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31.
Shimon Lecht Naomi Cohen-Arazi Gadi Cohen Keren Ettinger Tatjana Momic Michal Kolitz 《Journal of biomaterials science. Polymer edition》2014,25(6):608-624
One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, 1H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering. 相似文献
32.
Comparison of positive allergy skin tests among asthmatic children from rural and urban areas living within small geographic area. 总被引:1,自引:0,他引:1
Haim Bibi David Shoseyov David Feigenbaum Pnina Nir Rosa Shiachi Shimon Scharff Ronit Peled 《Annals of allergy, asthma & immunology》2002,88(4):416-420
BACKGROUND: Evidence of increased asthma and allergic response among urban versus rural residents has been reported. OBJECTIVE: To evaluate the prevalence of allergic response among asthmatic children from urban and rural areas living within close proximity. METHODS: In all, 448 asthmatic children from urban (363) and rural (85) areas were studied. The study group consisted of 234 9-year-olds and 214 12-year-olds. A health questionnaire was completed on each child who subsequently underwent allergic skin prick tests (SPTs). RESULTS: There was significantly more positive SPT response to house-dust mite, mold, cat, and cypress among asthmatic children from urban areas compared with children living in rural areas: 58.3% versus 37.6%, 46.1% versus 31.8%, 17.45 versus 5.9%, and 26.2% versus 15.3%, respectively. Positive SPT for indoor allergens were significantly greater among asthmatic urban residents than asthmatic rural residents: 63.3% versus 45.5%, respectively (P < 0.02). Positive SPT response to all the allergens checked was higher among the 12-year-old age group when compared with the 9-year-olds, 34.6% versus 22.7%, respectively (P = 0.05). CONCLUSIONS: Allergic response measured by SPT is significantly more common among asthmatic children from urban areas as opposed to rural, even though both areas are within small distance of one another. Further, asthmatic children living in urban areas demonstrated more allergic response to both indoor and outdoor allergens. The allergic response tends to increase with increased age in both urban and rural asthmatic children. 相似文献
33.
Although it has been recognized since the early days of Owen and Medawar that engraftment of donor stem cells, induced in utero spontaneously or intentionally neonatally, results in life-long unresponsiveness to donor alloantigens. However, successful induction of transplantation tolerance in adult life still represents an unsolved problem. Engraftment of donor stem cells using conventional modalities involves intensive myeloablative or lymphoablative immunosuppression, which is associated with toxicity and mortality and such methods are not suitable for organ allograft recipients. In this chapter, we present an innovative approach for induction of donor-specific unresponsiveness to bone marrow and organ allografts without myeloablative conditioning. Our methods is based on cyclophosphamide-induced, alloantigen-primed lymphocyte depletion. Cyclophosphamide is administered 1 day following infusion of donor hematopoietic cells, thus eliminating predominantly host T lymphocytes reacting against donor cell challenge, and resulting in relative unresponsiveness to donor alloantigens. Subsequently, life-long tolerance to fully mismatched donor skin allografts can be accomplished by a second infusion of stem cells from the same donor, with donor T cells displacing residual alloreactive host cells that may have escaped deletion. Taken together, we believe that induction of true permanent and specific tolerance to organ allografts using donor hematopoietic cells could become a clinical reality in the foreseeable future. 相似文献
34.
Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells 总被引:12,自引:0,他引:12
Naturally occurring CD4+CD25+ regulatory T (TR) cells play crucial roles in normal immunohomeostasis. CD4+CD25+ TR cells exhibit a number of interesting in vitro properties including a 'default state' of profound anergy refractory to conventional T cell stimuli. We investigated the in vitro activation requirements of CD4+CD25+ TR cells using bone marrow-derived DC, which as professional antigen presenting cells (APC) can support the activation of normal naive T cells. Comparison of different APC types revealed that LPS-matured DC were by far the most effective at breaking CD4+CD25+ TR cell anergy and triggering proliferation, and importantly their IL-2 production. Examination of Foxp3, a key control gene for CD4+CD25+ TR cells, showed this to be stably expressed even during active proliferation. Although CD4+CD25+ TR cell proliferation was equivalent to that of CD25- cells their IL-2 production was considerably less. Use of IL-2-/- mice demonstrated that the DC stimulatory ability was not dependent on IL-2 production; nor did IL-15 appear crucial but was, at least in part, related to costimulation. DC also blocked normal CD4+CD25+ TR cell-mediated suppression partially via IL-6 secretion. DC therefore possess novel mechanisms to control the suppressive ability, expansion and/or differentiation of CD4+CD25+ TR cells in vivo. 相似文献
35.
