The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS)

Mutations in the proline/tyrosine-nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinβ2 (Kapβ2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. The Kapβ2-binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif, a central arginine-rich α-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapβ2 and mutations of these residues decrease binding affinities for Kapβ2 (K(D) for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapβ2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated.     

Association of body image and health beliefs with health behaviors in patients with diabetes: a cross-sectional study

Purpose The purpose of this study was to investigate relationships between body image, health beliefs, and health behavior in patients with diabetes classified according to body mass index (BMI). Methods A cross-sectional study was conducted in a community hospital between January and April 2010. One-hundred-sixty-eight patients with diabetes were enrolled. Main measure was the previously published and validated Health Belief Questionnaire. Data were analyzed and compared between two groups, one with BMI ≥ 24 Kg/m(2) and another with BMI < 24 Kg/m(2). Results Perceived body image affected health behavior of patients with BMI ≥ 24 Kg/m(2) but did not affect health behavior in patients with BMI < 24 Kg/m(2). Multivariate analysis found a positive association between health behavior and appearance evaluation and between health behavior and health evaluation in high BMI group. No significant association was found between body image and health behavior in the low BMI group. Patients with high BMI had lower body image than patients with low BMI as demonstrated by results of appearance evaluation, health evaluation, prevention behavior, and benefits. Conclusions Perceived body image and health beliefs are associated with self-reported health behavior among patients with diabetes with BMI measurement greater than 24 Kg/m(2). Diabetes educators may apply the findings of this study and the Health Belief Questionnaire to instruct and monitor patients with diabetes about self management behaviors.     

单纯机械性菌斑控制对学龄前儿童变形链球菌的短期影响

目的评价用牙刷和牙线进行机械性菌斑控制对学龄前儿童变形链球菌的影响。方法检查者单盲的随机对照临床研究。将54名唾液中检出变形链球菌的3岁学龄前儿童纳入该研究,随机分为实验组和对照组。菌斑染色后,口腔医学生给实验组儿童用牙刷和牙线彻底清洁牙面菌斑,不用牙膏,每天一次,共10次。用Dentocult SMStrip mutans(D-SM)监测唾液中变形链球菌的水平。结果 10次机械性菌斑控制结束后,实验组的D-SM值由基线的1.82下降到0.95(P<0.001),干预结束后2周D-SM值上升到1.62。对照组D-SM值的波动无统计学意义。结论连续、彻底的单纯机械性菌斑控制能降低学龄前儿童变形链球菌水平,干预结束后该作用消失。     

新型磁力扩弓矫治器动物模型的建立

目的建立新型磁力扩弓矫治器扩大腭中缝的动物模型。方法选取4只青春期比格犬作为实验动物．随机分为实验组3只和对照组1只。实验组应用新型磁力矫治器开打腭中缝,通过影像学和组织学切片观察上颌扩弓效果。结果扩弓3个月后实验组的上颌牙弓明显被扩宽。组织学观察腭中缝明显增宽．大量胶原纤维和细胞沿扩张方向排列,有新骨形成。结论本研究成功建立了新型磁力扩弓矫治器的动物模型。     

射频温控热凝术治疗原发性三叉神经痛648例临床分析

目的:总结射频温控热凝术治疗648例原发性三叉神经痛患者的疗效和体会,探讨射频温控热凝术的方法、技巧和手术并发症的处理。方法:对2001年7月—2011年3月在我院分别采用眶下孔入路法、侧入路法、前入路法和其他入路进行射频治疗的648例原发性三叉神经痛患者临床疗效进行分析。结果:648例原发性三叉神经痛患者接受射频治疗,首次止痛率分别为眶下孔法98.3%、侧路法91.0%、前路法95.5%,首次射频治疗总有效率为96.0%,经6个月～2 a随访到的395例患者中,1年内复发率为9.6%,2年内复发率为20.5%,经再次射频治疗或手术治疗均获得完全止痛。结论:射频治疗原发性三叉神经痛疗效可靠,操作简便、适应证广、并发症较少,CT定位能提高穿刺精确度,减少并发症。     

全口义齿后牙排列倾斜角度对义齿稳定性的影响

目的:研究全口义齿排牙后牙不同倾斜角度对义齿稳定性的影响。方法:随机抽取临床模型,参照丸森贤二的分类法分别采用Monson型排牙法、anti-Monson型排牙法及flat型排牙法[5]进行后牙区排牙,以1cm厚的橡胶垫在患者口内做咀嚼测试并进行分析。结果:上颌义齿后牙的排牙角度始终是Monson型排牙法最稳定,flat型排牙法和anti-Monson型排牙法不稳定;下颌义齿后牙的排牙角度应根据牙槽嵴的形态选择不同的排牙法;结论:全口义齿后牙区排牙时,倾斜角度不同对义齿固位与稳定有重要影响。     

