RESUMEN
Defining HLA mismatch acceptability of organ transplant donors for sensitized recipients has traditionally been based on serologically defined HLA antigens. Now, however, it is well accepted that HLA antibodies specifically recognize a wide range of epitopes present on HLA antigens and that molecularly defined high resolution alleles corresponding to the same low resolution antigen can possess different epitope repertoires. Hence, determination of HLA compatibility at the allele level represents a more accurate approach to identify suitable donors for sensitized patients. This approach would offer opportunities for increased transplant rates and improved long term graft survivals.
Asunto(s)
Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Tolerancia Inmunológica , Inmunología del Trasplante , Alelos , Autoanticuerpos/inmunología , Antígenos HLA/genética , Humanos , Donantes de TejidosRESUMEN
Two novel alleles, human leukocyte antigen (HLA)-B*3569, -B*4450 and a confirmatory sequence of HLA-A*2631 were identified during a routine typing for the Brazilian Bone Marrow Donor Registry. Sequence analysis of coding exons 2 and 3 revealed a single nucleotide substitution in HLA-B*3569 and two single nucleotide substitutions in HLA-B*4450, compared with closely related alleles. At the protein level, these substitutions result in a change of a single amino acid residue in each of HLA-B*3569 and -B*4450 at positions 74 (Arg > Pro) and 80 (Thr > Ile), respectively. These variations are located in the highly polymorphic region at the end of the alpha(1) domain of the HLA molecule. It appears that HLA-B*3569 arose from the analogous HLA-B*3510 through a point mutation. However, HLA-B*4450 may have arisen from HLA-B*440301 and -B*4425 by gene conversion.
Asunto(s)
Sustitución de Aminoácidos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Mutación Puntual , Brasil , Femenino , Humanos , MasculinoRESUMEN
In natural killer cells, killer immunoglobulin-like receptors (KIRs) loci code for either inhibitory or activating receptors, and according to the number of genes present in each individual, it is possible to identify a high rate of polymorphism in the populations. We performed KIR typing by polymerase chain reaction-sequence-specific oligonucleotide probing in 402 Argentinean Caucasoid and in two Amerindian populations (101 Wichis and 54 Chiriguanos) from the North of Argentina. KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were always present, whereas the frequencies of KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 ranged between 84% and 96%. The frequencies of KIR2DS2, KIR2DL2, KIR2DL5, KIR2DS5, KIR2DS1 and KIR3DS1 ranged between 41% and 62%. The KIR2DS3 with a frequency of 29% in Argentinean Caucasoid population was present at a very low frequency in Amerindian populations. Haplotype segregation studies performed in 10 Wichi families showed the presence of only three haplotypes: A, B5 and B1. The Amerindian populations showed several similarities to Asian but not to Caucasoid populations with regard to the frequency of KIR2DS3, full-length KIR2DS4 gene and KIR2DL4 alleles.
Asunto(s)
Polimorfismo Genético , Receptores Inmunológicos/genética , Alelos , Argentina , Etnicidad/genética , Frecuencia de los Genes , Variación Genética , Antígenos HLA-C/genética , Haplotipos , Homocigoto , Humanos , Indígenas Sudamericanos/genética , Células Asesinas Naturales/inmunología , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL2 , Receptores KIR2DL3 , Receptores KIR2DL4 , Receptores KIR3DL1 , Receptores KIR3DL2 , Receptores KIR3DS1 , Población Blanca/genéticaRESUMEN
Two human leukocyte antigen (HLA)-DRB1 (HLA-DRB1*1376 and -DRB1*1465) and one HLA-A (HLA-A*2471) novel alleles have been identified in individuals from the Brazilian Bone Marrow Donor Registry. DNA sequencing of exon 2 for HLA-DRB1 alleles showed two and five nucleotide substitutions in -DRB1*1376 and -DRB1*1465, compared with closely related alleles, respectively. These substitutions result in a change of amino acid residues in HLA-DRB1*1376 at position 74 (Arg --> Glu) and in -DRB*1465 at positions 47 (Tyr --> Phe), 57 (Asp --> Ser) and 74 (Glu --> Ala). On the other hand, sequence analysis of exons 2 and 3 for HLA-A*2471 showed a single substitution, leading to a single amino acid change at position 151 (His --> Arg). These three novel alleles may have originated from other HLA alleles by gene conversion. However, it is also possible that HLA-A*2471 has evolved from one of the alleles of the HLA-A*2402 group through a point mutation.
