A study of DR2-LUM haplotype generation and the DRB6*0202 linkage to DRB1*1601.
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Cell Line↗
Biomedical subjects
P Varela
Publications and source records attributed to P Varela.
Three new HLA-G alleles and their linkage disequilibria with HLA-A.
Three new allelic forms of the HLA-G DNA sequence (HLA-G*II, HLA-G*III, and HLA-G*IV) have been identified. With the HLA-G*I sequence (previously designated HLA 6.0) as a reference, HLA-G*II shows a silent (G-->A) mutation at the third base of codon 57, HLA-G*III bears a non-synonymous (A-->T), but conservative, (Thr-->Ser) substitution at the first base of codon 31, and HLA-G*IV shows two silent substitutions: (A-->T) at the third base of codon 107 and (G-->A) at the third base of codon 57. A rapid method of singling out each allele on genomic DNA has been developed by using polymerase chain reaction amplification followed by restriction endonuclease treatment. Also, more or less strong linkage disequilibria has been found between most HLA-A alleles and either HLA-G*I or *II, both being the most prevalent alleles in the population, with a genotypic frequency of 0.55 and 0.38, respectively; HLA-G*III is very rare and HLA-G*IV has a genotypic frequency of 0.07. An evolutive classification of HLA-A alleles results according to their association with either HLA-G*I or HLA-G*II, which does not correlate with the classical serological cross-reacting groups classification. The finding of a strong and selective A/G linkage disequilibria with most HLA-A alleles, together with the existence of less frequent random A/G associations, may suggest that there exist in different haplotypes true and varied A/G genetic distances (and not a recombinational hotspot). It may be inferred from preliminary data that in primates HLA-A/G haplotypes bearing G*II may have appeared later than those bearing G*I.
Alleles↗
New DNA sequences for the human complement gene C4.
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Base Sequence↗
Evolutionary relationships of HLA-DR8 alleles and description of a new subtype (DRB1*0806) in the Algerian population.
A new HLA-DR8 allele (HLA-DRB1*0806) found in the Algerian population is described here. This allele has an exon-2 nucleotide sequence identical to that of the HLA-DRB1*0801 allele, except for a GGT to GTG change in codon 86, yielding an amino acid substitution (glycine to valine). This change is also found in other HLA-DRB1 and HLA-DRB3 evolutionary-related allele pairs. HLA-DRB1*0806 is the most frequent HLA-DR8 allele found in this population (three of eight HLA-DR8-positive individuals) and is included within the HLA-DQA1*0102-DQB1*0602 haplotype (HLA-DQ6 serotype). This combination of HLA-DQ alleles is sporadically found associated with other HLA-DR8 alleles in other ethnic groups, i.e., HLA-DRB1*0804 in Bushmen and in North American blacks and HLA-DRB1*0803 in African blacks. Also, the HLA-DRB1*0806-DQ6 haplotype only bears one HLA-DRB gene copy, a common characteristic of the HLA-DR8 haplotype family. An exon-2 HLA-DR8 dendrogram has also been constructed with the available sequence data, indicating that this new allele does not seem to be placed at a distance significantly different from the origin to that of HLA-DRB1*0804 (proposed to be the eldest in the HLA-DR8 allele diversification pathway). A possible HLA-DR8 evolutive pathway is postulated according to the available exon-2 HLA-DR8 allele sequences.
Algeria↗
Evaluation of immunocompetence and nutritional status in patients with bulimia nervosa.
Nutritional status of patients suffering from bulimia nervosa was evaluated by anthropometric, hematological, and immunological parameters in comparison with a healthy control group. Anthropometry showed no signs of malnutrition in either group. Bulimic patients showed a significant decrease in most of the routine clinical indexes related to red blood cells. Lymphocyte subsets CD2 and CD4 in bulimic patients were lower than in controls, whereas CD8 remained unmodified, leading to a lower CD4:CD8 in bulimic patients. The decreases in CD2 and CD4 numbers might be linked to an impaired cell-mediated immune function, as evaluated by the response to skin tests. The B lymphocyte subset was increased in the bulimic group. Innate immunity was impaired in the bulimic patients. Although anthropometric and most of the routine clinical parameters were within the normal range, these results might suggest that the depleted immune function accounts for a subclinical malnutrition status in bulimic patients.
