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Biomedical subjects

L Allende

Publications and source records attributed to L Allende.

At least 19 recordsLinked to original sources
PubMed2003

Toward gene therapy for human CD3 deficiencies.

The CD3 subunits of the T cell receptor-CD3 complex (TCR-CD3) help to regulate surface TCR-CD3 expression, and participate in signal transduction leading to intrathymic selection and peripheral antigen recognition by T lymphocytes. Humans who lack individual CD3 chains show impairments in the expression and activation-induced downregulation of TCR-CD3, and the defective immune responses that result may be lethal. We have investigated delivery of a normal CD3 chain to treat disorders of this type. Retroviral transduction of CD3gamma into CD3gamma-deficient peripheral blood T lymphocytes from two unrelated patients selectively corrected the observed TCR-CD3 expression and downregulation defects, but unexpectedly seemed to cause adverse effects that can be explained by an autoreactive recognition mechanism. These data support the feasibility of gene therapy for human CD3 deficiencies, but also suggest that gene transfer into postthymic lymphocytes carrying mutations on T cell recognition or activation pathways may disrupt their intrathymic calibration and become harmful to the host.

CD3 Complex↗
PubMed2001

The origin of Palestinians and their genetic relatedness with other Mediterranean populations.

The genetic profile of Palestinians has, for the first time, been studied by using human leukocyte antigen (HLA) gene variability and haplotypes. The comparison with other Mediterranean populations by using neighbor-joining dendrograms and correspondence analyses reveal that Palestinians are genetically very close to Jews and other Middle East populations, including Turks (Anatolians), Lebanese, Egyptians, Armenians, and Iranians. Archaeologic and genetic data support that both Jews and Palestinians came from the ancient Canaanites, who extensively mixed with Egyptians, Mesopotamian, and Anatolian peoples in ancient times. Thus, Palestinian-Jewish rivalry is based in cultural and religious, but not in genetic, differences. The relatively close relatedness of both Jews and Palestinians to western Mediterranean populations reflects the continuous circum-Mediterranean cultural and gene flow that have occurred in prehistoric and historic times. This flow overtly contradicts the demic diffusion model of western Mediterranean populations substitution by agriculturalists coming from the Middle East in the Mesolithic-Neolithic transition.

Alleles↗
PubMed2001

HLA molecular markers in Tuvinians: a population with both Oriental and Caucasoid characteristics.

HLA class I and class II alleles have been studied for the first time in the Turkish-speaking Tuvinian population, which lives in Russia, North of Mongolia and close to the Altai mountains. Comparisons have been done with about 11000 chromosomes from other worldwide populations, and extended haplotypes, genetic distances, neighbor joining dendrograms and correspondence analyses have been calculated. Tuvinians show an admixture of Mongoloid and Caucasoid characters, the latter probably coming from the ancient Kyrgyz background or, less feasibly, more recent Russian Caucasoid admixture. However, Siberian population traits are not found and thus Tuvinians are closer to Central Asian populations. Siberians are more related to Na-Dene and Eskimo American Indians; Amerindians (from nowadays Iberian--America) are not related to any other group, including Pacific Islanders, Siberians or other American Indians. The 'more than one wave' model for the peopling of the Americas is supported.

Alleles↗
PubMed2001

HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans.

Turkish and Kurdish HLA profiles are studied for the first time. The comparative study of their allele frequencies, characteristic haplotypes, genetic distances with other Mediterraneans is complemented by neighbor-joining dendrograms and correspondence analyses. Turks, Kurds, Armenians, Iranians, Jews, Lebanese and other (Eastern and Western) Mediterranean groups seem to share a common ancestry: the older "Mediterranean" substratum. No sign of the postulated Indo-European (Aryan) invasion (1200 B.C.) is detected by our genetic analysis. It is concluded that this invasion, if occurred, had a relatively few invaders in comparison to the already settled populations, i.e. Anatolian Hittite and Hurrian groups (older than 2000 B.C.). These may have given rise to present-day Kurdish, Armenian and Turkish populations.

