Detection of Anti-Extractable Nuclear Antigens in Patients with Systemic Rheumatic Disease via Fluorescence Enzyme Immunoassay and Its Clinical Utility

CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of anti-microbial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72−/− mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

Effects of diabetes and hypertension on oral mucosa and tgfß1 salivary levels

Abstract The aim of this study was to investigate salivary levels of TGFβ1 and proliferation/ maturation of epithelial mucosa cells in diabetic and hypertensive patients. Design: in this cross-sectional study, whole stimulated saliva and oral mucosa exfoliative cytology specimens were collected from 39 patients that were healthy (control, n=10) or presented history of arterial hypertension (HAS, n=9), diabetes mellitus (DM, n=10) or both (DM+HAS, n=10). Salivary flow rate (SFR), TGFβ1 level in saliva, AgNORs and the epithelial maturation were evaluated. Non-parametric Kruskal-Wallis test, followed by Dunn's multiple comparison post-test and the Spearman test correlation analysis were used. SFR showed a significant decreased in DM and DM+HAS (0.47±0.11 and 0.64±0.43 mL/min) when compared to control (1.4±0.38 mL/min). DM+HAS presented the highest value of TGFβ1 concentration (24.72±5.89 pg/mL). It was observed a positive correlation between TGFβ1 and glycaemia (R=0.6371; p<0.001) and a negative correlation between TGFβ1 and saliva (R=-0.6162; p<0.001) and glycaemia and SFR (R=-0.5654; P=0.001). AgNORs number and status of maturation of mucosa cells were similar for all conditions. DM and DM+HAS presented the lowest SFR, which correlated with increased TGFβ1 levels. Despite the higher TGFβ1 secretion it was not observed changes in the morphology or proliferation of epithelial cells when diabetes or hypertension was present.

Resumo O objetivo deste estudo foi investigar os níveis de TGFβ1 na saliva e a proliferação/maturação das células epiteliais da mucosa em paciente diabéticos e hipertensos. Neste estudo transversal, saliva estimulada e amostras de citologia exfoliativa de mucosa oral foram coletadas de um total de 39 pacientes que se apresentavam saudáveis (controle, n=10) ou com história de hipertensão arterial (HAS, n=9), diabetes mellitus (DM, n=10) ou ambos (DM+HAS, n=10). Taxa de fluxo salivar (SFR), níveis de TGFβ1 na saliva, AgNORs e maturação epitelial foram avaliados. Teste não-paramétrico de Kruskal-Wallis, seguido de comparação múltipla de Dunn e correlação de Spearman foram utilizados para as análises. SFR diminuiu significantemente em DM e DM+HAS (0,47±0,11 e 0,64±0,43 mL/min) quando comparado ao controle (1,4±0,38 mL/min). DM+HAS apresentou os maiores valores de concentração de TGFβ1 (24,72±5,89 pg/mL). Foi observada uma correlação positiva entre TGFβ1 e glicemia (R=0,6371; p<0,001) e uma correlação negativa entre TGFβ1 e saliva (R=-0,6162; p<0,001) e glicemia e SFR (R=-0,5654; p=0,001). Número de AgNORs e o padrão da maturação das células epiteliais foram similares entre os todos grupos. DM e DM+HAS apresentaram os menores valores de SFR, os quais foram correlacionados com o aumento nos níveis de TGFβ1. Apesar da maior secreção de TGFβ1, não foram observadas mudanças na morfologia ou proliferação das células epiteliais quando o paciente apresentava diabetes ou hipertensão.

