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P Varela

Publications and source records attributed to P Varela.

At least 55 records · Page 3Linked to original sources

Generation of the HLA-B35, -B5, -B16, and B15 groups of alleles studied by intron 1 and 2 sequence analysis.

HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons 2 and 3, which code for the molecule's alpha 1 and alpha 2 domains and include the antigenic peptide binding site. Recent studies have indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B*3906 and B*1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic polymorphism was found: namely, B*5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B*5101 and B*52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B*39061 and B*39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B*1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are also potentially useful to design DNA typing strategies.

Alleles↗

Immunocompetence in relation to a heat-processed diet (Maillard reaction) in weanling rats.

Diets containing unheated casein (CD; control) or a casein-glucose mixture (CGD) previously heated at 140 degrees for 2 h were fed to two groups of young rats for 21 d. Differences in body weight, feed consumption, thymus, and spleen growth, protein metabolism and in vivo immune response were then determined. For this last experiment, animals were inoculated with sheep erythrocytes (SRBC) on day 15 to provide an immunological challenge. No changes were seen in body weight, feed consumption or feed conversion ratios. Neither were significant differences found in spleen weight, protein content, DNA content, DNase (EC 3.1.4.6) activity or lymphocyte count, suggesting that spleen cell growth remained similar in all the animals studied. The CGD induced marked increases in thymus DNA content whilst the protein:DNA ratio became lower. Spleen RNA content was similar in all rats, but thymus RNA content was 29% lower in the CGD group, although this difference did not reach statistical significance. This fact might be a consequence of the low RNase (EC 2.7.7.16) activity and RNase:RNA ratios in the thymus glands of CGD-fed animals. Further, the number of splenic plasma cells secreting anti-SRBC antibodies (direct plaque-forming cells) was significantly decreased in the same group. It might be concluded that both diets are adequate for rat growth and that the differences observed in the thymus of CGD-fed rats may be directed towards preserving tissue function. Nevertheless, the CGD did cause immunological disturbances affecting the humoral immune response.

Animal Nutritional Physiological Phenomena↗

Interactions between nutrition and immunity in anorexia nervosa: a 1-y follow-up study.

Nutritional status and immunocompetence were evaluated in 15 patients suffering from anorexia nervosa in comparison with a control group (n = 15). After 1 y, data from six phases of the study were evaluated: immediately after admittance to the hospital (AN1), after 1 mo (AN2), after 2 mo (AN3), after 3 mo (AN4), after 6 mo (AN5), and after 1 y, (AN6). Patients recovered weight from AN4 until AN6 although, according to body mass index values, all patients had low weights during the 1-y follow-up. Likewise, leukocyte and lymphocyte values were borderline and lower in patients in all phases tested than in control subjects. All lymphocyte subpopulations were lower in AN1 and AN2 patients (inpatients) than in control subjects, except for CD19 cells, which remained unmodified. There seemed to be a recovery of lymphocyte subsets after hospitalization in AN3 and AN4 patients (outpatients), except for CD57, which remained below control values. However, there was a global decrease of the lymphocyte subsets in AN5 and AN6. Ratios of CD4 to CD8 cells were not altered but the ratio of CD2 to CD19 cells was lower in all phases except AN6. Moreover, cell-mediated immune function was impaired and none of the patients showed normal responses. Thus, despite the slight weight increase found in AN4, AN5, and AN6 and the apparent cell subset recovery after hospitalization, these results suggest a greatly depleted nutritional status that remained during the whole year in all patients.

Adolescent↗

Evaluation of nutritional status by immunologic assessment in bulimia nervosa: influence of body mass index and vomiting episodes.

