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2.
Br J Dermatol ; 167(1): 50-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22356121

RESUMO

BACKGROUND: Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. OBJECTIVES: This case-control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. METHODS: Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co-haemolysin CAMP factor, a putative virulence determinant. RESULTS: Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23-9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22-12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. CONCLUSIONS: We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.


Assuntos
Acne Vulgar/microbiologia , Biofilmes/crescimento & desenvolvimento , Propionibacterium acnes/fisiologia , Pele/microbiologia , Adolescente , Adulto , Biópsia/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
3.
Leukemia ; 25(4): 622-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21242996

RESUMO

The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.


Assuntos
Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 9/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética/genética , Adolescente , Criança , Pré-Escolar , Aberrações Cromossômicas , Bandeamento Cromossômico , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Prognóstico , Taxa de Sobrevida
4.
Clin Genet ; 68(6): 533-41, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16283884

RESUMO

Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), is a cancer susceptibility syndrome caused by germline mutations in mismatch-repair genes, predominantly MLH1, MSH2 and MSH6. A majority of the mutations reported are truncating, but for MSH6, missense mutations constitute over one third. Few have been proven pathogenic in functional studies or shown to segregate in families. In this study, we show segregation of the putative pathogenic MSH6 missense mutation c.1346T>C p.Leu449Pro with microsatellite instability-high Lynch syndrome-related tumours lacking MSH6 expression in a large 17th century pedigree. Another large family with the MSH6 nonsense c.2931C>G, p.Tyr977X mutation is similar in tumour spectra, age of onset and cumulative risk. These MSH6 families, despite their late age of onset, have a high lifetime risk of all Lynch syndrome-related cancers, significantly higher in women (89% by age 80) than in men (69%). The gender differences are in part explained by high endometrial (70%) and ovarian (33%) cancer risks added upon the high colorectal cancer risk (60%). The several occurrences of breast cancer are not due to the MSH6 mutations. These findings are of great importance for counselling, management and surveillance of families with MSH6 mutations.


Assuntos
Códon sem Sentido/genética , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Mutação de Sentido Incorreto/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Repetições de Microssatélites/genética , Linhagem , Fatores de Risco , Fatores Sexuais , Suécia/epidemiologia
6.
Br J Haematol ; 115(1): 25-33, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11722406

RESUMO

Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.


Assuntos
Leucemia Mieloide/tratamento farmacológico , Seleção de Pacientes , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Citogenética , Intervalo Livre de Doença , Feminino , Doenças Hematológicas/complicações , Humanos , Leucemia Mieloide/complicações , Leucemia Mieloide/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Indução de Remissão/métodos , Fatores de Risco , Taxa de Sobrevida
7.
Biochem Biophys Res Commun ; 284(5): 1155-61, 2001 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-11414704

RESUMO

Growth factor receptors are frequently amplified and over-expressed in various human cancers. Recently, a Drosophila cell surface protein, Kekkon-1, was found to participate in an epidermal growth factor (EGF) driven negative feedback loop. Kekkon-1 is induced by EGF, binds to the EGF-receptor, and inhibits receptor-mediated signaling. Here, we have searched for human genes with homologies to Kekkon-1 and identified human LIG1. The gene is the human homologue of mouse Lig-1 and is located on chromosome band 3p14, a region frequently deleted in various human cancers. It is predicted to encode a transmembrane cell-surface protein with extracellular leucine-rich repeats and immunoglobulin-like domains. LIG1 mRNA was detected in all tissues analyzed. The highest and lowest relative expression levels were found in brain and spleen, respectively, and differed by more than 200-fold. Taken together, our data are compatible with a role for LIG1 as a growth and tumor suppressor in human tissues.


