Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
Add more filters










Publication year range
1.
Clin Exp Immunol ; 129(2): 346-53, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12165093

ABSTRACT

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by repeated infections and hypogammaglobulinaemia. Additionally, T-cell abnormalities including lymphopenia, decreased proliferation to mitogens and antigens, and the reduced production and expression of cytokines, have also been observed. In this study we have investigated the expression of naive, memory and activation markers in T-cell subpopulations in 17 CVID patients in comparison to age-matched normal controls. The numbers of CD4+ T cells, including CD45RA+CD62L+ and, to a lesser extent, CD45RA-CD62L+/RA+CD62L- were significantly reduced in patients, whereas CD8+ T cells were within normal range. In contrast, HLA-DR+ cells were increased both in CD4+ and CD8+ T cells. To assess the thymic output, we analysed the presence of T-cell receptor excision circles (TRECs) in CD4+ and CD8+ T cells by quantitative PCR. TRECs were decreased significantly in patients and the rate of TREC loss was higher with increasing age. TRECs correlated with naive CD4+ T cells, whereas there was an inverse relationship between TRECs and CD8+HLA-DR+ and CD8+CD45RA-CD62L+/RA+CD62L- T cells. Our results suggest the presence of a defect in the naive T cell compartment with origin at the thymic level in CVID, and indicate that TREC may be a useful marker to monitor thymic function in this primary immunodeficiency.


Subject(s)
Common Variable Immunodeficiency/immunology , Receptors, Antigen, T-Cell/metabolism , T-Lymphocyte Subsets/immunology , Adult , Biomarkers , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Common Variable Immunodeficiency/genetics , Female , Gene Rearrangement, T-Lymphocyte , Humans , L-Selectin/metabolism , Leukocyte Common Antigens/metabolism , Male , Middle Aged , Thymus Gland/immunology
2.
Cir. pediátr ; 15(3): 114-117, jul. 2002.
Article in Es | IBECS | ID: ibc-14434

ABSTRACT

En el niño la hipertensión portal de origen presinusoidal (HPP) cursa sin daño funcional hepático, y con el tiempo tiende a compensarse mediante la creación de shunts espontáneos portosistémicos; no obstante, algunos sufren episodios de hemorragia gastrointestinal (HGI) que por su severidad o frecuencia, obliga a plantear la posibilidad de tratamiento quirúrgico. Objetivo. Valorar los resultados de la derivación mesocava (shunt meso-cavo, SMC) con injerto autólogo de vena yugular en niños con HPP.Material y métodos. De una serie de 32 niños con HPP tratados en nuestro hospital en los últimos 7 años, 10 sufrieron episodios de HGI que obligó a plantear una derivación quirúrgica. El tipo de shunt fue esplenorrenal distal en tres casos y mesocavo en siete; estos últimos constituyen el material de este estudio. La HPP fue ocasionada por transformación cavemomatosa de la porta (TCP) en seis y fibrosis hepática congénita (FHC) en uno. Previamente a la cirugía, la media de episodios de HGI fue de 9 (rango: 2-15); todos precisaron transfusión de hemoderivados y esclerosis de varices, y sonda con balón en dos; cinco fueron tratados con somatostatina y propranolol. La exploración con Doppler pulsado antes de la cirugía puso de manifiesto una intensa circulación colateral hepatófuga en todos los casos. Resultados. El flujo a través del shunt fue adecuado en todos excepto uno, que precisó de dilatación percutánea con balón. A excepción de éste, ninguno de los otros 6 niños ha vuelto a sufrir episodios de HGI. Los signos de hiperesplenismo regresaron o mejoraron en los siete casos, así como la circulación colateral en el seguimiento con Doppler pulsado, observándose velocidades de flujo adecuadas a través del shunt en todos los niños menos en uno. En los cuatro casos en los que se determinó la presión en el territorio esplácnico; ésta descendió alrededor del 50 por ciento de la original tras la apertura del shunt. En ninguno se ha observado encefalopatía, y sólo el enfermo con fibrosis hepática congénita muestra signos bioquímicos leves de disfunción hepática. El tiempo medio de evolución post-shunt es de 32 meses (rango: 8 meses-6 años).Conclusiones. El SMC evita la HGI en los casos de HPP que no responden al tratamiento conservador; su eficacia está en relación con una adecuada permeabilidad a través del injerto, y al menos en los casos de cavemomatosis portal (los más frecuentes de HPP en el niño), no produce disfunción hepática. El Doppler pulsado proporciona una información muy precisa de la situación postcirugía, siendo un método excelente de seguimiento de estos enfermos. (AU)


