P‐21POSITIVE PREDICTIVE VALUE OF CERVICAL SMEARS REPORTED AS MILD DYSKARYOSIS

Objective: Recent national guidelines (NHSCSP Document 20) recommend the referral of patients having the first occurrence of mild dyskaryosis. We evaluated the usefulness of this guideline and determined the positive predictive value (PPV) of conventional smears (CS) and ThinPrep samples (TP) reported as the first occurrence of mild dyskaryosis. Methods: This was a retrospective study where we looked at the cases of mild dyskaryosis from January’05 to June’05 received at our laboratory. Of these, the cases of mild dyskaryosis at the first instance were only taken into consideration. Histological diagnosis of these cases where available were retrieved from the laboratory database and were correlated with the cytological findings. Results: There were 1016 cases, which were reported as mild dyskaryosis. Out of them, 51.1% (519 cases) were first report of mild dyskaryosis: 61.8% (321 cases) and 38.2% (198 cases) were CS and TP respectively. Of these, 181 CS (56.4%) and 120 TP (60.6%) had a histological follow up. The results showed that 54.1% CS and 56.7% TP had a low‐grade outcome, 26.0% CS and 25.8% TP had a high‐grade outcome and 19.9% CS and 17.5% TP had a normal outcome. The PPV of mild dyskaryosis for CIN1 or worse result was 53.0% and 50.0% in CS and TP respectively. The PPV of mild dyskaryosis for CIN1 only was 27.1% and 24.2% in CS and TP respectively. Discussion: The difference in PPV for both systems is statistically insignificant. This result endorses usefulness of colposcopic referral after the first report of mild dyskaryosis.     

Photoaffinity labelling of a cytokinin-binding integral membrane protein in plant mitochondria

Two target polypeptides were detected by photoaffinity labelling of purified mung bean mitochondria using tritiated 2-azido-N⁶-benzylaminopurine. SDS-PAGE and fluorography of total mitochondrial proteins after the photoaffinity reaction showed a labelled 32 kDa polypeptide (intensely labelled) and a 57 kDa polypeptide (less intensely labelled). The latter was assumed to be the and/or subunit of F₁ATPase since it was the most abundant polpeptide in gels stained with Coomassie Blue. Partial purification of F₁ATPase demonstrated that the 32 kDa polypeptide was not a component of the ATPase complex. Fractionation experiments showed that the 32 kDa protein was integrally associated with mitochondrial membranes and could be enriched by simple washing and detergent extraction procedures.     

规范实验动物设施管理,提高科研服务质量

实验动物设施是医院科学研究的技术平台。如何利用有限的资源,全面提高实验动物中心科研服务水平是管理者亟待解决的问题。本文通过总结第四军医大学口腔医院实验动物中心的规范化建设及管理,探索提高实验动物中心运行效率和科研服务质量的方法。     

寨卡病毒,不仅仅是小头畸形

寨卡病毒(Zika virus,ZIKV)属于黄病毒科黄病毒属,由蚊虫叮咬传播。ZIKV发现于1947年。2007年以来,由于基因突变,ZIKV获得了更强的神经嗜性和在蚊虫体内播散的能力,因而在全球加快流行,并与成人吉兰-巴雷综合征和胎儿小头畸形的发生密切相关。最近的临床观察和动物研究进一步表明,ZIKV感染引起的临床症状复杂多样,所造成的疾病不仅仅是小头畸形,它还能够损伤雄性生殖系统,干扰下丘脑对神经内分泌系统的调节,引起多种激素分泌缺陷,导致生长发育迟缓和学习记忆能力损伤。因此,对于先天感染ZIKV的新生儿,不仅要在孕期监测小头畸形的发生,出生后也需进行长期的跟踪观察;对于出生后感染ZIKV的婴幼儿以及学龄前儿童,无论病情轻重,也需要进行随访,以明确ZIKV感染的远期影响。     

肥大细胞在肿瘤发生发展中的作用

肥大细胞是人体主要免疫细胞之一,因其作为导致过敏反应发生的最直接效应细胞而著称.肥大细胞最主要的结构特征为其胞内含有大量嗜碱性颗粒,该颗粒内又富含种类众多的生物活性物质,包括组胺、血管内皮生长因子(vascular endothelial growth factor,VEGF)、成纤维细胞生长因子(fibroblast...     

(99m)Tc(CO)(3)-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B cell non-Hodgkin's lymphoma (NHL)

To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+) precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with (90)Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent.     

裕固族血脂异常人群肠道菌群结构特征分析

探究生活在相同环境下的同一民族血脂异常人群与健康人群的肠道菌群差异,为血脂异常的精准预防和治疗提供参考。

收集甘肃肃南县裕固族血脂异常人群和健康人群粪便样本,提取细菌总DNA,通过16S rDNA高通量测序和生物信息学技术,分析2组人群肠道菌群的差异。

裕固族健康组人群肠道菌群分属26个门,73个纲,169个目,301个科,709个属,门水平上丰度＞1%的物种有4个,属水平上丰度＞1%的物种有22个。裕固族血脂异常组人群肠道菌群分属29个门,75个纲,280个目,304个科,702个属,门水平上丰度＞1%的物种有4个,属水平上丰度＞1%的物种有15个。裕固族血脂异常组人群肠道菌群与健康组间拟杆菌门、厚壁菌门、放线菌门水平以及F/B比值存在显著差异,Р＜0.05的差异物种有5个,Subdoligranulum、Christensenellaceae_R-7_group及Dialister与血脂水平呈负相关,Lachnoclostridium、Parasutterella与血脂水平呈正相关。

肃南县裕固族血脂异常组人群肠道菌群结构与健康组存在差异,为下一步关联分析肠道菌群与血脂异常及环境因素提供了基础数据。

     

Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia

The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P¹,P⁵-di(adenosine-5′) pentaphosphate (Ap₅A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap₅A, AMP, and adenosine 5′-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5′-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl⁻ channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia.     

Metal hyperaccumulation and bioremediation

The phytoremediation is an environment friendly, green technology that is cost effective and energetically inexpensive. Metal hyperaccumulator plants are used to remove metal from terrestrial as well as aquatic ecosystems. The technique makes use of the intrinsic capacity of plants to accumulate metal and transport them to shoots, ability to form phytochelatins in roots and sequester the metal ions. Harbouring the genes that are considered as signatures for the tolerance and hyperaccumulation from identified hyperaccumulator plant species into the transgenic plants provide a platform to develop the technology with the help of genetic engineering. This would result in transgenics that may have large biomass and fast growth a quality essential for removal of metal from soil quickly and in large quantities. Despite so much of a potential, the progress in the field of developing transgenic phytoremediator plant species is rather slow. This can be attributed to the lack of our understanding of complex interactions in the soil and indigenous mechanisms in the plants that allow metal translocation, accumulation and removal from a site. The review focuses on the work carried out in the field of metal phytoremediation from contaminated soil. The paper concludes with an assessment of the current status of technology development and its future prospects with emphasis on a combinatorial approach.