RESUMO
PURPOSE: Advances in treatment enables most patients with congenital heart diseases (CHD) to survive into adulthood, implying the need to address comorbid conditions in this growing cohort of patients. The aim of this study was to evaluate the prevalence of sleep-disordered breathing (SDB) and lung function abnormalities in patients with adult congenital heart disease (ACHD). METHODS: Patients with ACHD underwent level 3 sleep testing (Embletta MPR polygraphy) and pulmonary function testing. Results were stratified by the underlying haemodynamic ACHD lesion group. RESULTS: Patients with ACHD (n = 100) were middle-aged (42.3 ± 14.6 years), 54% male and slightly overweight (BMI 25.9 ± 5.5 kg/m2). Polygraphy revealed a prevalence of sleep apnoea of 39% with 15% of patients presenting with predominantly obstructive apnoeic episodes, while 23% of patients presenting primarily with central sleep apnoea. The distribution of mild, moderate, and severe sleep apnoea in the total study population was 26%, 7% and 6%, respectively. Comparison of apnoea-hypopnoea index, presence of sleep apnoea, and apnoea severity did not offer significant differences between the four ACHD lesion groups (p = 0.29, p = 0.41 and p = 0.18, respectively). Pulmonary function testing revealed obstructive lung disease in 19 of 100 patients. Concomitant chronic obstructive pulmonary disease and obstructive sleep apnoea were diagnosed in 3% of patients and were associated with profound nocturnal desaturation. CONCLUSION: The findings suggest a mild propensity amongst patients with ACHD to develop SDB that seems to be unaffected by the specific underlying congenital lesion.
Assuntos
Cardiopatias Congênitas , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Pessoa de Meia-Idade , Humanos , Masculino , Adulto , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Sono , PulmãoRESUMO
The direct comparison of day care pain patients with patients from other treatment sectors with respect to sociodemographic, pain-related and psychological characteristics has not yet been the subject of systematic analyses. The project core documentation and quality assurance in pain therapy (KEDOQ-pain) of the German Pain Society (Deutsche Schmerzgesellschaft e.V.) makes this comparison possible. This second analysis of the available KEDOQ data was intended to show how patients receiving day care treatment can be characterized using the core data set and whether and to what extent they differ from patients receiving outpatient or inpatient treatment. This is a continuation of the first publication, which showed remarkably small differences between outpatients and inpatients but did not include day care patients.The KEDOQ-pain data from 25 centers with a total of 8953 patients were evaluated. Patients had completed the German pain questionnaire (DSF) between January 2012 and March 2017 and received day care (nâ¯= 1264), outpatient (nâ¯= 4082) or inpatient (nâ¯= 3607) pain therapy treatment. Sociodemographic, pain-related and psychometric data of the DSF reported by patients were evaluated as well as physician information on the pain chronification stage and pain localization. The evaluation was descriptive and compared groups using univariate and multivariate procedures.Day care treated patients were significantly younger, had a higher level of education, were more frequently employed, reported higher impairment values and showed a higher severity index according to von Korff than inpatients and outpatients treated for pain. In addition, they described a shorter pain duration as well as worse habitual well-being (Marburg questionnaire on habitual well-being, MFHW). These predictors explained roughly half of the variance in the prediction of the day care treatment setting. The comparison of outpatients and inpatients showed significant group differences for some variables; however, the effects were very small.The evaluations suggest that pain therapy day care facilities treat a special group of pain patients that significantly differ from patients in other treatment sectors. Cautious conclusions are drawn regarding the systematic allocation of patients to care appropriate to their treatment needs.