Autoimmune Responses in Severe Asthma

Asthma and autoimmune diseases both result from a dysregulated immune system, and have been conventionally considered to have mutually exclusive pathogenesis. Autoimmunity is believed to be an exaggerated Th1 response, while asthma with a Th2 underpinning is congruent with the well-accepted Th1/Th2 paradigm. The hypothesis of autoimmune involvement in asthma has received much recent interest, particularly in the adult late-onset non-atopic patients (the “intrinsic asthma”). Over the past decades, circulating autoantibodies against diverse self-targets (beta-2-adrenergic receptors, epithelial antigens, nuclear antigens, etc.) have been reported and subsequently dismissed to be epiphenomena resulting from a chronic inflammatory condition, primarily due to lack of evidence of causality/pathomechanism. Recent evidence of ‘granulomas’ in the lung biopsies of severe asthmatics, detection of pathogenic sputum autoantibodies against autologous eosinophil proteins (e.g., eosinophil peroxidase) and inadequate response to monoclonal antibody therapies (e.g., subcutaneous mepolizumab) in patients with evidence of airway autoantibodies suggest that the role of autoimmune mechanisms be revisited. In this review, we have gathered available reports of autoimmune responses in the lungs, reviewed the evidence in the context of immunogenic tissue-response and danger-associated molecular patterns, and constructed the possibility of an autoimmune-associated pathomechanism that may contribute to the severity of asthma.

Cell proliferation markers at the invasive tumor front of oral squamous cell carcinoma: comparative analysis in relation to clinicopathological parameters of patients

Abstract Objectives To evaluate the number of AgNORs per nucleus and the expression of Ki-67 at the tumor invasion front (TIF) in relation to clinical parameters (TNM), TIF classification and the prognosis of oral squamous cell carcinomas in an Uruguayan population. Material and Methods This study was conducted through a retrospective survey from 2000 to 2010 at the National Institute of Cancer Montevideo, Uruguay and included 40 patients. The samples were obtained from the resection of the tumor and the TIF was defined according with Bryne, et al.5 (1992). Expression of Ki-67 was assessed by the percentage of positive tumor cells and the AgNOR was recorded as the mean AgNOR (mAgNOR) and the percentage of AgNOR per nucleus (pAgNOR). All analyzes were performed by a blinded and calibrated observer. Results No statistically significant association was observed between immunostaining of Ki-67 and AgNOR with the different types of TIF, regional metastasis and patients prognosis, however it was observed an increase in Ki-67 expression associated with worse patient's clinical staging, although not statistically significant. Conclusions Our results suggest that proliferation markers as AgNOR and Ki-67 are not prognostic markers at the tumor invasive front of carcinoma of oral squamous cell.

Assessment transcallosal Diaschisis in a model of focal cerebral ischemia in rats / Evaluación de la diásquisis transcallosa en un modelo de isquemia cerebral focal en ratas

Objective: To evaluate transcallosal changes after a local ischemic injury in rats by using the monoclonal marker anti-NeuN (Mouse anti-neuronal nuclei). Methods: Twenty eight adult, male, Wistar rats were subjected to focal injury in the right hemisphere. The technique used was the experimental model of focal ischemic injury through intraluminal suture of the middle cerebral artery. Analyses were made for the five groups: and after the lesion (control), at 24 h, 96 h, 10 days and 20 days. Exofocal neuronal damage was inferred from neuronal immunoreactivity changes to NeuN. Results: In the cortex contralateral to the lesion, immunoreactivity was diminished. This was most notable in the supragranular layers 24 h post ischemia. After 96 h, there was a generalized diminishment of the inmmunoreactivity in supra and infragranular layers. At 10 and 20 days, the tissue recovered some NeuN immunoreactivity, but there were set changes in the VI layer. Conclusion: The immunoreactive changes to NeuN support the process of interhemispheric diaschisis. Changes in immunoreactivity could indicate metabolic stress secondary to the disruption in connectivity to the site of lesion.

