Search PubMed⌕ Search

Biomedical subjects

F Figueroa

Publications and source records attributed to F Figueroa.

At least 37 records · Page 2Linked to original sources
PubMed1997

Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the zebrafish.

The LMP2 and LMP7 genes code for subunits of the proteasome, a multimeric enzymatic complex that degrades proteins into peptides. The two subunits replace corresponding constitutively expressed subunits during the immune response. Some of the peptides generated by the proteasome in the cytosol are transported by the products of the TAP1 and TAP2 genes into the lumen of the endoplasmic reticulum and are loaded onto the assembling MHC class I molecules. In mammals, the LMP2, LMP7, TAP1, and TAP2 genes reside in the class II region of the Mhc, closely linked to the RING3 gene. In the present study we identified, cloned, and sequenced the LMP, TAP2, and RING3 genes of the zebrafish, Danio rerio. We identified variants of these genes and used them in a segregation analysis of haploid embryos derived from heterozygous mothers. The analysis revealed that in zebrafish, the LMP2, LMP7, TAP12, and RING3 loci are closely linked but, in contrast to mammals, the LMP/TAP/RING3 cluster resides not in the Mhc class II but in the class I region. We also confirmed that in the zebrafish, the class I and class II regions are not linked to each other. In this species, therefore, the LMP/TAP/RING3 genes are clustered with the class I genes on a chromosome that apparently does not contain any class II genes. The linkage of LMP/TAP/RING3/class I may be the original and the LMP/TAP/RING3/class II a derived arrangement of these genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean Amerinds.

We have characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported here to agree with findings in other Amerind groups. The high frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas.

Alleles↗
PubMed1997

Class I mhc genes of cichlid fishes: identification, expression, and polymorphism.

Cichlid fishes of the East African Rift Valley lakes constitute an important model of adaptive radiation. Explosive speciation in the Great Lakes, in some cases as recently as 12 400 years ago, generated large species flocks that have been the focus of evolutionary studies for some time. The studies have, however, been hampered by the paucity of biochemical markers for phylogenetic reconstruction. Here, we describe a set of markers which should help to alleviate this problem. They are the class I genes of the major histocompatibility complex. We provide evidence for the existence of at least 17 class I loci in cichlid fishes, and for extensive polymorphism of three of these loci. Since the polymorphism has a trans-species character, it will be possible to use it in investigating the founding events of the individual species. The sequences of the cichlid class I fishes support the monophyly of actinopterygian fish on the one hand, and of tetrapods on the other.

Animals↗
PubMed1997

Mapping of mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerio.

The mammalian major histocompatibility complex (Mhc) consists of three closely linked regions, I, II, and III, occupying a single chromosomal segment. The class I loci in region I and the class II loci in region II are related in their structure, function, and evolution. Region III, which is intercalated between regions I and II, contains loci unrelated to the class I and II loci, and to one another. There are indications that a similar Mhc organization exists in birds and amphibians. Here, we demonstrate that in the zebrafish (Danio rerio), a representative of the teleost fishes, the class II loci are divided between two linkage groups which are distinct from the linkage group containing the class I loci. The beta2-microglobulin-encoding gene is loosely linked to one of the class II loci. The gene coding for complement factor B, which is one of the region III genes in mammals, is linked neither to the class I nor to the class II loci in the zebrafish. These results, combined with preliminary data suggesting that the class I and class II regions in another order of teleost fish are also in different linkage groups, indicate that close linkage of the two regions is not necessary either for regulation of expression or for co-evolution of the class I and class II loci. They also raise the question of whether linkage of the class I and class II loci in tetrapods is a primitive or derived character.

Animals↗
PubMed1997

HLA-DRB9--possible remnant of an ancient functional DRB subregion.

The DRB subregion of the HLA complex contains, in addition to the functional genes, a number of pseudogenes and gene fragments. Fourteen kilobases of DNA were sequenced from the segment upstream of the DRB9 gene fragment, as well as shorter segments from different HLA and corresponding ape haplotypes. The analysis of the sequences and restriction fragments indicates that the segment is a remnant of an ancient DRB subregion which may have been functional before the primate radiation and which later became the source of extant functional DRB genes in various primate groups, different ones in different groups. The remnant segment has remained constant in its organization for at least 4 million years. This constancy contrasts with the variability of the adjacent functional part of the DRB subregion occupied by the DRB1 and other loci. The constancy may be related to the monomorphism and evolutionary conservation of the DRA locus.

Base Sequence↗
PubMed1996

Identification of major histocompatibility complex genes in the guppy, Poecilia reticulata.

