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Cellular Composition (cellular + composition)
Selected AbstractsFine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitreCYTOPATHOLOGY, Issue 4 2003ska-Klencka The aim of the study was to examine whether evaluation of anisokaryosis is helpful in the cytological diagnosis of focal lesions in non-toxic recurrent goitre (NRG) after thyroidectomy for non-malignant goitre. Karyometric analysis was performed in routine cytological smears obtained from 80 females: 40 with focal lesions in non-toxic primary goitre (NPG) and 40 with NRG (postoperative histopathological examination revealed nodular goitre in both groups in all cases). We found that the level of anisokaryosis was significantly (P < 0.005) higher in NRG than in NPG. There were no significant differences between the two lesions, in cellular composition or thyroid follicular cell arrangement. Thus, isolated anisokaryosis, a feature of malignancy in patients without a prior thyroidectomy, has limited diagnostic value in recurrent goitre. [source] Increased numbers of mononuclear cells from blood and CSF expressing interferon-gamma mRNA in multiple sclerosis are from both the CD4+ and the CD8+ subsetsEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000E. Wallström Activated, cytokine-producing lymphocytes may regulate central nervous system (CNS) inflammation in multiple sclerosis (MS). We utilize a novel combination of in situ hybridization (ISH) and immunocytochemical staining of peripheral blood lymphocytes (PBLs) to identify spontaneously interferon-gamma (IFN,) mRNA expressing cells as CD4+ or CD8+. A major proportion of the IFN, mRNA expressing lymphocytes belonged to the CD4+ lineage, which concords with the cellular composition of MS brain lesions, findings in experimental models and the HLA class II haplotype association in MS. There were also significantly more CD8+ IFN, mRNA expressing lymphocytes in the MS patients compared with healthy controls, further suggesting the contribution of activated cells from this lineage in the inflammatory response in MS. Both CD4+ and CD8+ IFN, mRNA expressing cells were enriched in the cerebrospinal fluid (CSF) as compared with the peripheral blood of the MS patients. Combined with emerging genetic data on HLA class I influences, our data argues for a joint role of activated CD8+ and CD4+ cells in the pathogenesis of MS. [source] Angiogenic and lymphangiogenic microvessel density in recurrent pleomorphic adenomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2009Andresa B. Soares Background:, Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to determine if there is a difference between RPA and the pleomorphic adenoma (PA) without recurrence related to tumor blood and lymphatic vascularization. Moreover, we compared the microvessel density (MVD) between cell-rich areas (predominance of epithelial cells) and cell-poor areas (predominance of myxoid and chondroid areas) of the stroma of PA and RPA. In addition, immunohistochemical staining for the Ki-67 antigen was conducted simultaneously to evaluate cell proliferation in PA and RPA. Methods:, A total of 19 cases of PA and 24 cases of RPA, blood, and lymphatic vessels were analyzed by immunohistochemical technique using the antibodies CD34, CD105, D2-40, and Ki-67. Results:, Comparing no recurrent with recurrent tumor, no significant difference was found in terms of lymphatic vessel density, MVD, and proliferation index. When MVD and proliferation index were compared with different areas in cellular composition (cell-rich and cell-poor areas), there was a significant difference in PA, as well as in RPA. Conclusion:, This study shows that although RPA presents more aggressive clinical behavior than PA, there is no difference between tumor blood and lymphatic vascularization, suggesting that there is no correlation between vascularity and risk of recurrence. Furthermore, vascularized stroma in PA, as well as RPA, depends on the proportion of the cellular composition. [source] Leucocyte populations in respiratory syncytial virus-induced bronchiolitisJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2001PK Smith Objectives: To enumerate the cellular composition of the airways in infants with acute bronchiolitis. Methodology: Cells were obtained by airway lavage from the upper and lower airway and the peripheral blood of infants with respiratory syncytial virus (RSV)+ bronchiolitis, RSV, bronchiolitis and age-matched controls. Results: Neutrophils are the predominant cells present in the upper and lower airway. Neutrophils are present at a higher number/unit volume in the airway than in the peripheral blood. Conclusions: Neutrophils, being the dominant cellular infiltrate into the airway, are likely to contribute to the pathophysiology of bronchiolitis. Therapies targeted at limiting neutrophil influx or neutrophil-mediated damage in the airway may have a therapeutic role. [source] Monoclonal antibody against rat podocyte-derived macrophagic cells