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91.
Platelet formation is the consequence of caspase activation within megakaryocytes 总被引:21,自引:10,他引:21
De Botton S Sabri S Daugas E Zermati Y Guidotti JE Hermine O Kroemer G Vainchenker W Debili N 《Blood》2002,100(4):1310-1317
Platelets are formed from mature megakaryocytes (MKs) and arise from the development of long and thin cytoplasmic extensions called proplatelets. After platelet release, the senescent MKs (nucleus surrounded by some cytoplasm) undergo cell death by apoptosis. To explore the precise role of apoptosis in proplatelet formation, we grew human MKs from CD34(+) cells and assessed the possible role of caspases. Proteolytic maturation of procaspase-3 and procaspase-9 was detected by immunoblots in maturing MKs as well as in proplatelet-bearing MKs and senescent MKs. Cleavage of caspase substrates such as gelsolin or poly adenosine diphosphate (ADP)-ribose polymerase (PARP) was also detected. Interestingly, activated forms of caspase-3 were detected in maturing MKs, before proplatelet formation, with a punctuate cytoplasmic distribution, whereas a diffuse staining pattern was seen in senescent and apoptotic MKs. This localized activation of caspase-3 was associated with a mitochondrial membrane permeabilization as assessed by the release of cytochrome c, suggesting an activation of the intrinsic pathway. Moreover, these MKs with localized activated caspase-3 had no detectable DNA fragmentation. In contrast, when apoptosis was induced by staurosporine, diffuse caspase activation was seen; these MKs had signs of DNA fragmentation, and no proplatelet formation occurred. The pan-caspase inhibitor z-VAD.fmk as well as more specific inhibitors of caspase-3 and caspase-9 blocked proplatelet formation, whereas an inhibitor of calpeptin had no effect. Overexpression of Bcl-2 also inhibited proplatelet formation in maturing MKs. Thus, localized caspase activation is causal to proplatelet formation. We conclude that proplatelet formation is regulated by a caspase activation limited to only some cellular compartments. 相似文献
92.
Gabriel Nakache Lela Migirov Sharon Trommer Michael Drendel Michael Wolf Yael Henkin 《Acta oto-laryngologica》2015,135(9):907-913
Conclusions: In patients with total sudden sensorineural hearing loss (SSNHL), oral prednisone (OP) alone or intratympanic dexamethasone (ITD) alone have comparable results. The addition of salvage ITD following OP does not seem to add over either single modality treatment. Objectives: To study the effect of steroid-based treatments in patients with total SSNHL. Methods: The medical charts of 59 patients with total loss of hearing, defined as pure tone thresholds in the profound range (> 90 dB) with an unobtainable speech reception threshold (SRT) that were treated with OP (n = 20), ITD (n = 13), or OP followed by salvage ITD (n = 26) were analyzed. Response to treatment was evaluated by means of pure tone thresholds, SRT, and speech discrimination score (SDS), immediately after treatment and on a follow-up visit. Results: Forty-nine patients (83%) responded to treatment, with mean significant improvements of 36, 34, 31, and 25 dB at 500, 1000, 2000, and 4000 Hz, respectively. The mean improvement in SRT was 33 dB, and SDS improved by 32%. There were no differences in improvement in pure tone thresholds and SRT among the three treatment groups. The late effect of OP was similar to the effect of salvage ITD. 相似文献
93.
Background
The social–ecological environment of undocumented children of migrant workers includes varying levels of risk factors. Growing up in these conditions compromises children’s development on all levels. Many of these children are in need of psychotherapy, however, due to limited resources, only a few of them receive mental health aid.Objective
The present research undertook to construct and examine the effectiveness of a specialized group intervention program to enhance children’s self-efficacy and mental health.Methods
Participants were 70 children aged 8–12 of illegal migrant workers in Israel. The repeated measures design included completion of a self-efficacy scale and emotional, behavioral and social difficulties child-report and teacher-report measures. Children were randomly allocated to either an intervention or control group.Results
The first hypotheses predicting a greater improvement in self-efficacy between the pre-test and post-test for children in the intervention as opposed to control group was confirmed. The second hypothesis predicting a greater reduction in the self- and teacher-reports of emotional, social and behavioral difficulties was confirmed. The third hypothesis predicting a moderating relation between self-efficacy, group type and time on the dependent variables was confirmed only for children’s self-report of their difficulties.Conclusions
Findings provide evidence for the effectiveness of this short term playful intervention program for this group of disadvantaged children, suggesting its application to other at-risk groups of children. 相似文献94.