Assuntos
Hospital Dia , Pacientes Ambulatoriais , Manejo da Dor , Alemanha , Humanos , Pacientes Internados , DorRESUMO
A comparison of chronic pain patients in outpatient and inpatient treatment settings regarding pain-related and psychological characteristics, has not yet been systematically analyzed. The core documentation and quality assurance in pain therapy (KEDOQ-Schmerz) is a quality assurance system for documentation and quality management of pain therapy in different treatment settings. The system was initiated by the German Pain Society. We used KEDOQ-Schmerz data to describe differences between patients being treated in outpatient and inpatient settings with respect to social, pain-related and psychological factors. In total, the set of KEDOQ-Schmerz data analyzed included information from 4705 patients (from 13 clinics) collected between January 2012 and April 2016. Patients received either outpatient (n = 2682) or inpatient (n = 2023) treatment. The data analyzed comprised sociodemographic, pain-related and psychological data collected through the German Pain Questionnaire (DSF) at the beginning of treatment as well as information about pain chronification and pain localization provided by practitioners. The statistical analysis was carried out by descriptive and comparative data analysis using univariate and multivariate statistical methods. Patients with inpatient treatment were significantly older, more often female and more often had multiple pain localizations. They described stronger pain intensity and more frequently had a higher Mainz Pain Staging System (MPSS) score of pain chronification. They described a significantly poorer physical and mental health-related quality of life in the short form (SF-12) health survey, had significantly higher depression, anxiety and stress values (DASS) and a poorer habitual well-being in the Marburg questionnaire on habitual well-being (MFHW). Significant group differences had only small effect sizes. Even though most predictors for the inpatient treatment setting in multivariate analysis were significant, in total they explained less than 5% of the variance. The results indicate that pain therapy in specialized pain settings more and more has to manage patients with higher pain chronification, higher pain-related stress and previous therapy experience. The differences in patient characteristics between treatment settings are mostly clinically unimportant. Differences in clinical features do not declare the allocation to one treatment setting or the other.
Assuntos
Manejo da Dor , Qualidade de Vida , Feminino , Alemanha , Humanos , Pacientes Internados , Pacientes AmbulatoriaisRESUMO
The expression of the 330 kDa AN2 glycoprotein was studied in the rodent peripheral nervous system. AN2 is expressed by immature Schwann cells in vitro and in vivo and downregulated as the cells upregulate myelin genes. A subpopulation of nonmyelinating Schwann cells in the adult sciatic nerve retains expression of AN2. In rat sciatic nerve crushes, where Schwann cell numbers increase after initial axonal loss and markers of immature Schwann cells show an upregulation, no increased expression of AN2 was observed. In contrast, AN2 expression was upregulated in nerves from peripheral myelin protein-22-transgenic rats, where immature Schwann cells expand without axonal loss. Furthermore, coculture with neurons upregulated AN2 expression on Schwann cells in vitro. Polyclonal antibodies against AN2 inhibited the migration of an immortalized Schwann cell clone in an in vitro migration assay, and the purified AN2 protein was shown to be neither inhibitory nor permissive for outgrowing dorsal root ganglion neurites. AN2 is thus a novel marker for the Schwann cell lineage. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of purified AN2 from early postnatal mouse brain demonstrated that AN2 is the murine homolog of the rat NG2 proteoglycan.