Assuntos
Cromossomos Humanos Par 3 , Expressão Gênica , Glicoproteínas de Membrana/genética , Sequência de Aminoácidos , Mapeamento Cromossômico , Clonagem Molecular , DNA Complementar/análise , DNA Complementar/metabolismo , Humanos , Cariotipagem , Dados de Sequência Molecular , Homologia de Sequência , Distribuição Tecidual
8.
Eur J Oral Sci ; 109(1): 8-13, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11330937

RESUMO

A gene encoding the enamel protein ameloblastin (AMBN) was recently localized to a region on chromosome 4q21 containing a gene for the inherited enamel defect local hypoplastic amelogenesis imperfecta (AIH2). Ameloblastin protein is located at the Tomes processes of secretory ameloblasts and in the sheath space between rod-interrod enamel, and the AMBN gene therefore represents a viable candidate gene for local hypoplastic amelogenesis imperfecta (AI). In this study, the genomic organization of human AMBN was characterized. The gene was shown to consist of 13 exons and 12 introns. An alternatively spliced 45 bp sequence was shown not to represent a separate exon and is most likely spliced by the use of a cryptic splice site. The finding that there were no recombinations between an intragenic microsatellite and AIH2 encouraged us to evaluate this gene's potential role as a candidate gene for local hypoplastic AI. Mutation screening was performed on all 13 exons in 20 families and 8 sporadic cases with 6 different forms of AI. DNA variants were found but none that was associated exclusively with local hypoplastic AI or any of the other variants of AI in the identified Swedish families. This study excludes the coding regions and the splice sites of AMBN from a causative role in the pathogenesis of AIH2.


Assuntos
Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Cromossomos Humanos Par 4 , Análise Mutacional de DNA , Éxons , Humanos , Íntrons , Repetições de Microssatélites , Polimorfismo Conformacional de Fita Simples
9.
Int J Cancer ; 91(4): 486-91, 2001 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11251970

RESUMO

Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described.


Assuntos
Neoplasias Colorretais/genética , Neoplasias do Endométrio/genética , Repetições de Microssatélites , Neoplasias Primárias Múltiplas/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Pareamento Incorreto de Bases , Estudos de Coortes , Reparo do DNA , Saúde da Família , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Neoplasias Retais/genética , Fatores de Risco , Fatores Sexuais , Neoplasias Uterinas/genética
10.
Arch Ophthalmol ; 119(2): 260-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11176989

RESUMO

OBJECTIVE: To describe the phenotype of Bothnia dystrophy, an autosomal recessive retinal dystrophy with an R234W mutation in the RLBP1 gene encoding cellular retinaldehyde-binding protein. DESIGN: Medical records were reviewed retrospectively. Ophthalmologic examination, including kinetic perimetry and, in selected cases, adaptometry, color vision tests, fluorescein angiography, and electrophysiologic studies, was performed. The study included 24 individuals, all homozygous for an R234W mutation in the RLBP1 gene. RESULTS: Patients typically show night blindness from early childhood. In young adults, retinitis punctata albescens was observed, followed by macular degeneration and a decrease in visual acuity that led to legal blindness in early adulthood. Dark adaptometry and electrophysiologic testing showed an initial loss of rod function followed by a progressive reduction of the cone responses in older ages. CONCLUSIONS: Bothnia dystrophy is a unique retinal dystrophy belonging to the rod-cone dystrophies and has a high prevalence in northern Sweden. Fifty-seven cases of Bothnia dystrophy have been diagnosed, indicating a prevalence as high as 1 per 4500 population in the geographic area studied. A defect ability of mutated cellular retinaldehyde-binding protein to bind retinoid probably explains the defect rod function followed by central and peripheral degeneration. CLINICAL RELEVANCE: Retinal dystrophies associated with other mutations of the RLBP1 gene, including retinitis pigmentosa of Bothnia type, might account for a considerable number of cases of autosomal recessive retinitis pigmentosa in other geographic areas as well.