Adolescent↗
Nutritional status and immunocompetence in eating disorders. A comparative study.
Nutritional status and immunocompetence were evaluated in 26 patients suffering from anorexia nervosa (AN) (n = 16) or bulimia nervosa (BN) (n = 10) in comparison with a control group (n = 22). Body mass index (BMI) was lower in all patients than in controls, AN patients having the lowest values. Slight leukopenia together with relative lymphocytosis was shown in both AN and BN. The CD4/CD8 ratio was low in all patients, but more so for BN patients, although cell-mediated immune function was impaired to the same extent for both eating disorders. The complement system appeared to be damaged in all the patients in comparison with controls. These results may mean that the nutritional status of both syndromes was different. Although anthropometric measurements in the BN group may suggest a more acceptable nutritional status, immunological parameters were shown to be depleted at the same level as the AN group and even more impaired when judged by the lower CD4/CD8 values.
Adolescent↗
Identification and characterization of GroEL and DnaK homologues in Thiobacillus ferrooxidans.
The major heat shock proteins from Thiobacillus ferrooxidans were identified as DnaK and GroEL equivalents by Western blotting and analysis of the N-terminal amino acid sequence of spots isolated from dried 2-D polyacrylamide electrophoresis gels. The T. ferrooxidans chaperonins showed 70% and 80% identity with the Escherichia coli GroEL and DnaK, respectively. By using electrophoresis with a transverse pore gradient of cross-linked polyacrylamide and nondenaturing conditions followed by Western blotting, we found that the GroEL proteins from both bacteria formed a 14-mer, whereas E. coli DnaK protein existed partially as a dimer and the T. ferrooxidans DnaK-equivalent showed only a monomeric nature under our experimental conditions.
Amino Acid Sequence↗
Allelic diversity at the primate major histocompatibility complex DRB6 locus.
The HLA-DRB6 gene (also called DRB sigma/V1) has been found only in about 26% of human HLA haplotypes, i.e.; DR1, DRw10, and DR2-bearing ones (Corell et al. 1991). In contrast, exon-2 DRB6 sequences have been obtained from all tested primates: nine chimpanzees (Pan troglodytes), three gorillas (Gorilla gorilla) and three orangutans (Pongo pygmaeus); other apes which had already been sequenced (one gorilla and one chimpanzee) also had the DRB6 gene. Thus, all apes tested from three different species, some of them evolutionary separated by at least 14-16 million years, bear the DRB6 gene. In addition, more than one gene copy per haplotype has been found in one chimpanzee; this, together with the apparent loss of this gene in some of the human DR haplotypes, may indicate that the DR genome has undergone evolutionary changes more recently and more actively than class I or III genes. In addition, ten different and presumably allelic DRB6 exon-2 sequences have been obtained, and some of them coming from different species are more similar to each other than the one from the same species; this finding goes in favor of the trans-species theory of major histocompatibility complex polymorphism generation. Also, data are presented supporting that DRB6 may be one of the eldest genes of the DRB family, thus one of the first to diverge from the ancestral DRB gene.
Alleles↗
Allelic diversity at the primate major histocompatibility complex DRB6 locus.
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Base Sequence↗
Zinc status in anorexia nervosa.
