Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these differentially expressed factors. Furthermore, we conducted functional modules analysis in the network, and found that yellow and turquoise modules could separate samples efficiently. The groups classified in the yellow and turquoise modules had a significant difference in survival time, which was verified in another independent GC mRNA dataset (GSE62254). The results suggested that differentially expressed factors in the yellow and turquoise modules may participate in lymph node metastasis of GC and could be applied as potential biomarkers or therapeutic targets for GC.

Overexpression of ezrin and galectin-3 as predictors of poor prognosis of cervical cancer

The aim of this study was to explore the correlation of ezrin and galectin-3 expressions with prognosis in cervical cancer. The immunohistochemical method was applied to detect ezrin and galectin-3 expressions in normal cervix tissues (n=30), cervicitis tissues (n=28), cervical intraepithelial neoplasia (CIN) tissues (classified as I-III, n=89), and cervical carcinoma tissues (n=84). Follow-up was conducted for 5 to 78 months to analyze the correlation of protein expressions with prognosis. Ezrin and galectin-3 expressions in cervical cancer were significantly higher than in normal cervix, cervicitis and CIN (all P<0.05), and expressions in CIN were significantly higher than in normal cervix and cervicitis (both P<0.05). The expressions of ezrin and galectin-3 were both related with histological grade, deep myometrial invasion and lymph node metastasis (all P<0.05). Spearman analysis showed that ezrin expression was positively correlated with galectin-3 expression in cervical cancer (r=0.355, P<0.05). The survival rate of patients with high expressions of ezrin and galectin-3 was significantly lower than those with low expressions of proteins (both P<0.05). The expressions of ezrin and galectin-3, histological grade, depth of stromal invasion, and lymph node metastasis are risk factors affecting the survival rate of patients with cervical cancer. The expressions of ezrin and galectin-3 were correlated with the development of cervical cancer, and overexpressions of those proteins were indicative of poor prognosis in patients with cervical cancer.

Presence of Toll Like Receptor-2 in spleen, lymph node and thymus of Swiss albino mice and its modulation by Staphylococcus aureus and bacterial lipopolysaccharide.

Toll-like receptors (TLR) are a family of pattern recognition receptors identifying pathogen associated molecular patterns (PAMPs). They play a critical role in the innate immune response during the initial interaction between the infecting microorganism and phagocytic cells. Here, we verified the presence of TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation after infection with Staphylococcus aureus and Lipopolysaccharide (LPS) challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S. aureus infection, in thymus, spleen and lymph node of mice but their levels and mode of expression varied. When challenged with LPS no prominent changes in the expression of TLR-2 receptor was observed but its expression increased gradually with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2 expression was also found enhanced in infected splenic macrophages. By studying the serum cytokine profile the functionality of the receptor was measured. The results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss albino strain of mice and that they are modulated by S. aureus.

História da saúde da criança: conquistas, políticas e perspectivas / History of the child's health: conquers, policies and perspectives / Historia de la salud del niño: conquistas, políticas y perspectivas

Objetivou-se descrever e refletir sobre os aspectos relacionados à história social e às políticas públicas de assistência à saúde da criança no Brasil. Realizou-se breve contextualização histórica sobre as transformações no ser criança no Brasil e no mundo, apresentando-se as perspectivas referentes às políticas públicas de saúde da criança no âmbito nacional. Observou-se que a evolução histórica da participação da criança na sociedade encontra-se atrelada às mudanças nas políticas públicas de assistência, traduzida em queda da mortalidade infantil, aliada a desafios como a redução da morbimortalidade por agravos perinatais e causas evitáveis. Os avanços e conquistas na saúde da criança encontram-se em um movimento de mudança paradigmática para um modelo de construção de redes e da integralidade do cuidado. Esse contexto aponta a necessidade de formação de recursos humanos para esta área, tendo em vista à promoção e prevenção em saúde, assim como uma melhor qualidade de vida dessa população.

The aim of this study was describing and reflecting about the aspects related to the social history and public policies for the children's health assistance in Brazil. A brief historical contextualization was realized concerning changes on the way the society views the child in Brazil and around the world, also perspectives considering public policies for the children's health in the national context were presented. It was possible to identify that the historical evolution of the child participation in the society is linked to the changes in the assistance public policies, which were demonstrated in the child death decrease and associated to challenges, like the morbimortality reduction caused by perinatal injuries and avoidable causes. The advances and conquers in the child's health are evolved in a paradigmatic change movement into a model of a net formation and a comprehensiveness care. This context requires the human resources preparation for such area, based on the health promotion and prevention, as well as a better quality of life of the population.

