RESUMO
BACKGROUND: We have previously reported that about 30% of patients affected by a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia (termed El Bagre-EPF or pemphigus Abreu-Manu) have systemic compromise. In the current study, we focused on studying autoreactivity to the kidney and its pathological correlations. AIM: To investigate patients with El Bagre-EPF for renal compromise. METHODS: We performed a case-control study, enrolling 57 patients with El Bagre-EPF and 57 controls from the endemic area, matched by age, sex, race, work activity, demographics and comorbidities. We took skin and renal biopsies; performed direct and indirect immunofluorescence, immunohistochemistry (IHC), confocal microscopy, immunoblotting, direct and indirect immune electron microscopy; and tested kidney function in all living patients. We also used IHC to study seven kidney autopsy samples. RESULTS: Of the 57 patients, 19 had autoantibodies to kidney, with polyclonal reactivity (P < 0.01). Most cases were positive along the basement membrane of the proximal tubules, but in some cases there was also positivity against the glomeruli and/or mixed patterns. Fifteen patients had increases in serum urea and creatinine compared with controls (P < 0.01). The autoantibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARCVF) and myocardium-enriched zonula occludens-1-associated protein (MYZAP) (P < 0.01). All of the kidney disease autopsies showed alterations, mostly in the vessels. CONCLUSION: We demonstrate for the first time that one-third of patients with El Bagre-EPF have polyclonal autoantibodies to kidney. The kidneys showed a mixed histological pattern resembling lupus nephritis, with a diffuse proliferative Class IV (G) global diffuse pattern in active lesions, and additional interposition of membranoproliferative glomerulonephritis.
Assuntos
Autoanticorpos/análise , Doenças Autoimunes/imunologia , Doenças Endêmicas , Rim/imunologia , Pênfigo/imunologia , Pele/patologia , Adulto , Doenças Autoimunes/complicações , Estudos de Casos e Controles , Colômbia , Feminino , Humanos , Rim/patologia , Rim/ultraestrutura , Nefropatias/etiologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Pênfigo/complicações , Pele/imunologiaRESUMO
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
Assuntos
Adulto , Feminino , Humanos , Masculino , Asma/induzido quimicamente , Genes MHC Classe I/genética , Genes MHC da Classe II/genética , Isocianatos/toxicidade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Asma/genética , Variação Genética , Genótipo , Doenças Profissionais/genética , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
Assuntos
Apoptose/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , PPAR gama/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , PPAR gama/genética , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Ativação Transcricional , Regulação para CimaRESUMO
In this study the N400 of schizophrenics was compared with that of control subjects in a picture semantic-matching task. The comparison of N400 difference waveforms (subtraction of event-related potentials of congruent from those of incongruent trials) between control and patients was supplemented by separate analysis for congruent and incongruent trials. The N400 latency was delayed in patients. Also, the amplitude of N400 in the difference waveform was reduced in schizophrenics; however only congruent trials were different for patients (more negative) with respect to controls. This result is consistent with the hypothesis that schizophrenics use context poorly, but inconsistent with simple versions of the idea that associations are generally disinhibited in schizophrenia. Since the amplitudes of N400 and an auditory P300 were not correlated, a general processing deficit does not explain the results. Finally, by using picture matching, a cross-cultural comparison of N400 in schizophrenics from Cuba and China was possible, which indicated that the N400 abnormalities were similar in both groups.
Assuntos
Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Potenciais Evocados , Esquizofrenia/complicações , Semântica , Percepção Visual , Adulto , China , Comparação Transcultural , Cuba , Feminino , Humanos , Masculino , Psicologia do EsquizofrênicoRESUMO
In readers of English, involved in a rhyme judgement task, mismatch trials are associated with an enhanced N450 component of the Event Related Potentials (ERPs). It has been suggested that N450 is related to orthographic or phonological priming. In this paper ERPs were recorded during a phonological matching task, using pairs of logographically dissimilar Chinese characters. A pair was considered to match if they sounded alike with identical phoneme sequences. The subjects (native Chinese speakers) were instructed to ignore vowel-inflections, which in Chinese have lexical status. Since sublexical assembly of phonology is not used in reading Chinese characters, and the members of each pair were logographically dissimilar, match and mismatch trials did not suffer in the amount of orthographic or sublexical phonological priming. An enhanced negative component (latency near 400 msec), was observed in ERPs elicited by the second character in non-matching pairs. The negativity could be similar to N450. If this were so, then N450 could not be associated with orthographic priming, nor with sublexical phonology, but would probably be associated with postlexical processing. Also, in both readers of Chinese and English, the negativity enhanced in non-match trials is larger over the right side of the scalp, suggesting a similar brain lateralization of the underlying processes.