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91.
Endocrine studies in girls with precocious thelarche were compared with those of normal girls of similar ages. Girls with precocious thelarche showed breast development and oestrogenised vaginal smears as the only signs of precocious sexual development. A few of the girls were tall and some had advanced bone ages but these two findings were not consistently present in the same patient. Hormones--such as serum oestradiol, oestrone, delta 4-androstenedione, progesterone, dehydroepiandrosterone (DHEA), follicle-stimulating hormone, luteinising hormone, and prolactin, and urinary 17-ketosteroids--were measured. Only DHEA was different, being higher in girls with precocious thelarche. It is suggested that the high DHEA level may serve as a precursor for conversion to oestrogens in target tissues, breast, and vagina. This mechanism for oestrogenisation had been reported in other patients. 相似文献
92.
Druzijanić N Perko Z Kraljević D Juricić J Simunić MM Bilan K Krnić D Pogorelić Z Tomić S Srsen D 《Hepato-gastroenterology》2008,55(82-83):356-358
BACKGROUND/AIMS: Retrospective clinical study of patients with rectal tumors treated by transanal endoscopic microsurgery (TEM) using Ultracision. METHODS: From 1997-2006 54 patients were treated by excision of the rectal tumors situated in the middle and distal portion, using the harmonic scalpel. We treated 25 male (range 40-76 years) and 29 female (range 46-80 years) patients. Tumors were benign or well or moderately differentiated carcinomas in stage T1N0M0 or T2N0M0. Excision was done by Ultracision (UltraCision, Ethicon Endo-Surgery) to all patients. Preoperative examinations were: colonoscopy, biopsy, tumor markers, CT, transanal ultrasound, pelvic NMR, gynecological exam in females. The tumors were excised by harmonic scalpel after submucosal infiltration of adrenalin (1: 200 000) and 2% lidocaine. RESULTS: There was no morbidity or mortality in this group of patients. Histopathology was: Adenoma tubovillosum in alteratio maligna 20, adenocarcinoma (T1N0M0) 6, (T2N0M0) 8, adenocarcinoma with lymphatic vessels and perineural spaces invasion 1, adenoma villosum 12 and adenoma tubulare 7. After surgical treatment 8 patients underwent adjuvant radiotherapy. There was no local recurrence during this period. CONCLUSIONS: TEM is a method of choice in the treatment of rectal benign tumors and malignant tumors in stage T1N0M0, grade 1 and 2. Harmonic scalpel provides a safer, easier, and more precise surgical section through clean, bloodless and better visualized operative field. 相似文献
93.
Tuinstra RL Peterson FC Kutlesa S Elgin ES Kron MA Volkman BF 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(13):5057-5062
Proteins often have multiple functional states, which might not always be accommodated by a single fold. Lymphotactin (Ltn) adopts two distinct structures in equilibrium, one corresponding to the canonical chemokine fold consisting of a monomeric three-stranded beta-sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all-beta-sheet arrangement with no similarity to other known proteins. In physiological solution conditions, both structures are significantly populated and interconvert rapidly. Interconversion replaces long-range interactions that stabilize the chemokine fold with an entirely new set of tertiary and quaternary contacts. The chemokine-like Ltn conformation is a functional XCR1 agonist, but fails to bind heparin. In contrast, the alternative structure binds glycosaminoglycans with high affinity but fails to activate XCR1. Because each structural species displays only one of the two functional properties essential for activity in vivo, the conformational equilibrium is likely to be essential for the biological activity of lymphotactin. These results demonstrate that the functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures. 相似文献
94.
