Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Abstract: The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.
    Type of Publication: Journal article published
    PubMed ID: 28120103
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Genomic DNA digests of skin biopsies from 20 patients with cutaneous T-cell lymphomas and pseudolymphomas were studied by hybridization, using probes for the constant region of the T-cell receptor beta chain and the joining region of the immunoglobin heavy chain gene. Skin biopsies from all 20 patients contained a monoclonal T-cell population. In addition, DNA from 5 patients contained an immunoglobulin gene rearrangement. These results demonstrate that cutaneous T-cell lymphomas are clonal T-cell malignancies that frequently express a dual genotype, which may sometimes reflect the clonotypic heterogeneity of these disorders.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-1076
    Keywords: Key words Epidermal naevus syndrome ; Hypophosphataemic rickets ; Central nervous system anomalies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The epidermal naevus syndrome (ENS) is a rare dermatological condition consisting of congenital epidermal nevi associated with anomalies in the central nervous system, bones, eyes, hear or genito-urinary system. We report a new case of ENS associated with hypophosphataemic rickets. The girl was born with a mixed-type epidermal naevus and skeletal anomalies. Hypophosphataemic rickets was diagnosed at the age of 2.5 years. At 14 years of age, MRI of the head demonstrated right brain hypotrophy, a left temporal arachnoid cyst and asymetric lateral ventricles. We reviewed the literature and found 13 reported cases of ENS associated with hypophosphataemic rickets. Conclusion We report a further patient with epidermal naevus syndrome and hypophosphataemic rickets, followed from birth to the age of 15 years, who had structural central nervous system anomalies with normal intellectual functioning. A comprehensive neurological work up is recommended in patients with epidermal naevus syndrome.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-0584
    Keywords: Minimal residual disease ; Myeloblastic leukemia ; Immunophenotype ; Aberrant phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant lightscatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19) - lineage infidelity -; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33-CD13+, CD13-CD15+, HLADR+CD15+++, HLADR-CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0584
    Keywords: Key words Minimal residual disease ; Myeloblastic leukemia ; Immunophenotype ; Aberrant phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant light-scatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19) – lineage infidelity –; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33–CD13+, CD13–CD15+, HLADR+CD15+++, HLADR–CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 42 (1987), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-0428
    Keywords: Prediabetic ; standard oral glucose tolerance test (OGTT) ; intravenous tolbutamide test (ITT) ; rapid intravenous glucose tolerance test (IVGTT) ; blood sugar ; immunoreactive insulin (IRI) ; non-esterified fatty acids (NEFA) ; blunted insulin release ; early insulin response phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Vingt-deux sujets non-obèses, génétiquement prédiabétiques (issus de deux parents diabétiques) ont été comparés à 34 sujets normaux de même âge et de même poids, en ce qui concerne leur réponse à trois stimuli standardisés: test de tolérance au glucose oral (avec 100 g de glucose), test de tolérance au tolbutamide intraveineux (1 g) et rapide infusion intraveineuse de glucose (0.33 g/kg de poids corporel). La glycémie, l'insuline immunoréactive et les acides gras non-estérifLés (NEFA) ont été mesurés dans les deux groupes à l'état de jeûne et à différents intervalles de temps au cours de chacun des trois tests.-Les résultats n'ont montré de différence significative ni dans la tolérance aux hydrates de carbone, ni dans le comportement des taux de NEFA entre les sujets normaux et les prédiabétiques, à aucun moment au cours des tests choisis. Les taux à jeun d'insuline plasmatique immunoréactive étaient également étroitement comparables dans les deux groupes; ni la charge orale de glucose, ni l'injection intraveineuse de tolbutamide ne provoquait une libération d'insuline significativement différente chez les sujets normaux et les prédiabétiques. Cependant, la rapide infusion intraveineuse de glucose provoquait une sécrétion d'insuline nettement diminuée dans le groupe prédiabétique qui était plutôt limitée à la phase de réponse très précoce.-Nos résultats confirment fortement l'idée qu'une capacité diminuée à sécréter de l'insuline sous l'influence du stimulus spécifique constitué par la charge brutale de glucose intraveineux est un trait plutôt caractéristique de la cellule bêta pancréatique chez ces sujets qui sont fortement prédisposés au diabète sucré.
    Abstract: Zusammenfassung Die Reaktion von 22 normalgewichtigen genetischen Prädiabetikern, deren beide Elternteile Diabetiker waren, wurde mit der von 34 stoffwechselgesunden Freiwilligen entsprechenden Alters und Gewichtes verglichen. Als standardisierte Stimulationsmethoden dienten: der orale Glucosetoleranztest (100 g Glucose), der i.v. Tolbutamid-Toleranztest (1 g) und die schnelle i.v. Injektion von 0.33 g Glucose/kg Körpergewicht. Die Spiegel des Blutzuckers, des immunreaktiven Insulins und der unveresterten Fettsäuren (NEFA) wurden bei beiden Gruppen im Nüchternzustand und zu verschiedenen Zeiten während der 3 Tests bestimmt.-Die Resultate zeigten keine signifikanten Unterschiede in bezug auf die Kohlenhydrat-Toleranz und das Verhalten der NEFA zu irgend einem Zeitpunkt der benutzten Tests bei Normalpersonen und Prädiabetikern. Bei enger Übereinstimmung der Nüchternspiegel des plasma-immunreaktiven Insulins fanden sich auch keine signifikanten Unterschiede in der Ausschüttung nach oraler Glucosegabe oder i.v. Tolbutamidinjektion. Dagegen ergab sich nach schneller i.v. Glucoseinjektion eine deutlich verringerte Insulinfreisetzung bei der Gruppe der Prädiabetiker, die sich jedoch auf die Frühphase beschränkte. — Unsere Resultate sprechen durchaus dafür, daß eine verringerte Kapazität zur Ihsulinausschüttung nach dem spezifischen Reiz der i.v. Glucosebelastung ein Charakteristikum der Pankreas-β-Zelle der Menschen darstellt, die zum Diabetes mellitus prädisponiert sind.
    Notes: Summary Twenty-two non-obese genetic prediabetics (offspring with both parents diabetic) were compared with 34 normal volunteers, closely matched by age and weight, in their response to three standardized stimuli: oral glucose tolerance test (with 100 g of glucose), intravenous tolbutamide tolerance test (1 g) and rapid intravenous glucose infusion (0.33 g/kg body weight). Blood sugar, immunoreactive insulin and non-esterified fatty acids (N.E.F.A.) were estimated in both groups in the fasting state and at different time intervals during each of the three tests. — Results showed no significant differences (either in carbohydrate tolerance or in the behaviour of the N.E.F.A. levels) between normals and prediabetics at any time in the course of the selected tests. Plasma immunoreactive insulin fasting levels were also closely comparable in both groups, no significantly different insulin release in normals and prediabetics being elicited either by the oral glucose load or by the intravenous tolbutamide injection. However, the rapid intravenous glucose infusion brings about a markedly diminished insulin secretion in the prediabetic group limited to the very early response phase. — Our results strongly support the idea that an impaired ability to secrete insulin under the specific stimulus of the intravenous glucose is a distinguishing feature of the pancreatic beta cell in those humans pre-disposed to diabetes mellitus.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...