RESUMO
Three hundred million individuals are at risk of infection by schistosomes and around 200,000 die each year of this disease. Severe clinical disease in schistosomiasis is often the consequence of heavy infection which, in several endemic areas, are determined largely by the susceptibility/resistance of individuals. Previously, we reported evidence, based on a segregation analysis in Brazilian pedigrees, that intensity of infection by Schistosoma mansoni was influenced by a major gene, indicating that host genetic factors are probably critical in controlling schistosome infection and disease development. To localize this gene, referred to as SM1, we performed a genome-wide study on 142 Brazilian subjects belonging to 11 informative families Our results show a linkage to only one region, on chromosome 5q31-q33, with maximum two-point lod scores of +4.74 and +4.52 for D5S636 and the colony stimulating factor-1 receptor marker (CSF1R), respectively. This was corroborated by multipoint analysis, indicating a close proximity to CSF1R as the most likely location of SM1. This region contains several candidate genes encoding immunological molecules that were shown to play important roles in human protection against schistosomes.
Assuntos
Cromossomos Humanos Par 5/genética , Ligação Genética , Esquistossomose mansoni/genética , Brasil , Mapeamento Cromossômico , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Linhagem , Receptor de Fator Estimulador de Colônias de Macrófagos/genéticaRESUMO
Three hundred million individuals are at risk of infection by schistosomes, and thousands die each year of severe hepatic disease. Previous studies have shown that the intensity of infection by Schistosoma mansoni in a Brazilian population is controlled by a major gene, denoted as SM1. We report here the full results of a genome-wide search that was performed on this population to localise SM1. Two hundred and forty-six microsatellites were used for the primary map, and only one region in 5q31-q33 provided significant evidence of linkage. SM1 was subsequently mapped to this region, which contains several genes encoding cytokines or cytokine receptors which are involved in protection against schistosomes. Three additional regions, 1p22.2, 7q36 and 21q22-22-qter, yielded promising, although not significant, lod-score values. These regions contain candidate genes encoding cytokines or molecules relevant to anti-schistosome immunity.
Assuntos
Cromossomos Humanos Par 5 , Schistosoma mansoni/genética , Esquistossomose/genética , Animais , Sequência de Bases , Brasil , Mapeamento Cromossômico , Primers do DNA , Feminino , Ligação Genética , Humanos , Masculino , Linhagem , Esquistossomose/etnologia , Esquistossomose/patologia , Índice de Gravidade de DoençaRESUMO
Schistosomiasis is a major public health problem in many developing countries. Previous studies have shown that infection levels by Schistosoma mansoni in a Brazilian population is controlled by a major gene, denoted as SM1, which was mapped to chromosome 5q31-q33 by use of a model-based (logarithm of the odds [lod] score) analysis method. The present study is an autosome-wide scan searching for additional human loci implicated in the regulation of S. mansoni infection intensities. The weighted pairwise correlation model-free linkage method was used in order to consider large pedigrees and to conduct a 2-locus analysis (i.e., to search for a second locus taking into account linkage to 5q31-q33). The most significant linkage results were again obtained in the 5q31-q33 region. Two additional regions provided linkage results with significance levels around 0.001, 1p21-q23 (results independent of 5q31-q33) and 6p21-q21 (results in interaction with 5q31-q33). The investigation of these regions, which contain some candidate genes, is ongoing in other populations to confirm the role of these regions.
Assuntos
Cromossomos Humanos Par 5/genética , Esquistossomose mansoni/genética , Adulto , Brasil/epidemiologia , Criança , Mapeamento Cromossômico , Feminino , Ligação Genética , Predisposição Genética para Doença , Genoma Humano , Genótipo , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Esquistossomose mansoni/epidemiologia , Índice de Gravidade de DoençaRESUMO
There is accumulating evidence for the involvement of genetic factors in the human response to malaria infection, mostly based on results obtained in studies of severe clinical malaria. The role of major gene(s) controlling blood parasitemia levels in human malaria has also been detected by means of segregation analysis. To confirm and to localize such gene(s), we performed a sib-pair linkage analysis investigating the role of five candidate chromosomal regions: 6p21 (HLA-tumor necrosis factor region), 2q13-q21 (genes coding for interleukin-1 alpha and beta), 14q11 (locus coding for the alpha chain of T cell antigen receptor), 7q35 (gene cluster for the beta subunit of T cell receptor), and 5q31-q33, which includes several candidate genes and was recently linked to a locus controlling infection levels by Schistosoma mansoni, denoted as SM1. The analysis was carried out on nine families from a southern Cameroon village, and the phenotype under study was blood infection levels with Plasmodium falciparum. No linkage was found with any of the four markers outside the 5q31-q33 region. A trend in favor of linkage was observed in the distal part of the 5q31-q33 region, especially with the marker D5S636 (P < 0.05 using the Monte Carlo P value), which was the marker that provided the highest evidence for linkage with SM1. These results suggest that a locus influencing P. falciparum levels in malaria could be located in the same genetic region as that containing SM1, indicating that the 5q31-q33 region may be critical in the control of different parasite infections.
