RESUMO
OBJECTIVE: To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni's correction (p < 0.0033). RESULTS: AIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0-8.5) vs. 0.12 (0-8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0-26) vs. 7 (0-41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033). CONCLUSIONS: Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.
Assuntos
Hepatite Autoimune/epidemiologia , Hepatomegalia/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Adolescente , Idade de Início , Anticorpos Antinucleares/análise , Autoantígenos/análise , Brasil/epidemiologia , Criança , Feminino , Hepatite Autoimune/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Microssomos/imunologia , Músculo Liso/imunologia , Estudos RetrospectivosRESUMO
The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.
Assuntos
Autoantígenos/análise , Feto/química , Glicoproteínas/análise , Fosfoproteínas/análise , Proteínas/análise , Glândulas Salivares/química , Proteínas e Peptídeos Salivares/análise , Epitélio/química , Proteínas de Ligação a Ácido Graxo , Desenvolvimento Fetal , Idade Gestacional , Cabeça/embriologia , Humanos , Imuno-Histoquímica , Pescoço/embriologia , Palato/química , Palato/embriologia , Estudos Retrospectivos , Glândulas Salivares/embriologia , Fatores de Tempo , Língua/química , Língua/embriologiaRESUMO
Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.
Assuntos
Humanos , Fosfoproteínas/análise , Glândulas Salivares/química , Proteínas e Peptídeos Salivares/análise , Autoantígenos/análise , Glicoproteínas/análise , Proteínas/análise , Feto/química , Palato/embriologia , Palato/química , Glândulas Salivares/embriologia , Fatores de Tempo , Língua/embriologia , Língua/química , Imuno-Histoquímica , Estudos Retrospectivos , Idade Gestacional , Desenvolvimento Fetal , Epitélio/química , Cabeça/embriologia , Pescoço/embriologiaRESUMO
BACKGROUND: Bladder cancer is the second most common urological malignancy worldwide. CIP2A is a newly identified inhibitor of PP2A. Recent studies have highlighted a potential role for CIP2A in promoting the proliferation of several cancer cells. However, the role of CIP2A in bladder cancer still remains unclear. METHODS: The expression of CIP2A was detected by quantitative real-time polymerase chain reaction and IHC in bladder cancer tissues and bladder cancer cell lines. In addition, silencing of CIP2A with siRNA was performed in T24 cells, and the impact on proliferation, and apoptosis of T24 cells was analyzed. RESULTS: Our results found that CIP2A expression levels were higher in bladder cancer tissues and cell lines. Furthermore, CIP2A siRNA significantly reduced the proliferation rate of T24 cells, induced a significant population of early and late apoptosis, and could reverse EMT in T24 cells, indicates that CIP2A expression is increased in bladder cancer and implies a role of the protein in bladder cancer progression. CONCLUSIONS: These results suggest that CIP2A is involved in tumor progression, and thus CIP2A could represent selective targets for the targeted treatments of bladder cancer.
Assuntos
Autoantígenos/biossíntese , Transição Epitelial-Mesenquimal/fisiologia , Proteínas de Membrana/biossíntese , Neoplasias da Bexiga Urinária/patologia , Apoptose/fisiologia , Autoantígenos/análise , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/análise , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Regulação para CimaRESUMO
INTRODUCTION: The identification of molecules expressed selectively on the surface of retinoblastoma cells would allow applying targeted therapies. The Ganglioside, N-Glycolyl-GM3 (NeuGc-GM3), is an attractive candidate, as it has been detected in other paediatric neuroectodermic tumours, and it is not expressed in human normal tissues. The 14F7 antibody recognizes specifically the ganglioside NeuGc-GM3. PURPOSE: To characterize the expression of NeuGc-GM3 in retinoblastoma cell lines and in retinoblastoma tumours using the 14F7 monoclonal antibody. METHODS: We studied WERI-Rb1 and Y79 cell lines, 24 retinoblastoma primary tumours from unilateral and bilateral cases and two bone marrow biopsies from metastatic retinoblastoma. Tumours were classified into three groups: non-invasive (n = 13), invasive (n = 9) and metastatic (n = 2). Three eyes enucleated because of non-tumoural conditions were used as controls. Cell lines and tumour sections were studied by immunohistochemistry using the 14F7 antibody. NeuGc-GM3 expression was evaluated by analysing the percentage of positive tumoural cells and the staining intensity. These parameters were analysed comparatively among the three groups. RESULTS: Both retinoblastoma cell lines showed immunoreactivity to NeuGc-GM3 but WERI-Rb1 presented higher intensity than Y79. All the tumours studied showed strong immunoreactivity to NeuGc-GM3 with no significant differences among groups. In both bone marrow specimens, NeuGc-GM3 immunoreactivity was observed in retinoblastoma cells. In bilaterally enucleated cases, NeuGc-GM3 immunoreactivity was not altered before and after chemotherapy. Non-tumoural retinas were negative. CONCLUSIONS: NeuGc-GM3 is highly expressed in retinoblastoma cell lines, tumours and metastatic cells to the bone marrow, and it is not detectable in control eyes. There were no significant differences in the immunoreactivity to 14F7 among tumours from different disease stages. Its immunoreactivity did not change after chemotherapy.
Assuntos
Autoantígenos/análise , Gangliosídeo G(M3)/análogos & derivados , Neoplasias da Retina/química , Retinoblastoma/química , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Gangliosídeo G(M3)/análise , Gangliosídeo G(M3)/imunologia , Humanos , Técnicas ImunoenzimáticasRESUMO
Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. Esophageal involvement affects 50-90% of patients and is characterized by abnormal motility and hypotonic lower esophageal sphincter. Data on the association of esophageal abnormalities and age, gender, SSc subset or duration, autoantibody profile, esophageal symptoms, and medication are lacking or conflicting. The aim of this study was the evaluation of these associations in Brazilian sclerodermic patients from the Rheumatology Division, Clinics Hospital, Federal University, Minas Gerais. They underwent medical records review, clinical interview, and esophageal manometry. The normal cutoff level for lower esophageal sphincter pressure was 14 mmHg. Abnormal peristalsis occurred when less than 80% of peristaltic waves were propagated. P-values less than 0.05 were considered significant. Twenty-eight patients were included: 71% were women. The population presented medium age and disease duration of 46 years and 12 years, respectively. Cutaneous diffuse SSc occurred in 39% and its limited form in 61%. Dysphagia, pyrosis, and regurgitation occurred, respectively, in 71%, 43%, and 61% of patients. Lower esophageal sphincter pressure and number of peristaltic waves-propagated medias were, respectively, 17.2 mmHg and 2.3. SSc-related manometric abnormalities were present in 86% of patients. Manometry revealed distal esophageal body hypomotility, hypotonic lower esophageal sphincter, or both, respectively, in 82%, 39%, and 36% of patients. One patient presented the manometric pattern of esophageal achalasia. Male patients more frequently presented hypotonic inferior esophageal sphincter. Manometric findings have had no relationship with the other variables. Nifedipine use did not influence manometric findings.