RESUMO
INTRODUCTION: Uteroplacental acute atherosis is frequently observed in preeclampsia, and shares features with early atherosclerotic lesions, including artery wall foam cells. The lipid-associated proteins FABP4 (fatty acid binding protein 4), perilipin-2, and LOX-1 (lectin-like oxidized LDL-receptor 1) are involved in atherosclerotic foam cell formation. Increased levels of these proteins have been associated with preeclampsia systemically and in placental tissue. Their role in acute atherosis is yet unidentified. Our aim was to describe the presence of these proteins in acute atherosis, and compare our findings to what is known in early atherosclerotic lesions. METHODS: Serial sections of decidua basalis tissue from 12 normotensive (4 with acute atherosis) and 23 preeclamptic pregnancies (16 with acute atherosis) were stained with HE and immunostained for CK7, CD68, FABP4, perilipin-2, and LOX-1. Artery wall and perivascular protein expression was assessed in 190 spiral artery sections; 55 with acute atherosis. RESULTS: Acute atherosis foam cells were commonly positive for perilipin-2 (55%), less often for FABP4 (13%), and never for LOX-1. LOX-1 was frequently observed in intramural trophoblasts of normal spiral arteries. Perivascularly, LOX-1 positivity of decidual stromal cells surrounding arteries with acute atherosis was significantly increased as compared to arteries lacking acute atherosis (38% vs. 15%, p < 0.001). DISCUSSION: We found that perilipin-2 and FABP4 are expressed by acute atherosis foam cells, similar to atherosclerosis, supporting possible shared pathways for foam cell generation. Unlike atherosclerosis, LOX-1 is not present in acute atherosis, possibly explained by pregnancy-specific routes to decidua basalis foam cell generation.
Assuntos
Aterosclerose/metabolismo , Decídua/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Células Espumosas/metabolismo , Perilipina-2/metabolismo , Receptores Depuradores Classe E/metabolismo , Adulto , Aterosclerose/patologia , Decídua/patologia , Feminino , Células Espumosas/patologia , HumanosRESUMO
Information obtained from the autopsies of children, neonates, fetuses and embryos, may not only be useful to explain the loss experienced by the parents but also to estimate the risk of recurrence. The detection of diseases by an autopsy helps to reduce the risk as well as with the planning of the next pregnancy and the optimal care of mother and fetus. Although incidences are continually dropping, according to the World Health Organization (WHO) statistics each year at least 2.6 million children worldwide suffer intrauterine death after the 28th week of pregnancy. Despite a general decrease in the number of autopsies, the parents agreed to a post-mortem examination in 500 out of 512 cases. The post-mortem examination and interpretation of results of children differ from those obtained from adults. As a supplement to previous publications, this article discusses these differences and may provide standardized instructions on performing autopsies and evaluation of autopsy findings.
Assuntos
Autopsia/métodos , Anormalidades Congênitas/patologia , Documentação/métodos , Morte Fetal/etiologia , Fatores Etários , Causas de Morte , Implantação Tardia do Embrião , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Fotografação , Placenta/patologia , GravidezRESUMO
OBJECTIVE: At present there is no internationally accepted, clinically easy understandable, comprehensive morphological placental classification. This hampers international benchmarking and comparisons, and clinical research. STUDY DESIGN: Internationally published criteria on morphological placental pathology were collected, standardized and focused into a comprehensive diagnosis category system. The idea was to create a clinically relevant placental pathology scheme related to major pathological processes. A system of nine main diagnostic categories (normal placenta included) was constructed. Pathologists and obstetricians discussed the mutual understanding of the wording in the reporting. The previously published diagnostic criteria were merged, structured and standardized. Through an interobserver correlation study on 315 placentas from intrauterine deaths and 31 controls (placentas from live births) the microscopic criteria in this classification system were tested on user-friendliness and reproducibility. RESULTS: The clinical feedback has been very positive, focusing on the understandability and usefulness in patient follow-up. The interobserver agreement in the microscopic correlation study was in general good. The differences in agreement mainly reflected the degree of preciseness of the microscopic criteria, exemplified by excellent correlation in diagnosing acute chorioamnionitis. Maternal and fetal circulatory disorders need grading criteria and studies are needed to get more insight and clinical correlations of villitis and maturation disorders. CONCLUSION: The clinically oriented, unifying and simple placental pathology classification system may work as a platform for standardization and international benchmarking. Further research is needed to define diagnostic criteria in staging and grading of some main diagnostic categories.