Subject(s)
Child , Child, Preschool , Male , Infant , Female , Humans , Portasystemic Shunt, Surgical , Venae Cavae , Mesenteric Arteries , Hypertension, Portal , Jugular Veins , Follow-Up Studies , Severity of Illness Index
3.
Cir Pediatr ; 15(3): 114-7, 2002 Jul.
Article in Spanish | MEDLINE | ID: mdl-12601985

ABSTRACT

UNLABELLED: Presinusoidal portal hypertension (PPH) in children evaluates without functional hepatic damage, and with the time, trends to compensate through the creation of spontaneous portosystemic shunts. Nevertheless, some patients suffer episodes of gastrointestinal bleeding (GIB) that because of its frequency or severity, force to propose the change of surgical treatment. AIM: To evaluate the results of the mesocaval shunt (MCS) with autologous jugular vein in children with PPH. MATERIAL AND METHODS: Among the 32 children with PPH treated in our Hospital in the last 7 years, 10 had episodes of GIB that forced to perform a surgical shunt. The types of shunt were distal splenorenal in 3 patients and mesocaval in 7. These 7 cases are the material of this study. The origin of the PPH was a cavernomatosis transformation of the portal vein in 6 cases and a congenital hepatic fibrosis in 1. Before the surgery the average number of episodes of GIB was 9 (range 2-15); all the patients needed transfusion of blood products and variceal sclerosis. In 2 cases a tamponade with the Sengtaken balloon was required and 5 patients were treated with somatostatin and propranolol. The Doppler ultrasounds revealed and intense hepatofugal collateral circulation in all the cases. RESULTS: The initial flow through the shunt was adequate in all the patients except one who required a percutaneous balloon dilatation. Only this patient has suffered an episode of GIB. The hyperesplenism signs disappeared or improved in all the seven cases and the collateral circulation was significantly reduced. The pressure in the splenic territory decreased around 50% in the 4 patients that was measured. There were no cases of encephalopasty and only one child with congenital hepatic fibrosis shows signs of mild hepatic disfunction. The medium follow up post-shunt is 32 months (range 8 m-6 years). CONCLUSIONS: The MCS prevents the GIB in the PPH not responsive to the conservative treatment; its effectiveness is related with an adequate permeability though the graft and at least in the cases with portal cavernomatosis (the most frequent in children) doesn't produce hepatic dysfunction. Doppler ultrasounds give a very precise information about the post-surgical situation and are an excellent method of follow up.


Subject(s)
Hypertension, Portal/diagnosis , Hypertension, Portal/surgery , Jugular Veins/transplantation , Mesenteric Arteries/surgery , Portasystemic Shunt, Surgical , Venae Cavae/surgery , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Severity of Illness Index
4.
Genomics ; 65(1): 16-23, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10777661

ABSTRACT

Epidermal growth factor (EGF) repeat-containing proteins constitute an expanding family of proteins involved in several cellular activities such as blood coagulation, fibrinolysis, cell adhesion, and neural and vertebrate development. By using a bioinformatic approach, we have identified a new member of this family named MAEG (MAM- and EGF-containing gene; HGMW-approved gene symbol and gene name). Sequence analysis indicates that MAEG encodes a secreted protein characterized by the presence of five EGF repeats, three of which display a Ca(2+)-binding consensus sequence. In addition, a MAM domain is also present at the C-terminus of the predicted protein product. The human and murine full-length cDNAs were identified and mapped to human Xp22 and to the mouse syntenic region. Northern analysis indicates that MAEG is expressed early during development. Taken together, these data render MAEG a candidate for human and murine developmental disorders.


