In situ follicular neoplasia (ISFN) is defined as a monoclonal proliferation of B cells with immunophenotypic and genetic features of follicular lymphoma (FL) but confined to germinal centers of lymph nodes or other organs. It may not be associated with underlying overt lymphoma. It can be associated with lymphoproliferative disorders other than FL. A fifty-seven-year-old caucasian male initially presented with atypical chest pain, which led to cardiology evaluation. Patient underwent a coronary CT angiogram, which revealed a calcium score of 0, however also incidentally revealed mediastinal lymphadenopathy. Patient had a bronchoscopy which revealed no endobronchial lesions bilaterally. Using endo-bronchial ultrasound, right carinal lymph node was visualized, and trans-bronchial fine needle aspiration was performed. Cytology was positive for necrotic lesion with atypical cells. Patient had a dedicated CT scan of chest which showed enlarged sub-carinal lymph node measuring 3.3 x 3.0 cm. PET/CT scan showed increased uptake in the sub-carinal lymph nodes, also increased uptake of mid para-esophageal lymph nodes. It also showed some low-grade lymphadenopathy in right lower paratracheal region as well as mesenteric lymphadenopathy with misty appearance. Small pulmonary nodules were also noted in right middle and lower lobes with no associated uptake. Patient was scheduled for a mediastinoscopy and lymph node dissection. Patient proceeded with mediastinoscopy and a total of 4 lymph node specimens were removed from level 4R and level 7. Pathology from one of the lymph nodes revealed necrotizing granulomatous inflammation with staining consistent with histoplasmosis. Interestingly, two other lymph nodes showed in situ follicular neoplasia. Immunohistochemical stains demonstrated rare secondary lymphoid follicles with unremarkable morphology, showing strong germinal center staining with BCL2. FISH analysis was normal indicating absence of t(14;18). Pathology showed morphologically unremarkable B-cell nodules, concentrated in the cortical area which were CD20 positive and BCL2-positive. Patient underwent subsequent treatment with anti-fungal agents for the Histoplasmosis and is currently under surveillance for in-situ follicular lymphoma. In-situ follicular neoplasia is considered a premalignant lesion and a precursor of follicular lymphoma. Incidence of ISFN is difficult to ascertain, as it is usually a subclinical diagnosis. Incidence of FL is 3.18 per 100,000 population in the United States and findings suggest that ISFN is likely more frequent than that. Also, similar to FL, ISFN is seen in middle-aged and older individuals, mean age being around the fifth decade of life.Incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. Because some cases of ISFN are associated with prior or concurrent lymphoma, screening studies including computed tomography (CT) scan and bone marrow biopsy should be conducted after the diagnosis of ISFN is made. In the absence of overt lymphoma, it has been recommended that patients with ISFN be observed without chemotherapy, based on the very low incidence of progression into overt FL. The clinical significance of ISFN is not fully understood, however studies have demonstrated that incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. (

Marathon runners (N = 22) who had completed at least seven marathons (X ± SEM = 23.6 ± 5.7) and had been training for marathon race events for at least 4 yr (12.3 ± 1.3) were compared with sedentary controls (N = 18). Although the two groups were of similar age (38.7 ± 1.5 and 43.9 ± 2.2 yr, respectively) and height, the marathon runners were significantly leaner and possessed a VO2max 60% higher than that of the controls. Neutrophil counts tended to be lower in the group of marathoners, while other leukocyte and lymphocyte subsets were similar to controls. Mitogen-induced lymphocyte proliferation did not differ between groups. Natural killer cell cyto-toxic activity (NKCA) was significantly higher in the marathoners versus controls (373 ± 38 vs 237 ± 41 total lytic units, respectively, a 57% difference, P = 0.02). For all subjects combined (N = 40) and within the group of marathon runners (N — 22), percent body fat was negatively correlated with NKCA (r = -0.48, P = 0.002; r = -0.49, P = 0.019, respectively), and age was negatively correlated with Con A-induccd lymphocyte proliferation (r = -0.41, P = 0.009; r = -0.53, P = 0.011, respectively). These data indicate that NKCA but not mitogen-induced lymphocyte proliferation is higher in marathon runners relative to sedentary controls.