The guppy, Poecilia reticulata, a teleostean fish of the order Cyprinodontiformes, has been used extensively in studies of host-parasite interactions, courtship behavior, and mating preference, as well as in ecological and evolutionary genetics. A related species was among the first poikilotherm vertebrates to be used in the study of histocompatibility genes. All these studies could benefit from the identification and characterization of the guppy major histocompatibility complex (Mhc) genes. Here, both class I and class II genes of the guppy are described. The number of expressed loci, as determined by representation of clones in a cDNA library, sequencing, and Southern blot analysis, may be low in both Mhc classes: combined evidence suggests that there may be one expressed class II locus only and one or two expressed class I loci. The variability of aquaristic guppy stocks is very low: only three and two genes have been detected at the class I and class II loci, respectively, in the stocks examined. This genetic paucity is most likely the consequence of breeding practices employed by aquarists and commercial establishments. Limited sampling of wild guppy populations revealed extensive Mhc polymorphism at loci of both classes in nature. Comparison of guppy Mhc sequences with those of other vertebrates has revealed the existence of a set of insertions/deletions which can be used as characters in cladistic analysis to infer phylogenetic relationships among vertebrate taxa and the Mhc genes themselves. These indels are particularly frequent in the regions coding for the loops of alpha 1 and alpha 2 domains of class I proteins.

Amino Acid Sequence↗
PubMed1996

Identification and characterization of a new major histocompatibility complex class I gene in carp (Cyprinus carpio L.).

In this study we report the finding of three representatives of a new group of major histocompatibility complex class I sequences in carp: Cyca-12 (Cyca-UA1*01), a full-length cDNA; Cyca-SP1 (Cyca-UAW1), a polymerase chain reaction (PCR) fragment from cDNA; and Cyca-G11 (Cyca-UA1*02), a partial genomic clone. Comparison of the amino acid sequences of Cyca-12, Cyca-SP1, and Cyca-G11 with classical and non-classical class I sequences from other species shows considerable conservation in regions that have been shown to be involved in maintaining the structure and function of class I molecules. The genomic organization of Cyca-12 has been elucidated by analysis of a partial genomic clone (Cyca-G11, in combination with PCR amplifications on genomic DNA of a homozygous individual. Although the genomic organization is similar to that found in class I genes from other species, the 3' untranslated region contains an intron which is unprecedented in class I genes, and intron 2 is exceptionally large (+/-14 kilobases). Southern blot analysis indicates the presence of multiple related sequences. In phylogenetic analyses, the Cyca-UA sequences cluster with class I genes from zebrafish and Atlantic salmon, indicating that the ancestral gene arose before the salmonid/cyprinid split, approximately 120-150 million years ago. The previously reported class I Cyca-Z genes from carp and Caau-Z genes from goldfish cluster as a completely separate lineage. A polyclonal antiserum (anti-Cyca12) was raised against a recombinant fusion protein containing most of the extracellular domains of Cyca-12. The antibodies showed substantial reactivity to the recombinant protein and an Mr 45000 protein in membrane lysates of spleen and muscle, as well as to determinants present on leucocytes in fluorescence-activated cell sorter analyses. Erythrocytes and thrombocytes were found to be negative.

Amino Acid Sequence↗
PubMed1996

The HLA-DRB9 gene and the origin of HLA-DR haplotypes.

HLA-DRB9 is a gene fragment consisting of exon 2 and flanking intron sequences. It is located at the extreme end of the DRB subregion, whose other end is demarcated by the DRB1 locus. We sequenced approximately 1400 base pairs of the segment encompassing the DRB9 locus from eight human haplotypes (DR1, DR10, DR2, DR3, DR5, DR6, DR8, and DR9, the DR4 and DR7 having been sequenced by others earlier), as well as two chimpanzee, five gorillas, one orangutan and one macaque haplotype. The analysis of these sequences indicates that the DRB9 locus, which we estimate to be more than 58 million years (my) old, has been coevolving with the DRB1 locus for the last 4.2 my. As a consequence of this coevolution, the human DRB9 alleles fall into groups that correlate with the DRB1 allelic groups and with the gene organization of the human haplotypes. This observation implies that the present-day HLA-DR haplotype groups (DR1, DR51, DR52, DR8, and DR53) were founded more than 4 my ago and have remained intact (barring minor internal rearrangements that did not recombine the DRB1 and DRB9 genes) for this period of time. The haplotypes have been transmitted during speciations from ancestral to emerging species just like allelic lineages at the DRB1 locus. Thus not only allelic but also haplotype polymorphism evolves trans-specifically.

Animals↗
PubMed1996

Association of primary antiphospholipid syndrome with primary adrenal insufficiency.

The association of primary adrenal insufficiency with antiphospholipid antibodies is usually reported in the context of adrenal thrombosis or hemorrhage. We describe a 35-year-old woman who developed a primary antiphospholipid syndrome (spontaneous abortion, thrombocytopenia, and cerebrovascular occlusion) in association with primary adrenal insufficiency without evidence of suprarenal hemorrhage or thrombosis.

