Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.     

人类白细胞抗原分型技术的进展

学术背景：以往人类白细胞抗原分型主要采用血清学和细胞学方法，随着PCR技术、基因芯片技术及分子生物学技术的发展，已建立从基因水平上进行的人类白细胞抗原分型技术。目的：介绍人类白细胞抗原分型方法，为实际应用提供依据。检索策略：应用计算机检索PubMed1997—07／2007—07期间的相关文章，检索词“HLA technology”，并限定文章语言种类为English。同时检索万方数据库1997—07／2007—07相关文章，检索词为“人类白细胞抗原”，并限定文献语种为中文。共检索到相关文献142篇，选择与人类白细胞抗原分型技术有关的文献55篇。将初步筛选的文章进一步查找全文，排除综述和重复文献，内容相似的选择发表在权威杂志或近3年发表的文献，最后共纳入30篇进行综述。文献评价：文献对不同的人类白细胞抗原分型方法进行汇总分析，符合纳入标准的30篇文献中，6篇为中文文献，24篇为英文文献。资料综合：传统的人类白细胞抗原分型方法主要是血清学和细胞学方法，分型准确性较差。随着PCR技术的广泛应用，人类白细胞抗原基因分型方法得到了迅速的发展。序列特异性引物、序列特异性寡核苷酸探针、直接测序、基因芯片等各具特点的人类白细胞抗原分型技术不断出现，使人类白细胞抗原的分型更加准确、精细、简便、实用，为临床推广应用打下了基础。结论：各种人类白细胞抗原基因分型方法各有优势，不能相互替代，这也是由人类自细胞抗原系统的高度多态性和复杂性所决定的，根据不同的用途可选择相应的方法。     

Personality traits in established schizophrenia: aspects of usability and differences between patients and controls using the Swedish universities Scales of Personality

Background: Personality is considered as an important aspect that can affect symptoms and social function in persons with schizophrenia. The personality questionnaire Swedish universities Scales of Personality (SSP) has not previously been used in psychotic disorder.

Aims: To investigate if SSP has a similar internal consistency and factor structure in a psychosis population as among healthy controls and if patients with psychotic disorders differ from non-psychotic individuals in their responses to the SSP.

Methods: Patients with psychotic disorders (n?=?107) and healthy controls (n?=?119) completed SSP. SSP scores were analyzed for internal consistency and case-control differences by Cronbach’s alfa and multiple analysis of covariance, respectively.

Results: Internal consistencies among patients were overall similar to that of controls. The patients scored significantly higher in seven (Somatic trait anxiety, Psychic trait anxiety, Stress susceptibility, Lack of assertiveness, Detachment, Embitterment, Mistrust) and lower in three (Physical trait aggression, Verbal trait aggression, Adventure seeking) of the 13 scales of the inventory. In three scales (Impulsiveness, Social desirability and Trait irritability) there was no significant difference between the scoring of patients and healthy controls.

Conclusion: The reliability estimates suggest that SSP can be used by patients with psychotic disorders in stable remission. Patients score higher on neuroticism-related scales and lower on aggression-related scales than controls, which is in accordance with earlier studies where other personality inventories were used.     

HLA—DR2,DRB1＊0301,DQA1＊0501基因频率与肌炎及其临床表现的 …

目的：观察人类白细胞相关抗原ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１，ＤＱＡ１＊０５０１基因频率为多发性肌炎／皮肌炎（ＰＭ／ＤＭ）发病及其临床表现的关系，方法：特异性引物聚合酶链式反应（ＰＣＲ－ＳＳＰ）方法分别测定了３１例ＰＭ／ＤＭ患者及５０例正常人的ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１及ＨＬＡ－ＤＡＱ１＊０５０１的基因频率，结果：三种基因型在３１例肌炎患得中基频率分别为：６．４５％，９．６８％和７７．４     