reacts with crescent-forming cells in an experimental modelNEPHROLOGY, Issue 5 2003MICHIAKI ORIKASA SUMMARY: The origin of crescent-forming cells in crescentic glomerulonephritis has not been clarified in spite of the application of monoclonal antibodies (mAbs) against glomerular epithelial cells or monocytes/macrophages. This study was undertaken to characterize the cellular composition of crescents using a new marker, mAb OS-3, produced against macrophagic cells derived from podocytes in normal rat glomerular culture. Monoclonal antibody OS-3 was confirmed to be reactive with some normal epithelial cells of Bowman's capsule. Female Wistar Kyoto rats were injected with rabbit antiglomerular basement membrane (GBM) serum and killed at 2 h, 1, 3, 7, 14 days and 2 months, respectively. The mAb OS-3-positive cells were segmentally observed in glomeruli at 3 days, increased at 14 days, but decreased at 2 months. These cells lacked reactivity with antipodocalyxin in double immunofluorescence (IF) staining. In immunoelectron microscopy of a glomerulus on day 3 and 7, however, reaction products were observed within cells located on the outer surface of the GBM, which were considered to be podocyte in terms of its localization. In conclusion, we have shown a possibility that damaged podocytes partly constitute crescent-forming cells with phenotypic changes, visualized by positive staining with mAb OS-3. We propose a novel concept of crescent formation, suggesting that crescents may be partly composed of phenotypically changed cells, which could not be detected by typical markers for glomerular epithelial cells or monocytes/macrophages. [source] Low grade diffuse gliomas: Shared cellular composition and morphometric differencesNEUROPATHOLOGY, Issue 5 2008Sawako Kinjo Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy-eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas-Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software "Gunmetry." Twenty-two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis. [source] Recruitment of CD8+ T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 8 2009D. R. FARIA Summary Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a fivefold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-,+ and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+ granzyme A+ T cells is involved in lesion progression in human CL. [source] Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Ulrika Andréasson Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Proteomic analysis of human vessels: Application to atherosclerotic plaquesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2003Mari Carmen Duran Abstract Atherosclerosis is a chronic disease that affects medium and large arteries. This process originates from the interaction between cells of the arterial wall, lipoproteins and inflammatory cells, leading to the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in acute clinical complications such as myocardial infarction and stroke. Owing to the heterogeneous cellular composition of the plaques, a proteomic analysis of the whole lesion is not appropriate. Therefore, we have studied the proteins secreted by human carotid atherosclerotic plaques, obtained by endarterectomy. Normal artery segments and different regions of the surgical pieces (noncomplicated plaque, complicated plaque with thrombus) were cultured in protein-free medium and the secreted proteins (supernatants) analyzed by two-dimensional gel electrophoresis. Normal artery segments secreted a moderate number of proteins (42 spots). However in the two-dimensional (2-D) gels (pH 3,10) of segments bearing a plaque, the number of spots increased markedly (154). The number of spots also increased (202) in the 2-D gels of artery segments with a ruptured plaque and thrombus. Thus, the more complicated the lesion, the higher the number of secreted proteins, suggesting the production of specific proteins relating to the complexity of the atherosclerotic lesion. [source] Growth Phase and Elemental Stoichiometry of Bacterial Prey Influences Ciliate Grazing SelectivityTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2009DAVID F. GRUBER ABSTRACT. Protozoa are known to selectively graze bacteria and can differentiate prey based on size and viability, but less is known about the effects of prey cellular composition on predator selectivity. We measured the effect of growth phase and elemental stoichiometry of Escherichia coli on grazing by two ciliates, Euplotes vannus and Cyclidium glaucoma. Bacterial cells of a single strain were transformed with green and red fluorescent protein and harvested from culture at differing growth stages. Cells in exponential growth phase had low carbon:phosphorus (39) and nitrogen:phosphorus (9) ratios, while cells from stationary phase had high carbon:phosphorus of 104 and nitrogen:phosphorus of 26. When offered an equal mixture of both types of bacteria, Cyclidium grazed stationary phase, high carbon:phosphorus, high nitrogen:phosphorus