RESUMO
INTRODUCTION: The aim of the study was to examine possible risk factors for dropout from in-patient treatment for eating disorders (ED). MATERIALS AND METHODS: The present study consisted of a retrospective analysis of clinical and non-clinical available information about 186 patients suffering from ED consecutively admitted into the Villa Maria Luigia Private Hospital (Parma, Italy) in a three-year period (01/01/2006 - 31/12/2009). Sociodemographics, clinical history and current features, and results to the following psychometric instruments were analysed: Eating Disorder Questionnaire (EDQ), Predisposing, On-set and Maintaining risk factors list for Eating Disorders, Eating Disorders Inventory-II, Body Uneasiness Test and SCL-90. RESULTS: Of the 186 patients, 46 (24.7%) voluntarily left the treatment program prematurely. Predictive factors included poor educational and professional achievements, parents' divorcing, parents' history of substance abuse and difficulties in interpersonal relationships. DISCUSSION: Dropout is a multifactorial phenomenon with deep clinical consequences: the recognition of possible risk factors may support the choice of specific therapeutic strategies to improve the treatment of ED and its outcomes.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Pacientes Desistentes do Tratamento/psicologia , Adulto , Feminino , Hospitalização , Humanos , Itália , Masculino , Estudos Retrospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
T lymphocytes bearing the gammadelta T cell receptor are known to play an important role in the first-line defense against viral, bacterial and fungal pathogens. Two main subsets of gammadelta T cells are known, showing distinct functional behaviour: Vdelta2 T lymphocytes, circulating in the peripheral blood, are involved in the response to mycobacterial infections and certain viruses, including coxsakie virus B3 and herpes simplex virus type 2. Vdelta1 T cells are resident in the mucosal-associated lymphoid tissue and are reported to participate in the immunity against Listeria monocytogenes and cytomegalovirus. Vdelta2 T lymphocytes recognize non-peptidic phosphorylated metabolites of isoprenoid biosynthesis, expressed by mycobacteria, while Vdelta1 T cells mainly interact with MHC-related antigens (MIC-A and MIC-B) and with receptors, called UL-16 binding proteins, for the UL-16 protein produced by cytomegalovirus-infected cells. Both Vdelta1 and Vdelta2 T cells can produce interferon-gamma in response to MIC-A(+) cells or non-peptide antigens, respectively. Moreover, production of TNF-alpha by human Vgamma9/Vdelta2 T cells has been demonstrated in response to bacterial products and non-peptidic molecules. Recently, it has been reported that gammadelta T lymphocytes can produce IL-17 during Escherichia coli or Mycobacterium tuberculosis infections in mice. This is of interest as IL-17 is emerging as a cytokine crucial in the control of intracellular pathogens and fungi. In this review, we will discuss the possible role of IL-17 producing gammadelta T cells in the regulation of acute and chronic inflammation, focusing on the different response of the two subsets to mycobacterial, viral or fungal antigens.
Assuntos
Antígenos de Bactérias/imunologia , Candida albicans/imunologia , Inflamação/imunologia , Interferon gama/metabolismo , Interleucina-17/metabolismo , Mycobacterium tuberculosis/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Linfócitos T/imunologia , Doença Aguda , Animais , Diferenciação Celular , Doença Crônica , Humanos , CamundongosRESUMO
Engagement of NKG2D by their ligands (NKG2D-L), as the human major histocompatibility complex class I-related molecules MIC-A and the UL16-binding proteins, on cytolytic lymphocytes leads to the enhancement of antitumour effector functions. These ligands are missing or expressed at very low levels on leukaemic cells; furthermore, they can be shed by tumour cells and inhibit cytolytic activity of lymphocytes. Herein, we show that in vivo administration of all-trans-retinoic acid (ATRA) or the histone deacetylase inhibitor sodium valproate (VPA) to patients affected with acute myeloid leukaemia (AML) M3 or M1 respectively, leads to the induction of transcription and expression of NKG2D-L at the surface of leukaemic cells. Apparently, no detectable shedding of the soluble form of these molecules was found in patients' sera. Conversely, AML blasts from patients treated with chemotherapy not including ATRA or VPA did not show any induction of NKG2D-L transcription. Furthermore, upon therapy with ATRA or VPA, leukaemic blasts become able to trigger lytic granule exocytosis by autologous CD8(+) T and natural killer lymphocytes, as shown by CD107a mobilization assay, followed by leukaemic cell lysis. These findings indicate that ATRA and VPA may contribute to the activation of cytolytic effector lymphocytes in vivo, possibly enhancing their anti-leukaemic effect.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Ativação Transcricional/efeitos dos fármacos , Tretinoína/administração & dosagem , Ácido Valproico/administração & dosagem , Adulto , Idoso , Crise Blástica/tratamento farmacológico , Crise Blástica/patologia , Citotoxicidade Imunológica/efeitos dos fármacos , Feminino , Proteínas Ligadas por GPI , Inibidores de Histona Desacetilases , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Ligantes , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Tretinoína/farmacologia , Ácido Valproico/farmacologiaRESUMO