Assuntos
Antígenos de Diferenciação/biossíntese , Antígenos/biossíntese , Proteínas de Bactérias , Doença de Charcot-Marie-Tooth/genética , Bainha de Mielina/metabolismo , Proteoglicanas/biossíntese , Células de Schwann/metabolismo , Animais , Antígenos/análise , Antígenos/genética , Química Encefálica , Linhagem da Célula/fisiologia , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Gânglios Espinais/citologia , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos , Proteínas da Mielina/genética , Neuritos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato , Processamento de Proteína Pós-Traducional/genética , Proteoglicanas/análise , Proteoglicanas/genética , Ratos , Ratos Wistar , Células de Schwann/citologia , Nervo Isquiático/fisiologia , Homologia de Sequência de Aminoácidos , Degeneração Walleriana/metabolismoRESUMO
Four connexin32 (Cx32) cDNA clones isolated from a rat sciatic nerve cDNA library differ in the nucleotide sequence of their 5' untranslated region (UTR) from the corresponding Cx32 cDNA clones previously characterized from liver. The new Cx32 5'UTR sequence detected in the sciatic nerve cDNA clones is identical to one previously found in the 6.5 kb intron of the murine Cx32 gene. Using primer extension and S1 nuclease protection analysis, we determined the transcriptional starting point of this new alternative Cx32 transcript expressed in the sciatic nerve. This starting point is located 444 bp (409 bp) upstream of exon2 in a region previously described as an intron of the Cx32 gene in the rat (and mouse) genome, respectively. The alternative exon1B comprises 99 bp in rat, but 97 bp in the mouse genome, and is spliced to the same exon2 acceptor site also used for splicing of exon1 in liver. Both transcripts are likely to code for the same Cx32 protein whose reading frame is located in exon2. The putative promoter region, upstream of the alternative exon1B, contains a TATAAA motif and has been sequenced and noticed before by Miller et al. (Biosci. Rep. 8, 455-464, (1988)). The alternative exon1B transcript is highly expressed in the sciatic nerve, (i.e. Schwann cells) and very low in liver (i.e. hepatocytes). Its expression is regulated after sciatic nerve injury. The time course of expression was similar to previously established myelin genes and, therefore, we suggest that the expression of the alternative exon1B Cx32 transcript is related to the process of myelination. Very recently, we have characterized another alternative Cx32 exon1A which is transcribed in mouse embryonic stem cells but not in the sciatic nerve (Dahl et al., submitted for publication, 1995). Thus, the murine Cx32 gene is likely to be regulated by three alternative promoters that appear to be activated in a cell type-specific manner.
Assuntos
Conexinas/metabolismo , Junções Comunicantes/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Animais , Animais Recém-Nascidos , Sequência de Bases , Células Cultivadas , Clonagem Molecular , Conexinas/genética , Primers do DNA , DNA Complementar , Éxons , Expressão Gênica , Biblioteca Gênica , Íntrons , Masculino , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ratos , Ratos Wistar , Células de Schwann/citologia , Nervo Isquiático/citologia , Nervo Isquiático/lesões , Análise de Sequência , Homologia de Sequência do Ácido Nucleico , Endonucleases Específicas para DNA e RNA de Cadeia Simples/metabolismo , Proteína beta-1 de Junções ComunicantesRESUMO
A rat cDNA clone (pCD67) isolated from a cDNA library of regenerating sciatic nerve by differential hybridization screening revealed 75% homology on the nucleic acid level and 81% homology (including conservative amino acid changes) to the deduced amino acid sequence of the core protein of human dermatan/chondroitin sulfate proteoglycan decorin (PGII, PG40, PG-S2). Two transcripts of 1.3 and 1.75 KB very similar in size to the two decorin mRNA species previously identified in connective tissue were detected by Northern blotting in both normal and injured sciatic nerve and in the mature and embryonic rat brain. The steady-state level of the decorin 1.3 KB mRNA was very much higher in peripheral nerve than in the central nervous system or in other non-neural tissues (skeletal muscle, heart, colon, kidney). In situ hybridization experiments indicated that decorin mRNA is expressed by Schwann cells and vascular cells in peripheral nerve. In the spinal cord the ventral horn motor neurons and other neurons in gray matter showed specific hybridization signals. Furthermore, in situ hybridization indicated decorin expression in Purkinje neurons and cells of the molecular layer in cerebellum, and in neurons of the primary olfactory cortex and brainstem (pons). Our data clearly demonstrate decorin mRNA expression in distinct neural cell populations, suggesting yet unknown functions of this proteoglycan in the peripheral and central nervous system.
