuria gástrica, protegiéndose por alimentación mediante gastrostomía quirúrgica. Se dividieron en cuatro grupos en los que se combinó desnutrición (24-48 horas) y protección con suero fisiológico o glucosado. Todas las ratas presentaron desnutrición por disminución de peso; no mostrando las variables (pH, piqueteado hemorrágico, presencia y tamaño de las lesiones) diferencias significativas entre los grupos, pero los animales tuvieron menor número de lesiones que las encontradas en la bibliografía con el mismo modelo
Subject(s)
Animals , Rats , Enteral Nutrition , Gastric Mucosa , Stress, Physiological , Peptic UlcerABSTRACT
Se realizó un trabajo experimental en perros a efectos de comparar los efectos de la heparina cálcica y la enoxaparina sobre el desarrollo de hiperplasia intimal desarrollado en el Depto. Básico de Cirugía. No se encontraron diferencias significativas en el desarrollo del fenómeno analizado en las distintas series estudiadas con respecto al grupo control, por lo cual no se pudo poner en evidencia un efecto inhibidor sobre el desarrollo de hiperplasia intimal para ninguno de los fármacos estudiados.
