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BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.
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Adaptação Psicológica , Depressão/psicologia , Transplante de Rim/psicologia , Transplantados/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Work-related psychosocial factors have been associated with metabolic syndrome. However, no systematic reviews or meta-analyses have evaluated this association. METHODS: A systematic literature search was conducted, using PubMed, Embase, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies included those that examined the previously mentioned association; had a longitudinal or prospective cohort design; were conducted among workers; provided sufficient data for calculating odds ratios, relative risks or hazard ratios with 95% confidence intervals; were original articles in English or Japanese; and were published no later than 2016. Study characteristics, exposure and outcome variables and association measures of studies were extracted by the investigators independently. RESULTS: Among 4,664 identified studies, 8 were eligible for review and meta-analysis. The pooled risk of adverse work-related stress on metabolic syndrome onset was significant and positive (RR = 1.47; 95% CI, 1.22-1.78). Sensitivity analyses limiting only the effects of job strain and shift work also indicated a significant positive relationship (RR = 1.75; 95% CI, 1.09-2.79; and RR = 1.59; 95% CI, 1.00-2.54, P = 0.049 respectively). CONCLUSION: This study reveals a strong positive association between work-related psychosocial factors and an elevated risk of metabolic syndrome onset. The effects of job strain and shift work on metabolic syndrome appear to be significant.
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Síndrome Metabólica/psicologia , Local de Trabalho/psicologia , HumanosRESUMO
The mechanical behaviour of fibre-reinforced sands is primarily governed by the three-dimensional fibre architecture within the sand matrix. In laboratory, the normal procedures for sample preparation of fibre-sand mixtures generally produce a distribution of fibre orientations with a preferential bedding orientation, generating strength anisotropy of the composite's response under loading. While demonstrating the potential application of X-ray tomography to the analysis of fibre-reinforced soils, this paper provides for the first time a direct experimental description of the three-dimensional architecture of the fibres induced by the laboratory sample fabrication method. Miniature fibre reinforced sand samples were produced using two widely used laboratory sample fabrication techniques: the moist tamping and the moist vibration. It is shown that both laboratory fabrication methods create anisotropic fibre orientation with preferential sub-horizontal directions. The fibre orientation distribution does not seem to be affected by the concentration of fibres, at least for the fibre concentrations considered in this study and, for both fabrication methods, the fibre orientation distribution appears to be axisymmetric with respect to the vertical axis of the sample. The X-ray analysis also demonstrates the presence of an increased porosity in the fibre vicinity, which confirms the assumption of the "stolen void ratio" effect adopted in previous constitutive modelling. A fibre orientation distribution function is tested and a combined experimental and analytical method for fibre orientation determination is further validated.
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The previous reports suggest that obstructive sleep apnoea (OSA) is related to metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In addition, a possible relationship between obesity and the calcification of ligaments has been implied. However, the potential link between OSA and the calcification of ligaments has not been directly studied. In this present study, to investigate the potential link between OSA and the calcification of ligaments, we examined the prevalence of the calcification of ligaments in OSA patients and the relationship between these findings and OSA severity. Eighty consecutive patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full-night polyso-mnography were retrospectively recruited from May 2006 to July 2008. Each patient underwent cephalometric imaging examination before the arrangement of an oral appliance. One calibrated observer (YS) reviewed the cephalometric images for the presence of calcification of the nuchal ligament and osteophytes of the cervical spine. The prevalence of calcification of the nuchal ligament in OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a significant positive correlation between the severity of OSA (AHI) and the calcification of the nuchal ligament before and after adjusting for BMI. The prevalence of the calcification of the nuchal ligament in OSA subjects and snorers was higher than in previous studies with non-OSA subjects. In addition, it is suggested that the severity of OSA correlates with the presence of calcification of the nuchal ligament.