The nutritional status of 21 patients suffering from bulimia nervosa was evaluated by anthropometric and immunologic indexes in comparison with a control group (n = 15). In addition, the influence of body mass index (BMI; in kg/m2) values and vomiting episodes on the nutritional status of bulimic patients was assessed. Anthropometry showed no signs of malnutrition in either group, except for those patients with low weights (BMI < 19). Bulimic patients had lower lymphocyte counts than did control subjects, except for those without vomiting (NVBN). All T lymphocyte subsets tested as well as CD57 cells were lower (22% and 55%, respectively) in bulimic patients than in control subjects, but the CD19 cell subset remained unmodified. The low-weight bulimic group (LWBN) had lower CD4 cell counts than did the normal-weight (BMI > 19) bulimic group. The NVBN group had lymphocyte subpopulations similar to those in the control group, except for CD57, which was lower. The bulimic patients with vomiting had the lowest cell subset values. These results suggest a depleted nutritional status in all bulimic patients studied, even those with normal weights. The LWBN group had the most depleted nutritional status and the NVBN group was least affected at a subclinical level. CD57 can be considered a good marker of nutritional status in this syndrome because it was the only subpopulation altered in all groups.

Anthropometry↗

Human immunodeficiency virus infection and nutritional status in female drug addicts undergoing detoxification: anthropometric and immunologic assessments.

To clarify the interrelations among drug abuse, malnutrition, and immunosuppression, the effects of human immunodeficiency virus (HIV) infection on the nutritional status of 17 noninfected and 19 HIV-infected asymptomatic female drug addicts undergoing detoxification were evaluated by measuring anthropometric and immunologic indexes. Anthropometric measurements were normal in both groups as a result of weight gain (approximately 10 kg) in every patient after the detoxification period. Leukocyte and lymphocyte values and CD2 lymphocyte subset counts were also similar in both groups. CD4 counts (P = 0.04) and the ratio of CD4 to CD8 cells (P = 0.6 x 10(-4)) were lower whereas CD8 counts (P = 0.003) were higher in the HIV-infected than in the noninfected group. Responses to a delayed-hypersensitivity skin test were below normal in both groups but significantly more so in the HIV-positive group (P = 0.05). CD19 counts were lower (P = 0.02) and values for serum immunoglobulins G and M were higher (51% and 37%, respectively) in the HIV-infected females than in the noninfected women. These results may suggest that despite anthropometric recovery, the HIV-infected women had depleted immune function, resulting not only from HIV infection but also from the subclinical malnutrition triggered by previous drug addiction.

Adult↗

Effects of human immunodeficiency virus infection and detoxification time on anthropometric measurements and dietary intake of male drug addicts.

Anthropometric measurements and dietary intakes of male drug addicts (n = 62), infected (n = 23) or not infected (n = 39) with human immunodeficiency virus (HIV), who underwent two phases of detoxification (P1:15 d to 1 mo and P2: 5-6 mo) were assessed. Body weight, weight gain during detoxification, height, body mass index, and ideal body weight were measured. A prospective food-record questionnaire was compiled and energy and nutrient contents of ingested food were determined. Food intakes were compared with dietary recommendations for the Spanish population. At the time of the study, all patients had substantial weight gains, mostly in P1. Nutrient consumption was lower in P2 (energy, protein, and lipids) and in groups not infected with HIV. In P2, lipid intake was higher in the HIV-positive than in the HIV-negative group (P < 0.05, Student's t test). Moreover, an interactive effect of HIV by phase was shown for lipid intake (P = 0.04, two-way analysis of variance). Magnesium, folate, and vitamin E intakes were lower than recommended in nearly all patients. Energy, zinc, riboflavin, and vitamin B-6 intakes were lower than recommended or were borderline. HIV infection did not have a negative effect on anthropometric measurements or on nutrient intakes. The anthropometric assessment may suggest an adequate recovery of the indexes measured in all patients, which principally took place during P1. Measurement of nutrient intakes showed certain imbalances and deficits that should be corrected.

Adult↗

High polymorphism of Mhc-E locus in non-human primates: alleles with identical exon 2 and 3 are found in two different species.