Some aspects of zinc nutritive status in patients suffering from anorexia nervosa were evaluated. Basic anthropometric measurements, Zn levels in serum, urine and hair as well as serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH; Zn-dependent enzymes) and delayed dermal hypersensitivity were tested both in patients and in control subjects. The patients showed higher Zn levels in serum (123%), hair (85%) and urine (215%) than controls, whereas ALP and LDH values were 38 and 21%, respectively, lower than those from the control group. Half of the patients showed hypoergy, and less than 50% of them were able to show a normal immune response. These results suggest that Zn-dependent functions may be impaired in anorexia nervosa as a consequence of Zn unavailability.
Adolescent↗
The HLA-DRB6 locus defines an evolutionary supratypic group within the DRB family of genes.
A novel DRB gene member has recently been identified (DRB6). It defines a new supratypic group of HLA-DR alleles comprising the DR1-, DR2-, and DRw10-carrying haplotypes. The comparison of this gene either at the nucleotide or at the protein level with other HLA-DRB genes supports its inclusion in the DRB gene family and not in DPB or DQB gene families. Moreover, the construction of an evolutionary gene-tree shows that this gene is probably the eldest member of the DRB gene family. Contradictory expression results do not clarify whether or not DRB6 is a pseudogene.
Base Sequence↗
High frequency of the HLA-DRB1*0405-(Dw15)-DQw8 haplotype in Spaniards and its relationship to diabetes susceptibility.
A study of DR4 subtypes has been done in Spanish unrelated controls and insulin-dependent diabetics by using dot blot hybridization with specific DR4B1 exon-2 oligonucleotides and automated dideoxy DNA sequencing. Dw15-DQw8 is the predominant DR4 subtype present in our normal population (37%); this DR4 frequency characteristic singles out our population from all other Caucasoids tested so far and may also be a marker of the original Iberian paleo-North African population. Dw15-DQw8 is not significantly increased in our insulin-dependent diabetics sample and despite its relative high frequency in the control population it does not have a bearing in lowering insulin-dependent diabetes mellitus frequency of DR4-positive Spaniards. In addition, no particular DR4 split is by itself significantly increased in Spanish diabetics; this may indicate that selective diabetogenic environmental factors may be working upon DR4-positive individuals, but on genes (or gene products) other than DR or at least not upon the polymorphic sites of DRB1 exon-2 products.
Amino Acid Sequence↗
Serum lipids and apolipoprotein B values, blood pressure and pulse rate in anorexia nervosa.
Some risk factors associated with coronary heart disease (CHD) were evaluated in patients with different types of anorexia nervosa (AN). Anthropometric parameters, serum cholesterol, triglycerides and apoprotein (apo) B values, blood pressure and pulse rate were tested in 29 young female patients and 16 controls. Cholesterol, triglycerides and apo B were higher at the acute period of the illness (AN1), whereas at the chronic period the values of these parameters tended to normalize. Triglycerides were higher in patients who binge ate (bulimarexia). Systolic blood pressure decreased in all types of AN, while diastolic blood pressure decreased only in AN1; pulse rate was not altered. According to cholesterol and apo B values, AN patients may be at risk of CHD if they remain at low body weight.
Adolescent↗
Exon 2 DNA sequence of the HLA-DRw13b allele obtained from genomes of five different individuals.
Exon 2 nucleotide sequence of the DRB1 gene encoding the HLA-DRw13b allele defined by DNA-RFLP (Restriction Fragment Length Polymorphism) typing, has been obtained by using five heterozygous individuals genomic DNA and a non isotopic automated "dideoxi" methodology. Its comparison with other known homologous DRB1 sequences suggests that two different mechanisms which generate HLA allele variability may have occurred in this particular exon 2: a gene conversion between DRw11 or DRw13 as acceptors and DR4-Dw15 or DRw8.1 as donors and in addition, a non-conservative point mutation at base 221. The relationship between this HLA sequence characteristics and certain diseases susceptibility is discussed.
Alleles↗
[Nutritional utilization of a low protein diet in alloxan diabetic rats].
