Diagnostic capabilities of the x-ray endoscopic method of study in cholelithiasis]

The developed variants of the roentgenoendoscopic method for the examination of the pancreatobiliary system were employed in 256 patients with various diseases of the gallbladder and biliary duct. The results of application of these methods in 85 patients with cholelithiasis are presented. Different potentialities of the roentgenoendoscopic method and ultrasonic scanning for the assessment of the biliary system status in cholelithiasis were revealed. The findings recommend supplementing ultrasonic examinations with an optimal variant of the roentgenoendoscopic examination.     

Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification

MethodsThis was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed.ResultsHierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05–0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type.ConclusionsIntegrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic immunohistochemical panel and additional extended panels of discriminant markers are proposed as guidance for their pathological diagnosis.     

Genetic relationships between breeds of horses and ponies in the Netherlands

An investigation on the genetic relationships between 12 horse and pony breeds was performed, using blood protein variants as genetic markers. The relationships were established by the use of 5 different numerical taxonomic methods, 4 of which yielded very similar results. The relationships as estimated were evaluated on the basis of the breeds' historical development.     

Epigenetic polymorphism in populations of Apodemus sylvaticus and Apodemus flavicollis (Rodentia, Muridae)

The main object of this study was to use discontinuous variation as a means of measuring divergence between populations of A. sylvaticus (L.) and A. flavicollis (Melchior) from Britain and Eurasia. Samples from 17 populations (671 skulls) were each classified for 20 discontinuous morphological variants. The investigation has shown that certain epigenetic variants have a characteristic incidence in populations of the two species and that the relative incidence of the variants could be used as an aid to specific separation. The calculation of degree of divergence between the populations has made it possible to suggest the order in which populations are related to each other.     

The molecular genetic typification of planarians in the genus Bdellocephala (Dendrocoelidae, Tricladida, Turbellaria) from Lake Baikal with an assessment of their species diversity

Baikal planaria from genus Bdellocephala were typified using rDNA locus coding 5'--end domain of 18S ribosome RNA. Five colour forms of 24 possible variants that differ in diapason 0-1.3% of genotype were determined by comparative analysis of nucleotide sequences. The authors use back colour--one of the most variable and typical character in the given group--to collect material for investigation. It allows to minimize the size of investigation sample and at the same time to cover maximum variability of Bdellocephala. One of the positive result of molecular typification of colour forms was a discovery of unique individuals that belong to new species. Karyological analysis of colour forms shows variations in chromosome numbers that divide planaria into 3 groups (2n = 20, 24, 26). Comparative analysis of morphological and ecological characters and karyotypes of some forms united by the same genotype allows to distinguish them as separate species. Criteria of modern phenetic system of Baikal planaria are discussed.     

2010 Reviewers for Biotechnic & Histochemistry

Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (?) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (?), MUC2 (+) and CK17 (?), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (?) and CK17 (?) profile. More importantly, the MUC1 (+), MUC2 (?) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (?) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (?) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.     

大肠杆菌变种的两种分子生物学检测方法分析

目的:对大肠杆菌的一种重要的变种--肠出血性大肠杆菌O157-H7的几种检测方法进行比较研究.方法:以自动免疫磁珠收集系统(AIMS)、自动酶标免疫测试系统(VIDAS)与传统常规的分离方法进行对比分析.结果:运用自动免疫磁珠收集系统(AIMS)方法对80份可能含有肠出血性大肠杆菌O157-H7的实样进行检测,检出份数为6份,检出率为7.5％,而且在一周之内可以全部对上述检出实样进行鉴定.AIMS法能够检出浓度在10cfu/mL模拟实样之中的肠出血性大肠杆菌O157-H7,然后将此法与CHROMagar 0157琼脂板相结合,其效果则更为明显.而自动酶标免疫测试系统(VIDAS)与传统与的分离方法则检测的效果不佳,检出率为0.自动免疫磁珠收集系统(AIMS)检测方法与自动酶标免疫测试系统(VIDAS)、传统与的分离方法在检出率方面存在显著的统计学差异,P＜0.01.结论:运用自动免疫磁珠收集系统(AIMS)结合CHROMagar 0157琼脂板对出血性大肠杆菌O157-H7进行检测,检出率较高、灵敏度较高且快速便捷,可以用于O157-H7外环境检测与食品污染源的实际调查之中,应该对其加以广泛地推广并应用.     

