RESUMO
We studied disturbances of cellular energy exchange as one of the leading factors in the development of chronic inflammation in asthma. Comparison of the indicators of mitochondrial respiration and glycolysis in lymphocytes of children with bronchial asthma of different severity, children from the group of frequently ill, and conditionally healthy children showed that the degree of impaired energy metabolism correlates with the severity of the disease. In mild and compensated course of bronchial asthma, as well as in the group of frequently ill children, an increase in the activity of oxidative phosphorylation was observed, which was also accompanied by support in the form of glycolysis activation. This suggests that the energy supply mechanisms are preserved. In more serious cases (moderate bronchial asthma), mitochondrial respiration was hyperactivated with suppression or even absence of glycolysis in some cells. In children with severe bronchial asthma, depression of all studied dehydrogenases was observed, which is probably an unfavorable prognostic sign. These results make it possible to determine the indications for the choice of basic therapy drugs and can serve as a prognostic marker of the severity of the course of the disease.
Assuntos
Asma , Criança , Humanos , Asma/metabolismo , Linfócitos/metabolismo , Brônquios , InflamaçãoRESUMO
Background: Pulmonary hemodynamic disorders depend on the inflammatory phases and severity of the obstructive syndrome. However, the effect of asthma bronchial obstruction on the state of peripheral hemodynamics remains insufficiently known. Aims: To study the effects of airway obstruction on skin blood flow parameters and its regulatory systems in patients with persistent atopic bronchial asthma in the remission state. Materials and Methods: A comparative study of the skin peripheral blood flow in patients with bronchial asthma with severe airway obstruction (1st group) and without obstruction (2nd group) was conducted. 20 patients with confirmed diagnosis of atopic asthma of 5074 years old participated in the study. All patients received basic therapy in a constant dosing of high doses of inhaled glucocorticosteroids/long-acting beta-2-agonists. The control group included 20 healthy volunteers without evidence of bronchial obstruction. The study lasted for 3 months. The forced expiratory volume in 1 s (FEV1) was used to evaluate the bronchial obstruction by spirometry technique. Skin blood perfusion changes were recorded by laser Doppler flowmetry at rest and in response to short-term local ischemia. Registered peripheral blood flow signals were examined using the amplitude temporal filtering in five frequency intervals to identify the functional features of the peripheral blood flow regulation systems. Results: Consistent two-fold decrease of the oscillation amplitudes was found in the neurogenic interval at rest (p=0.031), as well as in the myogenic (p=0.043; p=0.031) and endothelial intervals (p=0.037; p≤0.001) both at rest and during the postocclusive reactive hyperemia respectively in the 1st group of patients with bronchial obstruction (FEV1 <80%) compared with the control group. No significant changes were revealed for skin blood flow parameters in the 2nd patient group (without obstruction, FEV1 >80%) in comparison to control subjects. Conclusions: The presence of bronchial obstruction has a significant impact on the changes of the amplitudes of skin blood flow oscillations in patients with bronchial asthma in the myogenic, neurogenic and endothelial intervals.
Assuntos
Obstrução das Vias Respiratórias , Asma/fisiopatologia , Microcirculação , Pele , Idoso , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/fisiopatologia , Asma/complicações , Feminino , Humanos , Hiperemia/diagnóstico , Fluxometria por Laser-Doppler/métodos , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/fisiopatologia , Espirometria/métodos , Estatística como AssuntoRESUMO
In the present study, the karyotype and chromosomal characteristics of 9 species of the Bagridae fish family were investigated using conventional Giemsa staining as well as dual-color fluorescence in situ hybridization to detect the 18S and 5S rDNA sites. In addition to describing the karyotype of several Bagridae catfishes, we established molecular cytogenetic techniques to study this group. The 9 species contained a diploid chromosomal number, varying from 50 (Pseudomystus siamensis) to 62 (Hemibagrus wyckii), while none contained heteromorphic sex chromosomes. 18S rDNA sites were detected in only 1 chromosomal pair among all species evaluated. However, 3 different patterns were observed for the distribution of the 5S rDNA: 2 sites were found in the genus Mystus and in P. siamensis, multiple sites were observed in the genus Hemibagrus, and a syntenic condition for the 18S and 5S rDNA sites was identified in H. wyckii. The extensive variation in the number and chromosomal position of rDNA clusters observed among these Bagridae species may be related to the intense evolutionary dynamics of rDNA-repeated units, which generates divergent chromosomal distribution patterns even among closely related species. In summary, the distribution of repetitive DNA sequences provided novel, useful information regarding the evolutionary relationships between Bagridae fishes.
