RESUMO
BACKGROUND: Despite similarities, neuromyelitis optica (NMO) can be distinguished from multiple sclerosis (MS) by clinical, radiological and serological findings. OBJECTIVE: This case-control study aimed to determine whether patients with NMO or with MS in an Afro-Caribbean population originating from French West Indies shared the same or different HLA class I and II pattern distribution. METHODS: The association with HLA class II (DRB1 and DQB1) alleles was tested in 42 NMO patients, 163 MS patients and 150 healthy controls. HLA-DRB1 and DQB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: By comparison with healthy controls, significantly increased frequency of HLA-DRB1 03 (26.2% vs. 13%, odds ratio 2.4, 95% confidence interval 1.31-4.28, p after correction, cp 0.045) was observed in patients with NMO. By contrast, in MS patients, HLA-DRB1 15 (24.8% vs. 13%, odds ratio 2.21, 95% CI 1.45-3.36, cp < 0.0015), but not DRB1 03 allele, was positively associated with the disease. Moreover, a modest protective effect of HLA-DRB1 11 in the MS group, independently of DRB1 15 association, was found (13.7% vs. 7% in controls, odds ratio 0.48, p 0.006), but did not survive Bonferroni correction. CONCLUSION: In conclusion, comparison of the HLA-DRB1 and DQB1 distribution in NMO and MS in this Afro-Caribbean population shows important differences in the HLA associations among NMO and MS.
Assuntos
População Negra/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Esclerose Múltipla/genética , Neuromielite Óptica/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Guadalupe/epidemiologia , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Esclerose Múltipla/etnologia , Esclerose Múltipla/imunologia , Neuromielite Óptica/etnologia , Neuromielite Óptica/imunologia , Razão de Chances , Fenótipo , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
We report the identification of a novel B*40 allele, officially named B*400204, found in a Martinican prospective bone marrow donor by means of sequence-based typing techniques. This novel allele differs from the B*400201 allele by a synonymous nucleotide exchange at codon 31 in exon 2 (ACG --> ACC).
Assuntos
Antígenos HLA-B/genética , Mutação/genética , Análise de Sequência de DNA , Sequência de Bases , Antígenos HLA-B/sangue , Antígeno HLA-B40 , Humanos , Martinica , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Homologia de Sequência do Ácido NucleicoRESUMO
Here, we report the identification of two novel human leukocyte antigen-DQB1 alleles, DQB1*030103 and DQB1*0505, found by routine typing using commercial kits.
Assuntos
Substituição de Aminoácidos/genética , Antígenos HLA-DQ/genética , Alelos , Sequência de Bases , Éxons/genética , Cadeias beta de HLA-DQ , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
Conducting multicentre operational research is challenging due to issues related to the logistics of travel, training, supervision, monitoring and troubleshooting support. This is even more burdensome in resource-constrained settings and if the research includes patient interviews. In this article, we describe an innovative model that uses open access tools such as Dropbox, TeamViewer and CamScanner for efficient, quality-assured data collection in an ongoing multicentre operational research study involving record review and patient interviews. The tools used for data collection have been shared for adaptation and use by other researchers.
Conduire des recherches opérationnelles multicentriques est un défi, particulièrement dans les contextes de ressources limitées, en tenant compte des questions de logistique de déplacement, de formation, de supervision, de suivi et de soutien à la résolution des problèmes; encore plus si cette recherche implique des entretiens avec des patients. Dans cet article, nous décrivons un modèle innovant qui utilise des outils à accès ouvert comme Dropbox, TeamViewer et CamScanner pour un recueil de données efficace et de qualité assurée dans le cadre d'une recherche opérationnelle continue multicentrique impliquant des revues de dossiers et des entretiens avec des patients. Les outils utilisés pour le recueil de données ont été partagés pour l'adaptation et l'utilisation par d'autres chercheurs.
