المؤلفون: S, Söder

المصدر: Der Pathologe. 37(Suppl 2)

مصطلحات موضوعية: Cartilage, Articular, Chondrocytes, Phenotype, Multigene Family, Osteoarthritis, Synovial Membrane, Cytokines, Humans, Matrilin Proteins, Bone and Bones, Cellular Senescence, DNA Damage

الوصف: Osteoarthritis is a complex disease involving not only the cartilage but also the adjacent bone and the synovial membrane. The etiology of osteoarthritis involves multiple factors. Unlike secondary forms of osteoarthritis, which are the result of other diseases or excessive mechanical stress, the origins of primary forms of osteoarthritis lie within the cartilage. In primary osteoarthritis complex interactions of cytokines leading to a derangement of homeostasis have been discovered, which lead to a slow and progressive degeneration of the cartilage and bone, ultimately resulting in destruction of the joint. Damage to the cartilage matrix is caused by an increased activity of matrix metalloproteases induced by catabolic cytokines. One of the initial events triggering these processes might be degenerative DNA alterations causing local defects in multiple genes leading to an impaired function of chondrocytes and a phenotype similar to senescence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::c3f3ae5fceaf4fe00578503fc2425371Test
https://pubmed.ncbi.nlm.nih.gov/27638529Test

المؤلفون: P, Komminoth

المصدر: Der Pathologe. 37(3)

مصطلحات موضوعية: Adult, Diagnosis, Differential, Male, Early Diagnosis, Chromosomes, Human, Pair 21, Endocrine Glands, Multigene Family, DNA Mutational Analysis, Humans, Female, Child, Polyendocrinopathies, Autoimmune, Transcription Factors

الوصف: Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::29e7a8c7b3a2503cb9bd0242bcd566aaTest
https://pubmed.ncbi.nlm.nih.gov/27099223Test

المؤلفون: P-U, Tunn, B, Gebauer, J, Fritzmann, M, Hünerbein, P M, Schlag

المصدر: Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen. 75(12)

مصطلحات موضوعية: Biopsy, Extremities, Sarcoma, Soft Tissue Neoplasms, Magnetic Resonance Imaging, Neoadjuvant Therapy, Diagnosis, Differential, Gene Expression Regulation, Neoplastic, Multigene Family, Positron-Emission Tomography, Humans, Neoplasm Metastasis, Tomography, X-Ray Computed, Ultrasonography

الوصف: Soft tissue sarcomas are characterized by their heterogeneity. With new diagnostic imaging techniques, low- and high-grade components of the tumor can be differentiated. Thus biopsies should be guided by imaging to assure representative specimens. Besides histopathology, the advent of chromosomal and gene expression analysis may allow more accurate classification in the near future. Gene expression profiling has already proven its value by finding new subclassifications in other tumor types. Furthermore, this technique is a promissing tool to predict the response of a tumor to neoadjuvant and adjuvant therapy. Up to now, response evaluation in neoadjuvant therapy is based on tumor size and not on vital tumor cells. Newer techniques (i.e., Magnetic-resonance-Spectroscopy, Molecular Imaging) can show the change of metabolism in neoadjuvant therapy and allow objective, comparative measurement of biological activity. The diagnostic of soft tissue sarcomas implies primarily a multidisciplinary approach for a stage associated therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::2060d1a65449ed82801d7d4ba834f93eTest
https://pubmed.ncbi.nlm.nih.gov/15368057Test

المؤلفون: K P, Sauer, M, Hoch

المصدر: Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS. 37(6)

مصطلحات موضوعية: Receptors, Notch, Transforming Growth Factor beta, Multigene Family, Mutation, Animals, Humans, Membrane Proteins, Nervous System Physiological Phenomena, Signal Transduction