Objetivo: Evaluar los cambios exofocales transcallosos después de lesión isquémica focal en ratas, mediante marcación inmunohistoquímica con el anticuerpo monoclonal anti-NeuN (Mouse Anti-Neuronal Nuclei). Métodos: Se intervinieron 28 ratas machos Wistar adultas. Mediante el modelo experimental de isquemia cerebral focal del territorio de la arteria cerebral media por filamento intraluminal, se les ocasionó una lesión focal en el hemisferio derecho. Posteriormente se evaluó el hemisferio contralateral, marcando la población neuronal con el anticuerpo monoclonal anti-NeuN. Se definieron cinco grupos de evaluación: uno de control, 24 h, 96 h, 10 días y 20 días. Se evaluaron los cambios neuronales exofocales después de la lesión con base en la observación de los cambios en la inmunoreactividad de las neuronas al NeuN. Resultados: Se redujo la inmunoreactividad en la corteza contralateral a la lesión. Este fenómeno fue más notable en las capas supragranulares después de 24 h post isquemia. Después de 96 h hubo una disminución generalizada de la inmmunoreactivity en las capas supra e infragranulares. A los 10 y 20 días, el tejido recobró alguna inmunoreactividad NeuN, estos cambios se dieron en la capa VI. Conclusiones: Los cambios inmunorreactivos a NeuN apoyan el proceso de diasquisis interhemisférica. Los cambios en la inmunorreactividad podrían indicar estrés metabólico secundario a la interrupción en la conectividad con el sitio de la lesión.

Human prefrontal layer II interneurons in areas 46, 10 and 24 / Interneuronas de la lámina II en las áreas prefrontales 46, 10 y 24 del humano

Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46. Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance. Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons. Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas. Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.

Antecedentes: La corteza prefrontal (CPF) representa el nivel más alto de integración y control de funciones psíquicas y comportamentales. Varias patologías como autismo, desórdenes de hiperactividad, depresión y esquizofrenia se han relacionado con alteraciones de la CPF. La lámina II de las áreas que constituyen la CPF posee un patrón de organización vertical, una alta densidad celular y la mayor proporción de neuronas no-piramidal/piramidal. Sin embargo, la distribución del componente inhibitorio en estas regiones no se ha descrito. Objetivo: En el presente estudio nos propusimos caracterizar la lámina II de las áreas 10, 24 y 46 del humano, particularmente su componente inhibitorio teniendo en mente su participación en procesos de actividad sostenida relevantes cuando desaparece el estímulo. Métodos: Se utilizaron muestras de cinco sujetos que fallecieron por causas diferentes a enfermedades del sistema nervioso. Se tomaron secciones de las áreas 10, 24 y 46 de Brodmann y se procesaron con los anticuerpos contra NeuN para determinar la población neuronal total y contra Parvalbumina (PV), Calbindina (CB) y Calretinina (CR) para analizar la población de interneuronas. Resultados: Los resultados no mostraron diferencias interhemisféricas entre las áreas. Sin embargo, las tres áreas seleccionadas son significativamente diferentes entre sí en todos los parámetros analizados. El área 46 posee la mayor densidad y tamaño de interneuronas positivas para PV. Conclusiones: La ausencia de asimetrías morfológicas no permite explicar las asimetrías funcionales. La lámina II del área 46 posee el sistema inhibitorio más poderoso. Teniendo en cuenta la arquitectura modular de las capas supragranulares, este sistema inhibitorio subyace a la actividad sostenida, eje fundamental de la memoria operativa.

Clinicopathologic features of embryonal tumor with multilayered rosettes and gene analysis on chromosome 19q13.42 / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and 19q13.42 gene changes in embryonal tumors with multilayered rosettes (ETMR).</p><p><b>METHODS</b>Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed in three ETMRs.</p><p><b>RESULTS</b>The average age of the patients were 34 months. Imaging revealed huge masses with inhomogeneous enhancement and two cases showed cystic lesions. Follow-up data showed 14 and 38 months survival in two children, the third had a recurrence 4 months after operation. Morphologically, the tumor was mainly composed of dense small primitive neuroepithelial cells in patchy or multilayer rosettes within a background of advanced neuronal differentiation, containing neurocytes, ganglion cells, and neuropil-like background. Immunohistochemical staining showed the neuronal marker, synaptophysin, was positive in differentiated areas. Nestin as a neural stem cell marker was immunoreactive in the primitive neuroepithelial cells including multilayered rosettes. Neurons with positive expression of NeuN were observed occasionally. Ki-67 index was up to 40%-80% in the undifferentiated cells and rosettes, but was only 1%-3% in the differentiated areas. CD99 was positive in perivascular papillary pattern areas in one case. 19q13.42 amplification was detected in more than 30% of tumor cells in all cases.</p><p><b>CONCLUSIONS</b>ETMR is a unique entity with distinctive clinical and pathological features. Chromosome 19q13.42 abnormality is valuable for confirming the diagnosis and for further treatment research.</p>

Significance of AgNOR in Salivary Gland Tumours.

