RESUMO
OBJECTIVE: To evaluate the role of secretory immunoglobulin E in the differential diagnosis of rhinitis in pregnant women. MATERIAL AND METHODS: The study involved 97 pregnant women with rhinitis symptoms and 23 healthy pregnant women without rhinitis symptoms. The first group of the study included 37 pregnant women with previously confirmed (anamnestically and immunologically) allergic rhinitis (AR), the 2nd group of the study included 30 pregnant women with suspected beginning of the AR, the 3rd group of the study was 30 women with pregnant women's rhinitis, diagnosed on the base of follow-up study. The study included: anamnesis taking, routine examination of ENT organs, general clinical examination, study of the level of total IgE in blood, nasal secretion cytology study, secretory IgE level in nasal secretion analysis, follow-up telephone gathered catamnestic data analysis. RESULTS AND DISCUSSION: When analyzing laboratory data, an increase in the average number of eosinophils in the blood was not detected in any group. When examining secretory immunoglobulin E of the nasal secretion in the group of patients with previously confirmed AR, this indicator averaged 2.9±0.7 kE/L, in the group with AR beginning - 5.5±2.6 kE/L, which exceeded the value in the control group (1.2±0.6 kE/l, p<0.05). In the group of patients with pregnant women's rhinitis, the indices of nasal IgE did not differ significantly from the control group (1.9±0.3 and 1.2±0.6 kE/L, respectively, p<0.05). CONCLUSION: The level of secretory nasal immunoglobulin E can be used in the differential diagnosis of rhinitis in pregnancy.
Assuntos
Rinite Alérgica/diagnóstico , Rinite , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imunoglobulina E , Mucosa Nasal , GravidezRESUMO
The purpose of the work was to study the sinusitis diagnostic and clinical features in pregnant women. The pregnant women group (27 human) with sinusitis from 816 pregnant women with nasal congestion and/or nasal discharge was analyzed. The examination included: taking anamnesis, ENT examining, clinical blood test. The frequency of sinusitis in pregnant women with complaints of nasal congestion and/or nasal discharge is 4.7%. The development of sinusitis was associated with inadequate treatment of chronic rhinitis during pregnancy in a third of cases. The course of sinusitis was characterized by the absence of intoxication and fever, in 78% of cases - by the absence of facial pain. In 74% of cases, the onset of the disease was erased. In pregnant women with sinusitis, in comparison with pregnant women with manifestations of chronic rhinitis, had a significant increase in ESR and a tendency to an increase of neutrophils. CONCLUSION: The development of sinusitis in pregnant women in a third of cases is due to the ineffective treatment of chronic rhinitis, and the erased clinical picture of the disease suggests the need for a thorough assessment of the anamnestic and clinical symptoms of the disease.
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Obstrução Nasal , Complicações na Gravidez , Rinite , Sinusite , Doença Crônica , Feminino , Humanos , GravidezRESUMO
A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams-Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 × 10â»6. This was largely explained by enrichment for members of the N-methyl-D-aspartate receptor (NMDAR) (P=4.24 × 10â»6) and neuronal activity-regulated cytoskeleton-associated protein (ARC) (P=3.78 × 10â»8) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia.
Assuntos
Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença , Esquizofrenia/genética , Esquizofrenia/patologia , Sinapses/genética , Sinapses/patologia , Complexo Relacionado com a AIDS/genética , Bulgária , Estudos de Casos e Controles , Saúde da Família , Feminino , Frequência do Gene , Genótipo , Humanos , Islândia , Japão , Masculino , Metanálise como Assunto , Análise em Microsséries , Modelos Biológicos , Densidade Pós-Sináptica/genética , Densidade Pós-Sináptica/patologia , Escalas de Graduação Psiquiátrica , Receptores de N-Metil-D-Aspartato , Transdução de Sinais/genética , Estatísticas não ParamétricasRESUMO
A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.