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Calcinose/patologia , Ligamentos Articulares/patologia , Osteófito/patologia , Apneia Obstrutiva do Sono/patologia , Ronco/patologia , Coluna Vertebral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Cefalometria , Vértebras Cervicais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Retrospectivos , Fatores de RiscoRESUMO
The purpose of this study was to observe the variations of cervical curvature in patients with infraocclusion, and to compare this with the controls. In this study, the infraocclusion criteria were defined with the Pr-id as <17 mm on the cephalometric image. The subjects were 32 patients with infraocclusion, and 28 controls which matched the distribution for gender and age. The six points of inquiry were as follows: (i) cervical vertebra height, (ii) neck alignment, (iii) ratio of lower facial height, (iv) vertical dimension of occlusion, (v) cervical angle and (vi) occlusal angle. In over 90% of the patients with infraocclusion, the cervical curvature was classified as straight or kyphosis. Conversely, in 36% of the control subjects, the cervical curvature was classified as lordosis. There was a weak positive correlation between the vertical dimension of occlusion and the cervical curvature in all subjects. In the control group, there was a significant and strong positive correlation between the age and cervical curvature, and a strong negative correlation between age and cervical angle and occlusal angle. Conversely, in the patients with infraocclusion, age was only correlated with the ratio of lower facial height. The prevalence of non-lordosis in the patients with infraocclusion was higher in comparison with the control group in our study, and the previous large-scale study of Japanese. However, there was merely a weak positive correlation between the cervical curvature and the vertical dimension of occlusion.
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Vértebras Cervicais/fisiopatologia , Eletromiografia , Cifose/diagnóstico , Lordose/diagnóstico , Má Oclusão/diagnóstico , Dimensão Vertical , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Humanos , Japão , Cifose/classificação , Cifose/fisiopatologia , Lordose/classificação , Lordose/fisiopatologia , Masculino , Má Oclusão/fisiopatologia , Pessoa de Meia-Idade , Postura , Resultado do TratamentoRESUMO
Periodontal diseases result from the interaction of bacterial pathogens with the host's gingival tissue. Gingival epithelial cells are constantly challenged by microbial cells and respond by altering their transcription profiles, inducing the production of inflammatory mediators. Different transcription profiles are induced by oral bacteria and little is known about how the gingival epithelium responds after interaction with the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. In the present study, we examined the transcription of genes involved in signaling transduction pathways in gingival epithelial cells exposed to viable A. actinomycetemcomitans. Immortalized gingival epithelial cells (OBA-9) were infected with A. actinomycetemcomitans JP2 for 24 h and the transcription profile of genes encoding human signal transduction pathways was determined. Functional analysis of inflammatory mediators positively transcribed was performed by ELISA in culture supernatant and in gingival tissues. Fifteen of 84 genes on the array were over-expressed (P < 0.01) after 24 h of infection with viable A. actinomycetemcomitans. Over-expressed genes included those implicated in tissue remodeling and bone resorption, such as CSF2, genes encoding components of the LDL pathway, nuclear factor-κB-dependent genes and other cytokines. The ELISA data confirmed that granulocyte-macrophage colony-stimulating factor/colony-stimulating factor 2, tumor necrosis factor-α and intercellular adhesion molecule-1 were highly expressed by infected gingival cells when compared with control non-infected cells, and presented higher concentrations in tissues from patients with aggressive and chronic periodontitis than in tissues from healthy controls. The induction in epithelial cells of factors such as the pro-inflammatory cytokine CSF2, which is involved in osteoclastogenesis, may help to explain the outcomes of A. actinomycetemcomitans infection.
Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Periodontite Agressiva/genética , Periodontite Crônica/genética , Citocinas/biossíntese , Gengiva/microbiologia , Transdução de Sinais/genética , Periodontite Agressiva/metabolismo , Apoptose , Aderência Bacteriana , Estudos de Casos e Controles , Linhagem Celular Transformada , Periodontite Crônica/metabolismo , Fatores Estimuladores de Colônias/biossíntese , Meios de Cultivo Condicionados , Células Epiteliais/microbiologia , Perfilação da Expressão Gênica , Gengiva/citologia , Gengiva/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Transcrição Gênica , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND AND OBJECTIVE: Cytolethal distending toxin (CDT) is a genotoxin produced by Aggregatibacter actinomycetemcomitans. In spite of its association with pathogenesis, little is known about the humoral immune response against the CDT. This study aimed to test whether subgingival colonization and humoral response to A. actinomycetemcomitans would lead to a response against CDT. MATERIAL AND METHODS: Sera from periodontally healthy, localized and generalized aggressive periodontitis and chronic periodontitis subjects (n = 80) were assessed for immunoglobulin G titers to A. actinomycetemcomitans serotypes a/b/c and to each CDT subunit (CdtA, CdtB and CdtC) by ELISA. A. actinomycetemcomitans subgingival levels and neutralization of CDT activity were also analyzed. RESULTS: Sera from 75.0% localized and 81.8% generalized aggressive periodontitis patients reacted to A. actinomycetemcomitans. A response to serotype b was detected in localized (66.7%) and generalized aggressive periodontitis (54.5%). Reactivity to A. actinomycetemcomitans correlated with subgingival colonization (R = 0.75, p < 0.05). There was no correlation between A. actinomycetemcomitans colonization or response to serotypes and the immunoglobulin G response to CDT subunits. Titers of immunoglobulin G to CdtA and CdtB did not differ among groups; however, sera of all generalized aggressive periodontitis patients reacted to CdtC. Neutralization of CDT was not correlated with levels of antibodies to CDT subunits. CONCLUSION: Response to CdtA and CdtB did not correlate with the periodontal status of the subject in the context of an A. actinomycetemcomitans infection. However, a response to CdtC was found in sera of generalized but not of localized aggressive periodontitis subjects. Differences in response to CdtC between generalized and localized aggressive periodontitis subjects indicate that CDT could be expressed differently by the infecting strains. Alternatively, the antibody response to CdtC could require the colonization of multiple sites.
Assuntos
Aggregatibacter actinomycetemcomitans/imunologia , Toxinas Bacterianas/imunologia , Imunidade Humoral/imunologia , Periodontite/microbiologia , Subunidades Proteicas/imunologia , Adolescente , Adulto , Aggregatibacter actinomycetemcomitans/classificação , Periodontite Agressiva/imunologia , Periodontite Agressiva/microbiologia , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/microbiologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Células CHO , Sobrevivência Celular , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Cricetinae , Cricetulus , Placa Dentária/microbiologia , Gengiva/microbiologia , Hemorragia Gengival/imunologia , Hemorragia Gengival/microbiologia , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Mutagênicos , Testes de Neutralização , Bolsa Periodontal/imunologia , Bolsa Periodontal/microbiologia , Periodontite/imunologia , Sorotipagem , Adulto JovemRESUMO
INTRODUCTION: Very little is known of the diversity and expression of virulence factors of serotypes of Aggregatibacter actinomycetemcomitans. Toxic activity on Chinese hamster ovary (CHO) cells and cdt and ltx genotyping were evaluated in A. actinomycetemcomitans serotypes. METHODS: Forty-one A. actinomycetemcomitans isolates were analysed for CHO cell growth inhibition. Genotyping was performed by polymerase chain reactions specific to the ltx promoter region, serotype-specific and cdt region and by sequencing of cdtB. RESULTS: cdtABC was detected in 40 strains. Analysis of the cdtA upstream region revealed 10 cdt genotypes. Toxicity to CHO cells was detected for 92.7% of the isolates; however, no correlation between the toxic activity and the cdt genotype was detected. Serotype c was more prevalent among Brazilian samples (68.0%). Four serotype b isolates from subjects with aggressive periodontitis were associated with high leukotoxin production and exhibited moderate to strong toxic activity in CHO cells, but were classified in different cdt genotypes. High levels of toxicity in CHO cells were not associated with a particular serotype; 57.1% of serotype a isolates presented low toxicity to CHO cells whereas the highly toxic strains belonged to serotypes b and c. Sequencing of cdtB revealed a single nucleotide polymorphism of amino acid 281 but this was not related to the toxic activity in CHO cells. CONCLUSION: Differences in prevalence of the low and highly cytotoxic strains among serotypes reinforce the hypothesis that serotype b and c isolates of A. actinomycetemcomitans are more virulent than serotype a strains.
