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Characterization of nuclear matrix protein alterations associated with renal cell carcinoma

UROLOGY 2007年第6期69卷 1227-1230页

作者： Cannon, Glenn M., Jr. Balasudramani, Manlrnaalha Getzenberg, Robert H. Univ Pittsburgh Dept Urol Pittsburgh PA 15213 USA Johns Hopkins Univ Hosp Brady Urol Res Inst Baltimore MD 21287 USA

Objectives Nuclear matrix proteins (NMPs), which constitute the nuclear skeleton, play a role in regulating gene expression and are thought to play an important role in carcinogenesis. Five NMPs specific to renal cell carcinoma (RCC) have been previously identified, RCCA 1 to 5. Our aim was to identify the sequence of these novel NMPs that are associated with RCC. Methods NMPs were extracted from five conventional clear cell RCC specimens from patients undergoing Surgical excision for presumed RCC. The RCCA proteins identified were analyzed by matrix-assisted light desorption ionization mass spectrometry to determine their peptide mass fingerprint. This fingerprint was then analyzed by searching the Mascot and National Institutes of Health BLAST (basic local alignment search tool) databases to determine protein identification. Results Only RCCA-1 and RCCA-2 were able to be consistently identified from each tumor specimen by the reverse staining method necessary to perform mass spectrometry. Mass spectrometry peptide mass fingerprinting revealed that RCCA-1 appears to be a differentially spliced form of nucleoporin p54 that has been identified in endometrial carcinoma. RCCA-2 was identified as an albumin-like protein. Conclusions This is the first report of nucleoporin p54 and albumin alterations in RCC. The identification of an abnormal nucleoporin in RCC suggests that alterations in nuclear transport might play a role in the development of this disease. The alterations in these NMPs suggest future areas for investigation in identifying diagnostic markers of, or therapeutic targets for, RCC.

关键词： Carcinoma Renal Cell Gene Expression Regulation Neoplastic Humans Kidney Neoplasms 癌肾细胞基因表达调控肿瘤肾肿瘤光谱法质量基质辅助激光解吸电离 Renal Cell Nucleo cytoplasmic Transport basic local alignment search tool Kidney Neoplasms Carcinoma United States National Institutes of Health Nuclear Matrix-Associated Proteins IONIZATION MASS SPECTROMETRY Gene Expression Regulation Nuclear Pore Complex Proteins

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Genetic characterization and phylogenetic analysis of Trypanosoma evansi in Iranian dromedary camels

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PARASITOLOGY REsearch 2013年第2期112卷 899-903页

作者： Pourjafar, Mehrdad Badiei, Khalil Sharifiyazdi, Hassan Chalmeh, Aliasghar Naghib, Mojtaba Babazadeh, Marzieh Alavi, Amir Mootabi Joshani-zadeh, Narges Hosseini Shiraz Univ Dept Clin Sci Sch Vet Med Shiraz Iran Vet Org Yazd Prov Yazd Iran

Whole blood samples were collected from 117 male clinically healthy Camelus dromedarius aged between 6 months to 18 years from several farms in Yazd Province of Iran. Trypanosoma evansi-affected camels were detected by Giemsa-stained blood smears, and the positive blood samples (4 out of 117) were submitted to PCR examination and phylogenetic analysis. basic local alignment search tool data of the obtained complete internal transcribed spacer (ITS) sequences revealed that they corresponded to those of T. evansi, Thailand cattle isolate (AY912276) with the homology of 99 %. Both phylogenetic trees generated by ITS1 and complete ITS were unable to clearly show inter- and intraspecific genetic diversity of Trypanosoma spp. isolates. The phylogenetic tree inferred from the ITS2 nucleotide sequences (569 bp) clearly showed the genetic diversity of the parasites. Phylogenetic and molecular analyses of this region showed that two distinct genotypes of T. evansi in Iranian dromedary camels are present. In contrast to the ITS1 and ITS2 regions, multiple alignment of the nucleotide sequence of the 5.8S rRNA showed a high degree of sequence conservation during evolution in various Trypanosoma spp.