Assuntos
Transtorno Bipolar/genética , Predisposição Genética para Doença , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Adulto , Idoso , Mapeamento Cromossômico , Europa (Continente)/epidemiologia , Europa (Continente)/etnologia , Éxons/genética , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Razão de Chances , Locos de Características QuantitativasRESUMO
We earlier reported a genome-wide significant linkage to schizophrenia at chromosome 17 that was identified in a single pedigree (C702) consisting of six affected, male siblings with DSM-IV schizophrenia and prominent mood symptoms. In this study, we adopted several approaches in an attempt to map the putative disease locus. First, mapping the source of linkage to chromosome 17 in pedigree C702. We refined the linkage region in family C702 to a 21-marker segment spanning 11.7 Mb at 17q23-q24 by genotyping a total of 50 microsatellites across chromosome 17 in the pedigree. Analysis of data from 1028 single nucleotide polymorphisms (SNPs) across the refined linkage region identified a single region of homozygosity present in pedigree C702 but not in 2938 UK controls. This spanned ~432 kb of the gene encoding protein kinase C, alpha (PRKCA), the encoded protein of which has been implicated in the pathogenesis of psychiatric disorders. Analysis of pedigree C702 by oligonucleotide-array comparative genome hybridization excluded the possibility that this region of homozygosity was because of a deletion. Mutation screening of PRKCA identified a rare, four-marker haplotype (C-HAP) in the 3' untranslated region of the gene, which was present in the homozygous state in all six affected members of pedigree C702. No other homozygotes were observed in genotype data for a total of 6597 unrelated Europeans (case N=1755, control N=3580 and parents of probands N=1262). Second, association analysis of C702 alleles at PRKCA. The low-frequency haplotype (C-HAP) showed a trend for association in a study of unrelated schizophrenia cases and controls from the UK (661 cases, 2824 controls, P=0.078 and odd ratio (OR)=1.9) and significant evidence for association when the sample was expanded to include cases with bipolar (N=710) and schizoaffective disorder (N=50) (psychosis sample: 1421 cases, 2824 controls, P=0.037 and OR=1.9). Given that all the affected members of C702 are male, we also undertook sex-specific analyses. This revealed that the association was strongest in males for both schizophrenia (446 male cases, 1421 male controls, P=0.008 and OR=3.9) and in the broader psychosis group (730 male cases, 1421 male controls, P=0.008 and OR=3.6). Analysis of C-HAP in follow-up samples from Ireland and Bulgaria revealed no evidence for association in either the whole sample or in males alone, and meta-analysis of all male psychosis samples yielded no significant evidence of association (969 male cases, 1939 male controls, 311 male probands P=0.304 and OR=1.4). Third, association mapping of the pedigree C702 linkage region. Independent of pedigree C702, genotype data from the Affymetrix 500k GeneChip set were available for 476 patients with schizophrenia and 2938 controls from the United Kingdom. SNPs in PRKCA showed evidence for association with schizophrenia that achieved gene-wide significance (P=0.027). Moreover, the same SNP was the most significantly associated marker out of the 1028 SNPs genotyped across the linkage region (rs873417, allelic P=0.0004). Follow-up genotyping in samples from Ireland, Bulgaria and Germany did not show consistent replication, but meta-analysis of all samples (4116 cases and 6491 controls) remained nominally significant (meta-analysis P=0.026, OR=1.1). We conclude that, although we have obtained convergent lines of evidence implicating both rare and common schizophrenia risk variants at PRKCA, none of these is individually compelling. However, the evidence across all approaches suggests that further study of this locus is warranted.
