Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Long-Term Improvements in Pulmonary Function 5 Years After Bariatric Surgery

Background

Obesity is associated with reduced pulmonary function. We evaluated pulmonary function and status of asthma and obstructive sleep apnoea syndrome (OSAS) before and 5 years after bariatric surgery.

Methods

Spirometry was performed at baseline and 5 years postoperatively. Information of asthma and OSAS were recorded. Of 113 patients included, 101 had undergone gastric bypass, 10 duodenal switch and 2 sleeve gastrectomy.

Results

Eighty (71 %) patients were women, mean preoperative age was 40 years and preoperative weight was 133 kg in women and 158 kg in men. Five years postoperatively, weight reduction was 31 % (42 kg; p?<?0.001) in women and 24 % (38 kg; p?<?0.001) in men. Forced expiratory volume in 1 s (FEV1) increased 4.1 % (116 ml; p?<?0.001) in women and 6.7 % (238 ml; p?=?0.003) in men. Forced vital capacity (FVC) increased 5.8 % (209 ml; p?<?0.001) in women and 7.6 % (349 ml; p?<?0.001) in men. Gender and weight loss were independently associated with the improvements in FEV1 and FVC. At follow-up, FEV1 had increased 36 % of the difference towards the estimated normal FEV1, and there was a corresponding 70 % recovery of FVC. These improvements occurred despite an expected decline in pulmonary function by age during the study period. Of the asthmatics and OSAS patients, 48 and 80 %, respectively, were without symptoms 5 years postoperatively.

Conclusions

Pulmonary function measured with spirometry was significantly improved 5 years after bariatric surgery, despite an expected age-related decline during this period. Symptoms of asthma and OSAS also improved.     

Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia

Ulotaront (SEP-363856) is a trace-amine associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity in Phase 3 clinical development, with FDA Breakthrough Therapy Designation, for the treatment of schizophrenia. TAAR1 is a G-protein-coupled receptor (GPCR) that is expressed in cortical, limbic, and midbrain monoaminergic regions. It is activated by endogenous trace amines, and is believed to play an important role in modulating dopaminergic, serotonergic, and glutamatergic circuitry. TAAR1 agonism data are reported herein for ulotaront and its analogues in comparison to endogenous TAAR1 agonists. In addition, a human TAAR1 homology model was built around ulotaront to identify key interactions and attempt to better understand the scaffold-specific TAAR1 agonism structure–activity relationships.     

Transfusion-transmitted malaria: current donor selection guidelines are not sufficient

A case of transfusion-transmitted malaria was identified in a 50-year-old male patient with sickle cell disease. The donor was Ghanaian, but had migrated to the UK some years previously and had not left the UK for 8 years. The donor met all of the extant donor selection guidelines [1] and a donation was consequently collected. However, on subsequent investigation of the case, the donor was found to be parasitaemic and have high titre malarial antibodies. As a result of this case, changes to the United Kingdom donor selection guidelines have been proposed. These changes will prevent any such further transmissions.     

AMP-18,一种新发现的胃黏膜保护因子

AMP-18是一种新发现的由胃腺体上皮细胞合成的小分子蛋白质,独特表达于胃黏膜,机体其他部位少见,胃癌组织中表达缺失．AMP-18 由185个氨基酸组成,除去N端信号肽(20个氨基酸)后大小约18 ku,第54-150个氨基酸组成高度保守的结构域(BRICHOS区域)承担主要的生理功能．AMP-18由胃腺体上皮细胞以胞吐的方式分泌到胃黏液中,他的合成和分泌与个体生长发育有关,并受福斯高林、吲哚美辛、地塞米松等药物的影响．目前发现 AMP-18的生理功能主要有促进胃黏膜上皮细胞的有丝分裂,促进细胞的迁徙,促胃肠黏膜损伤的修复,保持胃肠黏膜的完整等．