关键词： genetic diversity basic local alignment search tool Camelus dromedarius phylogenetic tree Trypanosoma evansi blood specimen internal transcribed spacers Base Sequence Trypanosoma

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The Development of a Tympanic Membrane Model and Probabilistic Dose-Response Risk Assessment of Rupture Because of Blast

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MILITARY MEDICINE 2020年第Sup1期185卷 234-242页

作者： Iyoho, Anthony E. Ho, Kevin Chan, Philemon L3 Appl Technol Inc 10180 Barnes Canyon Rd San Diego CA 92121 USA

Introduction There is no dose-response model available for the assessment of the risk of tympanic membrane rupture (TMR), commonly known as eardrum rupture, from exposures to blast from nonlethal flashbangs, which can occur concurrently with temporary threshold shift. Therefore, the objective of this work was to develop a fast-running, lumped parameter model of the tympanic membrane (TM) with probabilistic dose-dependent prediction of injury risk. Materials and Methods The lumped parameter model was first benchmarked with a finite element model of the middle ear. To develop the dose-response curves, TMR data from a historic cadaver study were utilized. From these data, the binary probability response was constructed and logistic regression was applied to generate the respective dose-response curves at moderate and severe eardrum rupture severity. Results Hosmer-Lemeshow statistical and receiver operation characteristic analyses showed that maximum stored TM energy was the overall best dose metric or injury correlate when compared with total work and peak TM pressure. Conclusions Dose-response curves are needed for probabilistic risk assessments of unintended effects like TMR. For increased functionality, the lumped parameter model was packaged as a software library that predicts eardrum rupture for a given blast loading condition.

关键词： exposure cadaver middle ear libraries risk assessment rupture software tympanic membrane tympanic membrane perforation basic local alignment search tool

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Anthropomorphic Blast Test Device for Primary Blast Injury Risk Assessment

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MILITARY MEDICINE 2020年第Sup1期185卷 227-233页

作者： Hsu, Yun Ho, Kevin Chan, Philemon L3 Appl Technol Inc 10180 Barnes Canyon RdSuite 100 San Diego CA 92121 USA

Introduction Blast overpressure health hazard assessment is required prior to fielding of weapon systems that produce blast overpressures that pose risk of auditory and nonauditory blast lung injuries. The anthropomorphic blast test device (ABTD) offers a single device solution for collection of both auditory and nonauditory data from a single blast at anthropometrically correct locations for injury risk assessment. It also allows for better replication of personnel positioning during weapons firings. The ABTD is an update of the blast test device (BTD), the current Army standard for collection of thoracic blast loading data. Validation testing of the ABTD is required to ensure that lung injury model validated using BTD collected test data and sheep subjects is still applicable when the ABTD is used. Methods Open field validation blast tests were conducted with BTD and ABTD placed at matching locations. Tests at seven blast strength levels were completed spanning the range of overpressures for occupational testing. Results The two devices produced very similar values for lung injury dose over all blast levels and orientations. Conclusion The ABTD was validated successfully for open field tests. For occupational blast injury assessments, ABTD can be used in place of the BTD and provide enhanced capabilities.

关键词： blast injuries risk assessment lung injuries devices medical basic local alignment search tool weapons

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Simulation of Cumulative Exposure Statistics for Blast Pressure Transmission Into the Brain

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MILITARY MEDICINE 2020年第Sup1期185卷 214-226页

作者： Tan, X. Gary Matic, Peter US Naval Res Lab Mat Sci & Technol Div Code 6300 4555 Overlook Ave SW Washington DC 20375 USA

Introduction This study develops and demonstrates an analysis approach to understand the statistics of cumulative pressure exposure of the brain to repetitive blasts events. Materials and Methods A finite element model of blast loading on the head was used for brain model biomechanical responses. The cumulative pressure exposure fraction (CPEF), ranging from 0.0 to 1.0, was used to characterize the extent and repetition of high pressures. Monte Carlo simulations were performed to generate repetitive blast cumulative exposures. Results The blast orientation effect is as influential as the blast overpressure magnitudes. A 75 degrees (from the side) blast orientation can produce CPEF values exceeding traumatic brain injury pressure thresholds >0.95 while, for the same blast overpressure, a 0 degrees (front) blast orientation results in a CPEF <0.25. Monte Carlo results for different sequences reflecting notional operational and training environments show that both mean values and standard deviations of CPEF reach the statistically equilibrium state at a finite value of n exposures for each sequence. Conclusions Statistical convergence of the brain pressure response metrics versus number of blasts for different exposures characterizes the transitions from "low" to "high" number of blasts and quantitatively highlights the differences between operational and training exposures.

关键词： brain pressure-physical agent blast cells basic local alignment search tool

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Having a BLAST with bioinformatics (and avoiding BLASTphemy)

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GENOME BIOLOGY 2001年第10期2卷 1-10页

作者： Pertsemlidis, Alexander Fondon, John W., III Univ Texas Southwestern Med Ctr Dallas Eugene McDermott Ctr Human Growth & Dev Dallas TX 75390 USA

searching for similarities between biological sequences is the principal means by which bioinformatics contributes to our understanding of biology. Of the various informatics tools developed to accomplish this task, the most widely used is BLAST, the basic local alignment search tool. This article discusses the principles, workings, applications and potential pitfalls of BLAST, focusing on the implementation developed at the National Center for Biotechnology Information.