الوصف: This review tries to establish a synthesis between the comparative/morphological approach and the molecular analysis of ontogenetic processes in development and evolution. We use the formation of the nervous system in metazoans as a paradigm to point out that highly conserved molecular mechanisms may be responsible to generate tissues and organ systems in bilateria. We discuss the conserved role of the Hox genes in anterior- posterior patterning, the function of the Achaete-scute genes and of the Notch/Delta signalling cascade in determining neural fates and the role of the BMP-4/Dpp-signalling pathway in positioning the neuroectoderm along the dorso-ventral axis of vertebrates and insects. We try to demonstrate that the evolution of complex body structures is based on modifying ontogenetic processes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::fa0be4dcb683752dd342dc018ee7d033Test
https://pubmed.ncbi.nlm.nih.gov/12063583Test

المؤلفون: B, Hube, D, Sanglard, M, Schaller, A, Ibrahim, F C, Odds, N A, Gow

المصدر: Mycoses. 41

مصطلحات موضوعية: Isoenzymes, Virulence, Gene Expression Regulation, Fungal, Hydrolysis, Multigene Family, Candida albicans, Endopeptidases, Mutation, Candidiasis, Humans, Membrane Proteins, Polymerase Chain Reaction

الوصف: Secreted Aspartate Proteinases (Sap) are among those factors of the human pathogen Candida albicans, which promote infections in the immunocompromised host. Sap isoenzymes are encoded by at least nine different genes (SAP1-9), which are differentially regulated in vitro. RT-PCR analysis during experimental infections and from patient samples confirmed the expression of SAP genes in vivo. However, while Sap2 is the dominant isoenzyme under culture conditions, other SAP genes are also expressed during infections. In order to investigate the role of single isoenzymes during the pathogenesis of candidosis, mutants were produced which harbour deletions in SAP1, SAP2, SAP3 and SAP4-6. Although only SAP2 and SAP4-6 mutants showed a strong reduction of proteolytic activity in vitro, all SAP mutants were significantly attenuated in systemic infections. In addition, SAP2, SAP3 and SAP4-6 mutants were clearly more sensitive to neutrophilic leucocytes compared to the wild type SC5314. These investigations show that several proteinase isoenzymes are likely to be involved in the pathogenesis of candidosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::ffcceca5006d50f728b307fdb7c3311eTest
https://pubmed.ncbi.nlm.nih.gov/9717386Test

المؤلفون: H R, Toka, O, Toka, F C, Luft

المصدر: Fortschritte der Medizin. 115(28)

مصطلحات موضوعية: Renin-Angiotensin System, Risk Factors, Mineralocorticoids, Multigene Family, Hyperaldosteronism, Hypertension, Chromosome Mapping, Humans, Water-Electrolyte Balance, Glucocorticoids

الوصف: Essential hypertension is a polygenic disease. Various genes responsible for rare monogenic forms of hypertension have been identified in the recent years. These are glucocorticoid remediable aldosteronism (GRA), Liddle's syndrome and apparent mineralocorticoid excess (AME). A fourth form, the Bilginturan syndrome is associated with brachydactyly and resembles essential hypertension. The investigations of the pathomechanisms in these rare diseases can help us to understand common hypertension.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::eb589c09d28a00c203ad765f239f5fc7Test
https://pubmed.ncbi.nlm.nih.gov/9445830Test

المؤلفون: V, Heussler, D, Dobbelaere

المصدر: Schweizer Archiv fur Tierheilkunde. 138(3)

مصطلحات موضوعية: Cysteine Endopeptidases, Base Sequence, Sequence Homology, Amino Acid, Multigene Family, Molecular Sequence Data, Animals, Amino Acid Sequence, Cloning, Molecular, Fasciola hepatica, Polymerase Chain Reaction, Genes, Helminth, Recombinant Proteins, DNA Primers