Our previous report showed that the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) blocks the inhibitory effect of morphine sulfate on E-rosette formation by human peripheral blood lymphocytes (PBL). In this study, additional in vitro effects of Tyr-MIF-1 on human PBL were studied. The percentages of positive cells for CD 2, a sheep erythrocyte receptor, CD 4 and CD 8 were unchanged after incubation of PBL with morphine or morphine plus Tyr-MIF-1. Tyr-MIF-1 was not mitogenic by itself. The addition of Tyr-MIF-1 did not increase the proliferative response of PBL to Con A, although morphine did. Tyr-MIF-1 did not activate PBL to produce IL 2 nor did it affect the production of IL 2 by Con A-stimulated PBL. The results suggest that Tyr-MIF-1 does not directly modulate CD 2, CD 4 and CD 8 expression, does not alter the proliferative response of PBL, and does not affect the production of IL 2.

Prolifererande verrukös leukoplaki, PVL, är en ovanlig sjukdom som yttrar sig genom multipla, vita förändringar i munslemhinnan som recidiverar och med tiden riskerar att utvecklas till cancer. Diagnosen kan endast ställas kliniskt när sjukdomsförloppet pågått under lång tid och det finns heller inga effektiva behandlingsmetoder. Etiologin till sjukdomen är okänd, men idag vet man att det finns ett samband mellan cancerutveckling och vissa virustyper.Syftet med studien är att undersöka om det går att påvisa humant papillom virus, HPV, i vävnadsprover från patienter som kan misstänkas ha PVL. Urvalet bestod av 11 patientfall, där vävnadsprover från biobanken vid avdelningen för oral patologi, Malmö högskola, samlats in och studerats med kromogen in situ hybridisering. Resultaten visade en högre förekomst av HPV i biopsier tagna i det senare skedet av sjukdomen jämfört med tidigare biopsier. En specifik HPV-genotyp kunde dock inte identifieras. I denna studie har det inte varit möjligt att påvisa HPV med in situ hybridisering, i ett tidigt staddium av PVL, som en möjlig indikator på sjukdomsutveckling. / Proliferative verrucous leukoplakia, PVL, is a rare disease that is characterized by multiple and recurrent white lesions in the oral epithelium which over time may develop into cancer. The diagnosis can only be made by the clinician when the disease has progressed for a long time. There is no effective treatment. The etiology of the disease is unknown but today it is known that there is a link between cancer and certain viruses.The purpose of this study is to investigate whether it is possible to detect human papilloma virus, HPV, in tissue samples from patients who possibly are affected by PVL.The selected samples consisted of 11 cases in which tissue samples from the biobank at the Department of Oral Pathology at Malmö University, were collected and HPV was detected by chromogenic in situ hybridization. The results showed a higher incidence of HPV in biopsies taken at a later stage of the disease compared with previous biopsies. However, a specific HPV genotype could not be identified.In this study, it has not been possible to demonstrate HPV with in situ hybridization at an early state of PVL as a putative indicator of disease development

Central to ocular health is the vitreous body, a complex, gelatinous tissue filling the space between the lens and retina. It is a natural polymeric hydrogel whose delicate architecture of collagen and hyaluronic acid loses its mechanical structure under the influence of degeneration or destruction, leaving the retina vulnerable to injury and disease. Since World War II, combat ocular trauma has increased six-fold while the population of aging veterans continues to grow in tandem. Compared to injuries in the civilian sector, injuries in theaters of combat operations are sustained in dirty, dusty, high-stress environments under hostile fire. These penetrating and perforating ocular injuries have predicable consequences, cascading into scarring on or under the retina (known as proliferative vitreoretinopathy or PVR). The growing population of aging veterans also faces a multitude of vitreous-related and vision-threatening pathologies. Current standards of care call for the removal and replacement of the vitreous, but contemporary substitutes are ill suited for long-term use. As such, there is critical need for development of a successful, long-term vitreous substitute. A biomimetic in situ forming hydrogel has been developed that utilizes a reversible disulfide cross-linker, enabling easy injection into the vitreous cavity. Recently, a copolymer has been introduced with this new formulation that possesses a unique comb-like structure whose characteristic bristles inhibit protein adsorption and cellular adherence, perfectly suited for the inhibition of PVR. The objective of this dissertation was to evaluate select formulations of this unique in situ forming hydrogel as potential vitreous substitutes. This was accomplished through rigorous in vivo rabbit modeled testing of long-term biocompatibility and bioperformance utilizing electroretinography, clinical examination, and histopathological assessment. We hypothesized that the in situ forming hydrogels would serve as a substantial improvement over the current gold standard, silicone oil, in terms of biocompatibility and the ability to inhibit PVR. / Bioengineering