Alleles↗
PubMed2000

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms.

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.

3' Untranslated Regions↗
PubMed2000

Lack of MHC-G4 and soluble (G5, G6) isoforms in the higher primates, Pongidae.

HLA-G is a class Ib (nonclassical) major histocompatibility complex (MHC) protein expressed at the materno-fetal interface that may inhibit natural killer (NK) cell-mediated lysis in an allotype-independent manner. The human MHC-G transcript is differentially spliced, giving rise to at least six different forms. In order to study the evolutionary importance of this phenomenon, the presence of alternative splicing in MHC-G mRNA molecules from Pongidae (Chimpanzee, Gorilla, and Orangutan) has been investigated in the present work, and three alternative spliced isoforms (i.e.: G1, G2, and G3) have been found, but not the G4 and the soluble G5 and G6 ones. In addition, a novel MHC-G isoform is described in Gorilla, "G2 short." This molecule is similar to the G2 isoform, but it lacks 29 amino acids normally encoded by exon 4. Our findings suggest that soluble isoforms are not necessary for MHC-G function(s) in Pongidae or that MHC-G is not a functional protein, because G1 is not necessary for survival in humans and Cercopithecinae bear stop codons in MHC-G exon 3.

Animals↗
PubMed2000

HLA genes in Arabic-speaking Moroccans: close relatedness to Berbers and Iberians.

The gene profile of Arabic-speaking Moroccans has been compared with those of other Mediterranean populations in order to provide additional information about the history of their origins. Our HLA data suggest that most Moroccans are of a Berber (Imazighen) origin and that Arabs who invaded North Africa and Spain in the 7th century A.D. did not substantially contributed to the gene pool; however, they imposed their advanced culture and their religion. Present-day Egyptians are also related to Moroccan Berbers and this supports an ancient Saharan origin for part of the present-day Mediterraneans, particularly for the Arabic-speaking ones (also Algerians) and also for the older substratum of Mediterranean people.

Alleles↗
PubMed2000

Homozygous HLA-G*0105N healthy individuals indicate that membrane-anchored HLA-G1 molecule is not necessary for survival.

HLA-G is expected to play an important role during fetal development. Recently, a healthy individual homozygous for the HLA-G*0105N allele has been described, suggesting that HLA-G expression was not essential for fetal survival. We now report studies of one family with five healthy siblings homozygous for HLA-G*0105N, who had been normally delivered; three of these siblings were females who also had normal deliveries. In addition, HLA-G*0105N cDNA has been fully sequenced, and normal G1 membrane anchored protein cannot be translated since after the codon 130 cytosine deletion (exon 3) a reading frameshift is observed leading to the existence of premature stop codon at position 189 (beginning of exon 4). Other protein isoforms (G2, G3 and G6), all containing the leader peptide and the alpha1 domain, are possible and their messenger mRNAs were found; any of these may undertake the necessary HLA-G functions. Our data show that the membrane anchored HLA-G molecule is not necessary in either mother or fetus for a normal pregnancy and survival. Also, individuals homozygous for HLA-G*0105N are healthy and with no indications of immunodeficiency or autoimmunity.

Alleles↗
PubMed2000

[Severe abdominal complications in patients treated with heart transplantation: the problem of clinical inexpressiveness].