Subject(s)
Epidermal Growth Factor/genetics , Glycoproteins , Growth Disorders/genetics , Growth Substances , Neoplasm Proteins , Peptides , X Chromosome/genetics , Amino Acid Sequence , Animals , Blotting, Northern , Calcium-Binding Proteins , Cell Adhesion Molecules , Chromosome Mapping , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Exons , Fetus/metabolism , Gene Expression Regulation, Developmental , Genes/genetics , Humans , Introns , Membrane Glycoproteins , Mice , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid
5.
Genomics ; 62(1): 113-8, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10585778

ABSTRACT

We report the identification of a new transcript homologous to the Drosophila staufen protein. This transcript, named STAU2 (HGMW-approved gene symbol and name), maps to the chromosome 8q13-q21 region. The full-length STAU2 cDNA is 4058 bp and contains an open reading frame of 479 amino acids. Analysis of the predicted protein product indicated the presence of three double-stranded RNA-binding domains. Best-fit analysis revealed a 48.5% similarity to the Drosophila protein and a 59.9% similarity to the recently described mammalian homolog hStau, indicating that at least two different transcripts with homologies to the fly protein are present in mammals.


Subject(s)
Chromosomes, Human, Pair 8/genetics , Drosophila Proteins , Drosophila melanogaster/genetics , Genes , RNA-Binding Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Binding Sites , DNA, Complementary/genetics , Expressed Sequence Tags , Gene Duplication , Gene Expression , Genetic Diseases, Inborn/genetics , Humans , Mammals/genetics , Molecular Sequence Data , Open Reading Frames , Protein Structure, Tertiary , RNA/metabolism , Sequence Alignment , Sequence Homology , Species Specificity
6.
Genomics ; 59(1): 51-8, 1999 Jul 01.
Article in English | MEDLINE | ID: mdl-10395799

ABSTRACT

We recently identified a gene responsible for an autosomal recessive form of hereditary spastic paraplegia (HSP). This gene encodes paraplegin, a mitochondrial protein highly homologous to the yeast mitochondrial ATPases Afg3p and Rcalp, which have both proteolytic and chaperone-like activities at the inner mitochondrial membrane. By screening the Expressed Sequence Tag database, we identified and characterized a novel human cDNA, ATPase family gene 3-like 2 (AFG3L2, Human Gene Nomenclature Committee-approved symbol), which is closely related to paraplegin. This cDNA encodes a 797-amino-acid predicted protein highly similar to paraplegin as well as to yeast Afg3p and Rca1p. Immunofluorescence studies revealed that AFG3L2 and paraplegin share a similar expression pattern and the same subcellular localization, the mitochondrial compartment. We subsequently mapped AFG3L2 to chromosome 18p11 by radiation hybrid analysis. AFG3L2 may represent a candidate gene for other forms of HSPs and possibly for other neurodegenerative disorders.


Subject(s)
Adenosine Triphosphatases/genetics , Genes/genetics , Metalloendopeptidases/genetics , ATP-Dependent Proteases , ATPases Associated with Diverse Cellular Activities , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Chromosome Mapping , Chromosomes, Human, Pair 18/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Fetus/metabolism , Fluorescent Antibody Technique , Gene Expression , Gene Expression Regulation, Developmental , Humans , Mitochondria/chemistry , Molecular Sequence Data , RNA/genetics , RNA/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution
7.
Hum Mol Genet ; 8(8): 1397-407, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10400986