Assuntos
Proteínas de Transporte/genética , Mutação Puntual , Retinaldeído/genética , Retinose Pigmentar/genética , Adolescente , Adulto , Idoso , Criança , Eletrofisiologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Células Fotorreceptoras de Vertebrados/fisiologia , Retinose Pigmentar/epidemiologia , Retinose Pigmentar/fisiopatologia , Estudos Retrospectivos , Suécia/epidemiologia , Acuidade Visual , Campos Visuais
11.
Blood ; 94(1): 283-90, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10381524

RESUMO

Rearrangements involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to 70% of infant leukemias. Loss of heterozygosity (LOH) has been shown for anonymous polymorphic markers at 11q23 in adult leukemias. To study LOH at the MLL locus, we have identified two new polymorphic microsatellite markers: a GAA repeat (mllGAAn) in intron 6 of the MLL gene and a GA (mllGAn) repeat in the 5' flanking region of the gene, approximately 2 kb upstream of the translation initiation codon. The heterozygosity index of mllGAAn is 0.54, which renders it useful for analyzing LOH. We screened two groups of leukemia patients to study LOH at the mllGAAn marker. Group A (n = 18) was selected on the basis of presentation before 18 months. Cytogenetic and reverse transcription-polymerase chain reaction analysis showed that 9 of these 18 children had translocations involving MLL. No LOH was observed. Group B (n = 36) were randomly selected children who had presented with leukemia between 1993 and 1994. Cytogenetic analysis of this group showed a variety of different chromosomal abnormalities. LOH was shown in 9 of 20 individuals (45%) who were informative. Microsatellite instability (MSI) was demonstrated in 1 of 18 individuals in group A and 5 of 36 individuals (13.9%) in group B. MSI and LOH were observed simultaneously in three individuals. Loss of an allele was confirmed in one individual by fluorescence in situ hybridization. Individuals with MSI or LOH at mllGAAn were selected for analysis at anonymous polymorphic markers D11S1364 and D11S1356, which flank the MLL gene. No LOH or MSI was observed at these markers in those individuals who were informative. These results show that LOH at the MLL gene locus is a common event during leukemogenesis. Furthermore, the presence of MSI at this locus suggests that the region is a hotspot for genetic instability.


Assuntos
Cromossomos Humanos Par 11 , Proteínas de Ligação a DNA/genética , Leucemia/genética , Perda de Heterozigosidade , Proto-Oncogenes , Fatores de Transcrição , Doença Aguda , Adulto , Fatores Etários , Criança , Pré-Escolar , DNA Satélite/genética , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia/fisiopatologia , Proteína de Leucina Linfoide-Mieloide , Polimorfismo Genético
12.
Mech Dev ; 80(1): 115-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10096070

RESUMO

Mll, Brg1 and Brm are vertebrate homologues of Drosophila trithorax group (trxG) genes. We isolated chicken Mll cDNA clones, and examined patterns of Mll, Brg1 and Brm expression in chick embryos. All three genes were expressed from embryonic stage 2 onwards. Mll transcripts were just detectable in all tissues by in situ hybridization, with highest level in dorsal neural tube and notochord. Brg1 transcripts were readily detectable in all tissues, with highest levels in dorsal neural tube, dorsal trunk epithelium and limb bud epithelium and mesenchyme. Brm transcripts were more restricted, being found in dermomyotome, notochord, dorsal limb bud epithelium, eye and the roof and floor plates of the neural tube.


Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila , Proto-Oncogenes , Animais , Embrião de Galinha , Proteínas de Ligação a DNA/metabolismo , Drosophila , Biblioteca Gênica , Hibridização In Situ , Modelos Genéticos , Proteína de Leucina Linfoide-Mieloide , Proteínas Nucleares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo
13.
J Interferon Cytokine Res ; 17(10): 637-45, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9355966

