Intra- and Interspecies Analyses of the Carcinoembryonic Antigen (CEA) Gene Family Reveal Independent Evolution in Primates and Rodents

Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders

Ubiquitous Nuclear Factors Bind Specifically to a 5′-Region Conserved in Carcinoembryonic Antigen-Related Genes

We recently cloned members of the murine carcinoembryonic antigen (CEA) gene family, some of which are differentially expressed during placental development. By intra- and interspecies sequence comparisons, we identified an element in the putative promoter and/or 5′-nontranslated region which is conserved within all human and rodent CEA-related genes analyzed so far. Using gel retardation analysis and DNasel hypersensitive site mapping, we now show that ubiquitously expressed nuclear factors specifically bind to the conserved region derived from the mouse gene Cea-2 in vitro and probably also in vivo. Another DNasel hypersensitive site lies within or close to a simple sequence motif [(GGA)n] located in the first intron of Cea-2. Such sequences have been reported to play a role in the regulation of certain genes. Therefore, this analysis has identified putative regulatory regions for Cea-2 and possibly CEA-related genes in general

Characterization of Murine Carcinoembryonic Antigen Gene Family Members

The carcinoembryonic antigen (CEA) is a human tumor marker whose gene belongs to a family with more than 20 members. This gene family codes for a group of proteins with in vitro cell adhesion properties and for a group of abundantly expressed pregnancy-specific glycoproteins (PSG) with unknown functions. As a basis for in vivo functional studies, we have started to analyze the murine CEA gene family and have identified five new members (Cea-2 to Cea-6). cDNA clones were isolated for Cea-2, Cea-3, and Cea-6. The deduced amino acid sequences of Cea-2 and Cea-6 indicate three IgV-like (N), followed by one IgC-like (A) domain (N1-N2-N3-A). We have also partially characterized the Cea-2 gene and two additional ones, Cea-4 and Cea-5. Cea-2 and Cea-4 are separated by only 16 kb, suggesting a close linkage of murine CEA-related genes, as found for the human CEA gene family. Cea-5 was located to the proximal region of mouse Chromosome (Chr) 7, which is syntenic to part of human Chr 19, containing the human CEA gene family cluster. Cea-2, Cea-3, and a Cea-4-like gene are differentially transcribed in the placenta during pregnancy, but not in other organs tested. This expression pattern strongly suggests that they represent counterparts of the human PSG subgroup members, despite the presence of multiple IgV-like domains, a feature not found for human PSGs. The more distantly related Cea-5 seems to be ubiquitously expressed. The putative promoter region of Cea-2 lacks typical TATA-or CAAT-boxes, but contains other conserved motifs that could play a role in the initiation of transcription

Chromosomal Localization of the Carcinoembryonic Antigen Gene Family and Differential Expression in Various Tumors

Carcinoembryonic antigen (CEA) is a glycoprotein which is important as a tumor marker for a number of human cancers. It is a member of a gene family comprising about 10 closely related genes. In order to characterize mUNAs transcribed from individual genes we have identified by DNA and RNA hybridization experiments, gene-specific sequences from the 3 ' noncoding regions of CEA, and of nonspecific cross-reacting antigen (NCA) mRNAs, which have been recently cloned. With these probes, CEA mRNAs with lengths of 3.5 and 3.0 kilobases and an NCA mRNA species of 2.5 kilobases were identified in various human tumors. A 2.2-kilobase mRNA species, however, could only be detected in leu kocytes of patients with chronic myeloid leukemia by hybridization with a probe from the immunoglobulin-like repeat domain of CEA. This region is known to be very similar among the various members of the CEA gene family, and indeed the probe hybridizes with all four mRNA species. In situ hybridization with a cross-hybridizing probe from the NCA gene localized the members of the CEA gene family to the short and to the long arm of chromosome 19. In addition, a CEA cDNA probe was found to hybridize to the long arm of chromosome 19 only

Entwicklung und Überprüfung einer Kurzskala zur Messung akademischen Betrugsverhaltens im Selbstbericht

Akademisches Betrugsverhalten ist ein bedeutsames Phänomen, zu dessen Prävalenz und Randbedingungen im Hochschulsektor deutliche Forschungslücken bestehen, insbesondere aufgrund Ermangelung valider und ökonomischer Selbstberichtsmaße. Die vorliegende Kurzskala zur Erfassung akademischen Betrugsverhaltens soll unter Bedingung hoher Testökonomie eine verhaltensbezogene Erfassung von akademischen Betrugsverhalten im Selbstbericht ermöglichen. Die Itemgenese orientierte sich an umfassenden englischsprachigen Verhaltensinventaren. Insgesamt werden mit jeweils einem Item die zentralen Komponenten „Nutzung unerlaubter Hilfsmittel und Hilfestellungen“, „Plagiarismus“ und „Täuschung zur eigenen Vorteilnahme“ erfasst. Analysen zur Testgüte des 3-Item-Maßes in einer Stichprobe von N = 1 994 Studierenden zeigen eine akzeptable interne Konsistenz und ein deutliches Muster konvergenter Validität (Assoziationen mit umfassenderen Verhaltensinventaren und der Persönlichkeitseigenschaft Ehrlichkeit / Bescheidenheit). Konfirmatorische Faktoranalysen verdeutlichen, dass sich die Skala für die latente Modellierung des Konstruktes eignet und sie messinvariant für verschiedene Fachgruppen sowie Geschlechter ist. In der Summe bietet die vorgestellte Kurzskala eine verhaltensbezogene, ökonomische und reliable Messung akademischen Betrugsverhaltens