Assuntos
Cromossomos Humanos Par 5 , Ligação Genética , Malária Falciparum/genética , Parasitemia/genética , Adolescente , Adulto , Animais , Camarões , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
The heterogenecity of keratohyalin (KH) has been demonstrated in rats, then in human warts where similar morphological features have been found and among them, dense homogeneous ovoïd single granules (SG) and composite granules (CG) apparently made up of single granules "coated" with a matrix. This work compares the ultrastructure of the KH of the tongue of newborn rats with that of common warts with and without post-fixation by OsO4, after oxydation by H2O2 and after pepsin treatment. The osmiophily of the SG is confirmed as well as the absence of osmiophily of the matrix of the CG. In man, however, the SG are resistant to oxydation by H2O2 and the CG matrix is oxydation sensitive whereas the opposite is observed in the case of rats. These differences show that it is impossible to deduce the composition of the KH in human warts from that of the rat despite their close ultrastructural resemblance but that important modification of the keratogenesis and KH formation are induced in the cells parasited by the virus of common warts.
Assuntos
Hialina , Queratinas/biossíntese , Verrugas/metabolismo , Animais , Animais Recém-Nascidos , Peróxido de Hidrogênio , Masculino , Osmio , Pepsina A , RatosRESUMO
We report the results of an ultrastructural study of the hyperkeratotic epidermis in 23 cases of palmoplantar keratoderma (PPK) comprising 8 inherited keratoderma, 8 keratoderma climactericum in menopausal women and 7 symptomatic keratoderma. In all but one of the cases of inherited PPK and keratoderma climactericum, composite keratohyalin (KH) granules were found in granular cells of the interductal epidermis, which were similar to those found in the rat and in some other conditions. In the cases of symptomatic keratoderma, e.g. secondary to eczema, the appearance of the KH granules did not differ from that of granules observed in two normal plantar skin samples. While the real role played by these granules is unknown, they could constitute a differentiation marker of intraepidermal duct cells, and their abundance in PPK suggest that intraepidermal sweat ducts may play a part in PPK histogenesis.
Assuntos
Grânulos Citoplasmáticos/ultraestrutura , Epiderme/ultraestrutura , Queratinas/análise , Ceratodermia Palmar e Plantar/patologia , Adulto , Idoso , Glândulas Écrinas/metabolismo , Glândulas Écrinas/ultraestrutura , Epiderme/metabolismo , Feminino , Humanos , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/metabolismo , Masculino , Menopausa , Pessoa de Meia-Idade , Esteril-Sulfatase , Sulfatases/metabolismoRESUMO
Are Epidermodysplasia verruciformis (E.V.) and disseminated flat warts different diseases? Are there any diagnostic criteria between them? In order to attempt answering these 2 questions, fundamental for prognosis and nosology, a comparative ultrastructural study was made of epidermal clear cells of 2 cases of E.V. and 4 flat warts from 4 patients of whom 3 were under immunosuppression drugs. The reason of cytoplasmic electron translucency was mainly a reduction in tonofilaments and keratohyalin amounts in E.V. and a centrifugal edema and vacuolization in flat warts. On the other hand, the number of ribosomes was raised in E.V. and reduced in flat warts. These findings allow differentiation between the 2 diseases and suggest a possible different host-virus relationship.