Hale GA Shrestha S Le-Rademacher J Burns LJ Gibson J Inwards DJ Freytes CO Bolwell BJ Hsu JW Slavin S Isola L Rizzieri DA Gale RP Laport GG Montoto S Lazarus HM Hari PN 《Biology of blood and marrow transplantation》2012,18(7):1036-1043.e1
We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched unrelated and HLA-mismatched related donor hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity conditioning (RIC), reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72 years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the major histology. Incidence of grades II-IV acute graft-versus-host disease (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at 3 years. Treatment-related mortality (TRM) at 100 days was 24%. Three-year overall survival (OS) and progression-free survival (PFS) were 41% and 32%, respectively. In multivariate analysis, use of antithymocyte globulin (ATG) and HLA mismatch were associated with increased TRM. High-grade histology, ATG use, and chemotherapy resistance were associated with lower PFS. Older age, shorter interval from diagnosis to HCT, non-total body irridiation (TBI) conditioning regimens, ex?vivo T cell depletion, and HLA-mismatched unrelated donors were associated with mortality. GVHD did not influence relapse or PFS. Older age, aggressive histology, and chemotherapy resistance correlated with poorer survival. For selected patients with NHL, lack of an available sibling donor should not be a barrier to allogeneic HCT. 相似文献
36.
Yarkoni S Prigozhina TB Slavin S Askenasy N 《Biology of blood and marrow transplantation》2012,18(4):523-535
T cell depletion prevents graft-versus-host disease (GVHD) but also removes T cell-mediated support of hematopoietic cell engraftment. A chimeric molecule composed of IL-2 and caspase-3 (IL2-cas) has been evaluated as a therapeutic modality for GVHD and selective ex vivo depletion of host-reactive T cells. IL2-cas does not affect hematopoietic cell engraftment and significantly reduces the clinical and histological severity of GVHD. Early administration of IL2-cas reduced the lethal outcome of haploidentical transplants, and survivor mice displayed markedly elevated levels of X-linked forkhead/winged helix (FoxP3(+); 50%) and CD25(+)FoxP3(+) T cells (35%) in the lymph nodes. The chimeric molecule induces in vitro apoptosis in both CD4(+)CD25(-) and CD4(+)CD25(+) subsets of lymphocytes from alloimmunized mice, and stimulates proliferation of cells with highest levels of CD25 expression. Adoptive transfer of IL2-cas-pretreated viable splenocytes into sublethally irradiated haploidentical recipients resulted in 60% survival after a lethal challenge with lipopolysaccharide, which is associated with elevated fractions of CD25(high)FoxP3(+) T cells in the lymph nodes of survivors. These data demonstrate that ex vivo purging of host-presensitized lymphocytes is effectively achieved with IL2-cas, and that IL-2-targeted apoptotic therapy reduces GVHD severity in vivo. Both approaches promote survival in lethal models of haploidentical GVHD. The mechanism of protection includes direct killing of GVHD effectors, prevention of transition to effector/memory T cells, and induction of regulatory T cell proliferation, which becomes the dominant subset under conditions of homeostatic expansion. 相似文献
37.