Assuntos
Sistema Nervoso/química , Proteoglicanas/genética , RNA Mensageiro/análise , Sequência de Aminoácidos , Animais , Northern Blotting , Sistema Nervoso Central/química , Sistema Nervoso Central/metabolismo , Clonagem Molecular , Colo/química , Colo/metabolismo , DNA/genética , Sondas de DNA , Decorina , Proteínas da Matriz Extracelular , Imuno-Histoquímica , Hibridização In Situ , Rim/química , Rim/metabolismo , Músculos/química , Músculos/metabolismo , Sistema Nervoso/metabolismo , Neurônios/química , Neurônios/metabolismo , Nervos Periféricos/química , Nervos Periféricos/metabolismo , Proteoglicanas/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Nervo Isquiático/química , Nervo Isquiático/metabolismo , Homologia de Sequência do Ácido NucleicoRESUMO
Regeneration of the peripheral nervous system after injury depends on a complex sequence of histopathological reactions that comprise a highly reproducible sequence of degenerative reactions, termed Wallerian degeneration. During this period a remodelling of the distal nerve stump prepares a microenvironment that permits successful regrowth of nerve fibers from the proximal nerve fragment. This stereotypical sequence of reactions is reflected by a differential and coordinate expression of genes with specific functions in the process of regeneration. This review will summarize cellular and molecular reactions that contribute to peripheral nerve regeneration including data of a pilot study in which membrane based cDNA array expression technology was applied. We examined the expression of 588 annotated genes in response to a crush lesion of rat sciatic nerves. Approximately 40 % of the genes spotted onto the array filters showed expression significantly above background and 55 of these detected genes represented differential expression profiles after nerve lesion. This approach revealed to be suitable for systematic screening of regeneration associated genes.
Assuntos
Regeneração Nervosa/genética , Nervos Periféricos/fisiologia , Animais , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Traumatismos dos Nervos Periféricos , Projetos PilotoRESUMO
Focal cortical lesions are associated with a functional downregulation of the GABAergic system in perilesional tissue lasting (at least) several weeks. The molecular mechanisms underlying this phenomenon are still poorly understood. Here we used RT-PCR to investigate whether mRNA-levels of two alpha-subunits of the GABAA-receptor (alpha1- and alpha2-subunits) change following ischemic cortical lesioning. The results show that 7 days after lesion induction mRNA-levels for both the alpha1- and alpha2-subunits are increased threefold in perilesional tissue ipsilateral, but not contralateral to the lesion. Taken together with the results of a previous immunohistochemical study in which a moderate decrease of the alpha1-subunit-protein and no change for the alpha2-subunit [T. Neumann-Haefelin, J.F. Staiger, C. Redecker, K. Zilles, J.M. Fritschy, H. Mohler, O.W. Witte, Immunohistochemical evidence for dysregulation of the GABAergic system ipsilateral to photochemically induced cortical infarcts in rats. Neuroscience (Oxford) 87 (4) (1998) 871-879] was observed, this is interpreted as a partial block of translation in the perilesional tissue surrounding cortical ischemic lesions.
Assuntos
Isquemia Encefálica/metabolismo , RNA Mensageiro/biossíntese , Receptores de GABA-A/genética , Regulação para Cima , Animais , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Lateralidade Funcional , Masculino , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoAssuntos
Anticorpos/isolamento & purificação , Complexo Antígeno-Anticorpo/isolamento & purificação , Antígenos/isolamento & purificação , Albumina Sérica/imunologia , Animais , Complexo Antígeno-Anticorpo/análise , Cromatografia por Troca Iônica , Humanos , Imunodifusão , Técnicas Imunológicas , Focalização Isoelétrica , CoelhosRESUMO
We have previously shown that Mst87F (previously called mst(3)g1-9), a gene which is exclusively expressed in the male germ line of Drosophila melanogaster, is subject to negative translational control. While transcription of this gene takes place premeiotically, translation occurs only after the elongation of spermatids is complete. We report here the identification of a sequence element within the first 45 nucleotides of the leader which is crucial for this translational regulation. Sequence comparison with six other genes, which form a gene family with Mst87F, shows the conservation of a twelve nucleotide element within this leader segment. It is found in all genes at positions +28 to +39 of the leader. Deletion of this element or alteration of two nucleotides by in vitro mutagenesis both lead to the breakdown of the translational control mechanism. The poly(A) tail of the Mst87F mRNA becomes longer and heterogeneous in length when the mRNA is recruited for translation. We present evidence that the control for this additional polyadenylation also resides within the conserved element of the leader.