Thirteen Mhc-E new sequences were found in eight individuals belonging to the Cercopithecinae family, i.e.: Macaca mulatta, Macaca fascicularis and Cercopithecus aethiops when studying E locus polymorphism. No changes were found in the invariant residues which are required for the correct conformation of the peptide presenting region which are conserved in classical Mhc class I molecules from fish and reptiles to humans; however, polymorphism of Mhc-E alleles is not limited to the three typical hypervariable regions per domain as it is in classical class I alleles. The rate of synonymous and nonsynonymous substitutions in the DNA sequence corresponding to the antigen binding site, compared to the remainder of exons 2 and 3 shows that the peptide-binding site is under high evolutionary pressure for stability since only synonymous substitutions have been found to be accepted in apes. Also, a clear example of trans-species evolution of allelism is found: two identical exon 2 and exon 3 sequences there exist belonging to individuals from different species (Mamu-Mhc-E*0101 and Mafa-Mhc-E*04). In addition, two Macaca mulatta individuals show an Mhc-E locus duplication. Finally, phylogenetic tree analysis shows that Mhc class I molecules found in Saguinus oedipus (described as Mhc-G homologues) are closer to Mhc-E sequences.

Alleles↗

Primate DRB6 gene expression and evolution: a study in Macaca mulatta and Cercopithecus aethiops.

DRB6 has been found to be transcribed in human and apes. Promoter region and exon 1 come from a 5' LTR from a mammary tumour retrovirus. However, the putative protein structure would be very different to other DR molecules and it is doubtful that it may function as an antigen presenting molecule. Primate DRB6 alleles previously published together with the two new macaque sequences reported here support the existence of a strong selective pressure working on exon 2 to generate stop codons at the end of the exon (between codons 74 and 94) during at least 23 million years. The topology of dendrograms constructed with different primate DRB6 alleles supports the "trans-species" evolution proposed for MHC class I, class II and possibly C4 genes. Finally, DRB6, which is one of the oldest DRB genes, has been lost in the HLA-DRB3 (or DR52) group of haplotypes (DR3, DR5, DR6 and DR8) and a small DRB6 sequence is present at the exon 2 first hypervariable region of DRB4 (or DR53) gene, which is present in DR4, DR7 and DR9 haplotypes.

Animals↗

HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques.

The powerful genetic polymorphism of the HLA system has been used to identify individuals and populations. Ethnic groups may be characterized by specific HLA allele frequencies and particular extended HLA haplotypes; also, genetic relationships among these groups may be deduced. In the present study, serology and DNA typing were used to detect HLA-A, -B, -C, -DR, and -DQ alleles in each individual and to calculate characteristic haplotypes in Algerians. These results were compared to those previously obtained in other populations, particularly northern Mediterraneans; genetic distances and their respective dendrograms place Basques and Spaniards closer to Algerians than to other Europeans. Also, characteristic Basque and/or Spanish haplotypes are found in Algerians; i.e., A30-B18-Cw5-DR3-DQ2 and A1-B57-Cw7-DR7-DQ2. This supports the evidence that the Algerian population, mainly its paleo-North African component (Berbers), has a common descent with Basques and Spaniards, probably reflecting a preneolithic relationship between Iberians and paleo-North Africans.

Africa, Northern↗

C4 gene polymorphism in primates: evolution, generation, and Chido and Rodgers antigenicity.

