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BACKGROUND AND OBJECTIVE: Complex relationships exist between diabetes and periodontal disease. Diabetes is accepted as a risk factor for periodontal disease, and recent evidence supports the existence of a bidirectional relationship between these two diseases. It has been hypothesized that inflammation, lipids and adipokines may mediate these relationships. However, research regarding the above relationships with respect to aggressive periodontitis is very limited. This pilot study aimed to investigate whether patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes and have altered serum levels of inflammatory mediators, lipids and adipokines. MATERIAL AND METHODS: Glycaemic control markers (random plasma glucose and glycated haemoglobin), inflammatory mediators (high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin-1ß, interleukin-6, interferon-γ and interleukin-18), lipids (triglycerides, total cholesterol and high-density lipoprotein-cholesterol) and adipokines (leptin, adiponectin and resistin) were measured in serum samples from 30 patients with aggressive periodontitis and 30 age- and sex-matched periodontally healthy control subjects, none of whom had a previous diagnosis of diabetes. RESULTS: Levels of glycaemic control markers, inflammatory mediators, lipids and adipokines were not significantly different (p > 0.05) between the aggressive periodontitis patients and healthy subjects for unadjusted and adjusted analyses (adjusting for body mass index, smoking, ethnicity, age and sex). The p-value for the adjusted analysis of adiponectin in female aggressive periodontitis patients compared with the female control subjects reached 0.064, the mean adiponectin level being lower in the female aggressive periodontitis patients (4.94 vs. 5.97 µg/mL). CONCLUSION: This pilot study provided no evidence to suggest that patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes or altered serum levels of inflammatory mediators, lipids and adipokines.
Assuntos
Periodontite Agressiva/sangue , Periodontite Agressiva/complicações , Complicações do Diabetes/sangue , Adipocinas/sangue , Adolescente , Adulto , Perda do Osso Alveolar/diagnóstico por imagem , Glicemia/análise , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Mediadores da Inflamação/sangue , Modelos Lineares , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Radiografia , Estatísticas não Paramétricas , Adulto JovemRESUMO
Decompressive craniectomy is a neurosurgical technique in which a portion of the skull is removed to reduce intracranial pressure. The rationale for this procedure is based on the Monro-Kellie Doctrine; expanding the physical space confining edematous brain tissue after traumatic brain injury will reduce intracranial pressure. There is significant debate over the efficacy of decompressive craniectomy despite its sound rationale and historical significance. Considerable variation in the employment of decompressive craniectomy, particularly for secondary brain injury, explains the inconsistent results and mixed opinions of this potentially valuable technique. One way to address these concerns is to establish a consistent methodology for performing decompressive craniectomies. The purpose of this paper is to begin accomplishing this goal and to emphasize the critical points of the hemicraniectomy and bicoronal (Kjellberg type) craniectomy.
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Lesões Encefálicas/cirurgia , Craniectomia Descompressiva/métodos , HumanosRESUMO
Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.
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Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/microbiologia , Memória Imunológica , Pulmão/imunologia , SARS-CoV-2/imunologia , Linfócitos B/patologia , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Feminino , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-IdadeRESUMO
Porphyromonas gingivalis lipopolysaccharide (LPS) (strain W50) interacts with Toll-like receptor 2 (TLR-2) leading to cytokine expression and inflammation, and thereby plays a key role in the pathogenesis of periodontal disease. The aims of this study were to investigate gene expression of key regulatory mediators of innate immune responses in a human monocytic cell line (THP-1) to P. gingivalis LPS and to compare these results with those obtained using the TLR-4 ligand, Escherichia coli LPS. Custom-made Taqman low-density arrays were used for expression profiling of 45 different cytokine-related genes. Both types of LPS highly up-regulated interleukin (IL)-1alpha and IL-1beta, IL-18 receptor (IL-18R), IL-18R accessory protein and IL-1 family (IL-1F)9. Expression levels of IL-1F6, IL-1F7 and caspase-1 were unaltered by either LPS. Genes for tumour necrosis factor-alpha, IL-6, leukaemia inhibitory factor and IL-32 were also highly induced by both LPS. For a subset of genes, including CXC chemokine ligand 5 (CXCL5), expression was induced only by E. coli LPS or was up-regulated more highly by E. coli compared with P. gingivalis LPS in THP-1 monocytes. A similar expression pattern was also observed in dendritic cells. Analysis of signalling pathways which lead to CXCL5 expression indicated that the mechanisms underpinning the differential responses did not involve the recruitment of different adaptor proteins by TLR-2 and TLR-4, and therefore occur downstream of the receptor-adaptor complex. We conclude that differences in signalling pathways activated by TLR-2 and TLR-4 ligands lead to differential innate immune responses which may be important in polymicrobial diseases such as periodontal disease.