El objetivo del estudio fue describir y reflexionar acerca de los aspectos relacionados con la historia social y las políticas públicas de asistencia de salud de niños en Brasil. Una breve contextualización acerca de las transformaciones en el modo de ser niño en Brasil y en el mundo, así como las perspectivas relacionadas a las políticas públicas de salud del niño en el contexto nacional. La evolución histórica de la participación del niño en la sociedad encuentra-se vinculada a las modificaciones de las políticas públicas de asistencia, que se mira en la reducción de la mortalidad infantil, acercada de desafíos como la reducción de la morbimortalidad por injurias perinatales y causas evitables. Los avanzos y conquistas na salud del niño se encuentran en uno movimiento de modificacion paradigmática para un modelo de construcción de redes y de la integralidad del cuidado. En este contexto se observa la necesidad de formación de recursos personales para esta área, con base en la promoción y prevención en salud y una mejor cualidad de vida de esa población.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

No abstract available.

Kinetics of IFN-Gamma and TNF-Alpha Gene Expression and Their Relationship with Disease Progression after Infection with Mycobacterium Tuberculosis in Guinea Pigs

PURPOSE: Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period. MATERIALS AND METHODS: We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-gamma and TNF-alpha), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs. RESULTS: The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-gamma and TNF-alpha was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs. CONCLUSION: Although IFN-gamma and TNF-alpha gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.

Diagnostic Performance of Thyroglobulin Value in Indeterminate Range in Fine Needle Aspiration Washout Fluid from Lymph Nodes of Thyroid Cancer

PURPOSE: The purpose was to compare the frequency of metastatic and nonmetastatic lymph nodes diagnosed by fine needle aspiration biopsy cytology (FNAC) and thyroglobulin concentration from fine needle aspiration biopsy washout fluid (FNAB-Tg) in an indeterminate range (0.2-100 ng/mL), and to evaluate the most appropriate threshold value of FNAB-Tg in an indeterminate range. MATERIALS AND METHODS: We performed ultrasound-guided FNAB and FNAB-Tg in suspicious metastatic cervical lymph nodes of papillary thyroid carcinoma and performed surgery. Ninety-five lymph nodes with indeterminate values of FNAB-Tg ranging from 0.2-100 ng/mL in ninety-two patients were included in this study. The diagnostic performances in multiple Tg levels (0.7, 1.0, 5.0, 10.0, 20.0, 50.0) were evaluated to compare with FNAB cytology using sensitivity, specificity, and accuracy with area under the curve (AUC) analysis. RESULTS: Forty-two were metastatic lymph nodes and fifty three were nonmetastatic lymph nodes. FNAB-Tg ranged from 0.22 to 90.9 ng/mL in metastatic lymph nodes (mean; 34.3+/-33.3 ng/mL) and 0.20 to 56.7 ng/mL in nonmetastatic lymph nodes (mean; 4.9+/-11.1 ng/mL) (p<0.001). The most excellent diagnostic performance was displayed in 5 ng/mL of FNAB-Tg with AUC of 0.76, sensitivity, specificity, accuracy, 69.0, 83.0, and 76.8, respectively. However, there was no significant difference from 10 ng/mL FNAB. CONCLUSION: We ascertained that 5 ng/mL yielded the most excellent diagnostic performance among FNAB-Tg levels in the present setting with a large series with the indeterminate range (0.2-100 ng/mL) of FNAB-Tg values. These results need additional confirmation under different laboratory conditions.

Correlação entre as medidas antropométricas e o comprometimento linfonodal de pacientes pós-menopausadas com câncer de mama / Correlation between anthropometric measurements an lymph node metastases in postmenopausal women with breast cancer