الوصف: RT-PCR and degenerative Oligonucleotide primers derived from conserved cysteine protease sequences were used to amplify seven different Fasciola hepatica cysteine protease cDNA clones (Fcp1-7). Five of the clones showed homology to proteases of the cathepsin L type, whereas two appeared to represent the cathepsin B family. The 5' and the 3' regions of Fcp1 were amplified using the rapid amplification of cDNA Ends PCR (RACE-PCR) protocol. The Fcp1 cDNA fragment was also subcloned in the expression vector pGEX and expressed as a glutathione-S-transferase (GST) fusion protein. Antibodies, raised in rabbits against the GST:Fcp1 fusion protein, were used in Western blot analysis to examine expression in different life-cycle stages of F. hepatica. In extracts from immature and adult parasites proteins of 30 and 38 kDa were detected. In other stages, proteins of different molecular weight were recognized by anti-GST:Fcp1 antiserum, indicating stage-specific gene expression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::7a48da64dcf4f078896ccb5766441277Test
https://pubmed.ncbi.nlm.nih.gov/8721186Test

المؤلفون: W, Haedicke, A, Greiner, C, Knörr, M, Eck, H K, Müller-Hermelink

المصدر: Verhandlungen der Deutschen Gesellschaft fur Pathologie. 80

مصطلحات موضوعية: Hybridomas, Base Sequence, Genes, Immunoglobulin, Multigene Family, Molecular Sequence Data, Immunoglobulin Variable Region, Humans, Lymphoma, B-Cell, Marginal Zone, Immunoglobulin Heavy Chains

الوصف: The antigen receptor of the MALT lymphoma cells provides crucial information, which may help to elucidate the pathogenesis of that tumor. Therefore hybridomas were produced from five MALT type lymphomas. The identity was proven by sequencing the VH chain of the tumor and the hybridomas. It could be shown the one step of subcloning and limiting dilution is necessary to obtain a monoclonal hybridoma in most cases. So it is indispensable to check the identity of the tumor antibody and the hybridoma antibody for each hybridoma. Otherwise it may be possible that bystander cells infiltrating the tumor, but not belonging to the malignant clone, get fused. Furthermore we provide evidence of an intra tumoral diversity within the MALT type lymphoma that was reflected by the different mutation pattern of the tumor derived hybridomas. Therefore the hybridomas are allowing investigation on the protein level about the hypermutation of the genes of the MALT lymphoma antibodies and the possible role antigenic selection within the tumor.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::7351e0662fae01ebd0aaedb171318ebfTest
https://pubmed.ncbi.nlm.nih.gov/9065034Test

المؤلفون: H, Reichenbach, H, Holland, B, Thamm, T, Theile

المصدر: Kinderarztliche Praxis. 61(7-8)

مصطلحات موضوعية: Male, X Chromosome, Intellectual Disability, Karyotyping, Multigene Family, Disorders of Sex Development, Chromosome Mapping, Humans, Infant, Abnormalities, Multiple, Sex Chromosome Aberrations

الوصف: A child with multiple abnormalities and intersexual external genitals is presented. The child has a male karyotype with a partial duplication Xp. Using additionally methods of molecular genetics the SRY-region was detected. We reviewed the only few persons described in the literature with male karyotype and partial duplications Xp. There are similarities in phenotype including sex inversion or intersexual genitals if the duplication is localised in the region Xp 21--Xp 22. Whether these affected patients represent a new syndrome is a moot point. We also found the aberrant X-chromosome in the mother of the child. In the present pregnancy of the mother there is, therefore, a risk of recurrence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::3785d7708112e7411e14d4b67d41e7f2Test
https://pubmed.ncbi.nlm.nih.gov/8271681Test

المؤلفون: W, Conca

المصدر: Immunitat und Infektion. 21

مصطلحات موضوعية: Arthritis, Multigene Family, Gene Expression, Humans, Metalloendopeptidases, Extracellular Matrix

الوصف: The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::3d7c37f364909a51de0aaa7133a49cb1Test
https://pubmed.ncbi.nlm.nih.gov/8344678Test