In this study, we analysed 30 patients with B-cell chronic lymphocytic leukaemia (CLL), compared with 10 healthy donors, for the expression and function of the leukocyte-associated Ig-like receptor-1 (LAIR-1). LAIR-1 is an inhibitory receptor containing a cytoplasmic tyrosine-based inhibitory motif (ITIM) that binds to the SH2 domain of phosphatases, leading to dephosphorylation of different kinases. Constitutive activation of c-Jun aminoterminal kinase (JNK), p38 mitogen-activated protein kinase and extracellular signal-regulated kinase, has been reported in CLL. We show that LAIR-1 is absent in high-risk (HR) CLL and differently expressed on intermediate- and low-risk CLL and the intensity of expression, which is always significantly lower than in healthy donors, correlates with disease stage and progression. Interestingly, both constitutive and sIgM-induced phosphorylation of p38 and JNK is inhibited by LAIR-1 through an ITIM-dependent signal, as demonstrated by the use of specific ITIM-binding peptides; importantly, this inhibitory signal is missing when LAIR-1 is not expressed as occurs in HR CLL. Moreover, engagement of LAIR-1 blocks constitutive and sIgM-induced Akt phosphorylation, besides nuclear factor kappa-B nuclear translocation, and prevents CLL division. These results suggest that CLL lacking LAIR-1 may miss one of the molecular mechanisms controlling B-cell activation and proliferation.
Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leucemia de Células B/metabolismo , Receptores Imunológicos/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Estudos de Casos e Controles , Divisão Celular , Progressão da Doença , Humanos , Leucemia de Células B/patologia , Fosforilação , Receptores Imunológicos/análise , Transdução de SinaisRESUMO
Gammadelta T lymphocytes are thought to be involved in multiple sclerosis (MS) pathogenesis. In this work, we discuss the characteristics of these cells and possible implications in the pathogenesis of MS, focusing on the mechanism(s) underlying extravasation and tissue localization. Phenotype and transendothelial migration of gammadelta T cells from healthy donors and patients with relapsing-remitting MS were studied. In MS patients the V delta 2 T cell subset, expressing NKRP1A/CD161 adhesion molecule, is expanded and capable of transendothelial migration. V delta 1/V delta 2 subsets use distinct signal transduction pathways: V delta 1 cells lack NKRP1A and express PECAM-1/CD31, which drives transmigration, while V delta 2 cells are PECAM-1 negative and use NKRP1A. V delta 2 migration is coupled with CAMKII, whereas V delta 1 depend on PI-3K. NKRP1A and PECAM-1 selectively activate the two pathways: indeed, oligomerization of NKRP1A on V delta 2 T cells leads to CAMKII activation, occupancy of PECAM-1 on V delta 1 cells triggers the PI-3K-dependent Akt/PKB pathway. Moreover, V delta 2 T cells are CXCR3(bright)CXCR4(dull), while V delta 1 are mostly CXCR4(+). V delta 1 and V delta 2 cells transmigrate in response to IP-10/CXCL10 and SDF-1/CXCL12 according to the expression of their specific receptors. In a fraction of V delta 1 T cells coexpressing CXCR3 and CXCR4, the homeostatic chemokine 6Ckine/SLC/CCL21 is more effective. IP-10/CXCL10 or 6Ckine/SLC/CCL21 and SDF-1/CXCL12-induced transmigration is coupled to PI-3K/Akt/PKB, but only CXCR3 is capable of inducing CAMKII activation. We suggest that both subsets of gammadelta T lymphocytes may migrate to the site of lesion in MS using two different signaling pathways to extravasate and responding to different chemokines.
Assuntos
Moléculas de Adesão Celular/metabolismo , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores CXCR4/metabolismo , Receptores de Quimiocinas/metabolismo , Linfócitos T/metabolismo , Movimento Celular , Humanos , Ligantes , Receptores CXCR3 , Linfócitos T/citologia , VirulênciaRESUMO
BACKGROUND AND OBJECTIVES: Human cord blood (CB) is an important source of stem cells which may be used for hematopoietic reconstitution as an alternative to bone marrow transplantation. Banking of CB would be accomplished by removing red blood cells (RBC) and plasma from CB collections. Our aim was to compare three different procedures for CB processing. MATERIALS AND METHODS: Poligeline, hydroxyethyl starch gel (HES) and gelatin were used as separation media in processing 79 CB units for RBC depletion and mononuclear cell (MNC) recovery. RESULTS: The best MNC recoveries were obtained performing the HES- and the gelatin-based procedures (80.9 and 84.7%, respectively), but the gelatin procedure allowed us to obtain the highest RBC depletion (96.4%); CD34+ cell recovery was higher using HES or gelatin as separation media (85.6 and 85.9%, respectively). CONCLUSION: The best results, as far as RBC removal and MNC recovery are concerned, were obtained by using gelatin as RBC sedimentation medium. Gelatin is a low-cost, animal-derived reagent, which has been successfully used for CB transplantation; the procedure is simple to perform and appears to be suitable for large-scale banking in view of CB transplantation.