The underlying cause of all vascular proliferative diseases is injury-induced activation of vascular endothelium and vascular smooth muscle cells (VSMC). Activated VSMC proliferate, than migrate from the arterial media to the intima, contributing to neointima formation. Activated immune cells, vascular cells, and their endogenous regulators mediate this complex process. One integral regulator of VSMC activation is allograft inflammatory factor-1 (AIF-1). AIF-1 is a cytoplasmic scaffold protein, expressed constitutively in lymphoid cells and induced in VSMC by injury. Stable over expression of AIF-1 increases VSMC proliferation and migration in vitro, causes increased injury-induced neointima formation, and increases Rac1 and p38 MAP Kinase activity. Recent studies show a correlation between VSMC expression of AIF-1 and atherosclerosis development. We hypothesize that VSMC over expression of AIF-1 contributes to atherosclerosis development by increasing activity of inflammatory signaling molecules, and that inhibiting VSMC AIF-1 expression will decrease injury-induced neointima formation. Rat carotid arteries transfected with AIF-1 si RNA adenovirus after balloon angioplasty developed significantly less neointima compared to controls. AIF-1 si RNA transfected VSMC proliferated significantly less than AIF-1 or GFP transfected VSMC, while AIF-1 si RNA transfection did not attenuate AIF-1-mediated migration. p38 inhibition showed that AIF-1-mediated proliferation is dependent on p38 activation while AIF-1-mediated migration is not. AIF-1 transgenic mice fed a high fat diet showed significantly more atherosclerotic lesions than WT littermates. Boyden Chamber assays showed OxLDL treatment increases VSMC migration but does not effect AIF-1-mediated migration. Expression of migration and inflammatory responsive genes in AIF-1 and XGal transfected VSMC after OxLDL treatment at various time points were examined. MMP-2 and -9 expression did not change. ICAM-1 and VCAM-1 expression increased in both groups. AIF-1 VSMC showed significantly higher ICAM-1 expression at baseline and early time points and elevated, but not significantly higher VCAM-1 expression at early time points. Western blots showed increased activation of NF-kB in AIF-1 transfected VSMC at baseline and 30 minutes after OxLDL stimulation compared to XGal transfected VSMC. Expression of the scavenger receptor receptors CD36 and SRA(I) expression increased after lipid treatment in AIF-1 and XGal transfected groups. AIF-1 VSMC showed sustained expression of both receptors after 16 hours of treatment compared to XGal VSMC, which showed decreased expression at that time point. CXCL16/PSOX expression increased with treatment, but differences in expression patterns were not seen between cell groups. Analysis showed significantly more OxLDL was taken up by AIF-1 VSMC compared to XGal VSMC. These data show that AIF-1 expression in VSMC is tightly linked to the vascular response to injury and development of vascular disease. Although AIF-1-mediated migration is not p38 dependent, AIF-1 may contribute to increased VSMC migration in part by upregulating NF- kB downstream effectors through increased NF-kB activity. AIF-1 may also speed the progression of atherosclerosis by increasing scavenger receptor expression and thereby increasing OxLDL uptake and foam cell formation. Although more study is required to fully elucidate the molecular mechanisms leading to AIF-1 mediated VSMC activation, these data have further established AIF-1 as an integral regulator of the VSMC response to injury. / Molecular and Cellular Physiology

