乳腺癌组织NRF-1表达及其意义的探讨

目的:探讨乳腺癌组织中核呼吸因子-1(NRF-1)蛋白表达与乳腺癌发生、发展及临床病理特征的关系。方法:采用免疫组化EnVision二步法,对211例乳腺癌组织和50例乳腺良性病变组织中NRF-1蛋白表达进行检测。结果:NRF-1蛋白表达定位于细胞核,着色呈棕黄色,乳腺癌中阳性表达(82.7%)低于乳腺良性病变组织阳性表达(100%),χ2=100.288,P=0.000;高分化乳腺癌NRF-1阳性率明显高于中、低分化乳腺癌(χ2=16.242,P=0.001;χ2=72.802,P=0.000),中分化乳腺癌也明显高于低分化乳腺癌,χ2=30.190,P=0.000。乳腺癌淋巴结转移患者NRF-1蛋白阳性表达率明显低于未转移者,χ2=12.025,P=0.007;TNM分期中I期NRF-1蛋白阳性表达率明显高于Ⅱ、Ⅲ期,χ2=12.025,P=0.007。结论:NRF-1蛋白的表达可能与乳腺癌的发生发展密切相关,可作为乳腺癌患者疾病进展监控和预后观测的指标,具有临床应用价值。     

Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin

Platelet functions such as aggregation and clot retraction are often abnormal in chronic mylogenous leukemia (CML) patients. However, the molecular mechanisms of these altered functions are unknown. As expression of the p210bcr-abl oncogene product, a constitutively active tyrosine kinase, is known to have an essential role in the pathogenesis of CML and tyrosine phosphorylation is intimately involved in various aspects of platelet activation, we examined the pattern of protein tyrosine phosphorylation in platelets from 15 CML patients by immunoblotting with a monoclonal antiphosphotyrosine antibody (4G10). Before and after stimulation with thrombin, the only consistent difference between normal and CML platelets was the presence of a tyrosine phosphorylated protein with a relative molecular weight of 39 kD. This tyrosine phosphorylated protein was identified as crid, an SH2, SH3 containing adapter protein. Thus, as previously demonstrated for neutrophils from CML patients, tyrosine phosphorylation of p39crkl persists in mature platelets. No tyrosine phosphorylation of crid was detected following stimulation with thrombin in normal platelets. However, crkl became incorporated into the Triton X-100 insoluble residue following thrombin stimulation in a manner dependent on platelet aggregation. Further, we found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes. This suggests that crkl may be involved in the reorganization of the cytoskeleton during normal platelet aggregation and its tyrosine phosphorylation in CML platelets may contribute to the abnormal platelet function in CML patients. Finally, we found that thrombopoietin induces tyrosine phosphorylation of crk1 in normal platelets and FDCP cells genetically engineered to express human c-Mpl. This suggests that crk1 can be phosphorylated by a kinase other than p210bcr-abl and that crk1 may have a role in signaling by thrombopoietin.     

添加谷氨酰胺的全胃肠外营养对造血干细胞移植术后常见并发症的防治作用

目的:严重的黏膜损伤是诱发造血干细胞移植后出现并发症的一常见原因,已有证据显示谷氨酰胺能降低接受化疗患儿黏膜炎的发生率。观察谷氨酰胺对异基因外周造血干细胞移植患者并发症及恢复的影响。方法:选择于2002-03/2006-11在河南省血液病研究所接受同胞异基因外周造血干细胞移植的48例血液系统肿瘤患者。所有患者及其家属对治疗和实验均知情同意,并经医院伦理委员会批准。所有患者移植前均处于完全缓解状态,营养中等或良好,心、肝、肾功能正常,将48例患者随机分为标准化全胃肠外营养液组(标准组,n=13)和加用谷氨酰胺的全胃肠外营养液组(谷氨酰胺组,n=35)。待患者中性粒细胞升至1.0×109L-1,且无任何感染指征,进行异基因外周造血干细胞移植。造血干细胞输注后第1天开始给予全胃肠外营养与胃肠外营养联合谷氨酰胺双肽,至中性粒细胞≥1.0×109L-1,且无消化道症状时停用。观察两组患者中性粒细胞恢复时间、出层流室时间以及关于感染、急性移植物抗宿主病等情况有无差异。结果:48例患者均进入结果分析。两组患者营养物质的摄入基本相同,谷氨酰胺组有6例发生黏膜炎,标准组有11例,差异显著(P<0.05);谷氨酰胺组有1例发生严重腹泻,标准组有5例,差异显著(P<0.05);谷氨酰胺组有3例发生临床感染,标准组有7例,差异显著(P<0.05);标准组中性粒细胞≥0.5×109L-1的持续时间短于谷氨酰胺组(P>0.05);谷氨酰胺组抗生素治疗时间及无菌病房居住时间较标准组短(P<0.05);两组急性移植物抗宿主病发生率差异无统计学意义(P>0.05)。结论:添加谷氨酰胺的全胃肠外营养可改善异基因造血干细胞移植患者的营养状态,减少感染及肠损害,减少急性移植物抗宿主病的发生,有利于异基因移植患者恢复。     