ABSTRACT

The B-box family is an expanding new family of genes encoding proteins involved in diverse cellular functions such as developmental patterning and oncogenesis. A member of this protein family, MID1, is the gene responsible for the X-linked form of Opitz G/BBB syndrome, a developmental disorder characterized by defects of the midline structures. We now report the identification of MID2, a new transcript closely related to MID1. MID2 maps to Xq22 in human and to the syntenic region on the mouse X chromosome. The two X-linked genes share the same domains, the same exon-intron organization, a high degree of similarity at the protein level and the same subcellular localization, both being confined to the cytoplasm in association to micro-tubular structures. The expression pattern studied by RNA in situ hybridization in mouse revealed that Mid2 is expressed early in development and the highest level of expression is detected in the heart, unlike Mid1 for which no expression was detected in the developing heart. Together, these data suggest that midin and MID2 have a similar biochemical function but a different physiological role during development.


Subject(s)
Calcium-Binding Proteins/genetics , Membrane Proteins/genetics , Microtubule Proteins , Nuclear Proteins , Saccharomyces cerevisiae Proteins , Smith-Lemli-Opitz Syndrome/genetics , Transcription Factors/genetics , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Chromosome Mapping , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Embryo, Mammalian/metabolism , Embryonic and Fetal Development , Exons , Fluorescent Antibody Technique, Direct , Gene Expression Regulation, Developmental , Humans , In Situ Hybridization , Intracellular Signaling Peptides and Proteins , Introns , Membrane Glycoproteins , Mice , Mice, Inbred C57BL , Microtubules/metabolism , Molecular Sequence Data , Muridae , RNA/genetics , RNA/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution , Ubiquitin-Protein Ligases , X Chromosome/genetics
8.
Genomics ; 58(1): 65-72, 1999 May 15.
Article in English | MEDLINE | ID: mdl-10331946

ABSTRACT

We have identified a novel gene with homologies to the Drosophila Sex comb on midleg (Scm) gene from the short arm of the X chromosome. Scm is a member of the Polycomb group (PcG) genes, which encode transcriptional repressors essential for appropriate development in the fly and in mammals. The newly identified transcript named SCML2 (sex comb on midleg like-2, HGMW-approved symbol) is ubiquitously expressed and encodes a protein of 700 amino acids. SCML2 maps very close to the recently identified SCML1, revealing the presence of a new gene cluster in Xp22. The homology and map location identify SCML2 as a candidate gene for Xp22-linked developmental disorders, including the oral-facial-digital type I (OFDI) syndrome. A study of the SCML1-SCML2 cluster in primates indicates that the two genes are localized to the same region in Old World monkeys, New World monkeys, and prosimians, suggesting that the duplication event leading to the formation of the SCML cluster on Xp22 occurred before primate divergence.


Subject(s)
DNA-Binding Proteins/genetics , Drosophila Proteins , Drosophila/genetics , Genes/genetics , Repressor Proteins/genetics , Transcription Factors , Amino Acid Sequence , Animals , Blotting, Northern , Cell Line , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Female , Gene Expression , Humans , In Situ Hybridization, Fluorescence , Male , Mice , Molecular Sequence Data , Multigene Family , Polycomb-Group Proteins , Primates , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution , X Chromosome/genetics
9.
Genomics ; 51(3): 427-33, 1998 Aug 01.
Article in English | MEDLINE | ID: mdl-9721213

ABSTRACT

Eukaryotic protein kinases are part of a large and expanding family of proteins. Through our transcriptional mapping effort in the Xp22 region, we have isolated and sequenced the full-length transcript of STK9, a novel cDNA highly homologous to serine-threonine kinases. A number of human genetic disorders have been mapped to the region where STK9 has been localized including Nance-Horan (NH) syndrome, oral-facial-digital syndrome type 1 (OFD1), and a novel locus for nonsyndromic sensorineural deafness (DFN6). To evaluate the possible involvement of STK9 in any of the above-mentioned disorders, a 2416-bp full-length cDNA was assembled. The entire genomic structure of the gene, which is composed of 20 coding exons, was determined. Northern analysis revealed a transcript larger than 9.5 kb in several tissues including brain, lung, and kidney. The mouse homologue (Stk9) was identified and mapped in the mouse in the region syntenic to human Xp. This location is compatible with the location of the Xcat mutant, which shows congenital cataracts very similar to those observed in NH patients. Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders.


