Cytolytic and cytotoxic activity of a human natural killer cell line genetically modified to specifically recognize HER-2/neu overexpressing tumor cells

NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have been previously reported to lyse HER-2/neu positive tumor cell lines through direct cell to cell contact. In the present study we have transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 ζ chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/ζ) specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both in vitro and in preclinical tumor models in vivo. More important we demonstrate that NK92.HER-2/neu/ζ cells constitutively secrete high levels of soluble scFv which mediate strong tumor cytostatic effects by directly binding on cell surface HER-2/neu. Our data uncover an additional mechanism through which NK92.HER-2/neu/ζ cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2/neu expressing cancers.     

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene

Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.     

组织工程化的雪旺细胞在视神经损伤修复中的应用

0 引言 视神经损伤(optic nerve injury)是常见的眼外伤类型,临床上常见各种面部及颅脑外伤如压迫、牵伸、撕裂、切断等原因致使视神经走行的某一段受损,如果治疗不及时可能造成患者视功能不可逆性的丧失.     

肼苯达嗪、卡托普利研究(Hy-C)

标题　用肼苯达嗪做直接血管扩张或用Ｃａｐｔｏｐｒｉｌｒ抑制血管紧张素转换酶对晚期心衰病死率的影响作者　ＦｏｎａｒｏｗＧＣ,ｅｔａｌ．ＪＡｍＣｏｌｌＣａｒｄｉｏｌ,１９９２,１９：８４２（英文）　　研究疾病：晚期心力衰竭。目的：比较血管紧张素转换酶抑制和直接血管扩张对晚期心衰预后的影响。　　设计：随机式。病人资料：１１７例充血性心力衰竭者,ＮＹＨＡⅢ级或Ⅳ级,休息时有血液动力学异常,为心脏移植做评估。随访：（８±７）个月。治疗方案：Ｃａｐｔｏｐｒｉｌ６．２５ｍｇ渐增至１００ｍｇ,每日４次,或者肼苯…     

Genetic counselling in multiple sclerosis: risks to sibs and children of affected individuals

Genetic factors are recognized as having important roles in both the overall etiology and the familial aggregation of multiple sclerosis (MS), leading to increased requests for genetic counselling. This paper is designed to provide familial risk data in a practical format for use during genetic counselling for MS. Depending on the amount of genetic sharing among family members, the relative risk of MS compared with that for the general population can range from 1 (adopted sibs and children of the MS proband, with whom they share no genetic material) to 190 (monozygotic co-twins of MS patients, with whom they share 100% of their genetic material). When counselling full sibs of MS patients, risks can be better calculated if information is available on the age of MS onset in the patient and whether or not one parent has MS.     

Intravitreal ranibizumab (Lucentis®) in the treatment of retinal angiomatous proliferation (RAP)

Background  Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Methods  Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Results  Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 μm, and decreased significantly to a mean of 224 μm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 μm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Conclusions  Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.     

Exploring adaptations to the clinical reasoning cycle for forensic mental health nursing: A qualitative enquiry

Forensic mental health nurses (FMHN) provide care to address the needs of people who have mental illnesses across a range of diverse settings. The Clinical Reasoning Cycle (CRC) has been identified as a potential framework to assist FMHNs; however, adaptations were required to reflect the unique nature of the clinical setting. This study aimed to explore adaptations made to determine suitability prior to implementation in practice. Nominal Group Technique was used to explore suggested adaptations determined from a previous study and reach a consensus on the changes. Fourteen senior nurses from a state-wide Forensic mental Health (FMH) service participated. A consensus was reached for two proposed changes. Data were analysed using thematic analysis. Three main themes were interpreted from the data; FMH adaptations are warranted, the focus of the CRC, and who owns the cycle? Nurses in this study considered the need to include offence and risk issues due to the impact these factors have on the therapeutic relationship and cognitive bias; however, they also identified the need to focus on recovery-oriented care while engaging in clinical reasoning. Nurses in this study also expressed some reluctance for nursing to ‘own' the model, due to concern that ownership may cause division among the team or result in inconsistency in care. However, some participant's suggested the CRC with adaptations assisted FMH nurses to articulate their specialist skills and knowledge to others and highlight the nursing contribution to care. Further work is needed to finalize adaptations with a focus on engaging the consumer carer workforce and interdisciplinary team.     

Severe anaphylactic reaction after blue dye injection for sentinel lymph node biopsy in breast surgery: Report of two cases and literature review

Anaphylactic reactions, and especially the severe ones (types III and IV), should be kept in mind as considerable adverse effects while using blue dyes for SLNB.