Assuntos
Aggregatibacter actinomycetemcomitans/genética , Aggregatibacter actinomycetemcomitans/fisiologia , Periodontite Agressiva/microbiologia , Toxinas Bacterianas/genética , Citotoxinas/genética , Animais , Toxinas Bacterianas/toxicidade , Células CHO/efeitos dos fármacos , Cricetinae , Cricetulus , Exotoxinas/biossíntese , Exotoxinas/genética , Variação Genética , Humanos , Polimorfismo de Nucleotídeo Único , Sorotipagem , Especificidade da Espécie , Virulência/genéticaRESUMO
Osteophytes of the cervical spine are usually seen in elderly adults. When prominent, they have been blamed for dysphagia, cough, dysphonia and dyspnoea. This paper reports on an obstructive sleep apnoea (OSA) patient with cervical spinal osteophytes, one cause of airway obstruction. A 75-year-old male complained of pronounced snoring. The diagnosis was mild OSA, apnoea hypopnoea index was 9.4. Patient reported no restrictions in neck movements, experiences of neck pain or neck trauma. Previously, patient underwent a tonsillectomy due to discomfort in the pharyngeal region. A lateral cephalometric image was taken to observe airway before oral appliance therapy. The image revealed the presence of large osteophytes or sclerotic enthesopathy, lying on anterior surfaces from the fourth to seventh cervical vertebrae. A computed tomography (CT) image revealed the relationship of airway position to the spine. In the reconstructed three-dimensional (3D) image, the airway appeared displaced to the right of the craniomandiblar bone, with the hyoid bone similarly displaced in a manner to that of the airway. The spine also appeared displaced to the left side ofcraniomandiblar bone. Additionally, the 3D image revealed calcification of the stylohyoideum ligament and ligamentum nuchae. This present case highlights the necessity of CT examination for OSA patients. There were several ligament calcifications in the head and neck region. Cervical spine osteophytes, as a component of Forestier's or cervical spine disease, have been associated with dysphagia and dysphonia. It was reported that bilateral vocal cord paralysis was caused by osteophytes compressing the post-cricoid area of larynx.
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Vértebras Cervicais/diagnóstico por imagem , Apneia Obstrutiva do Sono/diagnóstico por imagem , Ronco/diagnóstico por imagem , Osteofitose Vertebral/diagnóstico por imagem , Idoso , Humanos , Masculino , Apneia Obstrutiva do Sono/etiologia , Ronco/etiologia , Osteofitose Vertebral/complicações , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Cytolethal distending toxin (CDT) is a DNA-targeting agent produced by certain pathogenic gram-negative bacteria such as the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. CDT targets lymphocytes and other cells causing cell cycle arrest and apoptosis, impairing the host immune response and contributing to the persistence of infections caused by this microorganism. In this study we explored the effects of CDT on the innate immune response, by investigating how it affects production of nitric oxide (NO) by macrophages. METHODS: Murine peritoneal macrophages were stimulated with Escherichia coli sonicates and NO production was measured in the presence or not of active CDT. RESULTS: We observed that CDT promptly and significantly inhibited NO production by inducible nitric oxide synthase (iNOS) in a dose-dependent manner. This inhibition is directed towards interferon-gamma-dependent pathways and is not mediated by either interleukin-4 or interleukin-10. CONCLUSION: This mechanism may constitute an important aspect of the immunosuppression mediated by CDT and may have potential clinical implications in A. actinomycetemcomitans infections.
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Toxinas Bacterianas/farmacologia , Endotoxinas/farmacologia , Proteínas de Escherichia coli/farmacologia , Sequestradores de Radicais Livres/antagonistas & inibidores , Imunossupressores/farmacologia , Interferon gama/antagonistas & inibidores , Ativação de Macrófagos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Interleucina-12/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Receptor 2 Toll-Like/efeitos dos fármacosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Infusões Intra-Arteriais/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cateteres de Demora/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , HumanosRESUMO
A case of hepatocellular carcinoma (HCC) complicated by tumor thrombosis of the main trunk is presented. Four courses of hepatic arterial infusion therapy, via a subcutaneously implanted injection port, were performed using cisplatin (10 mg for 1 hour on days 1-5) and 5-fluorouracil (250 mg for 5 hours on days 1-5). After four courses of the chemotherapy, marked reduction in size of HCC and the tumor markers were noted. The esophageal varices and ascites were improved after the chemotherapy with a recanalization of the left branch of the portal vein. The patient was doing well with a survival period of 28 months after the chemotherapy. These encouraging results suggested that the present therapy, based on the biochemical modulation, was a useful option for advanced HCC with portal hypertension due to tumor thrombosis of the main portal vein.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hipertensão Portal/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Células Neoplásicas Circulantes , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/complicações , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Bombas de Infusão Implantáveis , Infusões Intra-Arteriais , Neoplasias Hepáticas/complicaçõesRESUMO
Twenty-nine-year-old twin brothers having the amyloidogenic transthyretin (ATTR) Val30Met gene developed the clinical symptoms of familial amyloidotic polyneuropathy (FAP) in 1995. The twins had the same educational background and lived in the same district. FAP manifestations were similar in both cases, although electromyographic examinations revealed sensorimotor polyneuropathy in No. 1 and sensory polyneuropathy in No. 2. DNA analysis revealed that they were monozygotic twins. In addition to environmental factors, genetic factors may play an important role in determining the onset of FAP.