Eleven new C4d genomic primate sequences of the fourth complement factor (C4) have been obtained. Seven of them belong to five species not yet explored for this gene: Pan paniscus (pygmy chimpanzee), Cercopithecus aethiops (green monkey), Macaca mulatta (rhesus monkey), Macaca fascicularis (cynomolgus), and Saguinus oedipus (cotton top tamarin). The New World monkeys (tamarins, four individuals) sequenced for C4 have a single C4d sequence only, which shows a B isotypic specificity and a Rodgers 3 (Rg3), Chido 1 (Ch1) antigenicity. Rg3 and Ch1 could thus be the oldest Rg/Ch specificity (at least 50 million years old) and Rg1, Rg2, Ch3, and Ch6 could be more recent human-specific antigens. Mechanisms of C4d polymorphism generation were analyzed by compiling all the presently available sequences. Examples of both point mutations and crossing-over events among C4d primate sequences could be detected. The problem of a possible trans-species inheritance of C4d polymorphism was addressed and two apparently contradicting dendrograms were obtained. One of them, constructed by using both exon and intron sequences, does not support trans-species evolution, but supports the proposed theory of extensive homogenization of the C4 genes occurring within each species, because alleles from each primate species cluster together. Another completely different dendrogram, obtained by using exon sequences only, suggests the existence of trans-species evolution for C4d polymorphism, because alleles belonging to different species cluster together in a way similar to that found for HLA class I or II alleles. However, orangutan sequences group together in both kinds of C4d sequence dendrograms and seem to have arisen from an ancestor different from that of chimpanzee, gorilla and man C4d sequences. Finally, further data have been obtained that support trans-species conservation of A-ness and B-ness and the existence of trans-specifically conserved allelic motifs, both in intronic and exonic sequences.

Amino Acid Sequence↗

New species-specific alleles at the primate MHC-G locus.

Six different ape MHC-G DNA sequences (four in humans: HLA-G*01011, HLA-G*II, HLA-G*0103, and HLA-G*IV; one in chimpanzees: Patr-G*I; and one in gorillas: Gogo-G*1) have been obtained. Only synonymous or conservative ("Thr"-to-"Ser") substitutions are allowed between the four human alleles. One allele of MHC-G exon-2 sequences has been found both in gorilla (Gorilla gorilla) and chimpanzee (Pan troglodytes). The Patr-G*I DNA sequence shows two nonsynonymous substitutions when compared with the human HLA-G*01011 sequence: "CGG"-to-"TGG" ("Arg"-to-"Trp") at codon 35 and "ATG"-to-"ATA" ("Met"-to-"Ile") at codon 76. One nonsynonymous "GAG"-to-"GGG" ("Glu"-to-"Gly") substitution is observed in the Gogo-G*I exon-2 DNA sequence, when compared with the human *01011 allele. None of these three different substitutions have been observed in humans and are, thus, considered species specific. Also, evidence is provided that the human HLA-G*II and G*0103 may have been originated after human speciation. Finally, phylogenetic relationships among the six MHC-G alleles, tamarins G-"like" alleles, and other human class I genes (both "classical" and "nonclassic") are discussed.

Alleles↗

Direct detection of Vibrio cholerae in stool samples.

A direct method to detect Vibrio cholerae in stool samples was developed by using a PCR procedure that did not require a DNA purification step. Dilution (1/100) of stool samples prevented inhibition of the reaction by contaminants, and two consecutive PCRs, the second one with a nested primer, achieved the desired sensitivity. Comparison of the results obtained from stool swab samples processed by the two-step PCR and by an enzyme-linked immunosorbent assay using GM1 as the capture molecule showed that the former is more sensitive and gave positive results even when V. cholerae was not culturable or dead.

Argentina↗

Identification of toxigenic Vibrio cholerae from the Argentine outbreak by PCR for ctx A1 and ctx A2-B.

A polymerase chain reaction (PCR) to detect a region of the A1 cholera toxin gene was applied to the identification of 43 Vibrio cholerae strains isolated from the recent outbreak in Argentina. A good correlation was observed between the GM1-enzyme-linked immunosorbent assay (GM1-ELISA) to detect the B subunit of the enterotoxin and PCR. However, a V. cholerae non-01 strain that was negative by the ELISA test, was positive by the PCR assay for the A1 region. A second PCR test to detect the A2-B coding region was developed to solve this case. We propose that routine detection of toxigenic V. cholerae by PCR should include analysis of A2-B coding region or the whole cholera toxin operon.

Argentina↗