A Comparison of Surgery and Family Medicine Residents' Perceptions of Cross-Cultural Care Training of Cross-Cultural Care Training

The need for physicians formally trained to deliver care to diverse patient populations has been widely advocated. Utilizing a validated tool, Weissman and Betancourt''s Cross-Cultural Care Survey, the aim of this current study was to compare surgery and family medicine residents'' perceptions of their preparedness and skillfulness to provide high quality cross-cultural care. Past research has documented differences between the two groups'' reported impressions of importance and level of instruction received in cross-cultural care. Twenty surgery and 15 family medicine residents participated in the study. Significant differences were found between surgery and family medicine residents on most ratings of the amount of training they received in cross-cultural skills. Specifically, family medicine residents reported having received more training on: 1) determining how patients want to be addressed, 2) taking a social history, 3) assessing their understanding of the cause of illness, 4) negotiating their treatment plan, 5) assessing whether they are mistrustful of the health care system and/or doctor, 6) identifying cultural customs, 7) identifying how patients make decisions within the family, and 8) delivering services through a medical interpreter. One unexpected finding was that surgery residents, who reported not receiving much formal cultural training, reported higher mean scores on perceived skillfulness (i.e. ability) than family medicine residents. The disconnect may be linked to the family medicine residents'' training in cultural humility — more knowledge and understanding of cross-cultural care can paradoxically lead to perceptions of being less prepared or skillful in this area.     

Psoriasis under the microscope

Histopathology is a major diagnostic tool in dermatology, particularly in psoriasiform diseases. Morphological studies showed that the initial event in psoriatic lesions is perivascular infiltrate, followed by dilatation of superficial papillary vessels. Proliferation of keratinocytes and neutrophil exocytosis are secondary events. Fully developed psoriasis has a very characteristic pattern, which includes elongation of rete ridges leading to regular acanthosis, oedema of the papillary dermis associated with tortuous dilated vessels, thinning of suprapapillar area, decreased thickness of granular layer, and exocytosis of neutrophils in the spinous layer (Kogoj's pustule) or in the cornified parakeratotic layer (Munro microabscesses). Pustular psoriasis is characterized by large or confluent intra‐epidermal multilocular pustules. Whatever the clinical variant of psoriasis, common morphological signs suggest that it is basically a unique pathological process, with many possible presentations according to various factors such as age, size and localization of lesions, or therapy. Similar microscopic elementary lesions indicate that Hallopeau's acrodermatitis continua, Reiter's disease and geographical tongue are variants of psoriasis. Because of the many faces of the disease, psoriasis can resemble many other squamous or pustular disorders. Differential diagnosis by microscopic analysis is based on pattern analysis, PAS (Periodic Acid Schiff) staining to rule out fungal infection, and immunohistochemistry to characterize lymphocytic infiltrate. Psoriasis is one of the most common inflammatory skin diseases. In its characteristic presentation, psoriasis comprises well‐circumscribed red scaly papules and plaques. In this form, the disease is generally easy to identify, especially when the elbows, knees and scalp are affected. Nevertheless, the term ‘psoriasis’ includes more clinical variants than any other inflammatory dermatosis: psoriasis vulgaris vs. pustular, localized vs. generalized, topographic variants, mucous membranes involvement, hair and nail lesions. Although some of these conditions might be extremely different from psoriasis vulgaris, common pathological findings can be identified in all of them. Microscopic analysis of psoriatic lesions may therefore help clinicians to make the diagnosis and to understand that, whatever the clinical presentation, signs and symptoms are mainly due to a unique pathological process.     

Defective T suppressor-inducer cell function in human immune deficiency virus-seropositive hemophilia patients

In human immune deficiency virus (HIV)-seropositive hemophilia patients, a low number of CD4 + lymphocytes is found, as well as a low CD4+/CD8+ ratio. In previous studies, it has been shown that antigen- specific T-helper cell (CD4+) function was present and no excessive antigen-specific T-suppressor cell (CD8+) function could be demonstrated. In this report, we studied another activity of CD4+ cells, namely the capacity to induce T-suppressor cell activity. The results clearly show a selective dysfunction of CD4+ suppressor-inducer (Tsi) cell function. Since these HIV-seropositive hemophilia patients showed the presence of activated B cells in the peripheral circulation refractory to antigen-specific T-helper cell signals and secreting specific antibodies spontaneously, we raised the hypothesis that the activated B cells in the patients activate the Tsi cells in vivo. This constant activation leads to a functional exhaustion of the Tsi cell pool.