Asunto(s)
Antígenos HLA-A/genética , Antígenos HLA-DR/genética , Adulto , Anciano , Alelos , Sustitución de Aminoácidos , Secuencia de Bases , Brasil , Exones , Femenino , Conversión Génica , Cadenas HLA-DRB1 , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Mutación Puntual , Polimorfismo de Nucleótido Simple , Sistema de Registros , Homología de Secuencia de Aminoácido , Donantes de TejidosRESUMEN
This study was designed to investigate the role of killer immunoglobulin-like receptor (KIR) genes in the outcome of hepatitis C virus (HCV) infection. In patients who cleared the virus (HCV RNA-) we found a decrease of 2DL2 (P= 0.04), and 2DS2 (P= 0.014) accompanied by an increase of 2DS5 (P= 0.04). Those RNA+ patients with elevated levels of hepatic transaminases (HCV RNA+ elevated alanine aminotransferase) showed an increased frequency of 2DS3 (P= 0.018). Additionally, in cirrhotic patients we found an increased frequency of individuals having two copies of 3DS1 and HLA-Bw4 (P= 0.016). We conclude that higher natural killer cytotoxicity might be associated with a worse progression of the HCV infection.
Asunto(s)
Hepatitis C/complicaciones , Cirrosis Hepática/etiología , Receptores Inmunológicos/genética , Adulto , Anciano , Alanina Transaminasa/análisis , Femenino , Frecuencia de los Genes , Genotipo , Antígenos HLA-B/genética , Hepacivirus/genética , Hepatitis C/genética , Hepatitis C/patología , Humanos , Células Asesinas Naturales/inmunología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , ARN Viral , Receptores KIR , Receptores KIR3DS1RESUMEN
The present study demonstrated that patients who have recurrent spontaneous abortions (RSA) presented a decreased number of killer immunoglobulin-like inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found increased in comparison with controls. Individuals AA will also be homozygous for 2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and therefore a weaker inhibition. The present study might support that in RSA patients, the balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss.
Asunto(s)
Aborto Espontáneo/genética , Fertilidad/genética , Antígenos HLA-C/genética , Receptores Inmunológicos/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Antígenos HLA-C/metabolismo , Humanos , Embarazo , Receptores Inmunológicos/sangre , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL2 , Receptores KIR2DL3RESUMEN
A total of 97 patients with tuberculosis (TB) and 51 controls from Xalapa, Veracruz, Mexico, were studied for the presence and absence of killer cell immunoglobulin-like receptor (KIR) genes. The number of patients with either KIR2DL1 or KIR2DL3 differed significantly compared with the controls. However, only the difference in KIR2DL3 remained significant after correction for the number of factors analysed. We also found KIR2DS2 with its presumed C1 group ligand less prevalent in TB patients than in the control group, but this result lost significance after correction.
Asunto(s)
Receptores Inmunológicos/genética , Tuberculosis/genética , Adulto , Femenino , Humanos , Masculino , México/epidemiología , Receptores Inmunológicos/clasificación , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL3 , Tuberculosis/epidemiologíaRESUMEN
The HLA class I genes display significant levels of polymorphism, which is principally due to hypervariable regions located in the second and third exons. To date, 286 HLA-B alleles have been identified and characterised. We describe a new HLA-B*07 allele present in a Cuban Caucasoid individual, which has been officially named HLA-B*0720.
Asunto(s)
Alelos , Antígenos HLA-B/genética , Secuencia de Bases , Cuba/etnología , Antígenos HLA-B/aislamiento & purificación , Antígeno HLA-B7 , Humanos , Masculino , Datos de Secuencia Molecular , Población Blanca/genéticaRESUMEN
The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation.
Asunto(s)
Genética de Población , Antígenos HLA-A/clasificación , Antígenos HLA-A/genética , Prueba de Histocompatibilidad/métodos , Reacción en Cadena de la Polimerasa/métodos , África , Alelos , Brasil , China , Genotipo , Humanos , Indígenas Norteamericanos , México , OmánRESUMEN
The molecular analysis of HLA class I loci has demonstrated that, although, the genetic profile is restricted in Amerindians, several micropolymorphisms may be important in conferring a biological advantage. We analyzed the HLA-A and B genetic profile of Seris, a Mexican Indian tribe living in northwestern Mexico in the state of Sonora. There are presently only 619 individuals. Our study included 100 Seris belonging to nine families. HLA-A and -B loci typing was performed by polymerase chain reaction using an amplification refractory mutation system (PCR-ARMS) on a select group of samples; all of them were typed by polymerase chain reaction using sequence-specific oliogonuoleotide probes (PCR-SSOP) at a low-intermediate resolution level. The correlation between the techniques was 100%. Only five HLA-A alleles and seven HLA-B alleles were found. A*0201, A*68, A*31, A*24, B*3501, B*40, B*51, B*3512 and B*15 were present in over 5% of the individuals. B*27052 was detected in 2%. B27 is absent in any other Mexican Indian groups previously studied. The presence of B27 may be the result of a founder effect due to different waves of southward migrations. The B-locus is more diverse and the prevalent haplotypes were: A*0201-B*3501, A*0201-B*40, A*0201-B*3512, A*31-B*51, A*68-B*3501 and A*68-B*40. This genetic profile is different from the pattern of other Mexicans. The phylogenetic tree suggests that Seris are more closely related to the Warao Indians from Venezuela, who live in a similar ecosystem, and to some groups of Argentina, than they are to the Mexican Lacandones who live in the jungle. These data emphasize the relevance of the interaction between genes and environment.