Assuntos
Peixes-Gato/genética , Análise Citogenética , Evolução Molecular , Genes de RNAr , Genoma/genética , Animais , Sequência de Bases , Cromossomos/genética , Diploide , Geografia , Hibridização in Situ Fluorescente , Cariotipagem , Mapeamento Físico do Cromossomo , RNA Ribossômico 18S/genética , RNA Ribossômico 5S/genética , Tamanho da Amostra , TailândiaRESUMO
Somatic mosaicism is present in slightly more than 50% of small supernumerary marker chromosome (sSMC) carriers. Interestingly, non-acrocentric derived sSMC show mosaicism much more frequently than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effect, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint of uniparental disomy (UPD). As it is under discussion to possibly replace standard karyotyping by methods like array-CGH, the impracticality of the latter to detect low-level sSMC mosaics and/or UPD has to be considered as well. Overall, sSMC mosaicism has to be studied carefully in each individual case, as it can be extremely informative and of importance, especially for prenatal genetic counseling.
Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Marcadores Genéticos , Mosaicismo , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos X/genética , Hibridização Genômica Comparativa/métodos , Feminino , Aconselhamento Genético , Humanos , Cariotipagem , Gravidez , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genéticaRESUMO
Genotype-phenotype correlations in patients with small supernumerary marker chromosomes (sSMC) are still difficult to asses. Here we review the presently known influence of chromosomal imbalance induced by sSMC size and origin, mosaicism of sSMC in different cells of the body and uniparental disomy (UPD) of sSMC's sister chromosomes on the clinical outcome.
Assuntos
Aberrações Cromossômicas , Cromossomos/genética , Mosaicismo , Dissomia Uniparental/genética , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Dissomia Uniparental/patologiaRESUMO
Multicolor banding approach, first introduced for human chromosomes only, was established as an optimal approach for karyotyping of murine chromosomes. Here we present the established mcb probe sets for all murine autosomes and the X-chromosome and review their potential application.
Assuntos
Bandeamento Cromossômico/métodos , Coloração Cromossômica/métodos , Cromossomos de Mamíferos , Animais , Bandeamento Cromossômico/normas , Coloração Cromossômica/normas , Hibridização in Situ Fluorescente , Cariotipagem , CamundongosRESUMO
Twenty-nine as yet unreported ring chromosomes were characterized in detail by cytogenetic and molecular techniques. For FISH (fluorescence in situ hybridization) previously published high resolution approaches such as multicolor banding (MCB), subcentromere-specific multi-color-FISH (cenM-FISH) and two to three-color-FISH applying locus-specific probes were used. Overall, ring chromosome derived from chromosomes 4 (one case), 10 (one case), 13 (five cases), 14, (three cases), 18 (two cases), 21 (eight cases), 22 (three cases), X (five cases) and Y (one case) were studied. Eight cases were detected prenatally, eight due developmental delay and dysmorphic signs, and nine in connection with infertility and/or Turner syndrome. In general, this report together with data from the literature, supports the idea that ring chromosome patients fall into two groups: group one with (severe) clinical signs and symptoms due to the ring chromosome and group two with no obvious clinical problems apart from infertility.