Addison Disease↗
PubMed1995

Evidence for insertion of a new intron into an Mhc gene of perch-like fish.

The evolution of the major histocompatibility complex (Mhc) has been studied to understand the origin of the immune system, of which it constitutes an essential part. In the present study, the Mhc is used to shed light on questions regarding the origin of introns and the phylogeny of fishes. The organization of the coding (exon) and non-coding (intron) regions of both class I and class II major histocompatibility complex (Mhc) genes is highly conserved in all vertebrate classes; the only variation observed until now is in the number of exons encoding the membrane-anchoring part. Moreover, there is a good correspondence between the exon-intron organization at the DNA level and the division into structurally and functionally defined domains at the protein level. Here we describe the first major exception to this uniformity. The immunoglobulin-like domain of the class II beta-chains in perch-like fishes (Percomorpha) is not encoded in one exon, as it is in all other vertebrates studied thus far, but in two exons. The length of the extra intron varies from gene to gene and from species to species, but is generally less than 200 base pairs (b.p.). Only one of the sequenced introns is about 500 b.p. long. In some of the genes, the intron contains a hexamer repeat. The repeat is present in the transcript at the site at which the intron interrupts exon 3 in the genomic DNA. The intron may therefore have arisen by repeated tandem duplication of this sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Molecular cloning of major histocompatibility complex class II B gene cDNA from the Bengalese finch Lonchura striata.

The only avian major histocompatibility complex (Mhc) genes thus far identified are from species of the relatively small order of Galliformes, while by far the largest order of Passeriformes (songbirds), containing some 60% of extant bird species, has not been studied at all in this regard. The Galliformes emerged more than 55 million years (my) ago, the Passeriformes some 25 my ago. Because of the potential for the use of Mhc genes as markers in the study of songbird populations, an attempt was made to clone class II B genes of a passeriform species, the Bengalese finch Lonchura striata acuticauda. Using a set of primers designed on the basis of known sequences, a probe corresponding to part of exon II was obtained by the polymerase chain reaction. The probe was then used to screen a Bengalese finch cDNA library and to isolate and sequence two nearly full-length clones. The sequences reveal the presence of one presumably functional class II B locus in this bird species.

Amino Acid Sequence↗
PubMed1995

Cloning and characterization of class I Mhc genes of the zebrafish, Brachydanio rerio.

The zebrafish (Brachydanio rerio) offers many advantages for immunological and immunogenetic research and has the potential for becoming one of the most important nonmammalian vertebrate research models. With this in mind, we initiated a systematic study of the zebrafish major histocompatibility complex (Mhc) genes. In this report, we describe the cloning and characteristics of the zebrafish class I A genes coding for the alpha chains of the alpha beta heterodimer and thus complete the identification of all four classes and subclasses of the Mhc in this species. We describe the full class I alpha cDNA sequence as well as the exon-intron organization of the class I A genes, including intron sequences. We identify three families of class I A genes which we designate Brre-UAA, -UBA, and -UCA. The three families originated about the time of the divergence of cyprinid and salmonid fishes. All three families are members of an ancient lineage that diverged from another, older lineage also represented in cyprinid fishes before the radiation of teleost orders. The fish class I A genes therefore evolve differently from mammalian class I A genes, in which the establishment of lineages and families mostly postdates the divergence of orders.

Amino Acid Sequence↗
PubMed1995

Antigenic specificity of lymphocytes isolated from valvular specimens of rheumatic fever patients.

T cell lines were established from both valvular specimens and peripheral blood lymphocytes from seven patients with well documented rheumatic heart disease. These cell lines were stimulated with either PHA or streptococcal antigens. Proliferation assays revealed that both valvular and peripheral blood T cell lines reacted to cell wall (CW) and cell membrane (CM) antigens obtained from rheumatic fever associated group A streptococci and not to nephritogenic strains. None of the cell lines reacted to M protein, myosin or other mammalian cytoskeletal proteins. The unique reactivity of rheumatic fever T cell lines only to cellular structures obtained from rheumatogenic strains suggests that these lines react to epitopes specific for antigens obtained from these strains.

Antigens, Bacterial↗
PubMed1995

Phylogenetic analysis of cichlid fishes using nuclear DNA markers.