Asunto(s)
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Indígenas Norteamericanos , Genética de Población , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Humanos , México/etnología , LinajeRESUMEN
In a previous study, DNA typing revealed that 25% of serological HLA-DR typings of kidney transplants were incorrect. In the current study, we analyzed whether this error rate had improved in recent years, and whether there were differences according to geographical region. From 1988 to 1991 the error rate of serological typing improved slightly in Western Europe from 19% to 16%, and in North America, from 21% to 16%. In Eastern Europe, the error rate decreased from 49% to 33% in 1991, whereas the rate remained high in South America at 60% in 1988 and 72% in 1991. The high error rates in South America and Eastern Europe reflected a lack of good quality serological typing reagents. The 16% typing errors in Western Europe and North America demonstrated the current limit of serological techniques for cadaver donor typing and underlined the need for prospective DNA typing.
Asunto(s)
Antígenos HLA-DR/sangre , Antígenos HLA-DR/genética , Prueba de Histocompatibilidad/métodos , Inmunología del Trasplante , ADN/sangre , Europa (Continente) , Europa Oriental , Humanos , Linfocitos/inmunología , América del Norte , América del SurRESUMEN
Delirium tremens might last for weeks and treatment requires massive benzodiazepine doses, yet it is possible to manage patients with this condition successfully. In this case of delirium tremens, standard agents at the usual recommended doses were not sufficient to achieve control of confusion and agitation or to stabilize neurologic and cardiovascular parameters. The patient required extraordinarily high doses of central nervous system depressants for an extended period. Midazolam, a short-acting benzodiazepine, was used but was associated with metabolic acidosis and was extremely expensive. Although high-dose midazolam should probably be avoided, extremely high dose benzodiazepine use for an extended period might be necessary in some cases. In this circumstance we advise diazepam because of its low cost and relative safety. The tendencies to withhold large doses for fear of side effects or to give up in cases requiring prolonged intensive support must be resisted to minimize the mortality from this severe illness.
Asunto(s)
Delirio por Abstinencia Alcohólica/tratamiento farmacológico , Benzodiazepinas/administración & dosificación , Anciano , Delirio por Abstinencia Alcohólica/economía , Costos de los Medicamentos , Humanos , Infusiones Intravenosas , Tiempo de Internación , MasculinoRESUMEN
O tratamento de potros recém-nascidos com flunixin meglumine na dose recomendada (1,1 mg/kg) näo provocou alteraçöes clínicas, paraclínicas ou histológicas comparativamente aos potros tratados com um placebo. Apenas a dose de 6,6 mg/kg é capaz de favorecer lesöes gastrintestinais
Asunto(s)
Animales , Animales Recién Nacidos , Clonixina/análogos & derivados , CaballosRESUMEN
A multicenter, double-blind, randomized, placebo-controlled trial was conducted to determine whether the addition of penicillin was superior to patient education and anti-inflammatory drug therapy for relief of the acute discomforts of pharyngitis caused by group A beta-hemolytic streptococcus (GABHS). One hundred seventy-eight patients, aged 4 to 29 years, received appropriate symptomatic therapy, including specific doses of aspirin or acetaminophen, plus penicillin (91 patients) or placebo (87) for the initial 48 hours of illness. All had 24-hour office and 48-hour telephone reevaluations. In 123 patients (57 with clinically severe pharyngitis), throat cultures yielded GABHS. Penicillin provided a margin of 20% improvement over anti-inflammatory therapy for the complaint of sore throat only after 48 hours of treatment (for the 123 patients with GABHS, p = 0.01; for the 57 with both severe pharyngitis and GABHS, p = 0.05). No significant improvement was noted for fever, malaise, odynophagia, exudate, adenitis, or pharyngitis. The failure of penicillin to provide much additional benefit makes its routine early prescription specifically for symptomatic relief questionable.
Asunto(s)
Acetaminofén/administración & dosificación , Aspirina/administración & dosificación , Penicilina G Benzatina/análogos & derivados , Penicilina G/análogos & derivados , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Adolescente , Adulto , Niño , Preescolar , Ensayos Clínicos como Asunto , Humanos , Penicilina G Benzatina/administración & dosificación , Distribución Aleatoria , Streptococcus pyogenes/efectos de los fármacosRESUMEN
"The present study takes a regional view of urbanization and migration in coastal Ecuador, and presents field data collected [in 1970 and 1971] in the port city of Manta. This study seeks to account for various national and international influences that work to shape conditions in Manta, and on the coast generally, and to specify and account for patterns of socieconomic inequality, particularly as they relate to migration and urbanization."