Treg cells are critical for the maintenance of immune homeostasis and suppression of naturally occurring self‐reactive T cells; however, in order to induce suppression Treg cells must first be activated via their T‐cell receptor by recognition of specific antigen–MHC complexes. In this issue of the European Journal of Immunology, Föhse et al. [ Eur. J. Immunol. 2011. 41: 3101–3113 .] shed light on the important question of the role of TCR diversity on Treg‐cell function by demonstrating that high TCR diversity is crucial for optimal Treg‐cell expansion, peripheral reshaping of the Treg‐cell TCR repertoire and in vivo suppressive capacity. In this Commentary, we discuss these findings and also propose a simple mathematical model to aid in the understanding of the relationship between Treg‐cell TCR diversity and the level of suppression delivered by Treg cells in vivo. 相似文献
38.
Smita S. Iyer Donald R. Latner Michael J. Zilliox Megan McCausland Rama S. Akondy Pablo Penaloza‐MacMaster Jeffrey Scott Hale Lilin Ye Ata‐Ur‐Rasheed Mohammed Tomoyuki Yamaguchi Shimon Sakaguchi Rama R. Amara Rafi Ahmed 《European journal of immunology》2013,43(12):3219-3232
CD4+ T follicular helper (TFH) cells are central for generation of long‐term B‐cell immunity. A defining phenotypic attribute of TFH cells is the expression of the chemokine R CXCR5, and TFH cells are typically identified by co‐expression of CXCR5 together with other markers such as PD‐1, ICOS, and Bcl‐6. Herein, we report high‐level expression of the nutrient transporter folate R 4 (FR4) on TFH cells in acute viral infection. Distinct from the expression profile of conventional TFH markers, FR4 was highly expressed by naive CD4+ T cells, was downregulated after activation and subsequently re‐expressed on TFH cells. Furthermore, FR4 expression was maintained, albeit at lower levels, on memory TFH cells. Comparative gene expression profiling of FR4hi versus FR4lo Ag‐specific CD4+ effector T cells revealed a molecular signature consistent with TFH and TH1 subsets, respectively. Interestingly, genes involved in the purine metabolic pathway, including the ecto‐enzyme CD73, were enriched in TFH cells compared with TH1 cells, and phenotypic analysis confirmed expression of CD73 on TFH cells. As there is now considerable interest in developing vaccines that would induce optimal TFH cell responses, the identification of two novel cell surface markers should be useful in characterization and identification of TFH cells following vaccination and infection. 相似文献
39.
Renal cell carcinoma invading the right ovarian vein: multidetector computed tomography and ultrasound Doppler findings 总被引:1,自引:0,他引:1
Ghersin E Leiderman M Meretik S Kaftori JK Amendola MA Engel A 《Journal of computer assisted tomography》2005,29(4):472-474
Multidetector computed tomography (MDCT) and Doppler ultrasound findings of a renal cell carcinoma invading the right ovarian vein are presented. An MDCT study performed for evaluation of macroscopic hematuria showed a heterogeneously enhancing malignant thrombus in the right ovarian vein that was in continuity with inferior vena cava and right renal vein thrombi of identical characteristics. Further investigation with Doppler ultrasound confirmed these findings and showed arterial blood flow of low resistance within the ovarian vein and inferior vena cava thrombi. To the authors' knowledge, this is the first report of MDCT and Doppler ultrasound findings of a renal cell carcinoma invading the right ovarian vein. 相似文献
40.
Hayashi Y Kimura A Kato S Koumura A Sakurai T Tanaka Y Hozumi I Sunden Y Orba Y Sawa H Takahashi H Inuzuka T 《Journal of the neurological sciences》2008,268(1-2):195-198
We report progressive multifocal leukoencephalopathy (PML) and CD4+ T-lymphocytopenia in a 71-year-old man with Sj?gren syndrome (SjS). The patient was admitted to our hospital because of progressive dementia and gait disturbance. T2-weighted MR images showed high-intensity lesions in his left frontal white matter thalamus, cerebellum and brainstem. A pathological diagnosis of PML was made by brain biopsy. SjS is frequently accompanied with immunological complications; however, there are few reports on PML in patients with SjS. Recently, isolated CD4+ T-lymphocytopenia is reported to be one of the based immunological conditions associated with the development of PML. In the present case, CD4+ T-lymphocytopenia was also observed on admission, which is also associated with SjS. 相似文献