Assuntos
Drosophila melanogaster/genética , Meiose/genética , Poli A/metabolismo , Biossíntese de Proteínas , Sinais Direcionadores de Proteínas/genética , RNA Mensageiro/metabolismo , Espermatócitos/metabolismo , Animais , Sequência de Bases , Citoplasma/metabolismo , Masculino , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/genética , Espermatócitos/ultraestruturaRESUMO
A characteristic feature of the vertebrate nervous system is the ensheathment of axons by myelin, a multilamellar membrane specialization produced by polarized glial cells. Although the main protein and lipid components of the myelin sheath are well characterized, relatively little is known about the mechanisms of their intracellular distribution to the respective sites of assembly within the myelin sheath. To analyze whether peripheral myelin protein trafficking is mediated by glycosphingolipid/cholesterol-enriched membranes (GEMs), we studied the association of established myelin proteins, peripheral myelin protein 22 (PMP22), protein zero (P0), plasmolipin, and myelin basic protein (MBP), with these membrane microdomains. To examine the association of the selected peripheral myelin proteins with detergent-insoluble GEMs, purified myelin from sciatic nerve of adult rat was extracted with Triton X-100 at 4 degrees C and 37 degrees C and, in additional experiments, was pretreated with the cholesterol chelator methyl-beta-cyclodextrin. The material was then centrifuged to equilibrium in sucrose gradients, and fractions were analyzed by Western blotting. Here we demonstrate for the first time that PMP22, P0, and plasmolipin prepared from purified peripheral myelin are associated with GEMs. To characterize whether the association of these proteins is a specialized feature of myelinating Schwann cells, we studied the distribution of PMP22, P0, and plasmolipin in transiently transfected HeLa cells. These experiments confirm the specific association of these proteins with GEMs in both neural and nonneural cell types.
Assuntos
Estruturas da Membrana Celular/química , Colesterol/análise , Glicoesfingolipídeos/análise , Proteínas de Membrana , Proteínas da Mielina/análise , Bainha de Mielina/química , Proteínas do Tecido Nervoso , Animais , Western Blotting , Técnicas de Cultura de Células , Células HeLa/química , Humanos , Proteína Básica da Mielina/análise , Proteína P0 da Mielina/análise , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Sistema Nervoso Periférico , Proteolipídeos/análise , Ratos , Ratos Wistar , Células de Schwann/química , Nervo IsquiáticoRESUMO
The peripheral myelin protein PMP22 gene has been described as a growth arrest-specific gene gas3 and has been identified as disease gene of various demyelinating neuropathies. The gene consists of two highly conserved alternative noncoding 5'-exons la (CD25) and 1b (SR13), respectively. Differential expression patterns of these transcripts in vivo and in vitro suggest a very complex mode of PMP22 gene regulation, which cannot be explained merely by transcriptional control. In fact, the PMP22 gene is regulated on different post-transcriptional levels. While reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed no alterations in stability for both PMP22 transcripts in randomly growing Schwann cell cultures of rat sciatic nerve for at least 8 hours, in serum-induced synchronized cultures of resting cells we observed a specific cell cycle-regulated degradation of both transcripts. We further prepared diverse PMP22/CAT fusion genes to study the influence of the alternative 5'UTRs on PMP22 translation. Transient transfection of NIH3T3-fibroblasts and rat Schwann cells demonstrated that the alternative 5'UTRs (CD25 and SR13) and the 3'UTR exert differential regulatory influences on the translation efficiency.