Assuntos
Doenças Placentárias/patologia , Placenta/anatomia & histologia , Placenta/patologia , Feminino , Morte Fetal/patologia , Hospitais Universitários , Humanos , Nascido Vivo , Noruega , Variações Dependentes do Observador , Doenças Placentárias/diagnóstico , Guias de Prática Clínica como Assunto , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Retrospectivos , Terminologia como AssuntoRESUMO
The HLA system, which represents the major histocompatibility complex (MHC) of man, encompasses approximately one thousandth of the human genome and is localised on the short arm of chromosome 6 (band 6p 21.3). The HLA gene complex shows an extreme polymorphism which can be demonstrated by molecular genetic methods. The genes so far recognised in the HLA can be subdivided into three major classes: 1) the HLA class I (HLA-ABC) and class II genes (HLA-D); 2) immune function related genes (C2, C4A, C4B, TNFA and TNFB, transporter and proteasome genes); 3) other genes apparently not related to immune functions (CYP 21, valyl-tRNA synthetase). The loci HLA-A, -B, and -C represent the classical HLA class I loci with gene products expressed on nearly all nucleated cells; HLA-E, -F and -G the non-classical HLA class I loci, code for products with a limited tissue distribution and a restricted polymorphism. Classical class I and II MHC antigens are integral membrane proteins composed of two pairs of structurally similar extracellular domains. The X-ray studies indicated the presence of peptides bound to HLA molecules within the groove. The groove has on its floor several amino acids where peptides, derived from the antigen being presented, are bound. Although the principle of allele specific motives ruling the peptide binding seems to be become more established, the further biological impact of the allelic variation remains subject for future studies.
Assuntos
Antígenos HLA/genética , Polimorfismo Genético/genética , Expressão Gênica , Frequência do Gene , Marcadores Genéticos , Humanos , Mutação Puntual/genéticaRESUMO
A large number of diverse diseases are associated with genetic markers of the MHC complex. The analysis of such disease associations is complicated by the diversity of genetic information located within the HLA complex. Recent advances in the structural analysis of HLA genes and gene products contribute a new perspective to questions of HLA-associated disease. HLA-associated disease are caused by an interplay of many different genes and environmental factors, where HLA complex genes most often confer the strongest genetic predisposition. With this knowledge at hand, identification of individuals at high risk to develop autoimmune and other potentially disabling diseases should be used in order to effectively prevent or halt disease development. This may be a major part of the clinical HLA field in the near future. In this article, we present and interpret some such recent information, especially a possible molecular mechanism of the HLA associations.
Assuntos
Doenças Autoimunes/genética , Marcadores Genéticos , Predisposição Genética para Doença , Antígenos HLA/genética , Doenças Autoimunes/imunologia , Suscetibilidade a Doenças/imunologia , Antígenos HLA/imunologia , HumanosRESUMO
Soluble class I human leukocyte antigens (sHLA) have been detected in serum, sweat, lymphatic fluid, urine and cerebrospinal fluid. The levels vary among different individuals and are significantly affected by inflammatory diseases and organ rejection. This article discusses the clinical significance of levels of serum HLA class I antigens, both in patients with viral diseases and following organ transplantation, as well as the potential involvement of such antigens in the immune response. The potential use of sHLA in clinical medicine is far-reaching. sHLA-peptide complexes may find wide application, particularly for the treatment recipients. Although further in vivo studies are required, available data show the efficacy of sHLA to regulate T-cell function.
Assuntos
Antígenos de Histocompatibilidade Classe I , Linfócitos T/imunologia , Imunologia de Transplantes , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Viroses/imunologiaRESUMO
The retrospective estimation of concentrations of soluble HLA class I antigens (sHLA-I) in blood serum and in other body fluids of patients was executed. The physiological concentration of sHLA-I is significantly upregulated in various diseases and during inflammation, and following organ transplantation. This suggested that sHLA-I might serve as a marker of pathological changes. Observed differences in sHLA-I levels among different diseases could reflect variability in genetic factors, pathophysiology or disease activity. The authors show on usefulness of obtained results to comparative analysis of particular HLA class I allospecificities concentrations characteristic for some diseases, for example HLA-Cw7 in patients with SNHL, or HLA-B27 in zzsk. Estimation of sHLA-I concentrations in blood sera of patients could represents a good diagnostic and prognostic marker in monitoring of course disease and its activity.