Assuntos
Escherichia coli/imunologia , Lipopolissacarídeos/imunologia , Monócitos/imunologia , Porphyromonas gingivalis/imunologia , Células Cultivadas , Quimiocina CXCL5/metabolismo , Regulação Bacteriana da Expressão Gênica/imunologia , Humanos , Interleucina-1beta/imunologia , Ligantes , Lipídeo A/análogos & derivados , Lipídeo A/imunologia , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Recent progress in advanced nuclear power development in the United States is revealing high potential for nuclear reactor systems that are smaller and easier to operate than the present generation. Passive, or intrinsic, characteristics are applied not only to provide inherent stability of the chain reaction but also to ensure continued cooling of the fuel and its containment systems even if a major breakdown of the normal cooling and control functions were to occur. The chance of a severe accident is thereby substantially reduced. The plant designs that are emerging are simpler and more rugged, have a longer life span, and place less burden on equipment and operating personnel. Modular design concepts and design standardization are also used to reduce construction time and engineering costs, giving promise that the cost of generating power from these systems will be competitive with alternative methods.
RESUMO
BACKGROUND AND OBJECTIVE: Interleukin-10 is a key immunoregulatory cytokine that may be of significance in the immunopathogenesis of chronic inflammatory diseases such as periodontal disease. Molecular genetic studies have defined a number of haplotypes that may be associated with differing levels of interleukin-10 secretion. The present study investigated the possible association between interleukin-10 gene polymorphism and periodontal disease progression. MATERIAL AND METHODS: Genomic DNA was obtained from 252 adults who were part of a prospective longitudinal study on the progression of periodontal disease in a general adult Australian population. Single nucleotide polymorphisms at positions -592 and -1082 in the interleukin-10 promoter were analysed using an induced heteroduplex methodology and used to determine interleukin-10 promoter haplotypes in individual samples. Periodontitis progression was assessed by measuring probing depths and relative attachment levels at regular intervals over a 5-year period. A generalized linear model was used to analyse the data, with age, gender, smoking status, interleukin-1 genotype and Porphyromonas gingivalis included as possible confounders. RESULTS: There was a significant (p approximately 0.02) main effect of interleukin-10 haplotypes, with individuals having either the ATA/ACC or the ACC/ACC genotype experiencing around 20% fewer probing depths of >or= 4 mm compared to individuals with other genotypes. Age and smoking had significant (p < 0.001) additional effects. CONCLUSION: These data suggest that the interleukin-10 genotype contributes to the progression of periodontal disease.
Assuntos
Interleucina-10/genética , Periodontite/genética , Periodontite/imunologia , Adulto , Fatores Etários , Alelos , Feminino , Haplótipos , Análise Heteroduplex , Humanos , Modelos Lineares , Masculino , Índice Periodontal , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , FumarRESUMO
Vasoactive intestinal peptide (VIP) is an immunoregulatory peptide, which inhibits LPS-induced cytokine secretion in myeloid cells and has beneficial effects in animal models of inflammatory diseases. We show for the first time that VIP decreases LPS-induced up-regulation of TLR2 and TLR4 by human monocytic THP1 cells and peripheral blood monocytes (PBM). VIP inhibited up-regulation of TLR4 expression in THP1 cells in response to LPS from Escherichia coli or the periodontal pathogen Porphyromonas gingivalis within 6 h poststimulation but had less of an effect on TLR2. After 24 h, P. gingivalis LPS-stimulated monocytic THP1 cells to differentiate into macrophages, which predominantly expressed TLR2, and E. coli LPS-stimulated THP1 differentiation to predominantly TLR4-expressing macrophages. VIP decreased monocyte differentiation to macrophages induced by LPS from either species and also reduced overall TLR2 and TLR4 expression in these cells. VIP had a similar effect on human PBM. The transcription factor PU.1 regulates TLR expression and has a central role in myeloid cell differentiation. VIP inhibited the nuclear translocation of PU.1 in LPS-stimulated THP-1 monocytes. VIP also inhibited the expression of the M-CSF receptor, which is regulated by PU.1. In summary, VIP inhibited LPS-induced differentiation of monocytes with a concomitant reduction in TLR2 and TLR4 expression. Although there was differential induction of TLR expression by LPS from P. gingivalis and E. coli, VIP inhibited the action of both of these LPS types on monocytes. The mechanism of action of VIP on monocyte differentiation may be via inhibition of the transcription factor PU.1.