Assuntos
Proteínas da Mielina/genética , Processamento de Proteína Pós-Traducional/genética , Regiões 3' não Traduzidas/genética , Células 3T3 , Regiões 5' não Traduzidas/genética , Animais , Sequência de Bases , Northern Blotting , Células Cultivadas , Cloranfenicol O-Acetiltransferase/biossíntese , Primers do DNA , Humanos , Luciferases/biossíntese , Camundongos , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , Ratos , Receptores de Interleucina-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células de Schwann/metabolismo , Transfecção/genéticaRESUMO
Metabotropic glutamate receptors (mGluRs) seem to be involved both in neuronal excitotoxicity evoked by pathological conditions such as ischemia, and in processes associated with neuronal plasticity and regulation of synaptic strength. Using semiquantitative reverse transcription-polymerase chain reaction, we measured the messenger RNA levels of mGluR2-5, 24 h and 7 days after experimentally induced focal cortical infarcts in rat motor cortex. The mRNA level of mGluR3 was strikingly decreased ipsilaterally after 24 h. On day 7, the expression of mGluR2 was down-regulated both ipsi- and contralaterally. Other receptors of this family showed either a slight or no regulation at both time points. The early changes in the expression pattern of mGluRs might be primarily linked to excitotoxicity processes which occur immediately after an ischemic lesion in cortex, whereas the delayed changes might represent one chain link in the cascade of compensatory mechanisms contributing to functional amelioration.
Assuntos
Isquemia Encefálica/metabolismo , Infarto Cerebral/metabolismo , Regulação da Expressão Gênica/fisiologia , Plasticidade Neuronal/genética , Neurotoxinas/genética , Receptores de Glutamato Metabotrópico/genética , Transcrição Gênica/fisiologia , Animais , Isquemia Encefálica/fisiopatologia , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Masculino , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Transtornos dos Movimentos/metabolismo , Transtornos dos Movimentos/fisiopatologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/genéticaRESUMO
Plasmolipin is a membrane protein and belongs to the tetraspan molecule (4TM) family, an expanding group of myelin proteins many of which could be linked to human hereditary demyelinating neuropathies. We have cloned and sequenced the mouse plasmolipin gene, revealing the common organization of the 4TM gene group with four exons and a large first intron. Western blot analysis with an antibody raised against the C-terminal intracellular part of the protein showed that plasmolipin is expressed not only in the nervous system and kidney, but also in a number of other tissues such as thymus, testis, lung, and thyroid gland. By means of radiation hybrid mapping and FISH analysis, we could localize the human plasmolipin gene to Chromosome 16q13 within the putative region of the Bardet-Biedl syndrome type 2 (BBS2) gene locus. BBS2 is a clinically and genetically heterogeneous group of disorders resulting in rod-cone dystrophy, obesity, postaxial polydactyly, renal dysfunction, and mental retardation, which were very recently associated with a novel gene designated BBS2. With respect to intrafamiliar variations in the manifestation of BBS, we suggest that plasmolipin might be either another candidate gene or a modifier of the BBS2 phenotype.
Assuntos
Síndrome de Bardet-Biedl/genética , Cromossomos Humanos Par 16/genética , Proteínas de Membrana , Proteínas do Tecido Nervoso , Proteolipídeos/genética , Animais , Mapeamento Cromossômico , Cricetinae , Regulação da Expressão Gênica , Genes , Humanos , Hibridização in Situ Fluorescente , Mesocricetus , Camundongos , Família Multigênica , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Especificidade de Órgãos , Proteolipídeos/biossíntese , Proteolipídeos/fisiologia , Mapeamento de Híbridos Radioativos , Ratos , Especificidade da EspécieRESUMO
BACKGROUND: The quality of life (QoL) of patients with malignant diseases decreases significantly. OBJECTIVE: The evaluation of QoL is generally not part of the management of patients with head and neck cancer. The aim of this study was to develop an additional disease- and treatment-specific questionnaire to evaluate QoL in surgically treated head and neck cancer patients. PATIENTS AND METHODS: The general QoL was evaluated with the QLQ-C30 questionnaire developed by the European Organisation of Research and Treatment of Cancer (EORTC). RESULTS: The disease-specific QoL was evaluated using the EORTC H&N35 module. The new questionnaire "Kiel Head and Neck 17" (KQL H&N-17) is a disease- and treatment-specific addition especially in regard to side effects caused by surgical treatment. CONCLUSIONS: A wide application of this whole concept is needed to obtain comparable results from studies suitable for evaluating QoL in patients receiving different treatments for their malignant diseases. Moreover, the effectiveness and quality of treatment could be controlled better, which would help to increase the QoL of these patients.