Diagnosis of Salivary gland tumours is challenging, because of wide variation in differentiation and overlapping morphological features. Sometimes, the difficulty encountered in distinguishing between pleomorphic adenoma, adenoid cystic carcinoma and adenocarcinoma. The objective is to study the application of AgNOR pattern in differentiating benign and malignant tumours of the salivary glands on Fine needle aspirates and their correlation with histopathology. Material and method: Cytological material was obtained by FNAC from forty three patients of salivary gland tumours. MGG and Pap stained smears were prepared for cytological interpretation. Histopathological study was done on routine formalin fixed and Haematoxylin & Eosin stained sections. Smears and sections were stained with Silver colloid stain for study of AgNOR counting. Results: AgNOR in benign tumours were small, round, uniform and less in number (1.02-1.97) while in malignant tumours they were very large, irregular, haphazardly distributed with high counts (1.23-16). Conclusion: Present study shows that count as well as morphology of AgNOR dots was helpful in differentiating between benign and malignant tumours and their grading of malignancy .

Serum anti-Ku86: a potential biomarker for early detection of hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical value of serum anti-Ku86 in early detection of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Expression levels of Ku86 protein in HCC and adjacent normal liver tissues were detected by Western blotting. Serum anti-Ku86 level in 83 patients with early HCC and 124 patients with liver cirrhosis were detected by enzyme-linked immunosorbent assay (ELISA). Chemiluminescence was used to measure the serum level of α-fetoprotein (AFP).</p><p><b>RESULTS</b>Expression of Ku86 protein in HCC was increased when compared with the adjacent normal liver tissues (0.21 ± 0.05 vs. 0.08 ± 0.02, P < 0.01). Serum anti-Ku86 level was significantly elevated in HCC patients compared with that in liver cirrhosis patients (0.47 ± 0.22 vs. 0.22 ± 0.06 Abs at 450 nm, P < 0.01), but there was no significant difference between HBV infection and HCV infection in HCC patients (0.51 ± 0.19 vs. 0.47 ± 0.24, P = 0.267). Of note, serum anti-Ku86 level was significantly decreased after surgical resection of the tumors in the 30 HCC cases tested (P < 0.01). The results of ROC analysis indicated a better performance of anti-Ku86 (0.857) than AFP (0.739) for early detection of HCC. In 83 HCC patients, the positive rate of anti-Ku86 was 61.4% (51/83), significantly higher than that of the AFP positive rate (27.7%, 23/83). The anti-Ku86 level was positive in 37 of 60 HCC cases with negative AFP. Combination assay of AFP and anti-Ku86 could detect 60 of 83 HCC cases (72.3%, 60/83). There was no significant correlation of anti-Ku86 and AFP (r = 0.156, P = 0.161).</p><p><b>CONCLUSIONS</b>Serum anti-Ku86 level is significantly elevated and is not related to HBV and HCV infection in HCC patients. Serum anti-Ku86 antibody may be a potential biomarker for early detection of HCC, and can be used in combination with AFP in clinics.</p>

Cellular proliferation markers in peripheral and central fibromas: a comparative study

ABSTRACT Objective: To perform a comparative study of the cellular proliferation in the peripheral and central fibromas. Material and Methods: Immunohistochemistry for PCNA and the AgNOR technique were performed in 9 cases of peripheral odontogenic fibroma (POF), in 4 cases of odontogenic fibroma (OdF), in 8 cases of peripheral ossifying fibroma (PEOF) and 7 cases of ossifying fibroma (OsF). The Kruskal-Wallis and Mann-Whitney tests were used for the statistical analyses. Results: Mesenchymal component of the central lesions presented a higher mean number of AgNOR per nucleus and PCNA index than did the peripheral lesions (P≤0.05). The mean number of AgNOR per nucleus in the epithelial component proved to be higher in the OdF than in the POF (P≤0.05). The mesenchymal and epithelial components presented similar mean numbers of AgNOR per nucleus and PCNA index in the OdF, as well as a similar mean number of AgNOR per nucleus in the POF. Conclusions: The mesenchymal component may well play a role in the differences between the biological behaviour of the central lesions as compared to the peripheral lesions. Moreover, considering that the epithelial and mesenchymal components in odontogenic fibromas presented a similar proliferation index, more research is warranted to understand the true role of the epithelial components, which are believed to be inactive in nature, as well as in the development and biological behaviour of these lesions. .

Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy.</p><p><b>METHODS</b>The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test.</p><p><b>RESULTS</b>There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).</p><p><b>CONCLUSION</b>SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.</p>

Clinicopathologic features of peripheral neuroblastic tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to evaluate the prognostic significance of these features.</p><p><b>METHODS</b>The clinical and pathologic findings were retrospectively reviewed in 121 cases of peripheral neuroblastic tumor. The clinical outcomes of patients were evaluated. The three-year event-free survival rate was analyzed, with respect to age of patients, Evan's staging, International Neuroblastoma Pathology Classification and mitosis-karyorrhexis index.</p><p><b>RESULTS</b>The median age at diagnosis was 2.7 years; and 96 cases (79.3%) occurred in patients younger than 5 years old. The number of cases in Evan's staging I, II, III, IV and IVs was 24, 39, 24, 29 and 5, respectively. There were 82 cases of neuroblastoma (NB) (including 2 cases of undifferentiated NB, 52 cases of poorly differentiated NB and 28 cases of differentiating NB), 9 cases of ganglioneuroblastoma, intermixed type (GNBi), 19 cases of ganglioneuroma, maturing type (GN) and 11 cases of ganglioneuroblastoma, nodular type (GNBn). Forty-nine cases were in the favorable histology subgroup and 72 cases in the unfavorable histology subgroup. The overall three-year event-free survival rate of the 121 cases was 73.0% ± 4.3%. The three-year event-free survival rates were associated with age (P = 0.002), Evan's staging (P = 0.000), histologic category (P = 0.000), mitosis-karyorrhexis index (P = 0.043), prognostic subgroup (P = 0.000).</p><p><b>CONCLUSIONS</b>Most of the peripheral neuroblastic tumors occur in the children younger than 5 years old. It is composed of NB, GNBi, GN and GNBn. The three-year event-free survival rate is approximately 70%. Significant prognostic parameters include age of patients, Evan's staging, International Neuroblastoma Pathology Classification and mitosis-karyorrhexis index.</p>

Neurogenesis in the dentate gyrus of the hippocampus in a rat model of intracerebral hemorrhage / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether intracerebral hemorrhage (ICH) can promote neurogenesis in the dentate gyrus (DG) of rat hippocampus.</p><p><b>METHODS</b>Western blot analysis, immunohistochemical staining, and immunofluorescent double labeling combined with confocal microscope were used to detect neurogenesis in the DG of the hippocampus in rats after ICH.</p><p><b>RESULTS</b>The expression of DCX protein in the ipsilateral DG of the hippocampus was enhanced in the rats 1 day after ICH (0.202∓0.062) as compared with that in normal rats (0.127∓0.088), reaching the peak level at 14 days (0.771∓0.108, P<0.01) and beginning to decrease at 28 days (0.582∓0.121, P<0.01). Meanwhile, DCX-positive cells and BrdU-positive cells, and DCX/BrdU double-labeled cells were detected in the DG of the hippocampus. Compared with those in the control group, BrdU/NeuN double-labeled cells were markedly increased in the granular cell layer of the DG at 28 days after ICH (1.808∓1.020 vs 5.654∓1.671, P<0.01).</p><p><b>CONCLUSION</b>ICH can promote neurogenesis in the DG of rat hippocampus.</p>

Knock-down of ERα36 impacts the expression of differentiation protein in PC12 cells / 生理学报