Assuntos
Líquidos Corporais/imunologia , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe I , Imunologia de Transplantes , Biomarcadores/análise , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Infecções/imunologiaRESUMO
Investigation of self-nonself recognition in the immune system has focused on classical class I and class II MHC antigens. Their extensive polymorphism and high level expression rendered them amenable to experimentation with the traditional immunologic tools, serology and transplantation. Much has been learned about their functions as a peptide--presenting receptors important for immune responses against pathogens. The central unit for regulation of the specific immune system is a trimolecular complex made up of the T cell antigen receptor (TCR), the MHC molecule and the MHC ligand. The third component is a peptide derived as a degradation product from a protein. During recent years there has been some progress in understanding the interaction between MHC molecules and their peptide ligands: MHC molecules are peptide receptors of peculiar specificity, being able to accommodate millions of different peptides provided they share some common features. In this review is to discuss the relationship between MHC molecules and their natural peptide ligands with special emphasis on MHC class I molecules, because more is known about these than class II molecules.
Assuntos
Antígenos HLA/fisiologia , Genes MHC Classe I/genética , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Ligantes , Oligopeptídeos/metabolismo , Polimorfismo Genético/genética , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
The immunogenetic analysis in 152 patients with sensorineural hearing loss (SNHL) was studied. HLA class I antigens and haplotypes were calculated on the basis of typical linkage between HLA-A, -B, and C loci. Soluble form of HLA antigens (sHLA-I) in blood serum in a semiquantitative microabsorption test according to McLean et al. were also determined. It was found that the frequency of HLA-A2, -A25(10), -B39(16), -Cw5, and -Cw7 were different in patients with SNHL in compared to the control group (n = 1554). This deference's were highly significant, especially for HLA-Cw7 antigens (chi 2 = 88.88; p < 0.0000...1). The frequency of haplotype HLA-A25-B18-Cw7 in patients was also different (f = 362 x 10(4) vs 51 x 10(4)), and highly significant compared to the healthy individuals (n = 1944) (chi 2 = 27.37; p < 0.0000...1). Among 23 typed HLA class I antigens, significantly higher mean level was observed for 14 sHLA antigens then in control group (n = 248). The levels of sHLA-I antigens in patients sera may suggests participation of sHLA molecules in etiopathogenesis of SNHL. This hypothesis may indicate the existence of autoimmunogenetic background of SNHL within high concentrations of certain sHLA-I antigens.
Assuntos
Antígenos HLA/imunologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , FenótipoRESUMO
Current opinions connected with HLA-E and HLA-F genes determining "nonclassical" (HLA-Ib) class I antigens of the Main Histocompatibility Complex MHC, and formed in the consequence of mutation or partial deletion of HLA-H pseudogene loci were presented. The expression of protein products of HLA-E and -F genes on some cells and tissues, their polymorphism, and also their biological functions in organisms were qualified by the use of molecular technics. The kind and frequency of occurrence of mutations 845 A (C282Y) and 187 G (H63D) in gene HLA-H were analysed, and in this context some genetic aspects of hereditary hemochromatozy (HH) were discussed.
Assuntos
Genes MHC Classe I/imunologia , Antígenos HLA/genética , Proteínas de Membrana , Regulação da Expressão Gênica , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Mutação , Antígenos HLA-ERESUMO
The recent advances about a new distinct family of polymorphic genes MIC (PERB11) "mapped" in the region of the major histocompatibility complex of antigens MHC were presented. Some aspects connected with their molecular organisation, degree of polymorphism, expression, and immunogenetical function were discussed. Special attention sacrificed to results of investigations over existence of particular MICA allele association with some diseases. Many relating problems, especially functional MICA and MICB genes are still in interests both clinicians, and immunogenetists.