Assuntos
Neoplasias Otorrinolaringológicas/psicologia , Complicações Pós-Operatórias/psicologia , Qualidade de Vida , Perfil de Impacto da Doença , Atividades Cotidianas/psicologia , Adaptação Psicológica , Humanos , Computação Matemática , Neoplasias Otorrinolaringológicas/cirurgia , Equipe de Assistência ao Paciente , Psicometria , Reprodutibilidade dos Testes , Ajustamento Social , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Disintegrins perform putative functions in cell adhesion, signaling and fusion. We have isolated a 2815-bp rat cDNA (CRII-7) representing a transcript that is differentially expressed during sciatic nerve regeneration. Nucleotide sequence comparison indicates that CRII-7 is the rat homologue to the recently cloned cDNAs MDC15 (ADAM 15) and metargidin (hMDC15) of mouse and human, respectively. The CRII-7 cDNA (rMDC15) encodes a membrane-anchored glycoprotein of approximately 85 kDa containing a disintegrin and a metalloprotease domain. Cellular metalloprotease disintegrins are a family of proteins (ADAMs or MDC proteins) with important roles, e.g., in cell-cell interactions during fertilization, muscle and nerve development, or tumor necrosis factor-alpha (TNF-alpha) cleavage. Northern blot analysis demonstrated a predominant expression of CRII-7/rMDC15 in the nervous system (PNS and CNS) and lung. Analysis of the CRII-7/rMDC15 transcript levels following peripheral nerve lesions demonstrated regulated mRNA expression during Wallerian degeneration and nerve regeneration. The steady-state levels of CRII-7/rMDC15 transcripts markedly increased within the first day after lesion and then steadily decreased for at least 4 weeks. CRII-7/rMDC15 mRNA expression was further examined during postnatal development and maturation of rat sciatic nerve and brain, as well as in cultured Schwann cells, meningeal fibroblasts, and astrocytes. In situ hybridization on paraffin sections showed the cellular localization of CRII-7/rMDC15 mRNA in Schwann cells and endothelial cells of peripheral nerve and in various neuronal populations in brain and spinal cord.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Nervo Isquiático/lesões , Proteínas ADAM , Animais , Astrócitos/citologia , Astrócitos/fisiologia , Sequência de Bases , Northern Blotting , Células Cultivadas , Sistema Nervoso Central/citologia , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/fisiologia , Clonagem Molecular , Colforsina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hibridização In Situ , Técnicas In Vitro , Meninges/citologia , Meninges/fisiologia , Dados de Sequência Molecular , RNA Mensageiro/análise , Ratos , Ratos Wistar , Células de Schwann/citologia , Células de Schwann/fisiologia , Nervo Isquiático/citologia , Nervo Isquiático/crescimento & desenvolvimento , Homologia de Sequência de Aminoácidos , Degeneração Walleriana/fisiopatologiaRESUMO
Two peripheral myelin protein PMP22 transcripts, CD25 and SR13, have been identified by Northern blot and RNA-polymerase chain reaction (PCR) methods in rat. The CD25 and SR13 mRNA species (each approximately 1.8 kb in size) differ significantly in their 5'-untranslated region (5'-UTR) sequences but encode the same protein. While CD25 mRNA is largely confined to the peripheral nervous system, the SR13 transcript is more ubiquitously expressed in rat tissues. Both transcripts are differentially expressed during postnatal sciatic nerve development. While CD25 expression steadily increases from low levels in neonates up to a maximum at postnatal day 14, SR13 mRNA levels are elevated at birth but decrease throughout adulthood. CD25 and SR13 transcripts are expressed at very low constant levels in developing and adult brain. In degenerating and regenerating segments of injured peripheral nerve changes in CD25 mRNA levels clearly resemble the expression pattern of other myelin genes, whereas expression of SR13 is inversely correlated with the time course of Schwann cell proliferation. In cultured rat meningeal fibroblasts SR13 mRNA expression is strictly growth arrest-specific and independent of forskolin. On the other hand, regulation of CD25 mRNA levels in these cells is more complex with respect to interfering effects of serum and forskolin. In cultured Schwann cells neither CD25 nor SR13 expression is growth arrest-specific. However, both transcript levels are consistently enhanced by forskolin under all conditions of cell growth tested. Expression of CD25 (but not SR13) depends on high Schwann cell density. Our results substantiate the hypothesis that PMP22 serves two biological functions, one related to cell growth (SR13) and another to myelination (CD25).