Organisms are continuously exposed to heterogeneous micro- and macro-parasitic species, hence simultaneous infections often occur in wild and farm environments. This joint project aimed to develop a co-infection model between chronic and acute infections, evaluating their impact on the fish immune system. Proliferative Kidney Disease was studied on farmed rainbow and brown trout during natural seasonal outbreaks, using a parasite gene (Tetracapsuloides bryosalmonae RPL18) as a proxy for assessment of parasite burden. In hosts with elevated susceptibility PKD pathogenesis was shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activity. Pathogen-free brown trout were exposed to Viral Haemorrhagic Septicaemia Virus (comparatively using European VHSV-Ia and North American VHSV-IVb strains) or to the bacterium Yersinia ruckeri. This European native species was highly resistant to the VHSV-IVb strain, which was undetectable in internal organs despite raising a strong antiviral and mucosal immune response. Following VHS and Yersiniosis infection, haemo-lymphopoietic organs were screened by RT-qPCR to assess the specific pathogen burdens and characterise the immune responses elicited. Transcription patterns were analysed for Interferons, CXC chemokines, SOCS (potential disease resistance biomarkers) and genes of the PACAP system. Lastly, PKD-infected brown trout were co-infected with VHSV-Ia, resulting in typical lesions while showing reduced and delayed mortality. PKD+/VHS+ fish were identified by RT-qPCR and histopathology screening. Pro-inflammatory and antimicrobial peptide genes were modulated following virus co-infection when compared to fish with single infection, with an earlier activation of cellular and humoral responses, and a stronger up-regulation of TH1 and antiviral genes. Oligonucleotide microarrays were used to assess the broader immune gene transcription modulation between single- and co-infected fish. Overall, the results suggest that the immune response of brown trout might be enhanced during the PKD/VHS co-infection.

This study investigated the role of tolerance induction in an inflammatory setting in regard to the early growth response genes Egr2 and Egr3. T cells robustly respond to pathogenic antigens during infection, but are tolerant to stimulation by self-antigens. The intrinsic mechanisms for self-tolerance in the periphery are still not clear. Egr2 and 3 are induced in tolerant T cells in response to antigen stimulation by NFAT-medicated tolerant signalling; however, their function in tolerant T cells is still unknown. The study demonstrated that Egr2 and 3, induced in tolerant T cells, are not directly involved in defective proliferation and IL-2 production, the hallmarks of T cell tolerance. However, they are essential for preventing inflammatory response of tolerant T cells. In the absence of Egr2 and 3, tolerant T cells show impaired proliferation and production of IL-2, but produce high levels of IFN-γ, a key inflammatory cytokine. This phenotype resembles CD4 T cells from autoimmune diseases such as lupus which show poor proliferative response, but hyper-inflammation. Our study demonstrated, for the first time, a distinctive mechanism to control inflammation from proliferative tolerance regulated by Egr2 and 3, which may be an important mechanism for the control of autoimmune diseases.

Submitted by (lucia.rodrigues@ufrpe.br) on 2016-06-02T14:14:51Z No. of bitstreams: 1 Flavio de Oliveira Silva.pdf: 1881383 bytes, checksum: d592819e85426667e7752e0e6bcbbf0f (MD5) / Made available in DSpace on 2016-06-02T14:14:51Z (GMT). No. of bitstreams: 1 Flavio de Oliveira Silva.pdf: 1881383 bytes, checksum: d592819e85426667e7752e0e6bcbbf0f (MD5) Previous issue date: 2012-02-02 / Lectins are proteins that bind specifically and reversibly to carbohydrates, showing several biological effects. In this work, we carried out a literature review about biological effects of lectin extracted from seeds of Canavalia brasiliensis (ConBr), a plant present in the northeastern and southern Brazil, which is popularly known as wild bean of Ceará. In addition, we carried out a study to analyze the modulating activity of ConBr on murine splenocytes, verifying its effect on cell viability and proliferation, cytokine and nitric oxide (NO) production. We have also performed a study to evaluate ConBr effect on B16F10 murine melanoma cells by analyzing the inhibition of cell proliferation and migration as well as apoptosis induction and synthesis of cytokines and NO. The results show that ConBr induced at concentrations of 2.5, 5.0 and 10 μg/ml promoted the proliferation of splenocytes, with high cell viability. Furthermore, the concentration of 10 μg/ml induced cytokine production and nitric oxide on B16F10 murine melanoma, it was observed that ConBr inhibited tumor cell proliferation inducing apoptosis. It was also observed nitric oxide and IL-12 production by B16F10 cells under stimulus. ConBr lectin possesses a biotechnological potential use as a mitogen and anti-tumor agent. / As lectinas são proteínas que apresentam a capacidade de se ligar de maneira específica e reversível a carboidratos, exibindo distintos efeitos biológicos. Neste trabalho, realizou-se uma revisão de literatura sobre os efeitos biológicos da lectina extraída das sementes da Canavalia brasiliensis (ConBr), uma planta presente no Nordeste e Sul do Brasil, que é conhecida popularmente como feijão bravo do Ceará. Além disso, realizou-se um estudo para analisar a atividade moduladora da ConBr sobre esplenócitos murinos, verificando-se sua ação sobre a proliferação e viabilidade celular, produção de citocinas e óxido nítrico (NO). Realizou-se também, um estudo para avaliar o efeito da ConBr sobre células B16F10 de melanoma murino, analisando-se a inibição da proliferação e migração celular, bem como a indução de apoptose e síntese de citocinas e NO. Os resultados demostraram que a ConBr induziu nas concentrações de 2.5, 5.0 e 10 μg/ml promoveu a proliferação de esplenócitos, com alto índice de viabilidade celular. Além disso, a concentração de 10 μg/ml induziu a produção de citocinas e óxido nítrico. Em células B16F10 de melanoma murino, observou-se que a ConBr inibiu a proliferação das células tumorais promovendo apoptose celular. Verificou-se ainda, a produção de óxido nítrico e da citocina IL-12 pelas células submetidas ao estímulo. A lectina ConBr possue um potencial uso biotecnológico como mitógeno e agente antitumoral.