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Neuropatias Amiloides , Pré-Albumina/genética , Gêmeos Monozigóticos , Adulto , Neuropatias Amiloides/genética , Humanos , Masculino , MutaçãoRESUMO
Since 1990, liver transplantation for familial amyloidotic polyneuropathy (FAP) has been carried out world-wide, and the outcome of the procedure seems to be promising. FAP is inherited systemic disease caused by mutated transthyretin. The most common cause is the valine to methionine substitution at position 30 (Met30). We have developed a scoring system for FAP Met30 that takes into account a variety of clinical symptoms of the disease. Six patients with FAP Met30 underwent extensive examinations according to our scoring system before and after transplantation. All patients survived the procedure and are alive after transplantation. Improvements of sensory and autonomic disturbances were observed during the initial 12 months after the procedure only, thereafter the patients' status remained unchanged. Following transplantation, no improvement of motor function and visceral organ damage were observed, but the modified body mass index improved in four of six patients after the operation. These results suggest that liver transplantation of FAP patients stops the progress of the disease, and that minor improvements are noted in several patients after the procedure. However, transplantation should be performed early after the onset of the disease in order to preserve the patients' functional status.
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Neuropatias Amiloides/cirurgia , Amiloide/genética , Transplante de Fígado , Pré-Albumina/genética , Adulto , Neuropatias Amiloides/diagnóstico , Neuropatias Amiloides/fisiopatologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Condução Nervosa , Transtornos de Sensação/diagnóstico , Resultado do TratamentoRESUMO
A 64-year-old Japanese male suffering from very slowly progressive amyloidosis was studied by immunohistopathologic, mass spectrometric, and molecular genetic methods. After confirming the immunoreactivity of transthyretin (TTR) in the amyloid deposits using an anti-TTR polyclonal antibody, matrix-assisted laser desorption ionization/time-of-flight-mass spectrometry (MALDI/TOF-MS) was employed to look for the presence of variant TTR(s) in the serum. Two variant forms of TTR, one with a molecular weight 32 Da greater and another with a molecular weight 19 Da less than that of normal TTR encoded by the two respective alleles, were detected in this patient. Direct sequence analysis confirmed the presence of a double substitution: one at codon 30 from GTG (Val) to ATG (Met) and the other at codon 104 from CGC (Arg) to CAC (His) in the two alleles. MALDI/TOF-MS of the parents of the proband revealed that his father was a heterozygote of ATTR Arg104His and his mother was a heterozygote of ATTR Val30Met. The total TTR and retinol binding protein (RBP) concentrations in the serum samples of the proband were very high compared with those of FAP ATTR Val30Met patients and control subjects. We report here a new compound heterozygote in the TTR gene with familial amyloidotic polyneuropathy (FAP).