Assuntos
Nevo/ultraestrutura , Lesões Pré-Cancerosas/ultraestrutura , Dermatopatias/patologia , Verrugas/patologia , Adulto , Citoplasma/ultraestrutura , Humanos , Corpos de Inclusão Viral/ultraestrutura , Masculino , Microscopia Eletrônica , Nevo/genética , Lesões Pré-Cancerosas/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/ultraestrutura , SíndromeRESUMO
Are Epidermodysplasia verruciformis (E.V.) and disseminated flat warts different diseases? Are there any diagnostic criteria between them? In order to attempt answering these 2 questions, fundamental for prognosis and nosology, a comparative ultrastructural study was made of epidermal clear cells of 2 cases of E.V. and 4 flat warts from 4 patients of whom 3 were under immunosuppression drugs. The reason of cytoplasmic electron translucency was mainly a reduction in tonofilaments and keratohyalin amounts in E.V. and a centrifugal edema and vacuolization in flat warts. On the other hand, the number of ribosomes was raised in E.V. and reduced in flat warts. These findings allow differentiation between the 2 diseases and suggest a possible different host-virus relationship.
Assuntos
Dermatopatias/patologia , Neoplasias Cutâneas/ultraestrutura , Verrugas/patologia , Adulto , Citoplasma/ultraestrutura , Humanos , Masculino , Microscopia Eletrônica , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Polyomaviridae , Pele/ultraestrutura , Dermatopatias/microbiologia , Neoplasias Cutâneas/microbiologia , Vacúolos/ultraestrutura , Verrugas/microbiologiaRESUMO
BACKGROUND: The association between mucosal oncogenic human papillomaviruses (HPV) and bowenoid papulosis or genital Bowen's disease is well documented. In contrast this association with extra-genital Bowen's disease is poorly studied. The aim of this study was to detect oncogenic (16/18, 31/33/51) and non oncogenic (8/11) mucosal HPV using a in situ hybridization method in 28 skin biopsy specimens of extra-genital Bowen's disease. PATIENTS AND METHODS: Twenty-eight cases of extra-genital Bowen's disease seen in the period 1990-96 in the Dermatology department were included: 19 women and 9 men (mean age: 72 years). Bowen's disease locations were: hands and feet (8 cases), limbs (11 cases), face (8 cases), trunk (1 case). Blinded histopathologic examination confirmed the diagnosis of Bowen's disease and signs of HPV infection (koilocytosis). In situ hybridization was performed using three biotinylated probes detecting HPV types 6/11, 16/18, 31/33/51. RESULTS: Oncogenic HPV genoma was detected in 8 skin samples (28.6 p. 100). In all these cases, 16/18 probe was positive and in two cases, both 16/18 and 31/33/51 probes were positive; 4/8 Bowen's diseases of the extremities were positive for HPV. Koilocytes were found in 6/8 of skin samples with positive HPV detection. DISCUSSION: Mucosal oncogenic HPV are detected by in situ hybridization in 28.6 p. 100 of extra-genital Bowen's disease. In situ hybridization is an easier technique than Southern-Blot hybridization which is the gold standard. Five studies reported similar results and three studies reported different results that we discuss. A precise understanding of oncogenic HPV implication in the development of extra-genital Bowen's disease could lead to the development of new therapeutic strategies (topical cidofovir or imiquimod).