Assuntos
Predisposição Genética para Doença , Proteína Quinase C-alfa/genética , Esquizofrenia/genética , Adolescente , Adulto , Alelos , Bulgária , Mapeamento Cromossômico , Cromossomos Humanos Par 17 , Feminino , Genótipo , Alemanha , Haplótipos , Humanos , Irlanda , Masculino , Repetições de Microssatélites , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Reino Unido , População Branca/genéticaRESUMO
The cost of genome-wide association (GWA) studies can be prohibitively high when large samples are genotyped. We conducted a GWA study on schizophrenia (SZ) and to reduce the cost, we used DNA pooling. We used a parent-offspring trios design to avoid the potential problems of population stratification. We constructed pools from 605 unaffected controls, 574 SZ patients and a third pool from all the parents of the patients. We hybridized each pool eight times on Illumina HumanHap550 arrays. We estimated the allele frequencies of each pool from the averaged intensities of the arrays. The significance level of results in the trios sample was estimated on the basis of the allele frequencies in cases and non-transmitted pseudocontrols, taking into account the technical variability of the data. We selected the highest ranked SNPs for individual genotyping, after excluding poorly performing SNPs and those that showed a trend in the opposite direction in the control pool. We genotyped 63 SNPs in 574 trios and analysed the results with the transmission disequilibrium test. Forty of those were significant at P<0.05, with the best result at P=1.2 x 10(-6) for rs11064768. This SNP is within the gene CCDC60, a coiled-coil domain gene. The third best SNP (P=0.00016) is rs893703, within RBP1, a candidate gene for schizophrenia.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Esquizofrenia/genética , Estudos de Casos e Controles , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Valores de ReferênciaRESUMO
We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Esquizofrenia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 10 , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Donor-related malignancy is a rare complication of organ transplantation. METHODS: In this case series, we discuss three cases of donor-related cancers in kidney transplant recipients who were registered in our center between 1979 and 2015. They account for an incidence of 0.29% of donor-related malignancies of a total of 1015 transplanted kidney grafts (deceased and living donors). The three cases that we describe presented in different ways and with different severity, although the response to the initiated treatment was comparable. RESULTS: All three patients not only survived their cancer episode but also had a complete oncological remission and underwent successful second kidney transplantation, accounting for a 100% survival rate in our small cohort. CONCLUSIONS: Despite the very low incidence of this complication, transplant clinicians must be aware of the occurrence of donor-related malignancies when selecting a donor and should be able to diagnose and treat a case of donor-related cancer.
Assuntos
Neoplasias Renais/etiologia , Transplante de Rim , Doadores de Tecidos , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Neoplasias Renais/epidemiologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Reoperação , TransplantadosRESUMO
Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.
Assuntos
Exoma/genética , Genes Recessivos/genética , Esquizofrenia/genética , Estudos de Casos e Controles , Família , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Masculino , Canais de Sódio Disparados por Voltagem/genéticaRESUMO
Abnormalities in synaptic connectivity and plasticity have been implicated in the pathophysiology of schizophrenia. Molecules involved in the development and maintenance of neural circuitry include the recently cloned protocadherins. Human protocadherin 8 (PCDH8) is homologous to 'arcadlin', a molecule shown to play a role in hippocampal synaptic function in the rat. The gene encoding PCDH8 maps to a region on chromosome 13 where linkage to schizophrenia has been reported. In this study, the entire expressed sequence of the PCDH8 gene and over 800 bp of the 5' flanking region were screened for polymorphisms in 30 DSM-IV schizophrenia individuals using Denaturing High Performance Liquid Chromatography (DHPLC). A total of nine single nucleotide polymorphisms were identified, including three in the first exon that are predicted to change the amino acid sequence. One polymorphism, causing the Trp7Arg change in the putative signal peptide, showed a trend towards excess of the arginine encoding allele in a case-control sample consisting of 520 DSM-IV schizophrenia patients and 535 matched controls from the UK (chi2=3.72, P [1 df]= 0.054). However, this polymorphism did not show preferential transmission to schizophrenic individuals in a separate sample of 203 proband-parent trios from Bulgaria. A second, rare single nucleotide variation, predicting the non-conservative amino acid change Glu39Ala, was found in one schizophrenic individual and their affected sibling but not in a further 352 affected individuals, nor 357 controls. These results suggest that any contribution of PCDH8 polymorphisms to schizophrenia susceptibility is likely to be weak, although the existence of rare variations of stronger effect cannot be excluded.