RESUMO
Tetrasomy 9p is a rare chromosomal syndrome and about 30% of known cases exhibit mosaicism. Approximately 50 of the reported cases with tetrasomy 9p mosaicism show a characteristic facial appearance, growth failure, and developmental delay. However, 3 patients with mosaicism for isochromosome 9p and a normal phenotype have also been reported. We report 2 additional cases of clinically normal young females with tetrasomy 9p mosaicism, one of whom also exhibited X chromosome aneuploidy mosaicism leading to an overall of 6 different cell lines. STR analysis performed on this complex mosaic case indicated that the extra isochromosome was of maternal origin while the X chromosome aneuploidy was of paternal origin, indicating a postzygotic event.
Assuntos
Aneuploidia , Mosaicismo , Adulto , Bandeamento Cromossômico , Cromossomos Humanos Par 9/genética , Cromossomos Humanos X/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Fenótipo , Gravidez , Aberrações dos Cromossomos Sexuais , Adulto JovemRESUMO
Since the first report in 1993, an ectopic centromere, i.e. neocentromere formation, has been reported in more than 100 small supernumerary marker chromosomes (sSMC), in 7 instances of centromere repositioning, and in about a dozen cases with more complex chromosomal rearrangements. Here we report 2 new cases with centromere repositioning and 3 neocentric sSMC consisting exclusively of heterochromatic material. Yet, no centromere formation was reported for the regions 18q22.1 and Xq27.1â¼27.2 as it was observed in the 2 cases with centromere repositioning here; in both cases, cytogenetically an inversion was suggested. Two of the 3 neocentric sSMC were derived from a short arm of an acrocentric chromosome. The remainder neocentric sSMC case was previously reported and was stainable only by material derived from itself.
Assuntos
Centrômero , Cromossomos Humanos Par 18 , Cromossomos Humanos X , Adulto , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , GravidezRESUMO
Centromere-near gain of copy number can be induced by intra- or inter-chromosomal rearrangements or by the presence of a small supernumerary marker chromosome (sSMC). Interestingly, partial trisomy to hexasomy of euchromatic material may be present in clinically healthy or affected individuals, depending on origin and size of chromosomal material involved. Here we report the known minimal sizes of all centromere-near, i.e., proximal auto-somal regions in humans, which are tolerated; over 100 Mb of coding DNA are comprised in these regions. Additionally, we have summarized the typical symptoms for nine proximal autosomal regions including genes obviously sensitive to copy numbers. Overall, studying the carriers of specific chromosomal imbalances using genomics-based medicine, combined with single cell analysis can provide the genotype-phenotype correlations and can also give hints where copy-number-sensitive genes are located in the human genome.
RESUMO
Lipopolysaccharides (LPS) and lipoteichoic acids (LTA) are the major inducers of the inflammatory response of blood cells caused by Gram-negative and some Gram-positive bacteria. CD14 is a common receptor for LPS and LTA that transfers the ligands to TLR4 and TLR2, respectively. In this work, we have demonstrated that the non-toxic LPS from Rhodobacter capsulatus PG blocks the synthesis of pro-inflammatory cytokines during the activation of blood cells by Streptococcus pyogenes LTA through binding to the CD14 receptor, resulting in the signal transduction to TLR2/TLR6 being blocked. The LPS from Rhodobacter capsulatus PG can be considered a prototype for developing preparations to protect blood cells against the LTA of gram-positive bacteria.
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Unbalanced chromosomal abnormalities (UBCA) are reported for >50 euchromatic regions of almost all human autosomes. UBCA are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. Here we report on a partial trisomy of chromosome 4 of the centromere-near region of the short arm of chromosome 4 present as a small supernumerary marker chromosome (sSMC). The sSMC was present in >70% of amnion cells and in 60% of placenta. Further delineation of the size of the duplicated region was done by molecular cytogenetics and array comparative genomic hybridization. Even though the sSMC lead to a partial trisomy of ~9 megabase pairs, a healthy child was born, developing normally at 1 year of age. No comparable cases are available in the literature. Thus, we discuss here the possibility of having found a yet unrecognized chromosomal region subject to UBCA.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 4 , Humanos , Hibridização in Situ Fluorescente , CariotipagemRESUMO
According to cytogenetic and molecular cytogenetic characterization, an otherwise not-altered chromosome 7 formed a neocentromere in band 7q32.1 in a clinically normal female. The alpha satellite sequence D7Z1 remained in its place but was not used for formation of the primary chromosomal incision. Similar observations of centromere repositioning have been made for chromosomes 3 (2x), 4, 8 and Y (2x). Even though data is available for some neocentromeres whose positions are correlated with evolutionary new centromeres for 7q32.1, no correlation could be found for an ancestral inactivated centromere in any of the presently living primates. Overall, we report a new case of centromere repositioning at a position not known to harbor an ancestral inactivated centromere.