Assuntos
Doença de Bowen/virologia , Hibridização In Situ , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/virologia , Idoso , Doença de Bowen/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/virologia , Humanos , Masculino , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Sensibilidade e Especificidade , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/patologia , Infecções Tumorais por Vírus/patologia , VirulênciaRESUMO
OBJECTIVE: To determine the prevalence of the Human Papillomavirus (HPV) in Human Immunodeficiency Virus (HIV) infected men, using clinical examination and molecular hybridization in situ. PATIENTS AND METHODS: From May 1995 to May 1997 we studied the prevalence, clinical and histological characteristics, the types and the evolution of the HPV lesions among 121 HIV-infected men. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/18 and 31/33/35 in 79 p. 100 (5/19) of the patients (17 biopsies). RESULTS: Sixteen per cent (19/121) of the patients are HPV infected: genital warts in 37 p. 100 (7/19), anal warts in 37 p. 100 (7/19), and ano-genital warts in 26 p. 100 (5/19) of the patients. In every case of anal codyloma, intracanalar lesions were found. In 47 p. 100 (9/19) of the cases, histological exam showed an intra-epithelial neoplasia. The HPV types 6/11, 16/18 and 31/33/51 were positive in 53 p. 100 (9/17), 35 p. 100 (6/17) and 35 p. 100 (6/17) biopsies respectively. High-risk types of HPV have been noted in 71 p. 100 (12/17) of the biopsies. The evolution of the clinical lesions was: recovering in 47 p. 100 (9/19) of the patients (after 3 months of treatment), recurrence in 16 p. 100 (3/19) of the anal warts (after 1 to 3 months of treatment), stabilization in 16 p. 100 (3/19) of the genital warts (after 6 months of treatment) and extension in 11 p. 100 (2/19) of the anogenital warts (after 3 months of treatment). CONCLUSION: The high prevalence of condyloma and dysplasia emphasizes the importance of the anogenital exam in HIV-positive patients. In case of anal lesions, anuscopy and biopsy are required. We insist on the need to closely follow these patients with HPV lesions in order to adapt treatment. Anal cytology and HPV-DNA detection by Hybrid Capture Assay, should be developed for screening and prevention of the malignant transformation of HPV lesions in this population.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Condiloma Acuminado/diagnóstico , Doenças dos Genitais Masculinos/diagnóstico , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Biópsia , Bissexualidade , Condiloma Acuminado/patologia , Condiloma Acuminado/virologia , Sondas de DNA de HPV , Seguimentos , Doenças dos Genitais Masculinos/patologia , Doenças dos Genitais Masculinos/virologia , Homossexualidade Masculina , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Pele/patologia , Pele/virologia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologiaAssuntos
Hepatopatias Parasitárias/genética , Esquistossomose mansoni/genética , Animais , Cromossomos Humanos Par 5/genética , Progressão da Doença , Ligação Genética , Predisposição Genética para Doença , Humanos , Hepatopatias Parasitárias/imunologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/patologia , Camundongos , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologiaAssuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , DNA Viral/análise , Hibridização In Situ/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/métodos , Infecções Tumorais por Vírus/virologia , Células , Citomegalovirus/genética , Infecções por Citomegalovirus/patologia , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Inclusão em Parafina , Infecções Tumorais por Vírus/patologiaRESUMO
Binding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population.
Assuntos
Predisposição Genética para Doença , Subunidade beta de Receptor de Interleucina-2/genética , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos , Humanos , Subunidade beta de Receptor de Interleucina-2/química , Janus Quinases/metabolismo , Estrutura Terciária de Proteína , Transdução de Sinais , SudãoRESUMO
The development of genetic epidemiology methods using recent human genetic mapping information together with the growing availability of candidate genes has led to major advances in the identification of host genes in human schistosomiasis. Two phenotypes have been studied so far in the infection by Schistosoma mansoni: infection levels by the parasite as measured by the faecal egg counts, and the severe hepatic fibrosis caused by S. mansoni assessed by ultrasound examination. The first study was performed on Brazilian pedigrees and provided strong evidence for a major gene controlling infection levels by S. mansoni denoted as SM1 which was mapped to chromosome 5q31-q33. This region contains several candidate genes involved in the regulation of the Th1/Th2 response, and the direct role of polymorphisms located within these genes is under investigation. The second study conducted in Sudan also showed the presence of a major gene influencing the development of severe hepatic fibrosis due to S. mansoni infection denoted as SM2. This gene is not located in the 5q31-q33 region, but maps to chromosome 6q22-q23 and is closely linked to the IFN-gamma R1 gene encoding the receptor of the strongly anti-fibrogenic cytokine Interferon-gamma. These findings indicate that two distinct genetic loci control human predisposition to schistosomiasis, SM1 located in the 5q31-q33 region which is likely to play a role in the Th1/Th2 differentiation, and SM2 in 6q22-q23 influencing disease progression with a possible involvement in the regulation of IFN-gamma.