Assuntos
Lipopolissacarídeos/antagonistas & inibidores , Monócitos/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Diferenciação Celular , Núcleo Celular/metabolismo , Células Cultivadas , Interações Medicamentosas , Humanos , Imunossupressores/farmacologia , Macrófagos/fisiologia , Monócitos/fisiologia , Transporte Proteico , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismo , Regulação para CimaRESUMO
IL-18 is a pro-inflammatory cytokine that is important in the regulation of T-cells and is elevated in inflammatory disorders such as periodontal disease. Vasoactive intestinal peptide (VIP) modulates immune responses to the periodontal pathogen Porphyromonas gingivalis (Pg). Our objective was to investigate the effect of Pg LPS on IL-18 and its natural inhibitor, IL-18 binding protein (IL-18BPa), in human monocytes, and the effect of VIP on this system. We demonstrated that Pg LPS induced both IL-18 and IL-18BPa secretion in cultures of the human monocytic cell line THP-1, as measured by specific ELISA. The addition of antibodies to IL-18BPa to the stimulated THP-1 cultures resulted in increased levels of free IL-18, indicating a specific interaction between IL18 and IL-18BPa in this system. VIP (10(-8)M) inhibited both IL-18 and IL-18Bpa secretion by stimulated monocytes. We conclude that IL-18 and IL-18BPa secretion by monocytes is part of the immune response to Pg, and that VIP can inhibit this process.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Interleucina-18/biossíntese , Lipopolissacarídeos/farmacologia , Monócitos/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Análise de Variância , Linhagem Celular , Humanos , Mediadores da Inflamação/farmacologia , Mediadores da Inflamação/fisiologia , Interleucina-18/antagonistas & inibidores , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Porphyromonas gingivalis/química , Peptídeo Intestinal Vasoativo/fisiologiaRESUMO
Different recombinations have been found at the Ig heavy chain gene loci in a number of sublines of the Burkitt lymphoma (BL) cell line Namalwa, following prolonged in vitro culture. The Namalwa sublines examined are DNA fingerprint-identical and derived from a monoclonal source. Recombinant DNA clones were used to map the Ig heavy chain gene mutations to a region between the VDJ and C mu segment of the locus. This region is associated with Ig heavy chain class switching in normal B cells. Of 24 clones established from one subline, three were found to have additional VDJ-C mu region mutations, indicating a high frequency of mutation at this locus.
Assuntos
Linfoma de Burkitt/genética , Região de Troca de Imunoglobulinas/genética , Cadeias mu de Imunoglobulina/genética , Recombinação Genética/genética , Linfócitos B/metabolismo , Sequência de Bases , Southern Blotting , Clonagem Molecular , Rearranjo Gênico , Humanos , Região de Junção de Imunoglobulinas/genética , Imunoglobulina M/genética , Região Variável de Imunoglobulina/genética , Dados de Sequência Molecular , Mutação/genética , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Células Tumorais CultivadasRESUMO
PURPOSE: Studies of tape recordings of cancer consultations have produced conflicting results. At the same time, audiotapes containing general information about cancer are poorly evaluated and are distributed to patients in an ad hoc manner. We compared the effects of both interventions on patient satisfaction, psychologic adjustment, and recall of information following their first consultation with a medical oncologist. PATIENTS AND METHODS: Patients (n = 142) were randomized to receive (1) an audiotape of their consultation, (2) an audiotape describing cancer in general terms, or (3) no tape. Recall of information was assessed in a structured interview 4 to 20 days after the consultation. RESULTS: Satisfaction with the consultation increased linearly from no tape to general tape to consultation tape. Satisfaction with the tape itself was higher in patients who received the consultation tape (satisfaction score, 61%) compared with those who received the general tape (43%). Average recall for all groups was 6.4 of the 25 items of information presented, and 2.4 of the six points identified as particularly important by the oncologist. The consultation tape did not improve recall over the no tape control, but the general tape caused a decrease of almost two items in total recall. Spontaneous (ie, unprompted) recall was significantly poorer with the general information tape. Psychologic adjustment to cancer was unaffected. CONCLUSION: We conclude that individual audiotapes have a limited potential to increase recall of information from the oncology consultation. General information tapes about cancer appear to inhibit recall actively.