Assuntos
Caderinas/genética , Testes Genéticos , Esquizofrenia/genética , Adulto , Sequência de Aminoácidos/genética , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Cromossomos Humanos Par 8 , Análise Mutacional de DNA , Éxons , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mapeamento de Nucleotídeos , Fenótipo , Polimorfismo Genético/genética , Polimorfismo de Fragmento de Restrição , Protocaderinas , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Análise de Sequência de DNARESUMO
BACKGROUND: Many observational studies have shown that alcohol consumption is associated with a reduced risk of ischaemic heart disease (IHD). IHD mortality has generally fallen in established market economies but not in some countries of Eastern Europe. Since the level of consumption of saturated fat does not explain these differences in trends, other associations with risk need to be explored. We investigated whether alcohol consumption also presents a U or J-shaped association with IHD risk in a case-control study in Bulgaria. METHODS: Cases (n = 155) were admissions to the cardiology unit, Central Clinical Hospital, Sofia, aged 45 to 69, with confirmed diagnoses of ischaemic heart disease. Controls (n = 154) were concurrent admissions for minor elective surgery. Measurements were made of blood pressure, height and weight and a blood sample was taken around three days after admission. Subjects were interviewed before discharge and asked about the type and amount of alcohol they consumed. RESULTS: Reported alcohol intake demonstrated a J-shaped association with the risk of IHD. The odds ratio (adjusted only for age and sex) was 0.67 (95% CI 0.34-1.28) for patients reporting 0.01-18 g/d of alcohol consumption daily, and 0.36 (95% CI 0.18-0.73) for 18.01-36 g/d, compared to patients reporting to be abstainers. The associations with alcohol intake remained statistically significant and unaltered after adjustment for established IHD risk factors: HDL cholesterol, body mass index, systolic blood pressure, family history, education, physical activity and risk factors significantly related with IHD: fruit and vegetables consumption, type of fat used in cooking, bread consumption. CONCLUSIONS: Our results are consistent with previous studies showing a J-shaped association between alcohol intake and IHD risk. The highest protective effect we observed for levels of alcohol intake 18.01-36 g/d, which corresponds to 100-200 ml wine or 1-2 beers, or little more than 50-100 ml spirits.
Assuntos
Etanol/uso terapêutico , Isquemia Miocárdica/prevenção & controle , Idoso , Pressão Sanguínea , Bulgária , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Gorduras na Dieta/administração & dosagem , Etanol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
PURPOSE: To analyse the incidence and mortality of some malignant diseases among the population living in regions of past uranium extraction in Bulgaria. MATERIAL AND METHODS: A retrospective study on cancer incidence and mortality in the population living around two regions with radioecological problems was conducted. According to the expected individual annual effective doses for the population, regions with expected highest radiation risk (average effective dose > 10 mSv per year) were the villages Yana, Eleshnitza and Seslavtzi (group A), and with expected relatively high radiation risk (average effective dose > 5 mSv per year) were the town of Buhovo, and the villages Dolni Bogrov and Gorni Bogrov (group B). The ecologically clean village German was chosen as a control settlement. The incidence and mortality of gastrointestinal tract cancers, bronchus and lung cancer, breast cancer, thyroid cancer, and myeloid leukaemia for the period 1995- 2001 were studied. RESULTS: The incidence of the gastrointestinal tract cancers in the population of German was significantly lower than those for Bulgaria and for group B. The mortality from this disease of groups A, B and Bulgaria were significantly higher than in the control settlement. Standardized mortality of lung cancer in the population of the villages with highest and relatively high radiation risk was significantly higher than in German and Bulgaria. CONCLUSION: The incidence and mortality changes of diseases studied are a consequence of the impact of many factors. Moreover, they do not characterize the impact of the radiation factor.
RESUMO
Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase beta/zeta (RPTPbeta), we postulated that simultaneous binding of MAGI proteins to RPTPbeta and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPbeta. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPbeta for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n= approximately 1400). PTPRZ1, which codes for RPTPbeta, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P=0.0003; gene-wide P=0.0064; hypothesis-wide P=0.026). The data provide evidence for a role of PTPRZ1, and for RPTPbeta signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPbeta in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.
Assuntos
Receptores ErbB/metabolismo , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Esquizofrenia/genética , Transdução de Sinais/fisiologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , Receptores ErbB/genética , Feminino , Glioma , Humanos , Imunoprecipitação/métodos , Masculino , Modelos Moleculares , Proteínas do Tecido Nervoso/genética , Neuregulina-1 , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases , Receptor ErbB-4 , Transfecção , Tirosina/metabolismoRESUMO
It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2-3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia.
Assuntos
Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Bulgária , Estudos de Casos e Controles , DNA/genética , Feminino , Hormônio do Crescimento Humano/genética , Humanos , Proteínas Substratos do Receptor de Insulina , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Irlanda , Desequilíbrio de Ligação , Masculino , Fosfoproteínas/genética , Reino UnidoRESUMO
The evaluation of bruise color imaging is a very important task in forensic medicine. However, there is no standardized methodology in carrying out this task. In this paper, an attempt was made to review the different papers published in the literature on the visual assessment of bruise age determination, and derive color charts of daily bruise aging. Based on the color charts derived, the following observations can be made: (i) the bruise is red for day 1, (ii) there is no dominant color for day 2, whereas for day 3, blue is becoming slightly dominant, (iii) green is becoming dominant for days 4-6, with yellow color emerging, (iv) for day 7, there is coexistence of green and yellow, (v) yellow is highly dominant for days 7 to 14, with brown emerging. These charts can serve as guidelines for the qualitative evaluation of bruise imaging by visual analysis. Clearly, the need exists for the quantitative analysis of bruise color imaging.