Subject(s)
Nerve Tissue Proteins , Protein Serine-Threonine Kinases/chemistry , X Chromosome/genetics , Amino Acid Sequence , Animals , CDC2 Protein Kinase/chemistry , Calcium-Calmodulin-Dependent Protein Kinases/chemistry , Chromosome Mapping , Cloning, Molecular , Cyclin-Dependent Kinases , Genetic Diseases, Inborn/genetics , Genetic Linkage/genetics , Haplotypes/genetics , Humans , Mice , Molecular Sequence Data , RNA Splicing/genetics , Restriction Mapping , Sequence Alignment , Sequence Analysis, DNA
10.
Nat Genet ; 17(3): 285-91, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9354791

ABSTRACT

Opitz syndrome (OS) is an inherited disorder characterized by midline defects including hypertelorism, hypospadias, lip-palate-laryngotracheal clefts and imperforate anus. We have identified a new gene on Xp22, MID1 (Midline 1), which is disrupted in an OS patient carrying an X-chromosome inversion and is also mutated in several OS families. MID1 encodes a member of the B-box family of proteins, which contain protein-protein interaction domains, including a RING finger, and are implicated in fundamental processes such as body axis patterning and control of cell proliferation. The association of MID1 with OS suggests an important role for this gene in midline development.


Subject(s)
Abnormalities, Multiple/genetics , Microtubule Proteins , Mutation , Nuclear Proteins , Transcription Factors/genetics , X Chromosome , Amino Acid Sequence , Animals , Child, Preschool , Chromosome Inversion , Cleft Lip/genetics , Cloning, Molecular , Deglutition Disorders/genetics , Female , Gene Expression Regulation, Developmental , Humans , Hypertelorism/genetics , Hypospadias/genetics , In Situ Hybridization , Male , Mice , Molecular Sequence Data , Tissue Distribution , Transcription Factors/metabolism , Ubiquitin-Protein Ligases
11.
Hum Mol Genet ; 6(7): 1137-45, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9215685

ABSTRACT

Through our transcriptional mapping effort in the Xp22 region, we have isolated by exon trapping a new transcript highly homologous to the Drosophila retinal degeneration C (rdgC) gene. rdgC encodes a serine/threonine phosphatase protein and is required in Drosophila to prevent light-induced retinal degeneration. This human gene is the first mammalian member of the serine-threonine phosphatase with EF hand motif gene family, and was thus named PPEF (Protein Phosphatase with EF calcium-binding domain). The expression pattern of the mouse Ppef gene was studied by RNA in situ hybridization on embryonic tissue sections. While rdgC is expressed in the visual system of the fly, as well as in the mushroom bodies of the central brain, we found that Ppef is highly expressed in sensory neurons of the dorsal root ganglia (DRG) and neural crest-derived cranial ganglia. The selective pattern of expression makes PPEF an important marker for sensory neuron differentiation and suggests a role for serine-threonine phosphatases in mammalian development.