Assuntos
Schistosoma mansoni/fisiologia , Esquistossomose/genética , Animais , Brasil/epidemiologia , Mapeamento Cromossômico , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 6/genética , Genes , Predisposição Genética para Doença , Genótipo , Interações Hospedeiro-Parasita/genética , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/genética , Cirrose Hepática/parasitologia , Contagem de Ovos de Parasitas , Linhagem , Fenótipo , Prevalência , Receptores de Interferon/genética , Receptores de Interferon/fisiologia , Schistosoma mansoni/imunologia , Esquistossomose/complicações , Esquistossomose/epidemiologia , Esquistossomose/imunologia , Senegal/epidemiologia , Sudão/epidemiologia , Células Th1/imunologia , Células Th2/imunologia , Receptor de Interferon gamaRESUMO
Parasites cause much suffering mainly in countries of the southern hemisphere. Hundreds of millions of individuals are infected by schistosomes, leishmanias, plasmodiums, trypanosomes, and various other parasites, and severe clinical disease occurs in a sizable fraction of the infected population causing death and severe sequelae. The outcome, asymptomatic, subclinical or clinical disease, of an infection depends mostly on the parasite and on its host. Several groups analyzing the genetics of human susceptibility to parasites have began to identify the critical steps of the pathogenic mechanisms in a few parasitic infections such as malaria and schistosomiasis. The present article, which is not meant to be an exhaustive review of the field, illustrates the progresses made in this field from pioneer studies in animals to works in endemic populations using modern strategies of human genetics.
Assuntos
Doenças Parasitárias/genética , Mapeamento Cromossômico , Eritrócitos/metabolismo , Predisposição Genética para Doença , Humanos , Doenças Parasitárias/parasitologiaRESUMO
Several lines of independent evidence suggest that human Natural Resistance Associated Macrophage Protein 1 gene (NRAMP1) is an important regulator of susceptibility to infectious diseases caused by certain intracellular pathogens. Here, we report the nucleotide sequence of 32198 bp of genomic DNA overlapping NRAMP1 on chromosomal region 2q35. The NRAMP1 gene spans 13604 bp. The gene and its 5' genomic region are highly enriched for DNA repeat sequences. A second gene was identified in the immediate vicinity of NRAMP1 and was tentatively named Nuclear LIM Interactor-Interacting Factor (NLI-IF) by analogy to its closest ortholog. The human NLI-IF gene begins 4721 bp downstream of the NRAMP1 stop codon and is composed of seven exons varying in size from 57 bp to 1644 bp. The gene gives rise to a 2655-bp mRNA transcript that contains a 783-bp open reading frame. The predicted molecular weight of the 261-amino acid NLI-IF protein is 29.2 kDa. Several putative gene regulatory elements were identified in the 5' upstream region of NLI-IF, including consensus binding sequences for Sp1, AP-2, NF-kappa B, and PU 1. The NLI-IF amino acid sequence has homology to proteins that have a high degree of homology with the NLI-interacting factor from Gallus gallus and are found in divergent species ranging from yeast to plants. NLI-IF is part of a human gene family encoding four related proteins of unknown function. Northern blot analysis of 15 different human tissues revealed a 2.6-kb NLI-IF mRNA that was ubiquitously expressed, but at varying levels. A second transcript with estimated size of 7 kb was expressed only in the placenta. Our data provide new sequence information about the NRAMP1 gene region that will be useful in the search for genetic variants causally involved in altered susceptibility to infectious diseases.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Cromossomos Humanos Par 2/genética , Genes/genética , Proteínas de Membrana/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , DNA/química , DNA/genética , DNA Complementar/química , DNA Complementar/genética , Éxons , Feminino , Expressão Gênica , Humanos , Íntrons , Dados de Sequência Molecular , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sequências Repetitivas de Ácido Nucleico , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Distribuição TecidualRESUMO
In a population-based case-control study, 182 human immunodeficiency virus (HIV)-positive persons and 135 healthy control subjects were enrolled from the metropolitan area of Medellin, Colombia. Four genotypes of the natural resistance-associated macrophage protein l (NRAMP1) gene (5' GT repeat, 274C/T, 469+14G/T, and 823C/T) were associated with altered risk of HIV infection (P=.013,.015,.020, and. 035, respectively). Three of these markers (5' [GT]n, 274C/T, 469+14G/T) are in strong linkage disequilibrium, and genotypes of these markers are associated with reduced risk of HIV infection with relative risks (RRs) of 0.35 (95% confidence interval [CI], 0.14-0.91), 0.31 (CI, 0.10-0.93), and 0.24 (CI, 0.08-0.72), respectively. Conversely, heterozygosity at the fourth independent marker (823C/T) was associated with increased risk of HIV infection (RR, 2.29; CI, 1.06-4.92). These findings suggest that NRAMP1 modifies risk of HIV infection.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Predisposição Genética para Doença , Variação Genética , Infecções por HIV/genética , Infecções por HIV/imunologia , Proteínas de Membrana/genética , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Soronegatividade para HIV/genética , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
It is a general rule that percutaneous absorption is increased when the site of application is occluded. In this study we compared the in vitro permeation profiles of two molecules with different physicochemical properties under occluded versus unoccluded conditions. Human abdominal skin samples were mounted on Dianorm Teflon macro 1 cells and Franz diffusion cells which represented occluded or unoccluded conditions, respectively. Our data show that occlusion increased the permeation of citropten (lipophilic compound) 1.6 times whereas that of caffeine (amphiphilic compound) remained unchanged. This lack of penetration enhancement under occluded conditions has also been observed by other authors, especially concerning hydrophilic and slightly lipophilic molecules. Our results support the view that occlusion does not necessarily increase the percutaneous absorption of a chemical.