ERα36 is a novel subtype of estrogen receptor alpha (ERα) known to play an important role in breast cancer development and widely expressed in normal tissues and cells including nerve cells. However, the expression and function of ERα36 in nerve cells have not been well elucidated. To examine whether ERα36 is involved in differentiation of nerve cells, the differentiated and undifferentiated PC12 (PC12D and PC12unD) cells were used. Transfection of ERα36-shRNA plasmid into PC12 cells was performed to establish the ERα36 gene knock-down cells model. Immunocytofluorescence and Western blot were used to analyze the expression of Nestin, β-tubulinIII and Neu-N in the PC12 cells. The results showed that ERα36 was expressed in both cell types. Compared with PC12D cells, PC12unD cells showed higher expression of Nestin and lower expression of β-tubulinIII. ERα36-shRNA-mediated knock-down of ERα36 expression enhanced the expression of β-tubulinIII and Neu-N, but attenuated Nestin expressions in PC12unD cells; ERα36 knock-down in PC12D cells mediated Nestin, β-tubulinIII and Neu-N in a contrary manner. These results indicate that ERα36 knock-down appear to be associated with inhibiting differentiation in differentiated cells and promoting differentiation in undifferentiated cells, suggesting that ERα36 is a dual regulator in nerve differentiation.

Clinicopathologic analysis of dysembryoplastic neuroepithelial tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, radiologic findings, treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT).</p><p><b>METHODS</b>The clinicopathologic and radiologic features were retrospectively analyzed in 10 cases of DNT.</p><p><b>RESULTS</b>Intractable partial seizure was the main presenting symptom in all patients. The tumor was located in temporal lobe (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI hypointense and T2WI hyperintense, with internal septation and hyperintense ring around the tumor seen on FLAIR image. There was neither peritumoral edema nor mass effect. Histologically, the tumor showed the presence of glioneuronal element, with oligodendrocyte-like cells, floating neurons, astrocytes and associated microcystic changes. Immunohistochemical study demonstrated positivity for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells. Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki-67 index were lower than 1% in all cases. Nine cases were treated by complete surgical excision and the remaining case was subtotally excised. No post-operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on follow up.</p><p><b>CONCLUSIONS</b>Correct diagnosis of DNT requires correlation with clinicopathologic, radiologic and immunohistochemical findings. Complete resection of the tumor and epileptogenic foci is the mainstay of treatment for DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or radiotherapy is not required.</p>

Degree of Agreement between Phadia EliA ENA and Euroimmun line Immunoassay; Comparison of Two Methods to Evaluate the Ability to Detect ENA Antibodies / 고신대학교의과대학학술지

OBJECTIVES: The purpose of this study is to compare newly developed assay for identification of ENA antibody, Phadia EliA ENA with Euroimmun line immunoassay by analyzing the degree of agreement and the individual antibodies between two methods. METHODS: A total of 82 patient samples were used. Indirect immunofluorescence assay using Hep-2 cell was performed to screen the antinuclear antibody (ANA). Euroimmun line immunoassay (LIA) and Phadia EliA ENA assay were tested to identify the antibodies against extractable nuclear antigens (ENAs). Kappa statistics was used to evaluate the degree of agreement. RESULTS: Mean age of patients was 41.0 (8-79), and the M:F ratio was 21:61. ANA was positive in 74 samples, and negative were 8 samples. Kappa analysis of the 82 tested samples showed a moderate strength of agreement (kappa = 0.521, P = 0.000). There were differences in the order of identified individual antibodies between two methods (Ro > La = RNP > Centromere > Sm > Scl-70 in Phadia EliA ENA, Ro > RNP > Sm>La > Scl-70 > Centromere=Jo-1 in Euroimmun LIA). Ro antibody was most frequently identified in Phadia EliA ENA negative-Euroimmun LIA positive specimens (Ro > RNP = Jo-1 > La = Sm = Centromere > Scl-70). CONCLUSIONS: A moderate strength of agreement was observed between the Phadia EliA ENA and the Euroimmun LIA. There seemed to be a significant difference in the ratio of individual antibodies, especially in the anti-Ro and Sm antibodies.