Introdução: Diversos estudos epidemiológicos observaram que mulheres obesas na pós-menopausa apresentam aumento de risco e mortalidade do câncer de mama. Apesar de não haver consenso, alguns estudos demonstraram maior grau de comprometimento dos linfonodos axilares nessas pacientes, o que pode contribuir para o pior prognóstico da doença nesse grupo. Objetivo: Avaliar a correlação entre as medidas antropométricas e o grau de comprometimento linfonodal axilar em pacientes pós-menopausadas com câncer de mama hormônio-responsivo. Métodos: Estudo prospectivo analítico com 57 mulheres com carcinoma ductal invasivo no estágio II, na pós-menopausa, com receptores hormonais positivos (receptor estrogênico e/ou receptor de progesterona - RE/RP), tratadas nos hospitais São Paulo e Pérola Byington. Logo após o diagnóstico foram realizadas as medidas antropométricas (IMC, CA, CQ e RCQ) das pacientes e, após o tratamento cirúrgico e avaliação histopatológica dos linfonodos axilares, realizou-se o estudo estatístico. Resultados: Observou-se associação significativa entre o número de linfonodos acometidos e o sobrepeso (IMC> 25 kg/m2) (p = 0,0329). Cerca de 64% das pacientes com mais de três linfonodos acometidos apresentaram IMC> 25 kg/m2. Entretanto, não houve diferença estatística entre as medidas antropométricas e a positividade dos linfonodos axilares de forma global. Conclusão: O número de linfonodos axilares comprometidos foi maior em pacientes com índice de massa corpórea entre 25 e 30 kg/m2.

Introduction: Several epidemiological studies have shown an increased risk and mortality in breast cancer of obese postmenopausal women. The higher number of lymph node metastases in these patients could contribute to poor prognosis. Objective: To evaluate the correlation between the anthropometric measurements and lymph node metastases in postmenopausal women with breast cancer expressing hormone receptors (ER/PgR). Methods: Prospective study with 57 women with invasive ductal carcinoma, stage II and estrogen receptor and/or progesterone receptor (ER/PgR) positivity treated in São Paulo and Pérola Byington Hospital. Anthropometric datawere obtained after the diagnoses, and statistical analysis was done after surgery treatment and definitive pathology results of axillary lymph nodes dissection. Results: There was a significant association (p = 0.0329) between the number of axillary lymph node metastases and overweight (BMI > 25 kg/m2). Almost 64% of patients with more than three lymph node metastases had more than 25 kg/m2. However, there were no statistical significance between the correlation of anthropometric measurements and the global number of axillary lymph node metastases. Conclusion: The number of axillary lymph node metastases was higher in patients with body mass index between 25 and 30 kg/m2.

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission.

Expression of E-cadherin in primary oral squamous cell carcinoma and metastatic lymph nodes: an immunohistochemical study.

BACKGROUND: E-cadherin plays an important role in cell-to-cell adhesion and cell motility and its loss is associated with oral squamous cell carcinoma (OSCC) progression. The aim of this study was to determine the expression of E-cadherin in various grades of OSCC and to correlate changes in the expression between these various grades and metastatic lymph nodes. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to detect E-cadherin expression in normal oral mucosa, primary OSCC (n = 37), and metastatic lymph nodes (n = 10). E-cadherin immunoreactivity was correlated with grades of differentiation and with clinicopathological features. RESULTS: E-cadherin immunoreactivity was found to inversely correlate with the loss of cell differentiation. The expression of E-cadherin decreased significantly in advanced cases of OSCC. However, increase in E-cadherin immunoreactivity was seen in early lesions, that is, in well differentiated (n = 9) and moderately differentiated OSCC (n = 13). Furthermore, E-cadherin was negative in majority of metastatic lymph nodes (7/10). CONCLUSIONS: Loss of the cell adhesion and E-cadherin plays an important role in progression of OSCC, that is, down regulation of its expression is associated with de-differentiation and metastasis.

Comparison of Her-2, EGFR and Cyclin D1 in Primary Breast Cancer and Paired Metastatic Lymph Nodes: An Immunohistochemical and Chromogenic In Situ Hybridization Study

The significant advance in the development of molecular-targeting drugs has made an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of primary tumors as well as their matching lymph node metastases using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73 breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance between the primary lesion and the metastatic regional lymph nodes in 82%, 90%, and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable agreement between primary tumors and metastatic regional lymph nodes. Although a statistically significant agreement was found in Her-2 expression, a relatively high discordance rate (18%) raises a little concern. Our findings suggest that the Her-2 status can be reliably assessed on primary tumor but a possible difference can be found in Her-2, EGFR, and cyclin D1 status between the primary and the metastatic sites and this possibility should be concerned in patients considering molecular targeted therapy or patients with progress of disease.

Transferrin receptor expression in reactive and neoplastic lesions of lymphnodes.