Assuntos
Absorção Cutânea/fisiologia , Fenômenos Fisiológicos da Pele , Cafeína/química , Cafeína/farmacocinética , Fenômenos Químicos , Físico-Química , Cumarínicos/química , Cumarínicos/farmacocinética , Difusão , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , SolubilidadeRESUMO
BACKGROUND: HSV fulminant hepatitis is a rare pathology. Rapid hepatic failure, as a consequence of extended liver damage, has generally been attributed to necrosis. As apoptosis can constitute another way for hepatocytes to die, we decided to investigate whether programmed cell death took place during HSV fulminant hepatitis. METHODS: Liver sections were obtained from two cases of fulminant herpetic hepatitis as well as from hepatitis B virus and Rickettsia-infected livers. Herpes simplex virus infection was confirmed using in situ hybridization. Apoptosis was assessed by histopathological examination, p53, activated-caspase 3 and Fas immunohistochemistry and TUNEL labeling. RESULTS: We report that the number of cells expressing activated-caspase 3 was largely increased in fulminant herpes simplex virus hepatitis, when compared to livers chronically infected by hepatitis B virus or from a Rickettsial acute hepatitis. Apoptosis of hepatocytes was confirmed by a positive double-staining for activated-caspase 3 and hepatocytes. Finally, the apoptotic process has progressed beyond the step of nuclear DNA cleavage as demonstrated by TUNEL labeling. CONCLUSION: These data as a whole show that apoptosis is responsible, at least partially, for liver damage during HSV fulminant hepatitis.
Assuntos
Apoptose/fisiologia , Falência Hepática/patologia , Fígado/patologia , Simplexvirus/patogenicidade , Biomarcadores , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Fígado/virologiaRESUMO
Epithelial glands were isolated from guinea-pig endometrium. In order to reduce the requirement for a serum supplement and the contamination by non epithelial cells in primary culture, various coatings of the culture dishes were tested using serum-free Ham's F12 containing defined chemicals including 17 beta-estradiol. While epithelial glands seeded on culture dishes coated with Matrigel, a basement membrane matrix-failed to spread, they formed on poly-D-lysine plus serum-coated dishes, a subconfluent monolayer (5-7 days) enriched in cytokeratin-immunostained cells (78%). Cells from subconfluent primary cultures, obtained on poly-D-lysine plus serum-coated dishes in serum-free hormonally defined medium, were passaged on Matrigel-coated dishes in serum-free hormonally defined medium. These subcultures contained, at confluence (4-5 days), a high percentage (greater than 95%) of cytokeratin-immunostained cells. These monolayers consisted of well-differentiated cells which exhibited ultrastructural features characteristic of endometrial epithelial cells. Moreover, these confluent cells contained 50% immunostained nuclei for progesterone receptors. Progesterone receptor amounts decreased in confluent subcultures treated with progesterone and became undetectable after long-term treatment, suggesting responsiveness of these cells to progesterone. This culture system provides a well-defined model for the study of protein synthesis and secretion by endometrial glandular epithelial cells under hormonal control.