La realización de investigaciones operativas multicéntricas puede ser problemática, sobre todo en los entornos con restricción de los recursos, habida cuenta de las dificultades en la organización de los desplazamientos, la capacitación, la supervisión, el seguimiento y el apoyo a la resolución de problemas; más aun, cuando la investigación precisa entrevistas a los pacientes. En el presente artículo se describe un modelo innovador que utiliza herramientas de libre acceso como las plataformas Dropbox, TeamViewer y CamScanner, con el fin de lograr una obtención de datos eficiente y de calidad garantizada, en una investigación operativa multicéntrica en curso que comporta el examen de las historias clínicas y entrevistas a los pacientes. Se comunican las herramientas utilizadas en la recogida de datos, con la finalidad de que otros investigadores puedan adaptarlas y las apliquen.
RESUMO
The emergence of multiple sclerosis in island societies has been investigated only in a few Caucasian populations living in temperate regions. The effect of human migration on the risk of developing this disease is still an open question because of possible genetic selection. We conducted an epidemiological study of the multiple sclerosis population in the French West Indies (Martinique and Guadeloupe), a population which includes large numbers of West Indians who have returned after emigrating to metropolitan France. Standardized incidence ratios (SIRs) for multiple sclerosis among migrants were calculated and their genetic characteristics were compared to those of non-migrants. The crude prevalence of multiple sclerosis was 14.8/10(5) on December 31, 1999 (95% CI: 11.9-17.7); and its crude mean annual incidence for the period July 1, 1999 to June 30, 2002 was 1.4/10(5) (95% CI: 1.0-1.8), confirming its emergence in the French West Indies. Recurrent neuromyelitis optica, which is virtually the only form of multiple sclerosis in black African populations in tropical regions, represented not >17.8% of these cases. During the 1,440,000 person-years of follow-up, 33 incidence cases were identified in migrants. Since the number of expected cases was 19.3, the overall SIR was 1.71 (95% CI: 1.19-2.38; P < 0.01) among migrants. The increase in the SIR was more marked if the stay was made before the age of 15 years (4.05, 95% CI: 2.17-6.83; P < 0.0001). European ancestry in the two migrating and non-migrating populations was similar. Martinique, which has a higher rate of return migration, has a higher prevalence of multiple sclerosis (21.0/10(5) versus 8.5/10(5)) and a higher incidence (2.0/10(5) versus 0.7/10(5)) than Guadeloupe. The emergence of the disease in the French West Indies is of environmental rather than genetic origin. It may be explained either through the introduction by migrants of precipitating environmental factors that operate in a critical way before the age of 15 years, and/or by the recent disappearance from the French West Indies of protective environmental factors acting before this age.
Assuntos
Emigração e Imigração , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Fatores Etários , População Negra , Meio Ambiente , Métodos Epidemiológicos , Feminino , França , Guadalupe/epidemiologia , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Esclerose Múltipla/etnologia , Esclerose Múltipla/genética , Classe Social , UrbanizaçãoRESUMO
BACKGROUND AND OBJECTIVE: A population-based study is reported of MS in French Afro-Caribbeans (FAC) in Martinique. FAC are descendants of interracial mating that occurred between French Caucasians and black Africans in the 17th and the 18th centuries. METHODS: The authors surveyed the entire island of Martinique (area 1,128 km(2), population 357,000) between November 1997 and October 1999. RESULTS: Sixty-two patients (46 females, 16 males, ratio 2.9:1) were identified with definite or probable disease by the Poser criteria. Prevalence for all patients on December 31, 1998, was 17.4/10(5) (95% CI 13.1 to 21.7) and 14.3/10(5) (95% CI 10.4 to 18.2) for clinically definite cases (n = 51). Age range of patients on prevalence day was 17 to 73 years (mean +/- SD 39 +/- 11.3 years). Mean age at onset was 31.2 +/- 11 years. Overall, 9.7% had primary progressive disease and 19.4% had benign MS. A low proportion of definite and probable MS cases had oligoclonal bands in CSF (50.9%). Seventeen patients, 13 of whom were alive on prevalence day, had a relapsing form of neuromyelitis optica. CONCLUSION: The island of Martinique appears to have a low to medium prevalence of MS. MS was almost unknown in FAC in Martinique until the late 1970s. The apparent recent increase may be explained by improved recognition of patients, increased availability of MRI for diagnosis, increased disease awareness among physicians, increased survival of MS patients, or an actual increase in disease frequency.