Assuntos
Divisão Celular/genética , Regulação da Expressão Gênica , Proteínas da Mielina/fisiologia , Bainha de Mielina/fisiologia , Animais , Sequência de Bases , Fenômenos Fisiológicos Sanguíneos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Colforsina/farmacologia , Meios de Cultura/farmacologia , Fibroblastos/metabolismo , Masculino , Meninges/metabolismo , Dados de Sequência Molecular , Proteínas da Mielina/biossíntese , Proteínas da Mielina/genética , Regeneração Nervosa , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoRESUMO
The cytokines SDF-1alpha and -1beta are two alternatively spliced variants of the CXC (alpha) chemokines that are highly conserved among species. SDF-1alpha was shown to function as a B-cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic HIV-1 strains and inducing cell death in human neuronal cell lines. In this report the cloning of the rat SDF-1beta cDNA and a new SDF-1 isoform, SDF-1gamma, are presented. Using Northern blot analysis, the expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF-1beta- and SDF-1gamma-mRNA expression is inversely regulated. Whilst SDF-1beta-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1gamma-mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF-1beta-mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF-1beta and SDF-1gamma mRNAs in the nervous system. Computer-assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides.
Assuntos
Processamento Alternativo/fisiologia , Química Encefálica , Quimiocinas CXC/genética , Regulação da Expressão Gênica no Desenvolvimento , Animais , Sequência de Bases , Encéfalo/crescimento & desenvolvimento , Quimiocina CXCL12 , Clonagem Molecular , Citocinas/genética , Hibridização In Situ , Dados de Sequência Molecular , Neurônios/fisiologia , RNA Mensageiro/análise , Ratos , Ratos Wistar , Células de Schwann/fisiologia , Nervo Isquiático/química , Nervo Isquiático/citologia , Nervo Isquiático/crescimento & desenvolvimento , Homologia de Sequência de Aminoácidos , Transcrição Gênica/fisiologiaRESUMO
We have isolated a 1.476 bp cDNA (NTII11) representing a transcript that is differntially expressed during sciatic nerve development and regeneration in the rat. Nucleotide sequence comparison indicates partial identity with a recently isolated plasmolipin cDNA. However, our clone extends the published sequence by 234 bp at the 5' end and predicts a protein that contains an additional 25 amino acids at th N-terminus. The open reading frame of th NTII11 transcript encodes a 19.4 kDa protein with four putative transmembrane domains. Northern blot analyses revealed a tissue-specific expression was confirmed by in situ hybridization, and cellular localization of plasmolipin mRNA was demonstrated in Schwann cells of the sciatic nerve and in glial cells of myelinated brain structures. The steady-state levels of plasmolipin mRNA were markedly altered (i) during development of sciatic nerve and brain. (ii) after sciatic nerve injury, and (ii) in cured Schwann cells maintained under different conditions of cell growth and arrest. Our data indicate a function of plasmolipin during myelination in the central as well as in the peripheral nervous system.