cells to 22% of initial abundance within 135 min, while Euplotes reduced these cells to 33%. Neither ciliate species decreased the abundance of the exponential phase cells, lower carbon:phosphorus and nitrogen:phosphorus, relative to control treatments. Because protozoa have higher nitrogen:phosphorus and carbon:phosphorus ratios than their prokaryotic prey, this study raises the possibility that it may be advantageous for protozoa to preferentially consume more slowly growing bacteria. [source] Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expressionARTHRITIS & RHEUMATISM, Issue 3 2010Patricia J. Hunter Objective To identify biomarkers in the first synovial fluid (SF) aspirate obtained from children with oligoarticular juvenile idiopathic arthritis (JIA), which could be used to identify children whose disease is likely to extend to a more severe phenotype. Methods Patients with recent-onset oligoarticular JIA were identified and grouped according to those whose mild disease persisted (persistent disease) or those whose disease would extend from a mild to more severe phenotype (extended-to-be disease) at 1 year after diagnosis. Flow cytometry was used to delineate differences in the mononuclear cell populations between the first blood sample and first SF aspirate from the same patient and between outcome (persistent versus extended-to-be) groups. Proportions of lymphocytes in the joint were modeled on chemotaxis of lymphocytes to CCL5, using Transwell migration assays. Levels of CCL5 in the SF were quantified by enzyme-linked immunosorbent assay. RNA profiles of SF mononuclear cells were compared between groups using the Affymetrix GeneChip hybridization protocol and hierarchical clustering analyses. Results Compared with peripheral blood mononuclear cells, SF mononuclear cells displayed an expansion of CD8+ T cells, reduced proportion of B cells, and expansion of CD16, natural killer cells. The lower CD4:CD8 ratio in the SF was recapitulated in vitro by the observed migration of blood T cells in response to CCL5. Synovial CCL5 levels were higher in children whose disease extended to a more severe phenotype. The CD4:CD8 ratio in the SF was significantly lower in patients with extended-to-be oligoarticular JIA (0.57 compared with 0.90 in the persistent disease group, difference 0.33, 95% confidence interval 0.04,0.62; P = 0.009). Gene expression profiling revealed that 344 genes were >1.5-fold differentially expressed between outcome groups (P < 0.05), and these included genes associated with inflammation and macrophage differentiation, which showed increased levels in patients with extended disease at 1 year, and genes associated with immune regulation, which showed increased levels in patients with persistent disease at 1 year. Conclusion Analyses of the proportions of synovial lymphocytes, levels of CCL5, and differential gene expression yielded potential biomarkers with which to predict the likelihood of extension of oligoarticular JIA to a more severe disease phenotype. [source] Bim,Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosisARTHRITIS & RHEUMATISM, Issue 2 2010John C. Scatizzi Objective Rheumatoid arthritis (RA) is a destructive autoimmune disease characterized by an increased inflammation in the joint. Therapies that activate the apoptotic cascade may have potential for use in RA; however, few therapeutic agents fit this category. The purpose of this study was to examine the potential of Bim, an agent that mimics the action of Bcl-2 homology 3 (BH3) domain,only proteins that have shown success in preclinical studies of cancer, in the treatment of autoimmune disease. Methods Synovial tissues from RA and osteoarthritis patients were analyzed for the expression of Bim and CD68 using immunohistochemistry. Macrophages from Bim,/, mice were examined for their response to lipopolysaccharide (LPS) using flow cytometry, real-time polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and immunoblotting. Bim,/, mice were stimulated with thioglycollate or LPS and examined for macrophage activation and cytokine production. Experimental arthritis was induced using the K/BxN serum,transfer model. A mimetic peptide corresponding to the BH3 domain of Bim (TAT-BH3) was administered as a prophylactic agent and as a therapeutic agent. Edema of the ankles and histopathologic analysis of ankle tissue sections were used to determine the severity of arthritis, its cellular composition, and the degree of apoptosis. Results The expression of Bim was reduced in RA synovial tissue as compared with controls, particularly in macrophages. Bim,/, macrophages displayed elevated expression of markers of inflammation and secreted more interleukin-1, following stimulation with LPS or thioglycollate. TAT-BH3 ameliorated arthritis development, reduced the number of myeloid cells in the joint, and enhanced apoptosis without inducing cytotoxicity. Conclusion These data demonstrate that BH3 mimetic therapy may have significant potential for the treatment of