Higher-Order Structure Characterization of Pharmaceutical Proteins by 2D Nuclear Magnetic Resonance Methyl Fingerprinting

A key challenge in the analytical assessment of therapeutic proteins is the comprehensive characterization of their higher-order structure (HOS). To directly assess HOS, a new type of assay is warranted. The most sensitive and detailed method for characterizing HOS is unquestionably nuclear magnetic resonance (NMR) spectroscopy. NMR spectroscopy provides direct information about the HOS at an atomic level, and with modern NMR spectrometers and improved pulse sequences, this has become feasible even on unlabeled proteins. Hence, NMR spectroscopy could be a very powerful tool for control of HOS following, for example, process changes resulting in structural changes, oxidation, degradation, or chemical modifications. We present a method for characterizing the HOS of therapeutic proteins by monitoring their methyl groups using 2D H, C-correlated NMR. We use a statistical model that compares the NMR spectrum of a given sample to a reference and results in one output value describing how similar the HOS of the samples are. This makes the overall result easy to interpret even for non-NMR experts. We show that the method is applicable to proteins of varying size and complexity (here up to ～30 kDa) and that it is sufficiently sensitive for the detection of small changes in both primary and HOS.     

Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) −174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 −174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32–0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) −174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00–1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55–0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37–0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59–3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 −174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.     

Distribution of KIR genes in the Croatian population

The KIR locus with genes involved in immune processes is among the most polymorphic and structurally diverse human loci. KIR genes encode activating and inhibitory receptors that differ in specificity for HLA class I ligands and signaling potential. These receptors are expressed principally by natural killer (NK) cells and subpopulations of T cells. This study represents the first report of the distribution of KIR genes, KIR genotypes and KIR/HLA pairs in 121 unrelated healthy Croatian individuals. Twenty-three different genotypes were observed in the Croatian population and all 16 KIR genes known to date were found. The most frequent KIR genotype was the AA genotype. All individuals had at least one inhibitory KIR/HLA pair with the majority of individuals with three inhibitory KIR/HLA pairs. The most frequent KIR/HLA pair was the KIR2DL3/C1 group. Our results demonstrated the similarity of the Croatian population’s KIR repertoire with other Caucasian populations reported so far.     

广东汉人HLA-DRB1基因的PCR-SSP定型分析及其对风湿热遗传易感性的研究

目的：研究ＨＬＡＤＲＢ１基因对风湿热的遗传易感性。方法：用ＰＣＲＳＳＰ方法对广东地区５１例风湿热患者和１０２位正常人的ＨＬＡＤＲＢ１基因进行定型分析且探讨ＨＬＡＤＲＢ１等位基因与风湿热的相关性。结果：风湿热患者ＨＬＡＤＲＢ１等位基因分布异常，其中，ＤＲＢ１０３０１基因频率为２３３％，而正常人仅为６５９％（校正Ｐ＜００５，相对危险率为４６７）。结论：ＤＲＢ１０３０１等位基因对风湿热有遗传易感作用     

New immunomodulatory role of neuropeptide Y (NPY) in Salmo salar leucocytes

Neuropeptide Y (NPY) plays different roles in mammals such as: regulate food intake, memory retention, cardiovascular functions, and anxiety. It has also been shown in the modulation of chemotaxis, T lymphocyte differentiation, and leukocyte migration. In fish, NPY expression and functions have been studied but its immunomodulatory role remains undescribed. This study confirmed the expression and synthesis of NPY in S. salar under inflammation, and validated a commercial antibody for NPY detection in teleost. Additionally, immunomodulatory effects of NPY were assayed in vitro and in vivo. Phagocytosis and superoxide anion production in leukocytes and SHK cells were induced under stimulation with a synthetic peptide. IL-8 mRNA was selectively and strongly induced in the spleen, head kidney, and isolated cells, after in vivo challenge with NPY. All together suggest that NPY is expressed in immune tissues and modulates the immune response in teleost fish.