Intracellular signaling pathways that regulate dendritic spine morphogenesis

Rac is a member of the Rho family of small GTPases and acts as a molecular switch. When GTP-bound, Rac binds specific effectors to induce downstream signaling events, including actin cytoskeletal rearrangements (Hall, Science 1998;279:509-514). Herein we review the recent evidence suggesting that Rac is involved in the morphogenesis of dendritic spines (Luo et al., Nature 1996;379:837-840; Nakayama et al., J Neurosci 2000; 20:5329-5338). In addition, we discuss how Rac activity is regulated by guanine nucleotide exchange factors, which may be further regulated by extracellular factors. Thus, the Rac signal transduction pathway may provide links between extracellular ligands or synaptic activity and the regulation of the actin cytoskeleton in spine morphogenesis.     

P波离散度对急性心肌梗死并发房颤的意义

目的　探讨P波离散度 (Pd)对急性心肌梗死并发房颤的预测价值。 方法　 选 36例急性心肌梗死并发房颤的患者 ,观察其P波离散度 ,P波最大时限 (Pmax)。选 80例单纯急性心肌梗死的患者 ,作对照分析。 结果　急性心肌梗死并发房颤的Pd、Pmax与对照组比较有明显差异 (P <0 .0 1)。 结论　P波离散度可作为急性心肌梗死患者并发房颤的一预测指标。     

电针治疗对老年性痴呆大鼠血清β淀粉样蛋白及生长因子水平的影响

目的:观察电针对老年性痴呆(AD)模型大鼠β-淀粉样蛋白及转化生长因子(TGF-α)的影响,揭示针灸治疗的作用机理和针灸治疗AD的免疫基础。方法:建立AD大鼠模型,随机分为电针组、喜得镇组、模型自然恢复组、假手术组,观察血清β-AP和TGF-α水平。结果:电针组和喜得镇组大鼠血清β-AP水平明显下降(P<0.05),但仍明显高于假手术组。结论:电针能降低AD模型大鼠血清中β淀粉样蛋白及TGF-α。     

腹腔镜手术治疗特殊部位异位妊娠11例报告

目的 探讨特殊部位异位妊娠的临床特点与腹腔镜手术治疗的可行性与安全性。方法 回顾分析1998年1月至2003年1月间经腹腔镜手术治疗的特殊部位异位妊娠的临床资料,包括输卵管间质部妊娠4例,卵巢妊娠4例,腹腔妊娠3例。结果 11例特殊部位异位妊娠的临床特点:平均停经时间以卵巢妊娠较短,而间质部妊娠时间较长;血β-HCG值以卵巢妊娠和腹腔妊娠较低,而间质部妊娠较高;腹腔镜手术治疗特殊部位异位妊娠效果:平均手术时间为(45.0±13.8)min,平均术中失血为(81.0±80.6)mL,平均住院时间为(3.0±0.6)d,腹腔镜手术成功率为91％。结论 腹腔镜手术治疗特殊部位异位妊娠是可行且安全的,但是应根据其特点选择术式并预防并发症。     

芬太尼透皮贴剂治疗中重度癌痛433例临床观察

目的:进一步评价芬太尼透皮贴剂治疗中、重度疼痛的疗效、安全性及对生活质量的影响,为临床合理用药提供参考资料.方法:采用多中心随机开放方法,对433例中、重度疼痛患者使用芬太尼透皮贴剂进行观察,芬太尼的初始剂量是2.5mg或参照吗啡芬太尼折算表计算,贴膜每3日更换1次,在使用期间根据疼痛情况进行剂量调整,直到患者无痛或基本无痛.结果:可评价患者336例,其癌痛缓解率100%,41.6%的患者第1次使用后未再进行剂量调整,57.3%的患者调整过1～3次.芬太尼的中位剂量7.5mg,其中92.9%患者在2.5～10mg之内.不良反应轻,主要为恶心、便秘、头晕、呕吐、嗜睡、排尿困难等.治疗后生活质量有明显改善.结论:芬太尼透皮贴剂治疗中、重度疼痛的疗效显著,使用方便,不良反应轻,能明显改善患者的生活质量,绝大多数患者的调整次数在3次以内,大多数患者的使用剂量在每3天2.5～10mg.     

结缔组织增生性小圆细胞肿瘤2例并文献复习

目的:分析结缔组织增生性小圆细胞肿瘤(DSRCT)的临床病理特征。方法:结合文献对2例相对少见的DSRCT进行临床、病理形态及免疫组化研究。结果:DSRCT由成团巢的小圆细胞和丰富的结缔组织间质组成。免疫组化:小圆形的肿瘤细胞vimentin( );desmin( );EMA( );CK( );NSE( )。结论:DSRCT为高度侵袭性肿瘤,主要累及腹腔或盆腔的腹膜,肿瘤由小圆细胞和丰富的结缔组织间质组成。     

Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus

BACKGROUND: In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates. METHODS: Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. RESULTS: The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection. CONCLUSIONS: The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.     

大肠癌患者骨髓微转移的基因研究

目的 探讨大肠癌患者骨髓中微转移基因检测的意义。方法 应用聚合酶链式反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）／银染技术,检测５１例大肠癌患者手术前、后不同时间骨髓中ｐ５３和Ｋ－ｒａｓ基因的突变状况。结果 ５１例患者术前骨髓中基因突变阳性者１９例,阳性率３７．２５％。阳性检出与Ｄｕｋｅ’ｓ分期、淋巴转移显著相关。术后经２～３个疗程的化疗后,１９例基因突变阳性的患者中１１例转阴。结论 大肠癌患者骨     

Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia.

The SH2 domain-containing inositol 5'-phosphatase (SHIP) is crucial in hematopoietic development. To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines. A somatic mutation at codon 684, replacing Val with Glu, was detected in one patient, lying within the signature motif 2, which is the phosphatase active site. The results of an in vitro inositol 5'-phosphatase assay revealed that the mutation reduced catalytic activity of SHIP. Leukemia cells with the mutation showed enhanced Akt phosphorylation following IL-3 stimulation. K562 cells transfected with the mutated SHIP-V684E cDNA showed a growth advantage even at lower serum concentrations and resistance to apoptosis induced by serum deprivation and exposure to etoposide. These results suggest a possible role of the mutated SHIP gene in the development of acute leukemia and chemotherapy resistance through the deregulation of the phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3)/Akt signaling pathway. This is the first report of a mutation in the SHIP gene in any given human cancer, and indicates the need for more attention to be paid to this gene with respect to cancer pathogenesis.     

Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

BACKGROUND: Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. METHODS: Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. RESULTS: Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. CONCLUSIONS: The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.