RA. [source] Extranodal lymphoid microstructures in inflamed muscle and disease severity of new-onset juvenile dermatomyositis,ARTHRITIS & RHEUMATISM, Issue 4 2009Consuelo M. López De Padilla Objective Juvenile dermatomyositis (DM) is an autoimmune disease of childhood characterized by lesions in skin and muscle that are populated by plasmacytoid dendritic cells (PDCs) and lymphocyte infiltrates. We undertook this study to examine the cellular composition, organization, and molecular milieu of the cellular infiltrates in muscle in juvenile DM and to correlate the infiltrates with clinical disease manifestations. Methods Since PDCs and lymphocyte foci express CCL19 and CCL21, we investigated for in situ formation of lymphoid microstructures that could be sites of extranodal immune activation. Results Analyses of muscle biopsy samples from children with new-onset juvenile DM showed 3 categories of lesions: diffuse infiltrates, lymphocytic aggregates lacking follicle-like organization, and follicle-like structures. The last of these exhibited elements of classic lymphoid follicles, including networks of follicular dendritic cells and high endothelial venules. They also expressed high levels of CXCL13 and lymphotoxins known to support lymphoid organogenesis. There were also resident naive CD45RA+ T cells and maternally derived B cells and PDCs. Patients with diffuse infiltrates or lymphocytic aggregates were responsive to standard therapy with steroids and methotrexate, but those with follicle-like structures tended to have severe disease that required additional agents such as intravenous Ig or rituximab. Conclusion These data suggest that lymphoneogenesis is a component of the early disease process in juvenile DM. Ectopic lymphoid structures could indicate a severe course of disease; their early detection could be a tool for disease management. [source] Clinical and Histological Aspects of CNV Formation: Studies in an Animal ModelACTA OPHTHALMOLOGICA, Issue thesis2 2008Nathan Lassota MD Abstract. The purpose of the present thesis was to develop an animal model of CNV in order to study the early formation of CNV and to test the effects of an anti-angiogenic treatment. Porcine eyes were chosen as a substrate for CNV induction, since they are similar to human eyes in terms of both macroscopic and microscopic morphology. However, a major difference is that pigs lack a fovea; instead they have a visual streak, with a relatively stable and high concentration of cones. By surgical perforation of Bruch's membrane we were able to induce formation of CNV membranes. The morphology and cellular composition of these membranes varied with the surgical technique employed. When RPE cells were locally removed at the time of perforation, the resulting CNV was thinner, contained fewer blood vessels and was less prone to leak on fluorescein angiography than when RPE cells were left intact at induction. The neuroretina overlying the perforation site was not damaged by any of the surgical techniques, thus allowing the subsequent retinal damage to be ascribed to the actual process of CNV formation. Using this animal model allowed us to directly map histological findings onto fluorescein angiograms and thereby perform meaningful correlations between histopathologic and photographic features. Such correlations have been hampered in human subjects, since human eyes are not enucleated as a consequence of CNV and are therefore only available for post-mortem studies. In such studies there often is a considerable time-gap between the death of the patient and the latest available fluorescein angiogram, thereby allowing macular pathology to evolve in the interim. Histological examination of the porcine membranes demonstrated that they were composed of RPE cells, glial cells, macrophages, endothelial cells, collagen and smooth muscle fibres, which are the same cellular and fibrillar elements that dominate human CNV membranes. The porcine model was applied to test the effects, in a randomized and masked fashion, of intravitreally injected bevacizumab. Bevacizumab, a pan VEGF A antibody, was found to reduce both the proliferation of endothelial cells in CNV membranes and the propensity to leak in fluorescein angiograms. Immunohistochemically, bevacizumab was detected in the inner limiting membrane, in retinal blood vessels and binding uniformly to the entire CNV membrane without any cellular predisposition. Based on the above findings we believe that the porcine CNV model shows a bearing to human disease and therefore might be used as a tool to obtain improved treatments for this debilitating condition. [source] Low grade diffuse gliomas: Shared cellular composition and morphometric differencesNEUROPATHOLOGY, Issue 5 2008Sawako Kinjo Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy-eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas-Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software "Gunmetry." Twenty-two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis. [source] | ||||||||||