Assuntos
Separação Celular/métodos , Sangue Fetal/citologia , Remoção de Componentes Sanguíneos , Transfusão de Eritrócitos , Gelatina , Humanos , Derivados de Hidroxietil Amido , Leucócitos Mononucleares/citologia , PoligelinaRESUMO
Umbilical cord blood (UCB) collected at delivery is a source of transplantable stem/progenitor cells; it represents an alternative to bone marrow to restore hematopoiesis in patients affected by malignant and non-malignant disease. Therefore, large-scale UCB banks would be a natural complement to bone marrow donor registries. Storage of unmanipulated whole UCB units requires a great number of liquid nitrogen containers. Separation of leukocytes allows UCB storage in smaller space, thus lowering banking costs; unfortunately, UCB processing may cause significant losses of stem cells. We report about the use of poligeline to remove erythrocytes from UCB units. After erythrocyte sedimentation at 1xg (30' or 40') or 50xg, leukocyte-rich supernatant was collected and centrifuged to recover the leukocyte pool in view of stem cell transplantation. Erythrocyte depletion was always satisfactory, ranging from 82.6% to 88.9%, but 1xg sedimentation for 40' enabled us to achieve the best CD34+ cell recovery (mean value 80.5%). The proposed UCB-processing method allowed us to lower the final sample volume down to 1/10 of the initial one, in this way making UCB banking feasible. Erythrocyte depletion took place directly in the collection bag, thus reducing microbial contamination risk.
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Preservação de Sangue , Mobilização de Células-Tronco Hematopoéticas , Leucaférese , Substitutos do Plasma , Poligelina , Bancos de Sangue , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas , HumanosRESUMO
Human von Willebrand factor (vWF) is synthesized as an extra large polymer; then, it is converted to lower molecular weight plasma multimers, originally composed of intact 225-kDa subunits, by a metalloproteinase. Proteolysis generates two fragments of 140-and 176-kDa, which originate from cleavage of peptide bond Tyr842-Met843 and which represent vWF residues 1-842 and 843-2050, respectively; a very small amount of 189-kDa fragment can also be found in normal plasma. We describe here a two-dimensional (2-D) method to analyze plasma vWF structure.
Assuntos
Eletroforese em Gel Bidimensional , Fator de von Willebrand/química , Biopolímeros , Humanos , Peso Molecular , Conformação ProteicaRESUMO
During the first six months of 1994 serum samples from 726 patients were assayed for anti-HCV antibodies of which 114 where found to be seropositive. After excluding those belonging to those categories known to be "at risk", the 93 remaining patients were evaluated from a clinical and chemico-clinical point of view. The distribution of seropositivity compared to age showed that around 70% of this sample were aged between 51 and 80 years old. In clinical terms 30% of patients were asymptomatic, while over 40% presented chronic hepatitis and 16% suffered from cirrhosis. Mean levels of bilirubinemia, SGOT, SGPT, AFP and gamma-GT were generally above normal. In particular, over 90% of transaminase values were found to belong to WHO hepatotoxic classes 0-2; only a few cases showed a very high level of hepatic toxicity, while over 25% showed normal hepatic function.
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Instalações de Saúde , Hepatite C/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Monitorização AmbulatorialRESUMO
In the present study both responsiveness and stimulatory capacity in autologous mixed lymphocyte reactions (AMLRs) of non-T/T and T/T type, as well as in allogeneic mixed lymphocyte reaction (MLR), were evaluated in 30 intravenous drug abusers (IDAs) infected by the human immunodeficiency virus (HIV) and in 10 HIV-negative IDAs. The production of interleukin 2 (IL2), and the expression of HLA Class II antigens and IL2 receptors by PHA-activated T lymphocytes were also evaluated. A severe impairment of both responsiveness and stimulatory capacity in MLR and AMLRs was found in the HIV-positive IDAs and not in the HIV-negative IDAs. The HIV-positive IDAs showed also a defective expression of HLA Class II antigens, whereas the IL2 production and the IL2 receptor expression were in the normal range. The present data are consistent with similar observations in male homosexuals with AIDS-related complex and confirm that the HIV infection induces a broad spectrum of immunological abnormalities leading to a progressive derangement of the immunocompetence.