INTRODUCTION: In transplanted patients, immunosuppressive drugs can mask habitual pathologies that impede their diagnoses and management. Abdominal pathology gives up to 2-20%, 50% of which is surgical, with a mortality of 10-40%. The most frequently detected pathologies are: acute pancreatitis, peptic ulceration and intestinal obstruction. OBJECTIVES: To determine the alarm parameters, more adequate diagnostic procedures and the most frequent causes of morbidity and mortality in order to attempt to avoid them. METHODS: In our center 225 heart transplantations were performed from May 1984 to October 1997. The severe abdominal complications, time of appearance, implication of immunosuppressive drugs and presence of rejection were studied in these patients. RESULTS: 35 severe abdominal complications were detected (incidence 12.9%), with the majority differing (> 1 year following transplant). The most frequently detected pathologies were digestive hemorrhages and perforations. Acute pancreatitis was 11%. The immunosuppressive drugs used were prednisona, cyclosporin and azathioprine. In 12 out of 29 patients the abdominal complication was in the context of acute rejection. CONCLUSIONS: Even with some non-specific abdominal symptoms in these group of patients it is important to rule out severe pathologies such as acute pancreatitis or empty viscera perforation. The detection of amylases and lypases in the blood and an echographic or tomographic abdominal study should be performed early with a digestive hemorrhage it is important to perform an endoscopy. If the surgical intervention seems imminent it's better to perform it without any delay, because it has been demonstrated that the delay is worse than the probable rejection.

Adolescent↗
PubMed1999

HLA in the Azores Archipelago: possible presence of Mongoloid genes.

The HLA profile of the Azoreans has been compared with those of other world populations in order to provide additional information regarding the history of their origins. The allele frequencies, genetic distances between populations, correspondence analyses and most frequent haplotypes were calculated. Our results indicate that the Azorean population most likely contains an admixture of high-frequency Caucasoid, Mongoloid and, to a lesser degree, Negroid HLA genes. The middle Atlantic Azores Archipelago was officially colonized by the Portuguese after 1439 and historical records are concordant with the existence of Caucasoid and Negroid population. However, Mongoloid genes were not suspected, but the Oriental HLA haplotypes A24-B44-DR6-DQ1, A29-B21-DR7-DQ2 and A2-B50-DR7-DQ2 are the fourth, fifth and sixth most frequent ones in Azores. A correspondence analysis shows that the Azorean population is equidistant from Asian and European populations and genetic distances are in some cases closer to the Asian than to European ethnic groups, and never are significantly different; also, B*2707 subtype is found in Asians and Azoreans (but not in Europeans) and the same Machado-Joseph Disease founder haplotypes (Chr 14) are found in both Japanese and Azoreans. It is proposed that a Mongoloid population exists in Azores; whether, the arrival occurred prior to discovery is undetermined.

Alleles↗
PubMed1999

Morbidity associated with long-term use of totally implantable ports in patients with AIDS.

To determine the morbidity associated with long-term use of a totally implantable central venous access device (Port-A-Cath [PAC]) in patients with AIDS, we studied 68 consecutive patients with AIDS requiring 79 such devices for long-term use, inserted over a period of 5 years. The total number of PAC-days was 20,159. At least one PAC-related complication occurred with 40 of 79 PACs (50.6% [95% confidence interval (CI): 39.6%-61.6%]), and 16 devices (20.2% [95% CI, 11.4%-29.0%]) had to be removed because of complications. Device-related infection occurred with 33 of 79 PACs (41.7% [95 CI, 30.8%-52.6%]). The predominant infection occurring with PACs was chamber infection, with an incidence of 0.16 per 100 PAC-days. The predominant organisms isolated from patients with chamber infections but also from those with device-related bacteremia were gram-positive cocci (79.4%). The presence of neutropenia (odds ratio [OR] = 9.72; 95% CI, 3.0-31.3; P < .001) and a CD4 cell count lower than 0.025 x 10(9)/L (OR = 6.14; 95% CI, 1.9-19.2; P = .002) were independent predictors of infection. The antibiotic lock technique was associated with decreased device loss when compared with isolated systemic antibiotic therapy (OR = 0.05; 95% CI, 0.0-0.59; P = .008). This technique may be useful to treat PAC infection in patients with AIDS, for whom the risk of PAC-related complications is very high.

AIDS-Related Opportunistic Infections↗
PubMed1998

Pluripotent protective effects of carnosine, a naturally occurring dipeptide.

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts. Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules. Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1998

Description of two Mhc-C-related sequences in the New World monkey Saguinus oedipus.