关键词： Query Sequence basic local alignment search tool Unrelated Sequence Ungapped alignment Good local alignment

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Using a public database of Neisseria gonorrhoeae genomes to detect mutations associated with zoliflodacin resistance

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2021年第11期76卷 2847-2849页

作者： Adamson, Paul C. Lin, Eric Y. Ha, Sung-Min Klausner, Jeffrey D. UCLA David Geffen Sch Med Div Infect Dis Los Angeles CA 90095 USA UCLA David Geffen Sch Med Los Angeles CA 90095 USA Univ Calif Los Angeles Dept Integrat Biol & Physiol Los Angeles CA USA USC Keck Sch Med Dept Prevent Med Los Angeles CA USA

Background: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat. Zoliflodacin is a novel antibiotic undergoing clinical trials for the treatment of gonorrhoea. While there are limited data regarding zoliflodacin resistance in N. gonorrhoeae, three amino acid mutations have been associated with increased MICs of zoliflodacin. Objectives: To determine the prevalence of three amino acid mutations associated with zoliflodacin resistance within a large, public database of nearly 13000 N. gonorrhoeae genomes. Methods: PathogenWatch is an online genomic epidemiology platform with a public database of N. gonorrhoeae genomes. That database was used to extract gyrB sequence data and a basic local alignment search tool (BLAST) search was performed to identify any of the three amino acid mutations in GyrB that are associated with increased zoliflodacin MICs: D429N, K450N or K450T. As a control for the search methodology, all GyrA sequences were also extracted and S91F mutations were identified and compared with the PathogenWatch database. Results: In total, 12493 N. gonorrhoeae genomes from the PathogenWatch database were included. Among those genomes, none was identified that harboured any of the three mutations associated with increased zoliflodacin MICs. One genome was identified to have a mutation at position 429 in GyrB (D429V). Conclusions: The findings suggest that the prevalence of the three mutations associated with zoliflodacin resistance in N. gonorrhoeae is very low. However, further research into the mechanisms of zoliflodacin resistance in N. gonorrhoeae is needed. Genomic epidemiology platforms like PathogenWatch can be used to enhance the global surveillance of AMR.

关键词： antibiotics mutation amino acids epidemiology gonococcal infection drug resistance microbial genome neisseria gonorrhoeae world health surveillance medical basic local alignment search tool malnutrition-inflammation-cachexia syndrome zoliflodacin

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MORPHOLOGICAL AND MOLECULAR TAXONOMY OF A NEW SPECIES OF FUNDULOTREMA AND COMMENTS ON GYRODACTYLUS STEPHANUS (MONOGENEA: GYRODACTYLIDAE) FROM FUNDULUS HETEROCLITUS (ACTINOPTERYGII: CYPRINODONTIFORMES) IN NOVA SCOTIA, CANADA

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JOURNAL OF PARASITOLOGY 2009年第4期95卷 846-849页

作者： King, Stanley D. Cone, David K. St Marys Univ Dept Biol Halifax NS B3H 3C3 Canada

Fundulotrema porterensis n. sp. (Monogenea: Gyrodactylidae) is described from the mummichog, Fundulus heteroclitus (L.;Cyprinodontidae), inhabiting Porters Lake, Nova Scotia, Canada. The new parasite species is characterized by having a ventral bar with small anterolateral processes and linguiform membrane, differentiating it from all other known species of Fundulotrema. The morphological description of F porterensis is supplemented with 1,011 sequenced base pairs (bp) of ribosomal DNA (rDNA) spanning both internal transcribed spacers (ITS-1 and ITS-2) and 5.8S regions of the genome. A BLAST (basic local alignment search tool) search revealed that the 5.8S (157 bp) region varied by I bp from Gyrodactylus turnbulli Harris, 1986 and G. pictae Cable, Oosterhout, Barson and Harris, 2005, which also infect cyprinodontids. Morphometrically, F porterensis most closely resembles Fundulotrema foxi (Rawson, 1973), but the 2 species are easily separated by length of hamuli (50.7 vs. 42.2 mu m, respectively), length of anterolateral process of the ventral bar (4.9 vs. 8.9 mu m), shape of marginal hooks, and shape of the ventral bar membrane. A morphological and molecular supplemental diagnosis of Glyrodactylus stephanus Mueller, 1937, from the mummichog, is also presented. This new material provides previously unrecorded information on the attributes of the ventral bar, marginal hooks, and also clarifies the structure of the male copulatory organ (MCO).