非手术干预引导骨再生术后屏障膜早期暴露的转归及其对骨愈合的影响

目的研究种植体植入同期引导骨再生(GBR)患者术后伤口裂开、屏障膜过早暴露于口腔环境后,非手术干预处理后的不同转归及其对种植区软硬组织的影响。方法 128例牙槽嵴骨量不足需行牙种植体植入同期GBR的患者纳入本临床研究。术后发现伤口早期局限性裂开后立即行1～3周的非手术干预治疗。分别记录术后2周内伤口裂开、3周非手术干预期间和Ⅱ期手术时软组织愈合的临床数据。分别于术后当天和Ⅱ期手术前拍摄术区的标准化根尖X线片,以评价膜暴露的不同转归对种植体骨结合、边缘骨吸收(MBL)的影响。结果 128例患者术后2周内伤口裂开的发生率高达52.34%。其中3例患者由于感染导致种植体骨结合失败,未能完成后续的实验。其余的125例患者根据伤口愈合情况将患者分为3组:(1)A组,伤口裂开伴脱细胞真皮基质(ADM)膜早期暴露,共53例;(2)B组,ADM膜早期穿孔伴覆盖螺丝暴露,共12例;(3)C组,伤口无裂开正常愈合,共60例。通过非手术治疗,A组所有膜早期暴露的患者暴露的膜均逐渐被牙龈组织重新覆盖。Ⅱ期手术时,种植体近远中MBL情况,A组有12例,吸收量分别为(0.48±0.19)mm、(0.52±0.24)mm,B组有11例,吸收量分别为(1.00±0.39)mm、(0.80±0.40)mm,C组仅2例发生MBL。t检验结果显示,A和B组内近中和远中的MBL差异均无统计学意义(P>0.05);A组和B组近远中MBL的组间差异有统计学意义(P<0.05),A组和C组近远中MBL的组间差异无统计学意义。结论及时非手术干预通过维持创面清洁、预防感染,推迟早期暴露膜在体内的降解,促进上皮愈合,降低对骨愈合的不利影响,是挽救GBR术后伤口裂开获得延期愈合的有效治疗方法。     

Small cell lung cancer presenting as dermatomyositis: mistaken for single connective tissue disease

Dermatomyositis (DM) is well-known to be associated with several types of malignancy. This case emphasizes the importance of a thorough examination for an underlying cancer, in patients with the symptoms of dermatomyositis. We report the case of a 62-year-old Chinese man who presented with a two-month history of edema of face and neck, together with erythema of the eyelids diagnosed of small cell lung cancer. Initially, it was thought to be single connective tissue disease such as DM. This study highlights the importance of a thorough physical examination when visiting a patient.     

The clinical impact of preoperative percutaneous drainage of abdominopelvic abscesses in patients with Crohn’s disease

Purpose

Although image-guided percutaneous drainage is increasingly being used to treat Crohn’s disease-related abdominopelvic abscesses, surgery is seldom avoided. The aim of this study was to compare outcomes following the treatment of intra-abdominal Crohn’s abscesses with percutaneous drainage followed by surgery to those after surgery alone.

Methods

We retrospectively reviewed the charts of patients treated for Crohn’s-related abdominopelvic abscesses at Mount Sinai Medical Center between April 2001 and June 2010. Patients who underwent drainage followed by surgery were compared to those who underwent surgery alone. Differences in operative and postoperative outcomes were compared.

Results

Seventy patients with Crohn’s disease-related abdominopelvic abscesses were identified, 38 (54%) of whom underwent drainage before surgery. Percutaneous drainage was technically successful in 92% of patients and clinically successful in 74% of patients. No differences in rate of septic complications (p?=?0.14) or need for stoma creation (p?=?0.78) were found. Patients who underwent percutaneous drainage had greater overall hospital lengths of stay (mean 15.8 versus 12.2?days, p?=?0.007); 8.6% of patients had long-term postponement of surgery after percutaneous drainage.

Conclusions

In our series, the treatment of Crohn’s abscesses with percutaneous drainage prior to surgery did not decrease the rate of postoperative septic complications.