Assuntos
Genes MHC da Classe II/genética , Esclerose Múltipla/epidemiologia , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/genética , Adolescente , Adulto , África/etnologia , Fatores Etários , Idade de Início , Idoso , Alelos , Feminino , Haplótipos , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Fatores SexuaisRESUMO
Several reports suggest that HTLV-I/HIV coinfection may be associated with an increased risk of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In HTLV-I-monoinfected patients, the occurrence of HAM/TSP is associated with high peripheral blood HTLV-I proviral load. Using a real-time quantitative PCR assay, we assessed the proviral DNA load in peripheral blood mononuclear cells (PBMCs) from 15 asymptomatic HTLV-I-monoinfected patients, 15 HTLV-I-monoinfected patients with HAM/TSP, and 25 HTLV-I/HIV-1 coinfected patients, including 4 with HAM/TSP. We also measured HIV-1 proviral DNA load in PBMCs from the coinfected patients. The median HTLV-I proviral loads were 6,800 and 4,100 copies per 10(6) PBMCs in the asymptomatic monoinfected and coinfected groups, and 58,800 and 43,300 copies per 10(6) PBMCs in the monoinfected and coinfected patients with HAM/TSP, respectively. The difference between HTLV-I proviral loads in HAM/TSP and asymptomatic monoinfected patients was statistically significant (p < 0.0001), but there was no difference between the HTLV-I-monoinfected and HTLV-I/HIV-1-coinfected groups. There was no correlation between HTLV-I and HIV-1 proviral load. HTLV-I proviral load did not correlate with the CD4+ T lymphocyte count. Among patients with no HTLV-I disease, the median copy number of HTLV-I per 10(6) circulating CD4+ T cells was 114,000 in the coinfected group and 16,700 in the monoinfected group, but the difference was not significant (p = 0.089). These data do not confirm the hypothesis in which HIV-1 coinfection would increase HTLV-I proviral burden in the PBMCs. However, depletion of the CD4+ T cell subset, the main target of HTLV-I, could be counterbalanced by an up-regulation of HTLV-I replication or by greater resistance of HTLV-I-infected cells to HIV-1-induced destruction.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , DNA Viral/sangue , HIV-1/genética , Infecções por HTLV-I/virologia , Paraparesia Espástica Tropical/virologia , Carga Viral , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Idoso , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Feminino , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Provírus/genéticaRESUMO
Red blood cells (RBCs) transfusion is a common practice in the treatment or for the prevention of complications of patients with sickle-cell disease. In surgery, pre-operative transfusions are frequently given to prevent peri-operative complications. There is no consensus however on the best regimen of transfusion for this purpose. The transfusion techniques are muliple. In addition, pre-operative transfusion therapy is reported to be largely responsible for an increased morbidity and mortality in patients with sickle cell anemia undergoing surgery. During the period 1990-2000, 16 patients (4 men and 12 women) with a mean age of 37 years and various major sickle cell hemoglobinopathies underwent 32 total hip arthroplasty for femoral head necrosis. Nine patients with sickle-cell trait were included as control group. Twelve of them had haemoglobin SS (HbSS), 2/16 had HbSC, 2/16 had HbS/betathalassemia. Operative transfusion were given in only 12/32 procedures, 4 were performed pre-operatively and 8 intra-operatively. Simple transfusion (mean: 2.5 packed red cells) were administered in all the procedures. The main complications observed in our patients were anemia by hemolysis and haemorrhagic shock, vaso-occlusive crisis and chest syndrome. Anemia requiring transfusions was significatively related to the procedures with pre-operative transfusion. In the light of our result, we would like to propose transfusional protocol--if needed--only intra-operatively.