Forensic botany: potential usefulness of microsatellite-based genotyping of Croatian olive (Olea europaea L.) in forensic casework
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Stambuk S Sutlović D Bakarić P Petricević S Andelinović S 《Croatian medical journal》2007,48(4):556-562
Aim
To assess genotyping with microsatellite-based markers of the olive (Olea europaea L.) for potential application of olive as legal case evidence, with regard to the degree of variability within the Croatian olive genomic pool and to the effectiveness of the chosen set of microsatellite-based markers in revealing olive divergence.Methods
The total of 44 autochthonous Croatian olive specimens were subjected to genotyping with 16 previously described and developed microsatellite-based markers. According to previous morphological analyses, 44 specimens were classified into 30 cultivars with the exception of an additional, previously unassigned specimen.Results
Genotyping of 44 specimens distinguished a total of 44 different genotype profiles by 16 microsatellite-based loci. Average expected heterozigosity amounted to 0.758, which points to significant diversity of Croatian olives.Conclusion
Croatian olive genotyping showed strong varietal discrimination up to the single tree and considerable potential application of olive as evidence in investigation of crime, accident, and suicide circumstances.Forensic botany is the study of plants and plant material with the purpose of presenting the plant evidence in court. It includes a number of disciplines, such as plant anatomy and systematics palynology, plant ecology, limnology, plant chemistry, and plant molecular biology (1). In spite of its high potential in assessing the legal case evidence, only a few cases of plant forensic investigation applying DNA profiling, when a suspect was linked to the crime scene, were described (2,3). Plant DNA profiling serves to identify the origin of detected plant material connected to a crime, suicide, or accident, and hence, it may contribute to identifying the location(s) where the event took place (primary scene), recent location of the body, whether a victim had been transferred or moved (secondary scene), and whether a suspect was present at a crime or accident scene (4,5). DNA profiling is also employed in solving the issues of narcotics and drug enforcement, as well as of unauthorized commercialization of some plants.Microsatellite-based genotyping, due to its great reproducibility and high degree of certainty in assigning the origin of a biological material that serves as legal case evidence, represents one of the most reliable DNA profiling methods in forensic investigation (6).Microsatellites, short tandem repeats (STR) or simple sequence repeats (SSR) consist of a number of tandemly repeated short DNA sequences (1-6 base pairs long). They are distributed throughout the eukaryotic genome. In addition, microsatellites are multiallelic due to their high intraspecies variability and are easily amenable to polymerase chain reaction (PCR)-based analysis. Both characteristics make them the DNA markers of choice for human DNA profiling analyses. However, microsatellite-based markers found their way of wider application in different branches of animal and plant sciences.Olea europaea L. is a diploid, outcrossing species. Cultivated olives have been reproduced mainly by vegetative propagation and sporadically by cross-breeding, which resulted in the creation of a number of varieties due to accidental crosses between cultivated forms or between wild and cultivated forms, but also due to accumulation of mutations, along with local selection of outstanding individuals. Hence, most olive cultivars have a local origin. More than 2000 cultivars have been documented in the Mediterranean region by means of their morphology (7).At present, microsatellite-based DNA sequences are the most appropriate genetic markers used in olive cultivar characterization and classification. Many microsatellites have been isolated from olives and their respective primer pairs have been developed (8-14).Due to their mainly local origin, specific olive cultivars are indigenous to specific geographical areas. In addition, the same cultivars grown in different environmental conditions have different genotype profiles. Both olive characteristics ensure their relevance in the assessment of the location of origin of the olive sample in question.Olive trees are abundant in Croatia. In order to assess the application potential of Croatian olive DNA profiling in forensic investigations, we genotyped the total of 44 specimens that comprise 30 cultivars and their 13 varieties, as well as one unassigned olive specimen. 相似文献95.