Hagit Peres Yael Glazer Daniella Landau Kyla Marks Hana’a Abokaf Ilana Belmaker Arnon Cohen Ilana Shoham-Vardi 《Maternal and child health journal》2014,18(8):1831-1845
To understand the pattern of utilization of ambulatory care by parents of children with special health care needs (CSHCN) and to explore parental challenges in coping with health maintenance of their infants after discharge from a neonatal intensive care unit (NICU). CSHCN require frequent utilization of outpatient ambulatory clinics especially in their first years of life. Multiple barriers are faced by families in disadvantaged populations which might affect adherence to medical referrals. Our study attempts to go beyond quantitative assessment of adherence rates, and capture the influence of parental agency as a critical factor ensuring optimal utilization of healthcare for CSHCN. A prospective, mixed-methods, cohort study followed 158 Jewish and Bedouin-Arab infants in the first year post discharge from NICU in southern Israel. Rates of utilization of ambulatory clinics were obtained from medical records, and quantitative assessment of factors affecting it was based on structured interviews with parents at baseline. Qualitative analysis was based on home visits or telephone in-depth interviews conducted about 1 year post-discharge, to obtain a rich, multilayered, experiential perspectives and explained perceptions by parents. Adherence to post-discharge referrals was generally good, but environmental, cultural, and financial obstacles to healthcare, magnified by communication barriers, forced parents with limited resources to make difficult choices affecting utilization of healthcare services. Improving concordance between primary caregivers and health care providers is crucial, and further development of supportive healthcare for CSHCN in concordance with parental limitations and preferences is needed. 相似文献
95.
96.
Alex Zendel Eylon Lahat Yael Dreznik Barak Bar Zakai Rony Eshkenazy Arie Ariche 《肝胆外科与营养》2014,3(5):295-302
Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested. 相似文献
97.
Noa Benaroya-Milshtein Alan Apter Isaac Yaniv Oded Yuval Boaz Stern Yael Bengal Yona Kodman Eliya Shemer Chaim Gideon Pick Ilana Buchval Avi Valevski 《Journal of neural transmission (Vienna, Austria : 1996)》2014,121(3):299-306
The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions. 相似文献
98.
Yael Rosenberg-Hasson Leo Hansmann Michaela Liedtke Iris Herschmann Holden T. Maecker 《Immunologic research》2014,58(2-3):224-233
Multiplexed fluorescence or electrochemiluminescence immunoassays of soluble cytokines are commonly performed in the context of human serum or plasma, to look for disease biomarkers and to monitor the immune system in a simple and minimally invasive way. These assays provide challenges due to the complexities of the matrix (serum or plasma) and the presence of many cytokines near the limit of detection of the assay. Here, we compare the readout of matched serum and plasma samples, which are generally correlated. However, a subset of cytokines usually have higher levels in serum, and the non-specific background is significantly increased in serum versus plasma. Presumably as a result of this non-specific background, disease-related decreases in low-abundance cytokines can sometimes be detected in plasma but not in serum. We further show, through spike recovery experiments, that both serum and plasma inhibit the readout of many cytokines, with some variability between donors, but with serum causing greater inhibition than plasma in many cases. Standard diluents from different vendors can partially reverse this inhibition to varying degrees. Dilution of samples can also partly overcome the inhibitory effect of the matrix. We also show that dilution is nonlinear and differentially affects various cytokines. Together, these data argue that (1) plasma is a more sensitive matrix for detecting changes in certain low-abundance cytokines; (2) calculation of concentrations in serum or plasma matrices is inherently inaccurate; and (3) dilution of samples should not be assumed to be linear, i.e., all comparisons need to be made among similarly diluted samples. 相似文献
99.
David Polak Ester Benzki‐Namdar Yael Houri‐Haddad Lior Shapira 《Journal of periodontology》2014,85(7):991-997
Background: Mucosal vaccination for preventing periodontitis shows promising results. However, various administration routes and adjuvants may have a substantial role in the efficacy of the vaccination. The aim of the study is to compare different modes of mucosal vaccination with whole‐cell Porphyromonas gingivalis and to test the role of various adjuvants as potential modifiers of this process. Methods: Mucosal vaccine was administered through oral or nasal routes to BALB/C mice. The tested adjuvants included Escherichia coli cholera toxin, E. coli labile toxin (LT), and unmethylated CpG dinucleotide (CpG). Control mice were vaccinated subcutaneously. Saliva and serum were collected; anti–P. gingivalis salivary immunoglobulin A (IgA) and serum IgG were quantified. A quantitative enzyme‐linked immunosorbent assay to measure anti–P. gingivalis IgA levels was established. In addition, cells were extracted from head and neck lymph nodes, and the relative CD8+ cells were quantified using flow cytometry. Results: All mucosal vaccination modes induced anti–P. gingivalis salivary IgA but not anti–P. gingivalis serum IgG. Subcutaneous vaccination induced both salivary IgA and serum IgG against P. gingivalis. Mucosal vaccination also induced greater establishment of CD8+ cells compared to the subcutaneous vaccination. Oral mucosal vaccinations with LT or CpG were the most efficient for salivary IgA expression and CD8 cell establishment in lymph nodes. Conclusions: Oral and nasal mucosal vaccination induced a local host response with little systemic effect. The use of CpG or LT as adjuvants with the oral mucosal vaccination was the most efficient vaccination mode in the present mouse model. 相似文献
100.
Yael Gozlan Daniella Aaron Yana Davidov Maria Likhter Gil Ben Yakov Oranit Cohen-Ezra Orit Picard Oran Erster Ella Mendelson Ziv Ben-Ari Fadi Abu Baker Orna Mor 《Viruses》2022,14(3)
A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load >1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n = 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p < 0.05). HBV genotype D prevailed (61/68), and >95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers. 相似文献