Assuntos
Anemia Falciforme/terapia , Artroplastia de Quadril , Transfusão de Sangue/estatística & dados numéricos , Necrose da Cabeça do Fêmur/cirurgia , Adolescente , Adulto , Idoso , Anemia Hemolítica/epidemiologia , Anemia Hemolítica/etiologia , Anemia Falciforme/complicações , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Perda Sanguínea Cirúrgica , Criança , Transfusão de Eritrócitos , Feminino , Necrose da Cabeça do Fêmur/etiologia , Genótipo , Doença da Hemoglobina C/complicações , Doença da Hemoglobina C/genética , Doença da Hemoglobina C/terapia , Humanos , Cuidados Intraoperatórios/estatística & dados numéricos , Complicações Intraoperatórias/prevenção & controle , Isquemia/epidemiologia , Isquemia/etiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/efeitos adversos , Cuidados Pré-Operatórios/estatística & dados numéricos , Estudos Prospectivos , Choque Hemorrágico/epidemiologia , Choque Hemorrágico/etiologia , Traço Falciforme/complicações , Traço Falciforme/genética , Traço Falciforme/terapia , Talassemia beta/complicações , Talassemia beta/genética , Talassemia beta/terapiaRESUMO
Using TPHA instead of VDRL for syphilis blood-screening since 1995 showed an important increase of positive blood donors in Martinique. Yaws, another treponema disease, has been present on the island until 1975-1980. Usual tests are unable to identify which type--venereal or non venereal--of treponema is involved. Our study, carried out from January 1995 to May 1999, compares actual serological and epidemiological characteristics of TPHA reactive donors to former studies. In our results, the frequency of reactive TPHA is about 1.04% in blood donations. Donors are carrying serological tracks of a past treponema disease with very low rate of antibodies, sometimes linked to yaws. Among donors aged 18 to 30, prevalence is low and is going to become similar to the rate observed in Continental France. This means that this problem will disappear in new donor generations. We suggest the possibility for them to continue blood donation, if their personal preliminary enquiry fits the admission criteria for blood giving.
Assuntos
Doadores de Sangue/estatística & dados numéricos , Testes de Hemaglutinação , Programas de Rastreamento/estatística & dados numéricos , Sorodiagnóstico da Sífilis , Sífilis/diagnóstico , Bouba/diagnóstico , Adolescente , Adulto , Distribuição por Idade , Idoso , Animais , Anticorpos Antiprotozoários/sangue , Cardiolipinas/sangue , Colesterol/sangue , Reações Cruzadas , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Morbidade/tendências , Fosfatidilcolinas/sangue , Estudos Prospectivos , Estudos Retrospectivos , Estudos Soroepidemiológicos , Especificidade da Espécie , Sífilis/epidemiologia , Sífilis/prevenção & controle , Sorodiagnóstico da Sífilis/métodos , Treponema pallidum/imunologia , Bouba/epidemiologiaRESUMO
We have compared the storage quality of three groups of 10 red blood cell concentrates of the AA, AS and AC haemoglobin phenotype. The 30 samples were drawn on CPD on day 0, and were centrifuged 6 hours later. Leukocytes were removed on D1 and the samples were kept at +4 degrees C for 42 days in SAG-mannitol. Viability tests were performed using a series of in vitro tests, including: ATP, 2,3-DPG, K+, glucose, lactic acid, pH, osmotic fragility tests and erythrocytic morphology determination. Results demonstrated a good functional quality for AS and AC haemoglobin RBCs. Higher 2,3-DPG levels were found in Hb AS and Hb AC. A lower osmotic fragility in Hb AC and AS RBCs versus Hb AA was observed; no significant difference was found in terms of ATP levels and other parameters. In addition no variation in S and C haemoglobin levels and no sickling were observed. In conclusion, these results indicate an overall good quality for haemoglobin AS and AC RBCs. Further in vivo studies must now be performed in order to confirm the transfusional quality of haemoglobin AS and AC RBCs.