Assuntos
Centrômero/patologia , Aberrações Cromossômicas , Cromossomos Humanos Par 7 , Amniocentese , Desenvolvimento Infantil , Pré-Escolar , Bandeamento Cromossômico , Mapeamento Cromossômico , Cromossomos Humanos Par 10 , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Valores de Referência , Recusa em Tratar , Ultrassonografia Pré-NatalRESUMO
Infertility is defined as the inability to conceive after one year of regular unprotected intercourse. Constitutional numerical and/or structural chromosomal aberrations like sex-chromosome aberrations are one of the possible factors involved in fertility problems. Reciprocal translocations between an X-chromosome and an autosome are rarely seen in men. Male carriers of an X-autosome translocation are invariably sterile, regardless of the position of the breakpoint in the X-chromosome. Breakpoints in autosomal chromosomes could also be involved in male infertility. In this paper, we describe a 31-year-old male with azoospermia. GTG banding with high resolution multicolor-banding (MCB) techniques revealed a karyotype 46,Y,t(X;1)(p22.3;q25), and we discuss how the breakpoint of this translocation could affect male infertility. As a conclusion, cytogenetic evaluation of infertile subjects with azoospermia should be considered in the first place before in vitro fertilisation procedures are planned.
Assuntos
Azoospermia/genética , Cromossomos Humanos Par 1 , Cromossomos Humanos X , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/genética , Translocação Genética , Adulto , Bandeamento Cromossômico , Humanos , Masculino , TurquiaRESUMO
13q deletion syndrome is characterized by mental and motor retardation, craniofacial dysmorphic facial appearance and various congenital malformations. In this article, we present a new case with 13q deletion syndrome phenotypically characterized by fish mouth, choanal atresia and severe mental and motor retardation. In order to determine the certain localization of deleted region high resolution multicolor-banding technique was performed and the karyotype determined as 46,XX,del(13)(q32q33.2). To come in future to a genotype-phenotype correlation, it is very important to delineate the deleted region in such cases in detail by cytogenetic/ molecular cytogenetic methods.
Assuntos
Anormalidades Múltiplas/genética , Atresia das Cóanas/genética , Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Deficiência Intelectual/genética , Anormalidades da Boca/genética , Anormalidades Múltiplas/diagnóstico , Pré-Escolar , Atresia das Cóanas/diagnóstico , Bandeamento Cromossômico , Feminino , Dedos/anormalidades , Humanos , Deficiência Intelectual/diagnóstico , Cariotipagem , Anormalidades da Boca/diagnóstico , Fenótipo , Sindactilia/diagnóstico , Sindactilia/genética , Dedos do Pé/anormalidadesRESUMO
Here we report the first case of an inverted duplicated neocentric small supernumerary marker chromosome present in a karyotype 47,XX,+mar(Y). As expected a partial disomy of Ypter to Yp11.2 did not lead to any major malformations. However, the formation of an inverted duplicated chromosome from a Y chromosome is not possible by a U-type exchange, as has been suggested for such kind of neocentric marker chromosomes. Thus, some evidence is here provided that this concept might not always be true.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Y , Isocromossomos , Feminino , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , MasculinoRESUMO
Small supernumerary marker chromosomes (sSMC) derived from chromosome 16 are rare and, so far, it is not yet clear which regions of chromosome 16 are critical and have clinical consequences. We have characterized two cases with a ring-shaped sSMC derived from chromosome 16. In case A the sSMC was encountered prenatally and was characterized using centromeric fluorescence in situ hybridization (FISH) probes, subcentromere-specific multicolor FISH (subcenM-FISH), reverse FISH and array-CGH, using a full-tiling BAC array specific for chromosome 16. Case B is a postnatal case and the sSMC was characterized by centromeric FISH probes and subcenM-FISH. Our results, using molecular cytogenetics, showed that both sSMC were derived from chromosome 16, resulting in a de novo mosaic partial trisomy of chromosome 16, involving euchromatic material from 16q. Array painting, in case A, allowed the localization of the sSMC breakpoints, revealing that the sSMC comprised the 33.43-47.02 Mb region of chromosome 16 (16p11.2 to 16q12.1), a region known to harbor some protein-coding genes. In general, the phenotypic consequences of a de novo marker chromosome are difficult to assess. Molecular cytogenetics techniques are a valuable tool for the accurate identification of the origin and content of marker chromosomes, contributing to a more informed prenatal counseling and patient follow-up. Besides multicolor FISH approaches, array painting, combining microdissection and array-CGH, is very useful for mapping size and breakpoints of marker chromosomes, since sSMC are often only present in a small percentage of cells.