Assuntos
Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Complexo Principal de Histocompatibilidade/genética , Polimorfismo Genético , Genótipo , Haplótipos , Homozigoto , Humanos , Desequilíbrio de Ligação , Seleção Genética , Relação Estrutura-AtividadeRESUMO
Current opinions connected with the role and significance of ubiquitous proteins--ubiquitins (Ub) were discussed. Genetic determination of ubiquitins and their expression in nature were considered. Thymic ubiquitin complex, as an extract from calf thymus gland (TFX) was also presented. Very important biological activities in some experimental models and usefulness of TFX in medical practice were presented.
Assuntos
Timo/metabolismo , Ubiquitinas/fisiologia , Animais , Bovinos , Humanos , Modelos Biológicos , Ubiquitinas/química , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMO
The results of hitherto researches over gene products of HLA-G locus, i.e. membrane bound forms (M*HLA-G) and soluble forms (S*HLA-G) were verified. Current opinions connected with synthesis and molecular organisation of five HLA-G isoformic molecules (HLA-G1, -G2, -G3, -G4, -G5) were presented. The polymorphism of HLA-G gene and its expression were qualified. Special attention has been turned on presumably significant function of HLA-G in maintenance of maternal-placenta immunological tolerance, binding of monomeric peptides, and antigens presentation, taking into consideration cytomegaloviruses (CMV). In spite of significant progress in the understanding of mutual relationship between mother and placenta many phenomena with participation of HLA-G gene products, especially in pathological conditions, are still unknown.
Assuntos
Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Troca Materno-Fetal/genética , Troca Materno-Fetal/imunologia , Polimorfismo Genético , Feminino , Antígenos HLA-G , Humanos , Imunidade Ativa , Imunidade Inata , Células Matadoras Naturais/imunologia , Placenta/imunologia , GravidezRESUMO
Variability of concentrations of s-HLA-I depending on allelic specificity substantiated realisation of research in population of 248 healthy, unrelated individuals. Defined phenotypes from tissue typing of polymorphic HLA complex enabled concentrations measurements of 1553 serum samples for HLA--A, B, and C loci determined antigens. Semi-quantitative technique of inhibition microcytotoxic reaction according to Tait et al. (1981) and Mclean et al. (1983) with usage of policlonal sera anti-HLA was applied. For most of numbers of the allelic specificity the concentration of antigen material in soluble form (s-HLA-I) in blood serum were nominally very high and high. For certain numbers of specificity e.g. HLA--A26, A29, B39, B52, B56, Cw5, Cw6 the percentage of sera, where the s-HLA concentrations were decreased was observed. The results were presented as mean values of inhibition microcytotoxic reaction--according to NIH classification. Authors point on usefulness of results for s-HLA comparative analysis of particular HLA allelic specificity, specific for certain diseases e.g. Cw7 for SNHL patients and B27 for ankylosing spongilitis.
Assuntos
Antígenos HLA/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Adulto , Alelos , Genética Populacional , Antígenos HLA/genética , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Fenótipo , Valores de Referência , SolubilidadeRESUMO
The purpose of the study was the analysis of HLA-AB haplotypes frequency in the families of children with coeliac disease. Haplotypes present in 46 probands' families including 69 affected children, 49 healthy siblings and 91 parents were verified. HLA antigens were typed by Terasaki and McClelland's routine two-step-microcytotoxic assay in NIH modification. Among 138 haplotypes, the following were significantly more frequent in affected children: HLA-A1-B8 (3116 x 10(4)), HLA-A3-B8 (290 x 10(4)) and HLA-A2-B8 (217 x 10(4)). Total frequency of haplotypes including HLA-B8 antigen in comparison to control population equalled 3986 x 10(4) vs. 763 x 10(4). HLA-A1-B8 haplotype frequency was twice lower in probands' healthy siblings and parents, equalling 1837 x 10(4) and 1868 x 10(4), respectively. Highly significantly more frequent HLA-A1-B8 haplotype found in probands' families may indicate the correlation between inherited gene products and increased risk of coeliac disease incidence.