Assuntos
Anemia Falciforme/sangue , Doadores de Sangue , Preservação de Sangue/normas , Transfusão de Eritrócitos , Hemoglobinas Anormais/genética , Heterozigoto , 2,3-Difosfoglicerato , Adolescente , Adulto , Idoso , Sobrevivência Celular/fisiologia , Ácidos Difosfoglicéricos/sangue , Estudos de Avaliação como Assunto , Feminino , Hemoglobina Falciforme/genética , Hemoglobinas/análise , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Fragilidade Osmótica , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
The purpose of this study was to confirm that ophthalmological features seen in patients in Martinique, French West Indies, could be linked to infection by HTLV-I. The authors studied 93 HTLV-I infected patients divided into 70 patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 23 asymptomatic HTLV-I carriers. They did a complete ophthalmological examination with an assessment of lacrymal secretion by means of three tests: Shirmer 1, break-up time and rose Bengal. Some patients had a biopsy of secondary salivary glands. When possible, detection of HTLV-I antibodies was carried out in the aqueous humor. In 45 of the 93 patients (48.4%) the presence of dry keratoconjunctivitis was recorded. In 22 of these 45 cases, a biopsy of the secondary salivary glands showed the presence of lymphoplasmocytoid infiltrations comparable to the glandular changes that occur with Gougerot-Sjögren syndrome. Among the 93 patients, 15 cases of uveitis were noted (16.1%) with 13 cases of anterior uveitis and 11 cases of vitritis. The inflammation was bilateral in 9 cases (9/15 = 60%). Two cases of cotton wool spots, 3 cases of abnormalities in the distribution of the retinal pigment and 7 cases of corneal lesions were also noted. Higher levels of anti-HTLV-I antibodies were detected in the aqueous humor of 3 patients with uveitis. The coexistence of dry eye (keratoconjunctivitis), uveitis and retinal microangiopathy in patients who are suffering from HAM/TSP could suggest the involvement of an autoimmune or immunological mechanism in the physiopathology of the illness.
Assuntos
Oftalmopatias/etiologia , Infecções por HTLV-I/complicações , Paraparesia Espástica Tropical/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Oftalmopatias/epidemiologia , Oftalmopatias/patologia , Feminino , Anticorpos Anti-HTLV-I/análise , Infecções por HTLV-I/epidemiologia , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/epidemiologiaRESUMO
We present the results of ophthalmologic examinations of a consecutive series of 30 patients with HTLV-I associated myelopathy. This is the first ophthalmologic prospective study reported outside the Japanese endemic area. Twenty-one of the patients (70%) had kerato-conjunctivitis sicca in addition to accessory salivary gland lymphocytary infiltration in 7. Two cases of uveo-papillitis, 1 case of cotton-wool spots and 3 cases of retinochoroidal degeneration were also observed. Moreover, an aliquot of the aqueous humour was collected from the anterior chamber in 5 patients and showed high titer of HTLV-I antibodies for the 2 patients with uveo-papillitis. We propose different hypotheses to explain the physiopathologic characteristics of these features.
Assuntos
Oftalmopatias/etiologia , Infecções por HTLV-I/complicações , Paraplegia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Martinica , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The diagnosis of primary HIV infection is a crucial element in the fight against the AIDS epidemic. Clinical manifestations associated with primary infection are nonspecific. Dengue is a possible differential diagnosis. CASE REPORT: A 15-year-old adolescent living in Martinique consulted for a syndrome suggestive of infectious mononucleosis. The annual dengue epidemic was at its acme at this time. Serum was positive for IgM and the diagnosis of dengue was retained. The diagnosis of recent HIV infection was made two months later (unprotected homosexual intercourse two weeks before onset of clinical signs). Retrospective analysis of the earlier samples at the time of the viral syndrome demonstrated that the patient actually had an acute retroviral syndrome. DISCUSSION: The clinical and biological manifestations of dengue and primary HIV infection are nonspecific and similar to those of infectious mononucleosis. Potential exposure to HIV and recent presence in endemic dengue regions (tropical areas in America, Asia and Africa) can provide helpful guidance for differential diagnosis.
Assuntos
Dengue/diagnóstico , Infecções por HIV/diagnóstico , Doença Aguda , Adolescente , Diagnóstico Diferencial , Humanos , Mononucleose Infecciosa/diagnóstico , Masculino , SíndromeRESUMO
The human T-lymphotropic retrovirus type I (HTLV-1), isolated in 1980, has been shown to be responsible for two distinct systemic diseases: adult T-cell leukemia and HTLV associated myelopathy (HAM). Recently, an ever increasing number of publications have described other disorders associated with HAM. We report a case of uveitis-optic disc neuritis which, to our knowledge, had not been previously described. The fact that both uvea and optic disc were inflamed would suggest that immune-mediated reactions are involved in the pathogenesis of HAM.