The recent explosive adaptive radiation of cichlids in the great lakes of Africa has attracted the attention of both morphologists and molecular biologists. To decipher the phylogenetic relationships among the various taxa within the family Cichlidae is a prerequisite for answering some fundamental questions about the nature of the speciation process. In the present study, we used the random amplification of polymorphic DNA (RAPD) technique to obtain sequence differences between selected cichlid species. We then designed specific primers based on these sequences and used them to amplify template DNA from a large number of species by the polymerase chain reaction (PCR). We sequenced the amplified products and searched the sequences for indels and shared substitutions. We identified a number of such characters at three loci--DXTU1, DXTU2, and DXTU3--and used them for phylogenetic and cladistic analysis of the relationships among the various cichlid groups. Our studies assign an outgroup position to Neotropical cichlids in relation to African cichlids, provide evidence for a sister-group relationship of tilapiines to the haplochromines, group Cyphotilapia frontosa with the lamprologines of Lake Tanganyika, place Astatoreochromis alluaudi to an outgroup position with respect to other haplochromines of Lakes Victoria and Malawi, and provide additional support for the monophyly of the remaining Lake Victoria haplochromines and the Lake Malawi haplochromines. The described approach holds great promise for further resolution of cichlid phylogeny.

Africa, Eastern↗
PubMed1995

[Treatment with cyclosporine of refractory rheumatoid arthritis].

Cyclosporine may be useful in the treatment of rheumatoid arthritis refractory to other immunosuppressive agents, in doses of less than 10 mg/kg/day to minimize its nephrotoxic potential, that is enhanced with prolonged use or concomitant administration of anti-inflammatory drugs. We report 15 patients aged 50 +/- 12 years with erosive rheumatoid arthritis lasting 5 +/- 4 years and refractory to other immunosuppressive agents. They were studied during one year and received cyclosporine in initial doses of 2.5 mg/kg/day that were increased to 5 mg/kg/day, assessing clinical response, blood pressure and serum creatinine. Nine patients, that received a maximal dose of 3.4 +/- 0.7 mg/kg/day during 7 +/- 4 months, improved; a 30% increase in creatinine was observed in 3, blood pressure raised in six and two had hepatic toxicity. In the six patients that did not improve, the mean treatment lapse was 4 +/- 3 months and the maximal dose achieved was 2.7 mg/kg/day; creatinine increased in one and blood pressure increased in 4. It is concluded that although the clinical response to cyclosporine was good, only 4 patients completed one year of treatment, due to the frequent secondary effects of the drug.

Adolescent↗
PubMed1994

Organization of Mhc class II B genes in the zebrafish (Brachydanio rerio).

Using three genomic phage libraries, we isolated 26 clones from the zebrafish MHC class II B region. By restriction mapping, the clones could be arranged into six clusters, most clusters consisting of several overlapping clones. The combined clusters cover a total of 161 kb of the zebrafish class II region. Hybridization with specific probes demonstrated the presence in the clusters of two class II A and six class II B genes. Sequencing of the B genes revealed that they represented six different families of class II loci. Only two of the class II B and one of the class II A genes are complete; the others are truncated pseudogenes. Only one of the class II B loci shows extensive restriction fragment length polymorphism. This is also the only locus found to be transcribed in organs with large numbers of lymphoid or myeloid cells. The zebrafish class II genes have promoter regions with sequence elements found previously in mammalian genes and known to be involved in regulation of expression. The exon-intron organization of the zebrafish class II genes is similar to that of the mammalian genes, but the introns are characteristically short, ranging in length from 74 to 362 bp. The distances between A and B genes in a given pair are also short, but the distances between B genes are as long as or longer than those between mammalian class II B genes. All of the zebrafish class II B genes appear to have arisen by duplication and diversification of a single ancestral B gene after the separation of bony fishes from other vertebrate taxa.

Amino Acid Sequence↗
PubMed1994

The origin of the primate Mhc-DRB genes and allelic lineages as deduced from the study of prosimians.

MHC class II genes of the DRB family were partially sequenced from 10 individuals representing six species of prosimians: Galago senegalensis, G. moholi, Otolemur garnetti, Loris tardigradus, Petterus (Lemur) fulvus, and Lemur catta. Altogether, 41 different genes were discerned, all distinct from genes identified previously. Comparative analysis of the sequences has led to the following conclusions. First, the DRB loci present in human populations diverged from one another before the divergence of prosimian and anthropoid primates. Second, major allelic lineages of the DRB1 locus, such as DRB1*03 (DRB1*13) and DRB1*04, were established more than 85 million years ago. Third, the DRB6 gene was inactivated before the separation of prosimians and anthropoids, and has remained a pseudogene for more than 85 million years. Fourth, the primate DRB region is structurally and functionally unstable. In Lemur catta, for example, all DRB genes have apparently been lost and their function taken over by DOB and/or DPB genes. DRB genes are, however, present in a related species, Petterus (Lemur) fulvus. Fifth, the prosimian DRB3 genes are all inactive; their function seems to have been taken over by new genes. Sixth, several of the prosimian DRB genes and pseudogenes have recently been duplicated. In Otolemur garnetti, for example, one chromosome carries at least three copies of the DRB3 pseudogene.

Alleles↗