Transferrin, the major iron binding protein in human plasma transports iron to various tissues. The first step in cellular iron uptake is binding of transferrin complex to the cell surface membrane by specific molecule known as transferrin receptors. Transferrin receptors are found in limited sites in normal tissues, in contrast, the receptors are widely distributed in majority of carcinomas and sarcomas. Presence of increased transferrin receptors implies a stage of moderate or less differentiation corresponding to elevated proliferative activity and therefore, has a prognostic value. Demonstration of transferrin receptors and its distribution pattern within a tumour as well as its quantitative determination can provide data helpful for, both, an additional understanding of tumour biology and as an approach for planning therapy. In present study, we analysed 60 cases, 30 each of reactive lymphadenitis and lymphomas for transferrin receptors using immunohistochemical technique (DAKO, Code-K0673). Grade II and Grade III intensity was recorded in the germinal centers and the histiocytes in sinus histocytosis indicating the proliferating cells and activated histocytes. Most of the low grade non-Hodgkin lymphomas (83.66%) showed weak (Grade I) positivity for transferrin receptors. Intermediate grade lymphomas showed moderate (Grade II) to high intensity (Grade III) for transferrin receptors (57.14% and 42.85%) respectively. Seventy five percent of high grade lymphomas showed strong (Grade III) positivity. All the 9 cases of Hodgkin lymphoma (100%) showed grade III positivity. Proportion of the cells within a tumour expressing transferrin receptors in high density are therefore likely to represent the growth fraction of the tumour.

Expression of Cyclin B1 and cdc2 in Nodal Non-Hodgkin's Lymphoma and its Prognostic Implications

To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.

Immunohistochemical localization of transferrin in human breast cancer tissue.

The present study was planned to detect the iron binding protein, transferrin (TR) in paraffin sections of the human breast tumors. The distribution of transferrin has been studied in 153 cases (63 benign lesions and 90 malignant tumors). The extent of staining reaction was determined by semiquantitative grading (weak, moderate and consistent). Positivity rate for transferrin was higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%) with significant p value (p = 0.0001) for both the groups. The intensity was variable in both the groups, being more intense in the malignant tumors. Tumors with higher grade of malignancy presented consistent positive staining along with the lymph nodes involved. The extent of immunoreactivity revealed a significant positive correlation with axillary lymph node status. However, no significant correlation was found with the age of the patients. Thus the study of transferrin in breast tumors besides being of prognostic significance helps in the further management of malignant lesions of the breast.

p53 protein expression and its prognostic importance in patients with nodal non-Hodgkin's lymphoma

To determine whether the p53 expression might be a predictor for treatment sponse and overall survival in nodal non-Hodgkin's lymphoma (NHL), we analyzed e expression of p53 in 69 NHL patients. p53 protein expression was analyzed by munohistochemistry with long-term follow up (1-148 months: median 12.2). p53 pression was noted in 23/69 (33.3%) patients. Complete response (CR) rate to stemic chemotherapy was correlated with stage (I/II) (p=0.038), but not with 3 expression (p=0.2856). Poor overall survival was associated with stage =0.0010) or IPI score (p=0.0076), but not with p53 expression (p=0.8601). From ratification analysis by stage, in stage III/IV patients, the p53 positive oup had a trend to be associated with poor overall survival than the p53 gative group. Multivariate analysis revealed that p53 positive group was sociated with less CR rate compared to the p53 negative group (p=0.046), ereas overall survival was correlated with stage (p=0.0320), not with p53 atus. p53 expression was associated with less CR rate in patients with DLBL. rther studies with large numbers of samples and homogenous group of NHL are eded to determine the prognostic value of cell cycle regulator, p53 in NHL.

Changes in the TBARs content and superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs and skeletal muscles of adrenodemedullated rats