Amir Momeni-Boroujeni Paulo Salazar Tao Zheng Nana Mensah Ivelise Rijo Snjezana Dogan JinYuan Yao Christine Moung Chad Vanderbilt Jamal Benhamida Jason Chang William Travis Natasha Rekhtman Marc Ladanyi Khedoudja Nafa Maria E. Arcila 《The Journal of molecular diagnostics : JMD》2021,23(3):310-322
Mutations in the epidermal growth factor receptor (EGFR) are the most common targetable alterations in lung adenocarcinoma. To facilitate rapid testing, the Idylla EGFR assay was incorporated as a screening method before next-generation sequencing (NGS). Validation and experience using an in-house developed analysis pipeline, enhanced with a manual review algorithm is described. Results are compared with corresponding NGS results. In all, 1249 samples were studied. Validation demonstrated 98.57% (69/70) concordance with the reference methods. The limit of detection varied from 2% to 5% variant allele frequency for total EGFR quantitation cycle between 20 and 23. Of the 1179 clinical cases, 23.41% were EGFR-positive by Idylla. Concurrent NGS was successfully performed on 94.9% (799/842) requests. Concordance of Idylla with NGS was 98.62% (788/799) and 98.50% (787/799) using our in-house and Idylla analysis pipelines, respectively. Discordances involved missed mutations by both assays associated with low tumor/low input. Incorporating a manual review algorithm to supplement automated calls improved accuracy from 98.62% to 99.37% and sensitivity from 94.68% to 97.58%. Overall reporting time, from receipt of material to official clinical report, ranged from 1 to 3 days. Therefore, Idylla EGFR testing enables rapid and sensitive screening without compromising subsequent comprehensive NGS, when required. Automated calling, enhanced with a manual review algorithm, reduces false-negative calls associated with low tumor/low input samples.Mutations in the epidermal growth factor receptor (EGFR) are the most common targetable alterations in lung adenocarcinoma (LUAD). In the United States, sensitizing mutations are present in roughly 15% to 20% of LUAD patients,1 but higher rates of up to 50% can be seen in select populations, such as those of Eastern Asian descent and some Latin American subsets.2, 3, 4 Prompt and robust identification of these alterations is a critical step in guiding initial treatment decisions in patients with advanced disease.In addition to EGFR, a complex array of clinically relevant molecular tumor biomarkers is rapidly emerging, making comprehensive testing of multiple genes a requirement. Current guidelines5,6 propose that testing algorithms should prioritize assessment for mutations in EGFR and fusions involving ALK and ROS1 over other markers to provide target turnaround times of ≤14 days5,7 but also endorse the use of next-generation sequencing (NGS) methods over single-gene assays to allow concurrent comprehensive assessment of other targetable biomarkers. Specifically for EGFR, methods should be molecular based and able to detect all sensitizing mutations with a population frequency of at least 1%.5Despite the agreement on the importance of biomarker assessment, molecular testing is still not performed in many patients8 with LUAD, even for EGFR, which has been part of standard of care analysis for over a decade. Inadequate or insufficient tissue for testing and long turnaround times are the most common barriers affecting compliance with the established guidelines. Obtaining sufficient tumor tissue for sampling from LUAD patients is challenging, placing distinct restrictions on clinical laboratories to perform comprehensive testing. To provide rapid and local testing for select markers, many laboratories still perform testing as a series of single-gene assays, which limits the number of tests that can be run before tissue exhaustion. Alternatively, many laboratories are adopting NGS, but often at the expense of longer turnaround time due to test complexity.Given the importance of both rapid and comprehensive assessment in this setting, a multitest approach, combining rapid screening for key biomarkers followed by broad NGS assessment, constitutes a suitable compromise. The success rate of this approach is contingent on highly optimized protocols and proper choice of technology to ensure that both tests can be performed with a high success rate. In this work, we describe our validation and clinical implementation of the Idylla EGFR assay (Biocartis, Mechelen, Belgium) as a rapid screening method for EGFR mutations before comprehensive NGS testing. The Idylla system has been recently introduced in both Europe and the United States as a simple, fully automated, quantitative real-time PCR (qPCR) platform that takes unextracted formalin-fixed, paraffin-embedded (FFPE) tissue sections as input material. Its cartridge-based design allows the analysis of single samples on demand, without the need for batching or for trained operators and, as such, can be used in most laboratories with minimal infrastructure. Analysis is performed through proprietary analysis pipelines with automatically generated reports.Because of the high variability imparted by the unguided input of unextracted material and the black box nature of the analysis using this system, the false negativity or false positivity of this assay when using minimal tissue is unclear. There is a growing body of evidence related to the assay and clinical experience with the system9,10; however, objective determination of performance metrics that new laboratories adopting the system as well as in-depth investigation of testing failure have remained limited. For the assessment of this platform, a custom in-house analysis pipeline was developed to analyze the raw data from the Idylla consoles and a set of assessment criteria were developed to facilitate mutation calling and flagging of samples with borderline quality characteristics and at risk for false-positive and false-negative calls. Our 1-year experience with the assay using a broad range of tissue types, beyond FFPE is described, with side-by-side comparisons with NGS testing and some of the lessons learned in the process are shared. 相似文献
96.
