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61.
62.
Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells 总被引:2,自引:1,他引:2
Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i). 相似文献
63.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
64.
The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or opportunistic microbial infection most commonly found in HIV positive individuals differ from one area to the other. The present study reports such findings in 67 HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T-lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures were performed. Serological diagnosis was performed when indicated. Viral study was done serologically. The distribution of CD4+ T-lymphocyte count in the studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16 patients (23.9%) with count more than 500 cells/microl. Among patients with low CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from fungal infections 66%, bacterial infections 57% and viral infections 4.8%. Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%), Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection included H. simplex to (4.8%). Fungal infections were the highest common infection in thus study. The most common microbial infection was Candida albicans. P. carinii and Cryptococcus neoformans were less common than found in other studies world wide. 相似文献
65.
Francesco Vairo Emanuele Nicastri Salma Masauni Yussuf Angela Cannas Silvia Meschi Mwanakheir AA Mahmoud Azza H. Mohamed Paul Mohamed Maiko Pasquale De Nardo Nazario Bevilacqua Concetta Castilletti Antonino Di Caro Vincenzo Racalbuto Giuseppe Ippolito 《Emerging infectious diseases》2014,20(3):465-468
We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections 相似文献
66.
Hassan Awada Reda Z. Mahfouz Ashwin Kishtagari Teodora Kuzmanovic Jibran Durrani Cassandra M. Kerr Bhumika J. Patel Valeria Visconte Tomas Radivoyevitch Alan Lichtin Hetty E. Carraway Jaroslaw P. Maciejewski Yogen Saunthararajah 《British journal of haematology》2020,188(6):924-929
The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1–2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly. 相似文献
67.
Hassan Awada Reda Z. Mahfouz Jibran Durrani Ashwin Kishtagari Deepa Jagadeesh Alan E. Lichtin Brian T. Hill Betty K. Hamilton Hetty E. Carraway Aziz Nazha Navneet S. Majhail Ronald Sobecks Valeria Visconte Matt Kalaycio Mikkael A. Sekeres Jaroslaw P. Maciejewski 《British journal of haematology》2020,189(2):318-322
T-cell large granular lymphocytic leukaemia (T-LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T-LGLL seen at our institution over the last 10 years, we encountered 15 cases following solid organ or haematopoietic stem cell transplantation. Here, we studied the clinical characterization of these cases and compared them to de novo T-LGLL. This experience represented a clear picture of the intricate nature of the disease manifestation and the complexities of several immune mechanisms triggering the clonal expansion. 相似文献
68.
Andrea Corbingi Idanna Innocenti Annamaria Tomasso Raffaella Pasquale Andrea Visentin Marzia Varettoni Elena Flospergher Francesco Autore Francesca Morelli Livio Trentin Gianluigi Reda Dimitar G. Efremov Luca Laurenti 《British journal of haematology》2020,190(6):901-908
The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4·8%), 149 (10%), 200 (13·2%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo-γ) and normal Ig levels (γ-normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment-free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels. 相似文献
69.
Yasser A. Radwan Ali M. Reda Mansour Ahmed Rizk George Malak 《European orthopaedics and traumatology》2014,5(3):253-260
Introduction
The purpose of this study was to assess the effect of osteoarthritis on the outcome of arthroscopic anterior cruciate ligament (ACL) reconstruction, and to assess the effect of the procedure on the progression of osteoarthritis.Material and methods
Forty-two patients, age above 40, presenting by symptomatic instability secondary to rupture of the ACL were enrolled in a prospective cohort study. Cases were divided into two groups according to the absence of osteoarthritic changes (group I, 19 patients) or presence of osteoarthritic changes (group II, 23 patients) in preoperative radiographs. ACL anatomic single bundle reconstruction by the anteromedial portal technique using hamstring autograft fixed by biodegradable interference fit screws was done for all patients, and a fixed postoperative rehabilitation protocol was applied. Data were recorded and statistical analysis of the preoperative, 1 year follow up, and final follow up (average 41 months in group I and 42 months in group II) results of both groups was conducted.Results
The average patient age at the time of operation was 44.5 years in group I versus 46.4 years in group II. The follow-up median pain scores, ROM, modified Lysholm scores were significantly better in group I compared to group II. On the contrary, the difference between preoperative and 1 year postoperative scores and the percentage of improvement of the modified Lysholm score were significantly higher in group II. Deterioration of the radiographic grade of osteoarthritis in the final follow-up was declared in 15.8 % of patients of group I and in 21.7 % of patients of group II (P?=?0.71). Age, concomitant meniscus injury, and presence of preoperative arthritic changes, and cartilage defect had no statistically significantly effect on the success rate. Patients who had ACL reconstruction more than 2 years after injury and those with higher body mass index (BMI) had worse outcome than those who had earlier reconstruction and lower BMI.Conclusion
Patients having preoperative mild to moderate arthritic changes will indeed benefit from ACL reconstruction at short term, although their overall functional outcome seemed to be inferior to the outcome of non-arthritic patients. However, osteoarthritic changes deteriorate over time in both groups especially when there is preoperative mild to moderate arthritic changes. 相似文献70.