Assuntos
Infecções por HTLV-I , Disco Óptico , Paraparesia Espástica Tropical , Uveíte Anterior/etiologia , Adulto , Feminino , HumanosRESUMO
We report the identification of a new HLA-A null allele, HLA-A*0115N. This null allele has been identified within the A*01 group by a combination of serological and molecular typing [Polymerase chain reaction (PCR) sequence-specific primers, PCR sequence-specific oligoprobes and sequence-based typing (SBT)] in a potential intrafamilial bone marrow donor from Martinique (French West Indies). To characterize this A*01 null allele, we performed DNA typing by PCR-SBT on genomic DNA from the beginning of exon 2 (position 84) through the end of the exon 4 (position 895) and revealed a nucleotide deletion at the end of the exon 3. This sole difference between the new allele and the HLA-A*0101 generates a premature stop codon (TGA) in the beginning of exon 4. This deletion most likely explains the lack of cell surface expression of the encoded protein despite the presence of A*01 allele. The absence of correct expression of the antigen on the cell surface was confirmed by one-dimensional isoelectric focusing (1D-IEF). To date, this is the fourth null allele described within the A*01 group.
Assuntos
Alelos , Éxons/genética , Antígenos HLA-A/genética , Deleção de Sequência , Sequência de Bases , Feminino , Antígeno HLA-A1 , Humanos , Martinica , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
We studied the ELSA-pS2 immunoradiometric kit (CIS Bio International) for pS2 protein assay in breast cancer cytosols according to classic validation methods. In addition, we studied correlations between pS2, steroid receptors, and cathepsin-D assays. Repeatability (CV = 1.5% to 4.8%) and reproducibility (CV = 1.6% to 4.9%) were good. The results were linearly related to pS2 concentrations between 205 and 2200 ng/L; the detection limit was 40 ng/L. The accuracy of the assay was measured by assessing recovery; analytical recoveries were near 100% throughout the standard curve. The use of different compounds for cytosol preparation (Tris 10 mmol/L or phosphate 25 mmol/L, KCl 0.4 mol/L, bovine serum albumin 1 g/L) had no effect on pS2 results. pS2 was assayed in breast tumor cytosols from 197 postmenopausal and 92 premenopausal patients. The mean value was 24 micrograms/g of protein; the median and 25th and 75th percentiles were 6, 1, and 23 micrograms/g protein, respectively. We observed a relation between concentrations of pS2 and those of estrogen and progesterone receptors, but there was no relationship between the concentrations of pS2 and cathepsin-D.
Assuntos
Neoplasias da Mama/metabolismo , Citosol/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas , Catepsina D/isolamento & purificação , Feminino , Humanos , Ensaio Imunorradiométrico , Kit de Reagentes para Diagnóstico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fator Trefoil-1 , Células Tumorais Cultivadas , Proteínas Supressoras de TumorRESUMO
Although the simultaneous transmission of either human immunodeficiency virus (HIV) and hepatitis C virus or HIV and hepatitis B virus from a single source has already been described, this is the first case of transmission to occur after a blow with the fist.