Made available in DSpace on 2014-08-20T14:37:59Z (GMT). No. of bitstreams: 1 dissertacao_fernanda_xavier.pdf: 2611334 bytes, checksum: 90b5b354699dc5901df46f1430425582 (MD5) Previous issue date: 2010-02-24 / The lesions of the penis and prepuce of the horse can be originated by trauma, bacterial or parasitic infeccions, and mostly neoplasms, causing productive and reproductive losses. For this study, several cases of proliferative lesions in the penis and prepuce of horses from the archives of the Laboratório Regional de Diagnóstico (LRD) of the Faculdade de Veterinária da Universidade Federal de Pelotas (UFPel) were reviewed, and penial lesions were obtained from a equine slaughterhouse located in the municipality of Pelotas, Rio Grande do Sul, Brazil. The materials were classified and macroscopic and histological aspects were evaluated. The samples were categoryzed as neoplastic and non-neoplastic and informations about the age, breed, and origin of the horses and anatomic location of the lesions were noted. Nineteen cases were obtained from the LRD-UFPel archives and 18 cases were obtained from the slaughterhouse. The lesions from the LRD were predominantely neoplastic - mostly squamous cells carcinoma, located more frequently in the prepuce of adult animals. Most of these horses were from the municipality of Pelotas, RS, Brazil. The samples collected from the slaughterhouse were predominately located in the prepuce of adult or old, gray, mixed breed horses. The lesions of these horses were predominantely non-neoplastic, mostly parasitic balanoposthitis caused by myiasis. These horses were from varied regions, including several Brazilian states. / Os distúrbios que ocorrem no pênis e prepúcio do cavalo podem ser de diversas origens como lesões por trauma, infecções bacterianas e parasitárias, e principalmente neoplasmas, cursando com perdas produtivas e reprodutivas. Realizou-se um estudo retrospectivo e prospectivo de lesões proliferativas de pênis e prepúcio de eqüinos. Para tal, foi realizada uma revisão nos casos recebidos no Laboratório Regional de Diagnóstico (LRD) da Faculdade de Veterinária da Universidade Federal de Pelotas (UFPel) e foram colhidas lesões penianas em linha de abate num Frigorífico de Eqüinos em Pelotas/RS. Os materiais foram classificados e seus aspectos macroscópicos e microscópicos foram avaliados. Os resultados foram organizados categorizando-se as lesões como neoplásicas e não neoplásicas e buscaram-se informações quanto à idade, raça e procedência dos animais e localização anatômica das lesões. Foram estudados 19 casos de portadores de lesões obtidos dos arquivos do LRD-UFPel e 18 casos forma obtidos na linha de abate do frigorífico. Nos casos provenientes do LRD houve um predomínio de lesões neoplásicas, principalmente carcinoma de células escamosas, em animais adultos localizados com maior freqüência no prepúcio. Os animais na maioria provinham do município de Pelotas/RS. Nas amostras colhidas no Frigorífico, predominaram aquelas localizadas no prepúcio, em animais adultos a velhos, a maioria dos quais sem raça definida. A pelagem mais observada foi a tordilha. Predominaram as lesões não neoplásicas principalmente, dentre as quais se destacaram as balanopostites parasitárias, causadas por miíases. Os animais tinham procedências variadas, pois o frigorífico recebe animais de vários estados brasileiros.