Nampt is involved in DNA double-strand break repair / 癌症

DNA double-strand break (DSB) is the most severe form of DNA damage, which is repaired mainly through high-fidelity homologous recombination (HR) or error-prone non-homologous end joining (NHEJ). Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer. Nicotinamide phosphoribosyltransferase (Nampt), which is involved in nicotinamide adenine dinucleotide metabolism, is overexpressed in a variety of tumors. In this report, we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80, which are key factors in HR and NHEJ, respectively. Depletion of Nampt by small interfering RNA (siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair. Furthermore, the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining, indicating a delay in the onset of cellular senescence in normal human fibroblasts. Taken together, our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair, contributing to the acceleration of cellular senescence.

Kaposi sarcoma in an HIV-negative Filipino man

INTRODUCTION: Kaposi sarcoma (KS) is a multicentric, vasoproliferative tumor. Human herpes virus 8 has been demonstrated to have a direct role in its development. Classic Kaposi sarcoma is seen in HIV-negative, elderly men, often of Jewish or Mediterranean lineage.CASE REPORT: A 78-year-old, HIV-negative man presented with a 4-year history of multiple nodules and plaques on both lower extremities. Histologic findings were consistent with nodular Kaposi sarcoma. Immunohistochemistry studies showed CD34+ cells. Tumor cells stained positive for HHV-8 latent nuclear antigen. As palliative treatment, the patient underwent external beam radiotherapy.CONCLUSION: Classic Kaposi sarcoma tends to run an indolent course. Progression of skin lesions however, can lead to immense discomfort and disfigurement. As there is no definitive treatment algorithm for KS, management decisions should be made judiciously to choose the most effective treatment that will cause the least morbidity.

Evaluation of proliferative activity in oral squamous cell carcinoma by the AgNOR staining method / Avaliação da atividade proliferativa do carcinoma espinocelular pelo método AgNOR

The objective of this study was to evaluate the cellular proliferative activity of argyrophilic nucleolar organizer regions (AgNORs) in a series of oral squamous cell carcinoma (OSCC) cases and to correlate this activity with the histopathologic grade of the tumor defined by the World Health Organization (WHO).Methodology: twenty cases of OSCC obtained from the Diagnostic Histopathology Service of UPF database were studied. Age, gender and ethnic origin of the patients and oral site affected by the tumor were obtained directly from the histopathologic reports. The AgNOR technique was used for histochemical analysis of the tumors.Results: there was a predominance of OSCC in male patients in the sixth decade of life. The lip was the most affected oral site and WHO grade I was the predominant histologic grade. The mean number of NORs per nucleus in the sample was 2.00 (standard deviation: 0.58). Pearson’s correlation test showed that the number of NORs in OSCC was directly correlated with histologic tumor grade (p = 0.021).Conclusion: the AgNOR method was useful as a diagnostic tool and prognostic indicator of OSCC when combined with conventional histopathologic analysis...

Avaliar a atividade proliferativa celular das regiões organizadoras nucleolares (AgNORs) em uma série de casos de carcinoma espinocelular da cavidade bucal (CECB) e correlacionar esta atividade com o grau histológico do tumor, definida pela Organização Mundial da Saúde (OMS). Metodologia: vinte casos de CECB estudados foram obtidos a partir de diagnóstico do Serviço de Diagnóstico Histopatológico da UPF. Dados relativos à idade, sexo e origem étnica dos pacientes, além da localização da lesão na cavidade bucal, foram obtidos a partir dos relatórios histopatológicos. A técnica de AgNOR foi utilizada para análise histoquímica dos tumores.Resultados: houve predomínio de CECB em pacientes do sexo masculino na sexta década de vida. O lábio foi o local mais afetado e o grau histológico I foi o predominante. O número médio de NORs por núcleo na amostra foi de 2,00 (desvio padrão: 0,58). O teste de correlação de Pearson mostrou que o número de NORs no CECB foi diretamente correlacionado com o grau histológico do tumor (p = 0,021). Conclusão: o método AgNOR foi útil como uma ferramenta de diagnóstico e indicador de prognóstico do CECB, quando combinado com a análise histopatológica convencional...