Thiobarbituric acid reactant substances (TBARs) content, and the activities of glucose-6-phosphate dehydrogenase (G6PDh), citrate synthase (CS), Cu/Zn- and Mn-superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) were measured in the lymphoid organs (thymus, spleen, and mesenteric lymph nodes (MLN)) and skeletal muscles (gastrocnemius and soleus) of adrenodemedullated (ADM) rats. The results were compared with those obtained for sham-operated rats. TBARs content was reduced by adrenodemedullation in the lymphoid organs (MLN (28 percent), thymus (40 percent) and spleen (42 percent)) and gastrocnemius muscle (67 percent). G6PDh activity was enhanced in the MLN (69 percent) and reduced in the spleen (28 percent) and soleus muscle (75 percent). CS activity was reduced in all tissues (MLN (75 percent), spleen (71 percent), gastrocnemius (61 percent) and soleus (43 percent)), except in the thymus which displayed an increment of 56 percent. Cu/Zn-SOD activity was increased in the MLN (126 percent), thymus (223 percent), spleen (80 percent) and gastrocnemius muscle (360 percent) and was reduced in the soleus muscle (31 percent). Mn-SOD activity was decreased in the MLN (67 percent) and spleen (26 percent) and increased in the thymus (142 percent), whereas catalase activity was reduced in the MLN (76 percent), thymus (54 percent) and soleus muscle (47 percent). It is particularly noteworthy that in ADM rats the activity of glutathione peroxidase was not detectable by the method used. These data are consistent with the possibility that epinephrine might play a role in the oxidative stress of the lymphoid organs. Whether this fact represents an important mechanism for the establishment of impaired immune function during stress remains to be elucidated

Expression of urokinase: type plasminogen activator, its receptor, and its inhibitor in gastric adenocarcinoma tissues

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.

Extrafollicular reticulum cells in pathologic lymph nodes

Extrafollicular reticulum cells in lymph nodes are heterogeneous. They express cytokeratins, desmin, and/or vimentin as their intermediate filament profile. Using those markers, we undertook an immunohistochemical study of human lymph nodes under various pathologic conditions. Samples included 15 simple reactive lymph nodes, 7 follicular hyperplasia, 1 necrotizing lymphadenitis, 4 tuberculous lymphadenitis, 13 malignant lymphoma (9 non-Hodgkin's and 4 Hodgkin's lymphomas), and 11 metastatic adenocarcinoma. In lymph nodes with follicular hyperplasia, cytokeratin and/or desmin expressing reticulum cells displayed a characteristic dendritic meshwork in the subcapsular, perisinusoidal, and paracortical regions. In other forms reactive lymph nodes, they were similarly distributed but were less prominent. By SDS-PAGE and immunoblotting, cytokeratin polypeptides were identified. In necrotizing lymphadenitis, they were increased and the pattern of distribution was disturbed. In tuberculous lymphadenitis, they were also increased and located at nongranulomatous as well as in perigranulomatous areas. In lymphomas the reticular meshwork was entirely obliterated. Cytokeratin or desmin expressing reticulum cells were rarely seen within tumors. The reticular meshwork was also obliterated in metastatic carcinoma. However, the meshwork was maintained in uninvolved areas. In conclusion, extrafollicular reticulum cells displayed characteristic patterns of distribution under various pathologic conditions, and may be implicated in the pathogenesis of those pathologic conditions in human lymph nodes.

Autonomic nervous system regulation of murine immune responses as assessed by local surgical sympathetic and parasympathetic denervation

En ratones sometidos a gangliectomia simpática cervical superior (SCGx) unilateral se estudió el efecto de la desnervación local sobre la respuesta imune de ganglios linfáticos submaxilares (SmLN). El contenido de norepinefrina (NE) de SmLN disminuyó en un 90% a los 7-20 dias luego de la SCGx uni o bilateral. Los SmLN ipsilaterales de ratones SCGx unilateralmente 10-20 días antes e inyectados i.d. o i.p. con eritrocitos de carnero mostraron una respuesta de células formadoras de placa (PFC) significantivamente mayor que el control invervado contralateral. En ratones inyectados con eritrocitos de carnero en al fase temprana de parálisis neural simpática (2 h luego de la SCGx), se detectó una respuesta PFC aumentada mientras que durante la fase de degeneración anterógrada de los terminales (6-24 h luego de SCGx), se observó una disminucióm crecimente de PFC. En ratones crónicamente SCGx se detectó también un aumento significativo en la hipersensibilidad por contacto y reacción alogeneica retardada en al oreja ipsilateral a la operación. Al inyectar células de SmLN desnervados a F1 de (BALB/c x C57Bl/6) o de (BALB/c x AKR) se obtuvbieron índices esplénicos significativamente mayores que los observados luego de inyectar células controles. La estimulación mitogénica en diferentes protocolos experimentales no resultó en diferencias significativas entre SmLN desnervados e inervados. Luego de la descentralización local por sección unilateral del tronco lingual-cuerda del tímpano, los SmLN ipsilaterales exhibieron menor respuesta PFC 8-28 días luego de la cirugía. Estos resultados indican función modulatoria del sistema nervioso autónomo en la respuesta inmune