Dietary control is known to influence diabetic processes. Therefore, the purpose of this work was to determine possible effects brought about by two different dietary protein levels on the nutritional diet utilization in alloxan-diabetic rats. Rats were divided in two groups: 1) One fed on 12% and 2) one a 4% protein diet. Each group was then divided into two subgroups: A) non diabetic and B) diabetic. Weight parameters, food intake, food efficiency (FE), digestive efficiency (DE), metabolic utilization (MU), retained N/ingested N ratio as well as initial and final glycemia were evaluated at the beginning and at the end of the experiment. A decrease in body weight, FE, DE and MU was observed in the control rats of group 2A, in comparison with the group 1A. Experimental diabetes led to increased FE in 1B group in relation to those of group 1A. Also decreased body weight and FE as well as increased food intake and DE were found in the control animals of 2B group. Glycemia increased in diabetic rats as compared with non-diabetic rats, in both groups, 1 and 2. The data suggest that under the experimental conditions cited, both the nutritional utilization of the diet and the diabetogenic status might be modulated by the dietary protein ingested level.
Alloxan↗
Nutritional status assessment of HIV-positive drug addicts.
Since human immunodeficiency virus (HIV) is known to lead to modifications of immune function and interrelationships among malnutrition, anergy and drug addiction have been shown, the aim of this work was to assess the nutritional status of 36 male heroin addicts under a period of detoxication (3 months). They were divided into two groups: (1) HIV negative (n = 20) and (2) HIV positive (n = 16); heights, weights and serum albumin concentration were measured and immune function was tested, using delayed hypersensitivity skin tests containing 7 antigens. No significant differences in anthropometric measurements were found between both groups, but anthropometric improvement was shown in every patient after the detoxication period. Serum albumin, often used as a classical index of malnutrition, remained within the normal values in both groups. The whole response to skin tests was depressed in both groups and no significant differences were shown between them. Therefore, these results might suggest that in spite of the apparent anthropometric recovery and the normal values of albumin, a subclinical malnutrition was indicated by the depressed immune function, which was more noticeable in the HIV-positive group.
Adult↗
[Influence of dietary protein levels on the electrophoretic pattern and plasma IgG and IgM levels in pregnant rats and their offspring].
In view of the influence that nutritional and physiological status exert on the immunological capacity of the subject, a study was carried out for the purpose of studying the changes induced by three protein levels in the diet: (4%, 10% (control), and 20%) on total plasma proteins (TPP) and their fractions, as well as Ig G and Ig M levels in non-pregnant (NP) and pregnant (P) rats and their offspring. Effect of the diet on adult rats--In non-pregnant rats submitted to the high protein diet, Ig G levels increased while TPP decreased in P rats fed on 4% and 20% protein diets. The higher the protein level in the diet, the higher were the TPP values. Effect of pregnancy--Ig G and Ig M levels suffered an increase in rats fed the 4% and 10% protein diets, while a decrease was observed in rats submitted to the 20% protein level diet. The TPP rate diminished in rats fed on the low protein diets, and increased when the highest protein diet was administered. Effect of the diet on offspring--Ig M levels were only detected in neonates from rats fed with the low and high protein diets. Moreover, the TPP rate increased as a direct function of the dietary protein intake.
Animals↗
[Changes in the metabolism of muscle RNA in rats given a high protein diet].
The effect of a high protein diet (20% casein + D,L-methionine) administered to adult Wistar rats on some aspects of muscle RNA metabolism has been studied. Body weight increased in spite of lower intake. However, gastrocnemius muscle remained unmodified, although protein content increased. Total RNA decreased in the whole muscle although RNA/DNA ratio did not change. Protein synthesis capacity diminished 81% relative to controls in spite the fact that an excessive amount of available amino acids exists. RNA loss might depend on a high catabolism, since acid RNase activity increased over control values. Therefore, it may be concluded that a high protein diet leads to a lower protein synthesis capacity through an elevated RNA breakdown.
Animals↗