Assuntos
Cromossomos Humanos Par 16 , Mosaicismo , Fenótipo , Hibridização Genômica Comparativa , Marcadores Genéticos , Genótipo , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Masculino , TrissomiaRESUMO
Directly transmitted unbalanced chromosomal abnormalities (UBCA) or euchromatic variants (EV) were recently reported for >50 euchromatic regions of almost all human autosomes. UBCA and EV are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. Here we report on partial trisomies of chromosome 10 within the pericentromeric region which were detected by standard G banding. Those were referred for further delineation of the size of these duplicated regions for molecular cytogenetics and/or array-CGH. Partial trisomies of chromosome 10 in the pericentromeric region were identified prenatally in seven cases. A maximum of three copies of the region from 10p12.1 to 10q11.22 was observed in all cases without apparent clinical abnormalities. The imbalances were either caused by a direct duplication in one familial case or by de novo small supernumerary marker chromosomes (sSMC). Thus, we report a yet unrecognized chromosomal region subject to UBCA detected in seven unrelated cases. To the best of our knowledge, this is the first report of a UBCA in the pericentromeric region of chromosome 10 that is not correlated with any clinical consequences.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 10 , Amniocentese , Bandeamento Cromossômico , Quebra Cromossômica , Hibridização Genômica Comparativa , Feminino , Dosagem de Genes , Duplicação Gênica , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Microdissecção , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Mapeamento Físico do Cromossomo , Diagnóstico Pré-NatalRESUMO
Here we report on three new patients with neocentric small supernumerary marker chromosomes (sSMC) derived from chromosome 2, 13 and 15, respectively. The sSMC(13) and sSMC(15) had inverted duplicated shapes and the sSMC(2) a ring chromosome shape. All three cases were clinically severely abnormal. A review of the available sSMC literature revealed that up to the present 73 neocentric sSMC cases including these three new cases have been reported. Seven of these cases were not characterized morphologically; in the remainder, 80% had an inverted duplication, 17% a ring and 3% a minute shape. 81% of the reported neocentric sSMC carriers showed severe, 12% moderate and 8% no clinical abnormalities. In summary, we report three more neocentric sSMC cases, provide a review on all up to now published cases, highlight their special characteristics and compare them to centric sSMC.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 2 , Criança , Bandeamento Cromossômico , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , CariotipagemRESUMO
Molecular characterization of breakpoints of chromosomal rearrangements is a successful strategy for the identification of candidate disease genes. Mapping translocation breakpoints and rearranged chromosomal boundaries is labor intensive and/or time consuming. Here, we present a novel and rapid procedure to map such chromosomal breakpoints by hybridizing amplified microdissection derived DNA of aberrant chromosomes to arrays containing genomic clones. We illustrate the potential of the technique by molecularly delineating the breakpoints in five small supernumerary marker chromosomes (sSMC) and mapping the breakpoints of five different chromosomal translocations.