Assuntos
Rememoração Mental , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Encaminhamento e Consulta , Gravação em Fita , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Lipopolysaccharide (LPS) from the Gram-negative pathogen Porphyromonas gingivalis (Pg) stimulates cytokine secretion in immune cells, and thereby initiates the inflammation associated with periodontitis. Modulation of pro-inflammatory cytokine activity is a plausible therapeutic target in periodontal disease. Vasoactive intestinal peptide (VIP) has a role in immunoregulation, and has been identified as a molecule with therapeutically beneficial immunosuppressive effects in inflammatory and autoimmune conditions. We aimed to investigate the effect of VIP on immune responses induced by Pg LPS in vitro. VIP (10(-8) M) significantly (P < 0.05) inhibits TNF-alpha production by human monocytic THP1 cells stimulated with Pg LPS. In parallel, we showed that VIP inhibits nuclear translocation of NFkappaB and c-Jun in a time-dependent manner, but does not decrease the expression of CD14 receptors. This is the first report to show the potential of VIP as an immunomodulator of Pg-stimulated inflammatory pathways in human monocytes.
Assuntos
Imunossupressores/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Monócitos/imunologia , Porphyromonas gingivalis , Peptídeo Intestinal Vasoativo/farmacologia , Células Cultivadas , Citocinas/antagonistas & inibidores , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Receptores de Lipopolissacarídeos/análise , Receptores de Lipopolissacarídeos/efeitos dos fármacos , Microscopia Confocal , Monócitos/efeitos dos fármacos , NF-kappa B/análise , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-jun/análise , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these genes was concordant, but in a significant minority of cases (6/24) the TCRG genes were in a different conformation at different clinical stages. In three of these patients (one null ALL, two T-ALL) the clonal TCRG rearrangements detected at presentation were absent at relapse possibly as a result of clonal regression. In one other patient (cALL), the TCRG locus at relapse was rearranged to V genes which are located downstream of the V genes found in the presentation rearrangement. This indicates that the relapse leukemic clone is probably the result of clonal evolution. In two patients (one cALL, one T-ALL) there were no clonally dominant rearrangements of the TCRG genes at presentation, but evidence for clonal rearrangements at relapse, possibly as a result of clonal progression. The structure of the IgH genes were determined in four of the six patients with clonal changes in the TCRG genes and were found to be concordant. The changes in TCRG gene structure were not restricted to ALL of any one particular age group, phenotype or duration of first remission. These data indicate that the assignment of clonal specific markers based upon the sequence of TCRG rearrangements at presentation may not always be useful in the detection of minimal residual disease in ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Adolescente , Adulto , Sequência de Bases , Southern Blotting , Criança , Pré-Escolar , DNA de Neoplasias/genética , Feminino , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Imunofenotipagem , Lactente , Leucemia-Linfoma de Células T do Adulto/genética , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genéticaRESUMO
Specific saturable receptors for epidermal growth factor (EGF) of high affinity (Ka 1.7 X 10(9) M-1) have been demonstrated on porcine thyroid membranes. Optimal conditions for EGF binding have been determined. TSH and other peptide hormones do not inhibit the binding of 125I-EGF and EGF does not inhibit 125I-TSH binding to thyroid membranes. The results suggest that EGF may be involved in the regulation of thyroid follicular cell growth and function.