Assuntos
Neuropatias Amiloides/genética , Mutação , Pré-Albumina/análise , Proteínas de Ligação ao Retinol/análise , Acetaldeído/análogos & derivados , Idoso , Amiloide/química , Amiloide/metabolismo , Neuropatias Amiloides/sangue , Neuropatias Amiloides/metabolismo , Duodeno/metabolismo , Heterozigoto , Humanos , Imuno-Histoquímica , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Pré-Albumina/genética , Análise de SequênciaRESUMO
The aim of the present study was to analyze the forms of wild type and mutated monomeric transthyretin (Val30Met) in the amyloid fibrils of patients with familial amyloidotic polyneuropathy by electrospray ionization mass spectrometry (ESI-MS). The solubility of amyloid fibrils from the vitrectomized samples was examined to determine the appropriate solution for ESI-MS. ESI-MS analysis revealed that heterozygotic Val30Met amyloid fibrils contained 14.6 +/- 7.5% normal TTR. In all samples, 3 different types of variant ATTR could be identified: Full length ATTR, and -57, and -157 (or 156) Da from ATTR Val30Met were found. The two peaks showing -57, and -157 (or 156) Da from ATTR Val30Met corresponded to the -Gly, and -Gly-Pro sequences of ATTR Val30Met from the N-terminal. The results illustrate the heterogeneity of ATTR amyloid deposits and this method may be very useful for analyzing amyloid fibrils in ATTR related amyloidosis.
Assuntos
Substituição de Aminoácidos , Neuropatias Amiloides/genética , Pré-Albumina/química , Idoso , Feminino , Humanos , Masculino , Metionina/química , Metionina/genética , Pessoa de Meia-Idade , Peso Molecular , Pré-Albumina/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Valina/química , Valina/genética , Corpo Vítreo/químicaRESUMO
We performed biochemical and immunological examinations of heterozygotic carriers of the transthyretin (TTR) mutant Y114C associated with familial amyloidotic polyneuropathy (FAP). The total serum TTR levels in Y114C TTR carriers were extremely low when analyzed by single radial immunodiffusion (SRID), whereas by indirect enzyme-linked immunosorbent assay (ELISA) procedure, their total TTR concentrations were increased. Recombinant homozygotic Y114C TTR showed no immunoreactivity towards a TTR antibody when analyzed by SRID, whereas by the ELISA procedure presented the same degree of reactivity as that of normal TTR or isolated serum heterozygotic Y114C TTR. These results indicate that immunodifusion based techniques cannot properly determine TTR serum levels in Y114C carriers. Analyses of serum TTR of the Y114C TTR carriers by electrospray ionization mass spectrometry (ESI-MS) with the orifice corn voltage at 60 V revealed a small peak of the free Y114C TTR in addition to large TTR peaks of normal TTR. The levels of the free mutant TTR increased with the orifice corn voltage at 90 V. In contrast, increase in orifice voltage from 60 to 90 V produced a reduction in the level of normal TTR. The results suggest a different pattern of association between monomers in Y114C relative to normal TTR.
Assuntos
Neuropatias Amiloides/sangue , Neuropatias Amiloides/genética , Mutação Puntual , Pré-Albumina/química , Pré-Albumina/genética , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Heterozigoto , Humanos , Imunoquímica , Espectrometria de Massas , Pessoa de Meia-Idade , Peso Molecular , Pré-Albumina/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
To date, conventional treatments for multiple intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgery are unsuccessful. The aim of this retrospective study was to evaluate the prognostic effectiveness of a new infusion chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU) via hepatic artery for HCC with multiple intrahepatic recurrence. Fifty-two patients, who had postoperative multiple recurrence of HCC (more than 3 tumors), were enrolled in this study. Thirty-one patients were treated by hepatic arterial infusion chemotherapy via a subcutaneously implanted injection port. A one-week course of this treatment consisted of daily administration of cisplatin (10 mg for 1 h on days 1-5) and subsequent daily administration of 5-fluorouracil (250 mg for 5 h on days 1-5). Three to six sequential one-week courses were performed (the CDDP,5-FU group). Twenty-one patients underwent conventional interventional therapies including transcatheter arterial chemoembolization, lipiodolization (the conventional group). The complete response rate and the effective response rate in the CDDP,5-FU group were 29.0% and 71.0%, respectively. The 5-year survival rate in this group was 45.7%, which was significantly better than that in the conventional group. Based on multivariate analysis, CDDP,5-FU hepatic arterial infusion chemotherapy was found to be significant in prolonging survival, and this treatment achieved favorable therapeutic results for multiple recurrence of HCC. As part of a multidisciplinary approach this treatment is expected to improve the prognosis of patients with advanced HCC.