Assuntos
Doença Celíaca/genética , Doença Celíaca/imunologia , Genes MHC Classe I , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Núcleo Familiar , PaisRESUMO
The aim of the study was the analysis of the frequency of HLA class I antigens in the Polish population of children suffering from coeliac disease and their families, as well as the estimation of the relative risk of incidence, etiologic fraction (EF) and preventive fraction (PF) indexes. Forty-six probands' families were included in the typing: 69 children with coeliac disease confirmed clinically and histologically, 49 healthy siblings and 91 parents. The HLA antigens were typed with routine Terasaki an McClelland's two-stage microcytotoxic assay in NIH modification. The following antigens occurred significantly more frequently (p < 0.0000...1) in phenotypes of children with coeliac disease: HLA-A1 (chi 2 = 35.90; RR = 4.3; EF = 0.44), -B8 (chi 2 = 88.20; RR = 8.8; EF = 0.58) and Cw7 (chi 2 = 55.24; RR = 7.5; EF = 0.69). The positive correlation for the specificity of HLA-A1, -B8 was proved also in siblings (chi 2 = 16.03; chi 2 = 18.10) and parents (chi 2 = 15.67; chi 2 = 32.67). The presence of antigens HLA-A1, -B8 in the phenotype may be the risk factor predisposing for the manifestation of hypersensitivity to gluten.
Assuntos
Doença Celíaca/imunologia , Antígenos HLA , Antígenos de Histocompatibilidade Classe I , Adulto , Estudos de Casos e Controles , Doença Celíaca/etiologia , Doença Celíaca/genética , Criança , Feminino , Frequência do Gene , Genes MHC Classe I , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Núcleo Familiar , Pais , Fenótipo , Polônia , Fatores de RiscoRESUMO
The aim of the study was to evaluate the functional state of peripheral blood neutrophils in patients with chronic active viral hepatitis. Twenty-six patients with HBV, HCV or CMV in different clinical status were included in the analysis. In the study, the number of leukocytes and neutrophils was determined. The metabolic activity of neutrophils was examined in NBT reduction tests i.e. spontaneous (NBTsp) test and the one stimulated with LPS E. coli (NBTst). The results were analysed in relation to disease advancement and the type of viral infection. The data obtained from the affected patients were compared with the results from 46 healthy subjects. Most patients displayed neutropenia. It was found that the number of NBT positive cells and the coefficient of neutrophil metabolic activity (CNMA) in NBT sp test were highly significantly increased. The majority of patients had reduced values in NBTst test, which suggested lack of response to LPS E. coli by neutrophils. These findings may reflect the state of inflammation in the body. NBT reduction tests may be useful in monitoring metabolic activity of neutrophils in patients with chronic active viral hepatitis.
Assuntos
Hepatite Crônica/sangue , Hepatite Viral Humana/sangue , Neutrófilos/metabolismo , Adulto , Idoso , Infecções por Citomegalovirus/sangue , Feminino , Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Humanos , Técnicas In Vitro , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Nitroazul de Tetrazólio/metabolismoRESUMO
Although externally exposed ventricular assist devices are associated with extremely high mortality rates, salvage may be accomplished by early aggressive wound debridement, transposition of a well-perfused autologous tissue (such as omentum), dead space obliteration, and adequate external coverage using vascularized tissue. The temporary suppression rather than the total eradication of the infection should be the goal of these procedures.
Assuntos
Coração Auxiliar , Infecções Relacionadas à Prótese/cirurgia , Retalhos Cirúrgicos , Adulto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Free muscle transfer for facial reanimation can be facilitated by the use of a linear gastrointestinal stapler. This technique not only offers reliable muscle insertion at the recipient site but also helps to provide an adequate motor unit by facilitating safe muscle debulking, splitting, and tailoring.
Assuntos
Músculos Faciais/cirurgia , Paralisia Facial/cirurgia , Retalhos Cirúrgicos , Grampeamento Cirúrgico , Adulto , Criança , HumanosRESUMO
Treatment of chronic liver disease, including primary sclerosing cholangitis (CSP) is a difficult and still not fully solved problem. Both monotherapy and combined pharmacological therapy have shown little effect in inhibiting the disease process and preventing complications. The objectives of ubiquitin biotherapy were restitution of the immune system and inhibition of the disease process along with the stimulation of regenerative processes of the liver. In 1994 in Gastroenterological Clinic attempts at ubiquitin biotherapy were made with the use of thymus extract (TFX-JELFA ini.), which proved to be the ubiquitin preparation that was not only active in the immune system but also played a significant role in regenerative and adjuvant processes. It has been shown that ubiquitins play an essential role in proteolysis of proteins, their intracellular elimination and in the apoptosis. The early results of the clinical observations and laboratory tests indicate a gradual improvement and inhibition of the disease process the patient with CSP.