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Receptores de Superfície Celular/metabolismo , Glândula Tireoide/metabolismo , Animais , Membrana Celular/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB , Cinética , Masculino , Camundongos , Suínos , Temperatura , Tireotropina/metabolismoRESUMO
Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods. Three projection systems emerge from the dorsal column nuclei, decussate via internal arcuate fibers, and form the contralateral medial lemniscus (ML). At the obex, some fibers split off the ML and course dorsolaterally, forming an ascending lateral system which fits the "lemniscal adjunct channel" (LAC) concept of Graybiel ('72). The ML continues rostrally as the "main lemniscal line channel" (MLLC). At the inferior colliculus, some LAC fibers terminate in the pontine nuclei, parabrachial, dorsal reticular nuclei, and the external and ventral medial part of the central nucleus of the inferior colliculus. More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC. In the diencephalon, gracile fibers leave the MLLC and form a crescentlike terminal field along the extreme lateral border of the ventral posterior lateral nucleus (VPL) of the thalamus. Cuneate MLLC fibers terminate in a bandlike formation in the VPL medial to the gracile termination. The third fiber system, the cuneocerebellar projection, emerges from the cuneate, the external cuneate nuclei, and the "cellular bridge" and immediately enters the ipsilateral inferior cerebellar peduncle. Upon entering the cerebellum, the major fiber component remains ipsilateral and terminates as vertical bands in vermal and paravermal lobules, and lobules I through IVa. The posterior cerebellar lobe contains terminal bands in lobules VII-IX, the copula pyramidis, and the paramedian lobule. It is concluded that the dorsolateral fiber system conforms to Graybiel's LAC. It is more divergent and probably less modality specific, whereas the medial lemniscal system conforms to the MLLC, which is said to be modality specific, less divergent, and locked to specific sensory-motor response characteristics. The topography of cerebellar terminal bands indicates that there is sensory-motor representation from all parts of the body to all parts of the cerebellum, at least in the rat.
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Córtex Cerebelar/citologia , Diencéfalo/citologia , Bulbo/citologia , Mesencéfalo/citologia , Núcleos Talâmicos/citologia , Vias Aferentes/citologia , Animais , Autorradiografia , Transporte Axonal , Peroxidase do Rábano Silvestre , Colículos Inferiores/citologia , Ratos , Ratos EndogâmicosRESUMO
Antibodies that inhibit the stimulation of the thyroid by TSH have been studied in 63 patients with primary hypothyroidism of whom 34 had thyroid atrophy and 29 goitrous Hashimoto's thyroiditis. The method used measured the secretion of tri-iodothyronine (T3) from porcine thyroid slices incubated in vitro. The aims of the study were to assess the frequency and clinical correlates of blocking antibodies in an unselected series of patients, to establish their IgG nature and to examine their action in relation to the TSH receptor. Blocking antibodies were found in 25% of patients and occurred in association with both atrophic (32%) and goitrous (17%) hypothyroidism. These antibodies did not bind TSH (with one exception) nor did they inhibit binding of TSH to its receptor (also with one exception). Blocking-antibody activity was abolished by treatment of the serum with anti-hIgG or with protein A, and the activity was purified from serum by affinity chromatography on protein A sepharose-4B, thus establishing the IgG nature of the antibodies. The stimulation of T3 secretion by thyroid-stimulating antibodies was also blocked and in one case, where IgG did not block stimulation by bTSH, stimulation by hTSH was blocked. Antibodies blocking the action of TSH probably represent an important mechanism in the pathogenesis of primary hypothyroidism in some patients.
Assuntos
Anticorpos/imunologia , Autoanticorpos/imunologia , Hipotireoidismo/imunologia , Tireotropina/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Autoanticorpos/metabolismo , Bioensaio , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide , Masculino , Pessoa de Meia-Idade , Receptores da Tireotropina/metabolismo , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Tireoidite Autoimune/imunologia , Tireotropina/metabolismoRESUMO
The development and evaluation of a TSH radioligand receptor assay for TSH-binding-inhibiting immunoglobulins and its application to the study of patients with Graves' disease are described. Optimal conditions for the binding of 125I-TSH to solubilised thyroid membranes are defined. Polyethylene glycol precipitation was employed to prepare immunoglobulins from serum for assay and gave results comparable to ammonium sulphate precipitation. Immunoglobulins from normal serum did not interfere in the assay; preparations from patients with untreated Graves' disease gave positive results in 44 out of 56 cases. Coefficients of intra- and inter-assay variation were 7.0% and 9.8% respectively. The method is therefore not only sensitive and reproducible but is sufficiently simple and rapid for routine application.