关键词： genome molecular taxonomy morphological taxonomy molecular taxonomy basic local alignment search tool Comment Nova Scotia Killifish Canada Genome internal transcribed spacers new species Advanced materials Harris

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Evaluation of Blast Overpressure Exposure Effects on Concentration of Antibiotics in Mice

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MILITARY MEDICINE 2020年第Sup1期185卷 256-262页

作者： Antonic, Vlado Sajja, Venkatasivasaisujith Sousa, Jason Nguyen, Ken Alamneh, Yonas Garry, Brittany Medina-Rojas, Maria Wilder, Donna Chau Vuong Potter, Brittney Zurawski, Daniel Shearer, Jonathan Black, Chad Demons, Samandra Long, Joseph Tyner, Stuart CCCRP 722 Doughten St Ft Detrick MD 21702 USA Walter Reed Army Inst Res Wound Infect Dept 503 Robert Grant Ave Silver Spring MD 20910 USA Walter Reed Army Inst Res Ctr Mil Psychiat & Neurosci Blast Induced Neurotrauma Branch 503 Robert Grant Ave Silver Spring MD 20910 USA Walter Reed Army Inst Res Expt Therapeut Branch 503 Robert Grant Ave Silver Spring MD 20910 USA

Objective Infection as sequelae to explosion-related injury is an enduring threat to our troops. There are limited data on the effects of blast on antibiotic pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. The observational study presented here is our Institute's first attempt to address this issue by combining our existing interdepartmental blast, infection modeling, and in vivo PK/PD capabilities and was designed to determine the PK effects of blast on the first-line antibiotic, cefazolin, in an in vivo mouse model. Methods A total of 160 male BALB/c mice were divided to sham and blast (exposed to blast overpressure of 19 psi) in two biological replicates. At 1 hour after blast/sham exposure, the animals received IV injection of cefazolin (328 mg/kg). Animals were euthanized at 3 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, or 10 hours after the injection. Plasma and liver were analyzed for concentration of cefazolin using mass-spectrometry. Results We observed increases in the concentration of cefazolin in the plasma and liver of blast exposed animals at later time points and increase in elimination half-life. Conclusion Our results indicate that blast-induced physiologic changes significantly influence cefazolin PK and suggest that efficacy could be affected in the context of the blast;assessment of efficacy and PD effects require further investigation. Metabolic changes resulting from blast may influence other classes of antibiotics and other therapeutics used with these injuries. Therefore, this may have important treatment considerations in other areas of military medicine.

关键词： antibiotics cefazolin plasma liver mice basic local alignment search tool

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Materials Characterization of Cranial Simulants for Blast-Induced Traumatic Brain Injury

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MILITARY MEDICINE 2020年第Sup1期185卷 205-213页

作者： Wermer, Anna Kerwin, Joseph Welsh, Kelsea Mejia-Alvarez, Ricardo Tartis, Michaelann Willis, Adam New Mexico Inst Min & Technol Dept Chem Engn 801 Leroy Pl Socorro NM 87801 USA Michigan State Univ Dept Mech Engn 1449 Engn Res Ct A117 E Lansing MI 48824 USA San Antonio Mil Med Ctr Dept Neurol 3551 Roger Brooke Dr San Antonio TX 78219 USA

Introduction The mechanical response of brain tissue to high-speed forces in the blast and blunt traumatic brain injury is poorly understood. Object-to-object variation and interspecies differences are current limitations in animal and cadaver studies conducted to study damage mechanisms. Biofidelic and transparent tissue simulants allow the use of high-speed optical diagnostics during a blast event, making it possible to observe deformations and damage patterns for comparison to observed injuries seen post-mortem in traumatic brain injury victims. Methods Material properties of several tissue simulants were quantified using standard mechanical characterization techniques, that is, shear rheometric, tensile, and compressive testing. Results Polyacrylamide simulants exhibited the best optical and mechanical property matching with the fewest trade-offs in the design of a cranial test object. Polyacrylamide gels yielded densities of similar to 1.04 g/cc and shear moduli ranging 1.3-14.55 kPa, allowing gray and white matter simulant tuning to a 30-35% difference in shear for biofidelity. Conclusions These materials are intended for use as layered cranial phantoms in a shock tube and open field blasts, with focus on observing phenomena occurring at the interfaces of adjacent tissue simulant types or material-fluid boundaries. Mechanistic findings from these studies may be used to inform the design of protective gear to mitigate blast injuries.

关键词： blast injuries traumatic brain injuries cadaver cattle gelatin gel optics phantoms imaging shock cranium diagnosis personal protective equipment blast cells brain tissue white matter compression basic local alignment search tool chief complaint

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