Subject(s)
Calcium-Binding Proteins , Drosophila Proteins , Neural Crest/physiology , Neurons, Afferent/enzymology , Phosphoprotein Phosphatases/genetics , Retinal Degeneration/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Chromosome Mapping , Cranial Nerves/physiology , DNA, Complementary , Embryo, Mammalian/physiology , Ganglia, Spinal/physiology , Gene Expression Regulation, Developmental , Genetic Linkage , Humans , In Situ Hybridization/methods , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Molecular Sequence Data , Mutation , Phosphoprotein Phosphatases/metabolism , Polymorphism, Single-Stranded Conformational , RNA , Sequence Homology, Amino Acid , Tissue Distribution
12.
Genomics ; 42(2): 192-9, 1997 Jun 01.
Article in English | MEDLINE | ID: mdl-9192838

ABSTRACT

We recently reported the isolation of two new members of the sulfatase gene family, arylsulfatase D (ARSD) and E (ARSE), located approximately 50 kb from each other in the Xp22.3 region. Mutation analysis indicated ARSE as the gene responsible for X-linked recessive chondrodysplasia punctata. Expression of the ARSE gene in COS cells resulted in a heat-labile arylsulfatase activity that was inhibited by warfarin. At the same time, we detected the presence of a 1.2-kb fragment located at approximately 60 kb from ARSD and ARSE with significant homology to these two genes, suggesting the existence of another sulfatase gene, arylsulfatase F (ARSF), in Xp22.3. We have used a combined approach of long-range genomic sequencing and screening of cDNA libraries to isolate the ARSF gene. Expression of the ARSF cDNA in COS cells resulted in a heat-labile arylsulfatase activity that is not inhibited by warfarin, supporting our hypothesis that only ARSE is specifically inhibited by warfarin and is most likely involved in warfarin embryopathy. Genomic analysis revealed that ARSF has an intron/exon organization highly similar to those of ARSD and ARSE, which is also shared by another Xp22.3 sulfatase gene, ARSC (arylsulfatase C, also known as steroid sulfatase), with the splice sites occurring at the same position in all four genes. The data obtained from sequence analysis and presented in this paper indicate that the ARSC, ARSD, ARSE, and ARSF genes are more similar to each other than to other members of the sulfatase gene family, supporting our hypothesis that they represent a subfamily of related proteins created through duplication events that occurred in an ancestral pseudoautosomal region.


Subject(s)
Arylsulfatases/genetics , X Chromosome/genetics , Amino Acid Sequence , Animals , Arylsulfatases/classification , Arylsulfatases/metabolism , Base Sequence , COS Cells , Chromosome Mapping , DNA, Complementary/genetics , Evolution, Molecular , Exons , Genome, Human , Humans , Molecular Sequence Data , Multigene Family , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Transfection
13.
Hum Mol Genet ; 5(4): 423-31, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8845834

ABSTRACT

An obligatory crossing-over event between the X and Y chromosomes in mammals occurs at each male meiosis within the 2.6 Mb of DNA defining the pseudoautosomal region (PAR). Genes located within or near the human PAR have homologous copies on the X and Y chromosomes, escape X inactivation and appear to be highly divergent throughout evolution. We have characterized the genomic structure of two genes from a recently identified cluster of sulfatase genes (ARSD and ARSE) located in the Xp22.3 region, and of their homologs on the Y chromosome. Our results indicate that the ARSD and ARSE genes from within this cluster have a conserved genomic organization, shared also by another Xp22.3 gene, STS, but completely different from that of all the other sulfatase genes. Sequence analysis of the Y-linked homologs indicate that they represent truncated pseudogenes. Sequence identity values between the X and Y copies of each gene is on average 91%, significantly higher than the values obtained by comparing different members of the family. FISH mapping experiments performed in several primate species revealed an identical localization of the X-linked copies to that in man, but different localizations of the Y homologs. Together, our data indicate that the cluster of sulfatase genes on human Xp22.3 was created through duplication events which probably occurred in an ancestral PAR, and support the view that the PAR has undergone multiple changes during recent mammalian evolution.


Subject(s)
Arylsulfatases/genetics , Multigene Family , X Chromosome , Animals , Base Sequence , Chromosome Mapping , DNA , Evolution, Molecular , Humans , Molecular Sequence Data , Primates/genetics , Pseudogenes , Sequence Homology, Nucleic Acid , Y Chromosome
SELECTION OF CITATIONS
SEARCH DETAIL
...