Assuntos
Cor , Contusões/diagnóstico , Contusões/patologia , Medicina Legal/métodos , Sensibilidades de Contraste , Medicina Legal/instrumentação , Humanos , Fotografação , Reprodutibilidade dos Testes , Pele/patologia , Fatores de Tempo , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/patologiaRESUMO
The arterial hypertensive syndrome was studied in 216 patients with bronchial asthma, 17 to 67 years of age (mean age 43.6 years), duration of the disease form 1 up to 19 years. To all patients bicycle ergometry with a permanent load of 60 W for 5 min. was applied. The results showed that in 145 patients (67.12%) arterial hypertensive syndrome was present during the bronchopulmonary obstruction. In 105 of these patients (48.6%) the hypertension was pulmonogenic and in 40 patients (18.51%) the arterial hypertension was an accompanying disease. In 62 patients (28.70%) the pulmonogenic hypertension was of a labile type and in 43 patients (19.90%) it was stable. A marked correlation was found between the values of the increased arterial pressure and the indices of bronchopulmonary obstruction--forced expiratory volume/min, Tiffneau's index, maximal expiratory flow, mean maximal expiratory flow. Hypotensive treatment is recommended in patients with stable pulmonogenic hypertension and with accompanying arterial hypertension only.
Assuntos
Asma/complicações , Hipertensão/etiologia , Adolescente , Adulto , Idoso , Asma/diagnóstico , Pressão Sanguínea , Doença Crônica , Teste de Esforço , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Testes de Função RespiratóriaRESUMO
For a 10 year period 1005 patients with bronchial asthma were treated. 203 (20.19%) of these patients, from 17 up to 71 years of age (mean age 44.2 years) and duration of the disease from 2 up to 28 years, had been in asthmatic state. For this 10 year period 72 (35.46%) of these 203 patients had been in asthmatic state from 2 to 7 times with an interval of 1.5 to 3.5 years. The asthmatic state is a frequent and severe complication of bronchial asthma sometimes with lethal outcome. As risk factors for the development of asthmatic state in asthmatic patients can be pointed out the insufficient treatment of the asthmatic attacks before admittance to the hospital, ill founded corticosteroid treatment and late search for medical help. The antibiotic therapy in patients with an asthmatic attack due to pulmonary infection influences favourably the bronchial obstructive syndrome and is the best prophylaxis of asthmatic state parallel with founded corticosteroid treatment, well organized prophylactic medical care and improvement of the medical knowledge of asthmatic patients.
Assuntos
Asma/complicações , Asma/prevenção & controle , Estado Asmático/prevenção & controle , Adolescente , Adulto , Idoso , Asma/tratamento farmacológico , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Estado Asmático/etiologiaRESUMO
The efficacy of the inhalation treatment of bronchial asthma with low heparin doses was studied in 107 patients 18 to 65 years of age (mean age 43.9 years), men 46 (46.99%), women 61 (57.09%), duration of the disease from 1 up to 18 years. 29 patients (27.10%) had atopic bronchial asthma, 78 patients (72.90%) had mixed and infectious-allergic bronchial asthma. In all patients the disease was in a state of aggravation with various degree of bronchial obstruction. The results of the study show that heparin applied by inhalation in low doses of 5000 U in the course of 10-12 days is highly effective. Positive effect was found in 101 patients (94.39%) and in 84 of them (78.50%) it was considered as very good. Marked good effect was registered in patients who received corticosteroids simultaneously and their doses could be reduced or their application discontinued. It is suggested that the good results of the heparin inhalation treatment were to some extend due to the environmental conditions of the region of Sandanski, South West Bulgaria, where the study was carried out. The resort zone Sandanski is well known for its bioclimatic conditions which are favourable for the treatment of non-specific respiratory infections.