The role of large pedigrees in an era of high-throughput sequencing

Rare variation is the current frontier in human genetics. The large pedigree design is practical, efficient, and well-suited for investigating rare variation. In large pedigrees, specific rare variants that co-segregate with a trait will occur in sufficient numbers so that effects can be measured, and evidence for association can be evaluated, by making use of methods that fully use the pedigree information. Evidence from linkage analysis can focus investigation, both reducing the multiple testing burden and expanding the variants that can be evaluated and followed up, as recent studies have shown. The large pedigree design requires only a small fraction of the sample size needed to identify rare variants of interest in population-based designs, and many highly suitable, well-understood, and available statistical and computational tools already exist. Samples consisting of large pedigrees with existing rich phenotype and genome scan data should be prime candidates for high-throughput sequencing in the search of the determinants of complex traits.     

Preparation and Properties of Clostridium thermocellum Lichenase Deletion Variants and Their Use for Construction of Bifunctional Hybrid Proteins

Major properties (pH and temperature optimum, stability) of lichenase (b-1,3-1,4-glucanase) deletion variants from Clostridium thermocellum were comparatively studied. The deletion variant LicBM2 was used to create hybrid bifunctional proteins by fusion with sequences of the green fluorescent protein (GFP) from Aequorea victoria. The data show that in hybrid proteins both GFP and lichenase retain their major properties, namely, GFP remains a fluorescent protein and the lichenase retains activity and high thermostability. Based on the results of this investigation and results that have been obtained earlier, the use of the deletion variants of lichenase and the bifunctional hybrid proteins as reporter proteins is suggested.     

Development of a method for the quantitative determination of Bordetella pertussis toxin and the prospects of its use for diagnosis

Two variants of the enzyme immunoassay (EIA) systems for the determination of B. pertussis toxin (BPT), the "double sandwich" system and the competitive assay system, have been developed. For the titration of BPT in B. pertussis antigens the use of fetuin as the affinity base is preferable, and not antibodies from different paired animals. Of the two variants, the competitive EIA is more promising for diagnostic purposes.     

The manifestations of the epidemic process in shigellosis and their theoretical interpretation]

This work, based on the retrospective analysis of shigellosis morbidity among organized groups of adults, as well as the whole population of the city, demonstrates the manifestations of the epidemic process. Water supply was common in the city, while water consumption was autonomous. The organized groups of adults did not use the products of the local milk-processing factory. The following facts were established. The dynamics of morbidity in Flexner's dysentery showed the change of dominating variants of the infective agent, which reflected the action of internal mechanisms of the development of the epidemic process. The role of Sonne dysentery in the total structure of shigellosis morbidity did not correlate with the consumption of milk and milk products. The theory of the self-regulation of the parasitic system and the theory of correspondence served as the basis for the theoretical interpretation of the manifestations of the epidemic process of Shigella infections. To ascertain the real correspondence of individual Shigella species to concrete transmission factors, further investigation are necessary.     

In vivo evolution of X4 human immunodeficiency virus type 1 variants in the natural course of infection coincides with decreasing sensitivity to CXCR4 antagonists

CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-restricted (R5) HIV-1 variants. Early after their first appearance in vivo, X4 HIV-1 variants additionally use CCR5. The ability to use CCR5 in addition to CXCR4 is generally lost late in infection. Here we studied whether this evolution of the coreceptor repertoire is also reflected in a changing sensitivity of X4 variants to CXCR4 antagonists such as peptide T22 and the synthetic compound AMD3100. We observed differences in the concentrations of CXCR4 antagonists needed to suppress replication of X4 HIV variants from different patients. In general, late X4 HIV variants were less sensitive to AMD3100 than were early R5X4 HIV variants. The differences between early R5X4 HIV variants and late X4 variants were less pronounced for T22-mediated inhibition. These results suggest an ongoing evolution of X4 virus variants toward more efficient usage of the cellular entry complex.     

Design of single assembly line for the delayed differentiation of product variants

Delayed Product Differentiation (DPD) can reduce the manufacturing complexities arising due to the proliferation of products variety. A new optimization model constructs the optimum layout of delayed differentiation assembly lines for a mix of products to be manufactured by the same system and optimizes the position of the differentiation points. This model employs a classification tool (Cladistics) used in biological analysis and modifies it for use in planning DPD assembly lines configurations in order to incorporate the assembly precedence constraints, required production rates of different product variants and existing production capacity of work stations. The optimum layout configuration ensures that the quantities required of different products are produced on the same line; while achieving balance, minimizing duplication of stations and maximizing the overall system utilization. The developed model has been applied to a group of automobile engine accessories normally assembled on different lines. The use of Cladistics to analyze product variants that are candidates for delayed assembly is an original approach for designing the assembly line layout and identifying the best differentiation points. It also helps rationalize the design of product variants and their features to further delay their assembly differentiation and achieve economy of scale without affecting their functionality.     

Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis

Genome-wide association studies (GWAS) conducted using commercial single nucleotide polymorphisms (SNP) arrays have proven to be a powerful tool for the detection of common disease susceptibility variants. However, their utility for the detection of lower frequency variants is yet to be practically investigated. Here we describe the application of a rare variant collapsing method to a large genome-wide SNP dataset, the Wellcome Trust Case Control Consortium rheumatoid arthritis (RA) GWAS. We partitioned the data into gene-centric bins and collapsed genotypes of low frequency variants (defined here as MAF ≤0.05) into a single count coupled with univariate analysis. We then prioritised gene regions for further investigation in an independent cohort of 3,355 cases and 2,427 controls based on rare variant signal p value and prior evidence to support involvement in RA. A total of 14,536 gene bins were investigated in the primary analysis and signals mapping to the TNFAIP3 and chr17q24 loci were selected for further investigation. We detected replicating association to low frequency variants in the TNFAIP3 gene (combined p = 6.6 × 10^?6). Even though rare variants are not well-represented and can be difficult to genotype in GWAS, our study supports the application of low frequency variant collapsing methods to genome-wide SNP datasets as a means of exploiting data that are routinely ignored.     

Lexical Variation and Change in British Sign Language

This paper presents results from a corpus-based study investigating lexical variation in BSL. An earlier study investigating variation in BSL numeral signs found that younger signers were using a decreasing variety of regionally distinct variants, suggesting that levelling may be taking place. Here, we report findings from a larger investigation looking at regional lexical variants for colours, countries, numbers and UK placenames elicited as part of the BSL Corpus Project. Age, school location and language background were significant predictors of lexical variation, with younger signers using a more levelled variety. This change appears to be happening faster in particular sub-groups of the deaf community (e.g., signers from hearing families). Also, we find that for the names of some UK cities, signers from outside the region use a different sign than those who live in the region.     

The clinal variability of the B-chromosome system in the East Asian mouse Apodemus peninsulae from Buryatia and Mongolia]

Karyological investigation of 22 East-Asiatic mice from different points of the North Mongolia showed the availability in all the mice from 1 to 13 B chromosomes, including from 1 to 5 middle-sized and small two-shoulder chromosomes, from 0 to 11 dot-like B chromosomes, and, seldom, 1 small acrocentric B chromosome. Nearly every mouse is characterized by its variant of B-chromosome system. Most frequent mice with 3, 4 and 8 B chromosomes were met. The comparison of the B-chromosome system variants in mice from Buryatia, Chita Province (USSR) and the North Mongolia, showed an increase in the number of B chromosomes, mainly at the expense of the number of dot-like B chromosomes, in the direction from Ulan-Ude to the south and to the east.     

Ig gamma restriction fragment length polymorphisms indicate an ancient separation of Caucasian haplotypes.

This investigation was undertaken to study genetic variation in the human immunoglobulin gamma heavy-chain (IgG) genes using Southern blot hybridization techniques to identify restriction fragment length polymorphisms (RFLPs). A genomic Ig gamma-1 clone was used as a probe, and variants were identified with two restriction enzymes (R.E.), each of which defined RFLPs at two separate IgG loci. Once alleles and haplotypes were determined, molecular localization of the alleles was made through genetic analysis of recombinant haplotypes and through the use of regional specific subclones. Linkage between the newly defined RFLPs and switch region variants as well as protein allotypic markers (Gm) was complete. This analysis included markers for Ig Mu, Alpha 1, Alpha 2, Gamma 1, Gamma 2, Gamma 3, and Pseudo Gamma. The picture that emerges from the molecular study of two common haplotypes, each with many rare variants resulting from recombination or mutation, confirms and extends the earlier immunological observations. The accumulated differences between the two major Caucasian IgG haplotypes indicate that their separation may be ancient and maintained through heterozygote advantage.     

Electron microscope examination of two plaque variants from a nuclear polyhedrosis virus of the alfalfa looper, Autographa californica

This investigation looks into the ultrastructural differences between plaque variants of the alfalfa looper nuclear polyhedrosis virus. The variants exhibit distinct differences in polyhedra morphology and enveloping of the nucleocapsids.Tissues from larvae infected per os or subcutaneously with virus from one type of plaque always contained virus representative of both plaques. This was not true of the in vitro cultured cells. In those cells, a culture infected with one plaque type always developed infections that were typical of that particular plaque.