Assuntos
Infecções por HIV/transmissão , Hepatite C/transmissão , Exposição Ocupacional , Polícia , Violência , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report on the frequency of genetic mutations associated with drug resistance in antiretroviral treatment-naive patients from Martinique (French West Indies), where zidovudine (ZDV) has been available since 1987 and where combination therapy developed simultaneously with its use in continental France. Genotypic resistance was studied in plasma HIV RNA from samples collected between 1988 and 1998 from 70 antiretroviral-naive study subjects, half presenting with either primary infection or documented seroconversion. A line probe assay (LIPA) was used to detect substitutions on the reverse transcriptase (RT) codons 41, 69, 70, 74, 184, and 215. Direct sequencing was used to complete the data for RT codons which were uninterpretable by LIPA. Of these patients, 17 harbored mutated viruses with one or more mutations in the RT gene codons analyzed. ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively. Mutant strains L74V (didanosine [ddI] and dideoxycytidine [ddC]) were detected in 3 patients and M184V (lamivudine/ddI/ddC) in 4 patients. However, pure mutant results at one or more codons of interest were observed in only 5 (7%; 95% confidence interval [CI], 1%-13%) patients, all involving ZDV resistance. One carried both mutations T215Y and M41L known to confer a high degree of phenotypic resistance to ZDV. Among a subgroup of 28 patients with a timepoint of infection after 1995, 24 [86%; approximately 95% CI, 73%-99%) presented with a wild-type pattern. The significance of the high prevalence of mixed patterns observed in drug-naive patients remains unclear. However, the frequency of primary mutant genotypes associated with high levels of drug resistance is low in Martinique and in this study we did not observe any currently increased tendency in this frequency.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , Mutação , Zidovudina/farmacologia , Resistência Microbiana a Medicamentos/genética , Quimioterapia Combinada , Feminino , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Masculino , Martinica/epidemiologia , Reação em Cadeia da Polimerase/métodos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/farmacologia , Análise de Sequência de DNA/métodosRESUMO
The Martinican population is mainly the product of admixture between African people and French Caucasians. The aim of the present study is to investigate at the DNA level the polymorphism of HLA class I (HLA-A, HLA-B) and class II (HLA-DRB1, DQB1 and DPB1) genes in a population of 100 Martinicans. Allelic distributions and interlocus linkage disequilibria were compared to those observed in a French Caucasian population and in African or North American African populations. Our data revealed a higher degree of polymorphism in Martinicans than in Caucasians and showed a prominant contribution of African origin in the admixed genetic feature of this population. African characteristic alleles were significantly represented in Martinicans: A*30, *33 *34, *66, *74, *8001, B*1510, *35, *42, *53, DRB1*0302, *0804, *1202, *1304, *1503, DPB1*0101, *1701, *1801, *3901. Moreover a higher diversity of A*-B* and DRB1*-DQB1* associations was observed in Martinicans compared to Caucasians which also reflects the African genetic background of this population. In the whole, using PCR-based genotyping methods for HLA class I and class II loci, this study allows a preliminary description of HLA allele distribution in this Caribbean island and gives new elements which may be helpful in the anthropologic field as well as in HLA and disease association studies.
Assuntos
Alelos , Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Haplótipos , África/etnologia , População Negra/genética , França/etnologia , Frequência do Gene , Marcadores Genéticos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DP/genética , Cadeias beta de HLA-DP , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Desequilíbrio de Ligação , Martinica , Polimorfismo Genético/genética , População Branca/genéticaRESUMO
Among candidate genes involved in multiple sclerosis (MS) genetic susceptibility, MHC genes and particularly HLA-DRB1*1501-DQB1*0602 haplotype play a major role. Based on the strong linkage disequilibrium observed in Caucasians between DRB1*1501 and DQB1*0602 alleles, it is still impossible to draw a firm conclusion about the DRB1 or DQB1 locus involvement. In order to address this issue a strategy associating a genetic and a functional approach was conducted in a population of-non-Caucasian MS patients. We observed that in Martinicans (55 MS and 100 controls), the DRB1*15 and DRB1*07 alleles were positively associated with the disease. However in Martinicans the most common DRB1*15 subtype was *1503 and not *1501. Moreover, in Martinicans, the frequency of DQB1*0602, found in association with other DRB1 alleles than DRB1*15 (42% of DQB1*0602 haplotypes), was not increased in DRB1*15-negative MS patients, suggesting a neutral role of DQB1*0602 in MS genetics. In a second step, we demonstrated the capability of the DRB1*1503 allele associated with MS in Martinicans to present the immunodominant autoantigen MBP 85-99 peptide to a DRB1*1501 restricted MBP specific T cell line. Interestingly, structural features of DRB1*1501 or DRB1*1503 molecules are in good fit with the hypothesis that *1501 and *1503 molecules may act similarly in MS development by presenting the same immunodominant MBP peptide. On the whole, our results show a prominent role of the DRB1 locus (DRB1*1501 and/or DRB1*1503 alleles) in the immunodominant MBP 85-99 peptide presentation to genetically different MS patients and suggest a neutral role of the DQB1 encoded molecule in MS susceptibility.