Assuntos
Doença de Graves/imunologia , Imunoglobulina G/análise , Sulfato de Amônio , Membrana Celular/metabolismo , Precipitação Química , Humanos , Imunoglobulina G/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide , Polietilenoglicóis , Ensaio Radioligante , Glândula Tireoide/metabolismo , Tireotropina/imunologia , Tireotropina/metabolismoRESUMO
BACKGROUND: Early-onset periodontal diseases (EOP) are caused by interactions between host factors, specific microbial pathogens, and environmental factors. It is, therefore, of interest to investigate the nature of host factors as they may provide useful risk markers and reveal important information regarding the disease pathogenesis. Genetic polymorphisms in the vitamin D receptor (VDR) gene are associated with parameters of bone homeostasis and with diseases in which bone loss is a cardinal sign, in particular osteoporosis. Rapidly progressive bone loss is one feature of EOP. We, therefore, sought to determine whether EOP is associated with a polymorphism in the VDR gene. METHODS: A restriction fragment length polymorphism (RFLP) for Taq I in exon nine of the VDR gene was analyzed by PCR, followed by restriction digestion with Taq I and gel electrophoresis. We analyzed the genotypes of 69 EOP patients, including 20 patients with unequivocal evidence of localized disease (L-EOP), and 72 controls with no history of EOP. RESULTS: The genotype distribution in the L-EOP patient group was 7 (35%), 5 (25%) and 8 (40%) and in the control group 31 (43.1%), 36 (50.0%) and 5 (6.9%) for TT, Tt and tt respectively (where t and T represent the alleles with and without the Taq I RFLP respectively). Chi2 analysis indicated that the distribution of the genotypes between these two groups was highly significantly different (P = 0.001). Allele frequencies were 47.5% and 52.5% for T and t in the L-EOP group; 68.1% and 31.9% in the control group, showing a significant association between the prevalence of the less frequent allele (t) and L-EOP (P = 0.017). There was no significant difference in the genotype distribution or the allele frequencies between the control samples and the larger EOP patient group (n = 69) which included patients with generalized and localized disease. CONCLUSIONS: These data indicate that carriage of the less frequent allele of the Taq I RFLP (t) in the VDR gene significantly increases the risk of developing L-EOP. However, VDR genotype may not affect the incidence of all cases of EOP. These findings contribute to our understanding of the genetic basis for periodontal disease and may help define sub-groups of this disease which share common pathogenic factors.
Assuntos
Periodontite Agressiva/genética , Polimorfismo Genético/genética , Receptores de Calcitriol/genética , Adolescente , Adulto , Alelos , Perda do Osso Alveolar/genética , Biomarcadores/análise , Osso e Ossos/metabolismo , Distribuição de Qui-Quadrado , Códon/genética , Intervalos de Confiança , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Eletroforese em Gel de Ágar , Éxons/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Homeostase/genética , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
Creative questioning that is based on nonverbal inner listening can lead to new insights, discoveries, and perspectives. Though very challenging, the mythology of reaching the listening hole can help the student develop an ear for keys or gaps in his or her perceptions about phenomena. It can help develop respect for the rich lode of nursing experience from which researchable questions can be developed. Finally, creative research questioning introduces a new mental discipline that can lead to a fresh perception of nursing practice questions. The value of the process outweighs the risks and difficulties.
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Criatividade , Processos Mentais , Pesquisa em Enfermagem/educação , Terapia de Relaxamento , Ensino/métodos , Comunicação , HumanosRESUMO
A case is described in which, due to long-term repeated exposure to the same body of diatom-containing water, comparable diatom findings in the tissues and environmental samples were not acceptable as proof of drowning. A commonly overlooked pitfall limiting the value of acid-digestion in marine cases is emphasized.
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Diatomáceas/citologia , Afogamento/diagnóstico , Medicina Legal/métodos , Mudanças Depois da Morte , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Therapeutic and investigational phlebotomy can produce iron deficiency severe enough to warrant iron therapy or even replacement blood transfusion. This complication of modern medicine is not adequately recognized.