Jurisic V Colic S Jurisic M 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2007,50(4):233-238
TNF-alpha is a pleiotropic cytokine that is considered as a primary modifier of inflammatory and immune reaction in response to various inflammatory diseases and tumour. We investigated levels of TNF-alpha in 43 radicular cysts and 15 odontogenic keratocysts, obtained from patients undergoing surgery, under local anaesthesia, and after aspiration of cystic fluid from non-ruptured cysts. TNF-alpha is elevated in both cysts' fluid, but higher values were found in radicular cysts in comparison to keratocysts. The significantly higher concentration of TNF-alpha was associated with smaller radicular cysts, higher protein concentration, higher presence of inflammatory cells in peri cystic tissues, and the degree of vascularisation and cysts wall thickness (Mann-Whitney U-test, p < 0.05). No correlation was found based on these parameters in odontogenic keratocyst, but all cysts have detectable concentrations of TNF-alpha. We here for the first time present that a difference in the concentration of TNF-alpha exists between these two cystic types. 相似文献
97.
Vulic M Strinic T Tomic S Capkun V Jakus IA Ivica S 《European journal of obstetrics, gynecology, and reproductive biology》2011,158(2):225-228
Objectives
The objective of this study was to determine whether or not the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AT1R), and angiotensinogen (AGT) gene polymorphisms are associated with idiopathic recurrent spontaneous abortions (RSAs) in Korean women.Study design
A total of 251 patients with unexplained consecutive pregnancy losses, and 126 healthy controls with at least one live birth and no history of pregnancy loss.Result
The odds ratios (ORs) of the ACE ID (OR = 2.423; 95% confidence interval (CI) = 1.417–4.142; p = 0.001) and the ACE II (OR = 2.050; 95% CI = 1.143–3.675; p = 0.018) for the ACE DD genotype were significantly different between patients with idiopathic RSA and controls; however, there were no significant differences between patients and controls with respect to the AT1R 1166A>C and AGT M235 T polymorphisms. In a haplotype-based analysis of I-A (p = 0.010), D-A (p = 0.004), I-A-T (p = 0.033), D-A-T (p = 0.0005), and D-C-T (p = 0.013) polymorphism pairs with synergistic effects derived by the MDR method in patients and in controls showed significant results.Conclusion
This study suggests that ACE, AT1R and AGT polymorphisms and haplotypes are a genetic determinant for the risk of idiopathic RSA in Korean women. 相似文献98.
Sundov Z Kunac N Capkun V Kalebić M Druzijanić N Puljak L Tomić S 《Hepato-gastroenterology》2011,58(107-108):763-768
99.
100.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises approximately 50% of primary gastric lymphoma. Proliferation of tumor cells infected with Helicobacter pylori is facilitated by the presence of T cells activated by H. pylori antigens. Unlike the majority of MALT lymphomas, tumors bearing the t(11;18)(q21;q21) resulting in production of a chimeric protein API2/MALT1 are often resistant to H. pylori eradication therapy, and require more aggressive therapeutic approach including chemotherapy. The authors hypothesize that a subset of patients with translocation-positive MALT lymphoma might benefit from a novel therapeutic approach that would address intercellular communication pathways between various cell types in the tumor microenvironment. A subset of T cells called regulatory T cells (Tregs) are one of the major immunomodulators of antitumor response mechanisms. There are several potential tools that could have a substantial impact on this particular T cell population, such as interleukin (IL)-15, indoleamine 2,3-dioxigenase (IDO), anti-CD25 antibodies. Introducing some of these components into treatment protocols for patients with API2/MALT1 translocation-positive MALT lymphomas might also prove to be benefitial for other lymphomas with increased number of intratumoral Tregs. 相似文献