Two new Mhc class I partial exon 1, intron 1, exon 2, intron 2 and partial exon 3 DNA sequences from the New World monkey Saguinus oedipus (Saoe) are described. These two sequences show certain Mhc-C sequence-specific changes. The only difference between these two new sequences is a productive substitution at position 152 [GCG (Ala)-->GAG (Glu)]. This change occurs in a position which in Mhc classical class I molecules affects the interaction between the peptide and the T-cell receptor. A dendrogram with Mhc sequences from different loci and different species was constructed, which clearly shows that these two new sequences cluster closer to Mhc-C sequences than to others. These data suggest that the new sequences may be related to the Mhc-C locus, and they have been named Mhc-Saoe-CR*01 and -CR*02. However, they share only a few of the conserved residues (from gorilla to human) of Mhc-C sequences, which suggests that the relationships with an ancestor of the Mhc-C lineage are very distant or that these two sequences are products of convergent evolution to perform a C locus related function. Furthermore, in the fragment of DNA sequenced, there is a loss of two invariant residues conserved in antigen-presenting molecules from reptiles to humans; thus, it is unlikely that these two Mhc-C-like sequences have an antigen-presenting function, or even that they are two alleles of a pseudogene; however, the G + C percentage (86.1%) at the third base of codons approaches that of an expressed gene in Saoe. It is concluded that Mhc molecules with C-locus characteristics existed in primates 50 million years ago and that this does not support a more recent origin of Mhc-C genes.

Alleles↗
PubMed1997

[Gastric metastasis of breast carcinoma].

Although distal dissemination from breast cancer is commonly found in bones, lungs, liver and brain, others less common sites have been occasionally reported. A 60 year-old woman with long standing disseminated breast cancer disease was admitted to our hospital with upper gastrointestinal bleeding. At endoscopy, an abnormal area was seen in the lesser curvature of the stomach. Invasion of the gastric wall by metastases from carcinoma of the breast was diagnosed in the biopsy. No further treatment was warranted and the patient died soon thereafter. Gastric metastases are primarily located in the submucosa and muscular layers of the stomach. Lack of mucosal involvement suggests a blood-borne spread. Although our patient had no progesterone receptors in the primary breast tumor, previous studies have suggested that the presence of receptors may facilitate gastrointestinal spread. Gastric metastases from extraintestinal cancers may be asymptomatic, and are usually late events in the progression of the disease.

Adenocarcinoma↗
PubMed1996

Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome.

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.

Fatty Acids, Monounsaturated↗
PubMed1994

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↗
PubMed1994

Peripheral blood reduction of memory (CD29+, CD45RO+, and "bright" CD2+ and LFA-1+) T lymphocytes in Papillon-Lefèvre syndrome.

A Papillon-Lefèvre patient with characteristic chronic periodontal disease and palmoplantar keratoderma was studied over a 4-year period. An abnormal T-cell phenotype was steadily observed in peripheral blood; both low numbers of CD29+ and CD45RO+ cells and a low density surface expression of CD2 and LFA-1 molecules were found. T-cell activation through CD3, CD2 and ConA, PWM and IL-2 receptors was normal; however, there was impairment in the activation via CD28. CD2, LFA-1 and CD45 molecules were normal in charge and molecular weight. There was no tissue sequestering of T lymphocytes in periodontal lesions, but rather a relative T-cell reduction. It is suggested that an important decrease of the so-called "memory/hyperreactive" (CD45RO-positive) T cells does exist; therefore, hyperreactive T cells would not be available in sufficient numbers to leave the bloodstream through blood vessel endothelium, and the periodontium would be left without these important defenses and thus exposed to chronic infections. A disregulated factor affecting the transition from "naive" to "memory" T cells and the increase in certain surface molecules expression (i.e., CD2, LFA-1, CD29, and CD45RO) or the reversion from memory to naive T cells may be responsible for the disease pathogenesis. CD2 and LFA-1 molecule synthesis might be conjointly regulated on T lymphocytes.

Adolescent↗