Comparison of marker gene expression in chondrocytes from patients receiving autologous chondrocyte transplantation versus osteoarthritis patients

Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans, but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT. Gene expression profiles were determined using quantitative RT-PCR for type I, II and X collagen, aggrecan, IL-1β and activin-like kinase-1. Furthermore, we tested the capability of osteoarthritic chondrocytes to generate hyaline-like cartilage by implanting chondrocyte-seeded collagen scaffolds into immunodeficient (SCID) mice. OA chondrocytes ex vivo showed highly elevated levels of IL-1β mRNA, but type I and II collagen levels were comparable to those of healthy chondrocytes. After primary culture, IL-1β levels decreased to baseline levels, while the type II and type I collagen mRNA levels matched those found in chondrocytes used for ACT. OA chondrocytes generated type II collagen and proteoglycan-rich cartilage transplants in SCID mice. We conclude that after expansion under suitable conditions, the cartilage of OA patients contains cells that are not significantly different from those from healthy donors prepared for ACT. OA chondrocytes are also capable of producing a cartilage-like tissue in the in vivo SCID mouse model. Thus, such chondrocytes seem to fulfil the prerequisites for use in ACT treatment

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Immunology and genetics of type 1 diabetes

Type 1 diabetes is one of the most well-characterized autoimmune diseases. Type 1 diabetes compromises an individual's insulin production through the autoimmune destruction of pancreatic Β-cells. Although much is understood about the mechanisms of this disease, multiple potential contributing factors are thought to play distinct parts in triggering type 1 diabetes. The immunological diagnosis of type 1 diabetes relies primarily on the detection of autoantibodies against islet antigens in the serum of type 1 diabetes mellitus patients. Genetic analyses of type 1 diabetes have linked human leukocyte antigen, specifically class II alleles, to susceptibility to disease onset. Environmental catalysts include various possible factors, such as viral infections, although the evidence linking infections with type 1 diabetes remains inconclusive. Imbalances within the immune system's system of checks and balances may promote immune activation, while undermining immune regulation. A lack of proper regulation and overactive pathogenic responses provide a framework for the development of autoimmune abnormalities. Type 1 diabetes is a predictable and potentially treatable disease that still requires much research to fully understand and pinpoint the exact triggering events leading to autoimmune activation. In silico research can aid the comprehension of the etiology of complex disease pathways, including Type I diabetes, in order to and help predict the outcome of therapeutic strategies aimed at preserving Β-cell function. Mt Sinai J Med 75:314–327, 2008. © 2008 Mount Sinai School of MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60987/1/20052_ftp.pd

The 3-triangle method preserves the posterior tibial slope during high tibial valgus osteotomy: first preliminary data using a mathematical model

Purpose Despite much improved preoperative planning techniques accurate intraoperative assessment of the high tibial valgus osteotomy (HTO) remains challenging and often results in coronal over- and under-corrections as well as unintended changes of the posterior tibial slope. Noyes et al. reported a novel method for accurate intraoperative coronal and sagittal alignment correction based on a three-dimensional mathematical model. This is the first study examining preliminary data via the proposed Noyes approach for accurate intraoperative coronal and sagittal alignment correction during HTO. Methods From 2016 to 2020 a total of 24 patients (27 knees) underwent HTO applying the proposed Noyes method (Noyes-Group). Radiographic data was analyzed retrospectively and matched to patients that underwent HTO using the conventional method, i.e., gradual medial opening using a bone spreader under fluoroscopic control (Conventional-Group). All operative procedures were performed by an experienced surgeon at a single orthopaedic university center. Results From the preoperative to the postoperative visit no statistically significant changes of the posterior tibial slope were noted in the Noyes-Group compared to a significant increase in the Conventional-Group (p = 0.01). Regarding the axial alignment no significant differences between both groups were observed pre- and postoperatively. The number of over- and under-corrections did not differ significantly between both groups. Linear regression analysis showed a significant correlation of the postoperative medial proximal tibial angle (MPTA) with the position of the weightbearing line on the tibial plateau. Conclusion The 3-triangle method by Noyes seems to be a promising approach for preservation of the posterior tibial slope during HTO