RESUMO

Interferon-alpha constitutes a complex gene family with 14 genes clustered on the short arm of chromosome 9. More than 50 sequence variants have been described. However, an extensive genetic polymorphism has not been seen in the few population studies reported so far. As many of the sequence variants reported were derived from tumor cell lines, we have investigated whether IFN-alpha genes are unstable in tumor cells. Using fluorescence-assisted mismatch analysis (FAMA), combined with allele-specific primer extension, RFLP analysis, and direct sequencing, we detected in a panel of 14 tumor cell lines two new sequence variants of the IFNA1 and IFNA13 genes. Further two-point mutations were found in tumor samples from leukemias (n = 10) and renal cell carcinomas (n = 17) not seen in normal tissues. In the IFNA17 gene, three new sequence variants were detected, one in a tumor cell line and two in tumor biopsy specimens. Besides these individual point mutations, two new polymorphisms were found in each of the IFNA13 and IFNA17 genes. No new variants were found in the IFNA2 and IFNA10 genes. The results suggest that new sequence variants of the IFN-alpha genes occur relatively frequently in tumors or in tumor cell lines.


Assuntos
Variação Genética , Interferon-alfa/genética , Biópsia , Carcinoma de Células Renais/genética , Mapeamento Cromossômico , Humanos , Neoplasias Renais/genética , Leucemia/genética , Família Multigênica , Mutação , Polimorfismo de Fragmento de Restrição , Células Tumorais Cultivadas
14.
Hum Hered ; 47(4): 185-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9239504

RESUMO

Interferon-alpha (IFN-alpha) is a protein family controlled by altogether 26 different IFN-alpha genes. We have previously described an SspI polymorphism in the IFN A17 gene and an association between the SspI A2 allele and nasopharyngeal cancer. In this paper we present data on ethnic differences with respect to IFN A17 SspI allele frequencies. Thus the frequency of the SspI A1 allele was high in two different Chinese populations (51 and 48%, respectively) and much lower (11%) in Swedes. Intermediate values were found in African Blacks (32%), Indians (25%), Saamis (29%) and Finns (24%). The very pronounced differences between major ethnic groups make the IFN A17 SspI polymorphism a very informative anthropological marker system and suggest that it may be balanced and maintained by natural selection.


Assuntos
Etnicidade/genética , Genética Populacional , Interferon-alfa/genética , Alelos , Povo Asiático/genética , População Negra/genética , DNA/análise , Frequência do Gene , Humanos , Polimorfismo Genético , População Branca/genética
15.
Carcinogenesis ; 18(4): 645-7, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9111194

RESUMO

Nasopharyngeal carcinoma, which is very frequent in southern China, has in previous investigations been found to be associated with a number of risk factors, including a disease susceptibility gene linked to the HLA-region, p53 alleles and deletions of the chromosome 9p21-22 region, which includes the IFNA and p16 loci. We have therefore studied 64 patients (54 males and 10 females) with nasopharyngeal carcinoma and 99 healthy controls from the Guizhou province in southern China with respect to association with the SspI polymorphism at the IFNA17 locus, and the possible interaction between IFNA17 and p53 alleles in the etiology of nasopharyngeal carcinoma. The frequency of the SspI A1 allele was much higher (P < 10(-10)) in Chinese patients and controls than in a previously reported study of Swedes. Among the patients there was a significant increase in the frequencies of the SspI A2 allele (P = 0.011) and SspI 2-2 genotype with an OR (odds ratio) of 2.76, 95% CI = 1.13-6.73 in relation to the SspI 1-1 type. When combinations of SspI and the p53 codon 72 (BstUI) genotypes were studied a highly significant risk figure was found for the SspI 2-2/BstUI 1-1 (pro/pro) combination (OR = 8.2, 95% CI = 2.2-30.0). No other combinations showed significant risk figures. There was no significant interaction between the SspI 2-2 and BstUI 1-1 types indicating that IFN-alpha and p53 genotypes behave as independent risk factors. Since IFN-alpha is located close to the tumor suppressor gene p16, and intronic p53-haplotypes show stronger association with nasopharynx cancer than the codon 72-polymorphism, both associations may be due to linkage disequilibrium with adjacent genes influencing cell-cycle control.


Assuntos
Alelos , Genes p53 , Interferon-alfa/genética , Neoplasias Nasofaríngeas/genética , Desoxirribonucleases de Sítio Específico do Tipo II , Feminino , Predisposição Genética para Doença , Humanos , Masculino
16.
Am J Hum Genet ; 59(3): 570-8, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8751858

RESUMO

A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases "nested" PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-alpha 1 and interferon-alpha 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines.


Assuntos
Variação Genética/genética , Interferon-alfa/genética , Polimorfismo Genético , Sequência de Bases , Primers do DNA , Feminino , Frequência do Gene , Genes/genética , Humanos , Desequilíbrio de Ligação , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase/métodos , Suécia
17.
Vopr Virusol ; 34(2): 150-5, 1989.
Artigo em Russo | MEDLINE | ID: mdl-2503938

RESUMO

Certain characteristics of immunosorbents prepared on the basis of aminocellulose and oxycellulose were determined. The affinity chromatography of sera from influenza-virus-immunized mice was shown to yield with the former of the immunosorbents a fraction of antibody in which the relative portion of antibodies detectable by neutralization test was higher than that in the original hyperimmune serum. The preparation of pure antibodies obtained with the oxycellulose-based immunosorbent contained antibodies detectable by NT and HI test in a ratio similar to that in the unfractionated hyperimmune serum. It is concluded that aminocellulose and oxycellulose differ in the nature of chemical interaction with influenza virion proteins owing to which differences in the pattern of interaction of immunosorbents prepared on their basis with virus-specific antibodies are observed. The process of influenza virion neutralization by antibodies was also shown to be a multi-hit reaction, the ratio of NT- and HI-detectable antibodies in a preparation affecting the kinetics of the virus-neutralizing effect of the substance. An increase in the preparation of a portion of NT-detectable antibodies reduced the time in which the number of antibody molecules sufficient for virus particle neutralization is adsorbed to it.


Assuntos
Anticorpos Antivirais/análise , Celulose/análise , Soros Imunes/análise , Vírus da Influenza A/imunologia , Animais , Anticorpos Antivirais/isolamento & purificação , Formação de Anticorpos , Cromatografia de Afinidade/métodos , Soros Imunes/isolamento & purificação , Imunodifusão/métodos , Imunoglobulinas/análise , Técnicas de Imunoadsorção , Imunoadsorventes , Camundongos , Testes de Neutralização/métodos
18.
Vopr Virusol ; 33(3): 281-6, 1988.
Artigo em Russo | MEDLINE | ID: mdl-3176427

RESUMO

The studies demonstrated that antibody synthesis under conditions of the investigated fatal influenza infection differs in certain parameters from that in non-fatal infection. The mouse-pathogenic A/PR8/34 strain of influenza virus actively induced synthesis of antibodies detectable both by HI and NT. The less pathogenic A/Krasnodar/101/59 strain induced synthesis of antibodies detectable by NT sufficiently well but was a poor inducer of antibodies inhibiting virus hemagglutination of chick erythrocytes. Antibodies detectable by HI and NT appear to represent different molecules of immunoglobulins which differ in their immunochemical properties. These antibodies could be separated by means of affinity chromatography on an immunosorbent. The results of the above studies confirm that the protective and virus-neutralizing activity of an immune preparation in passive immunization is determined by the qualitative and quantitative composition of antibodies in a given preparation. The ratio of virus-induced antibodies may possibly determine the severity of the course and outcome of primary influenza infection.


Assuntos
Anticorpos Antivirais/biossíntese , Soros Imunes/isolamento & purificação , Vírus da Influenza A/imunologia , Animais , Anticorpos Antivirais/análise , Formação de Anticorpos , Especificidade de Anticorpos , Cromatografia de Afinidade , Testes de Inibição da Hemaglutinação , Soros Imunes/imunologia , Imunização , Vírus da Influenza A/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia
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