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991.
Cunningham AR Moss ST Iype SA Qian G Qamar S Cunningham SL 《Chemical research in toxicology》2008,21(10):1970-1982
Structure-activity relationship (SAR) models are powerful tools to investigate the mechanisms of action of chemical carcinogens and to predict the potential carcinogenicity of untested compounds. We describe here the application of the cat-SAR (categorical-SAR) program to two learning sets of rat mammary carcinogens. One set of developed models was based on a comparison of rat mammary carcinogens to rat noncarcinogens (MC-NC), and the second set compared rat mammary carcinogens to rat nonmammary carcinogens (MC-NMC). On the basis of a leave-one-out validation, the best rat MC-NC model achieved a concordance between experimental and predicted values of 84%, a sensitivity of 79%, and a specificity of 89%. Likewise, the best rat MC-MNC model achieved a concordance of 78%, a sensitivity of 82%, and a specificity of 74%. The MC-NMC model was based on a learning set that contained carcinogens in both the active (i.e., mammary carcinogens) and the inactive (i.e., carcinogens to sites other than the mammary gland) categories and was able to distinguish between these different types of carcinogens (i.e., tissue specific), not simply between carcinogens and noncarcinogens. On the basis of a structural comparison between this model and one for Salmonella mutagens, there was, as expected, a significant relationship between the two phenomena since a high proportion of breast carcinogens are Salmonella mutagens. However, when analyzing the specific structural features derived from the MC-NC learning set, a dichotomy was observed between fragments associated with mammary carcinogenesis and mutagenicity and others that were associated with estrogenic activity. Overall, these findings suggest that the MC-NC and MC-NMC models are able to identify structural attributes that may in part address the question of "why do some carcinogens cause breast cancer", which is a different question than "why do some chemicals cause cancer". 相似文献
992.
Muhammad Ismail Rahat Ali Muhammad Shahid Muhammad Asaf Khan Muhammad Zubair Tayyaba Ali 《Drug and chemical toxicology》2018,41(1):22-26
Chlorpyrifos is a commonly used organophosphate insecticide that causes toxicological effects in aquatic organisms especially in fish. This study determined the effects of chlorpyrifos on the genotoxic and hematological parameters of freshwater fish, Labeo rohita. The genotoxic effects of different sublethal concentrations of chlorpyrifos were investigated in the erythrocytes of Labeo rohita (commonly known as Rohu) using the Micronucleus test. Effects of chlorpyrifos on the hematological parameters of the fish were also observed. Fish specimens were exposed to three sublethal concentrations of chlorpyrifos viz., sublethal I (SL-I, 1/6th of LC50?=?~73.8?μg/L), sublethal II (SL-II, 1/4th of LC50?=?~110.7?μg/L) and sublethal III (SL-III, 1/2nd of LC50?=?~221.4?μg/L) for 96?h. Blood samples were collected at every 24?h and were subjected to the Micronucleus assay. The observed micronucleus frequencies were concentration and time-dependent. The MN induction was significantly highest (p?0.01) at all the concentrations on 96-h exposure. During the experimental period, hematological parameters like total erythrocytes count (TEC), hemoglobin (Hb) and packed cell volume (PCV) decreased, whereas total leukocytes count (TLC) increased. This study indicated that the Micronucleus assay is a useful tool to detect genotoxic potential of chlorpyrifos in fish. 相似文献
993.
OBJECTIVES: To develop an easy, rapid and reproducible spot-inoculation method for phenotypic detection of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases and to make the existing three-dimensional extract test more convenient for use in routine diagnostic laboratories. METHODS: ESBL and AmpC producing and non-producing isolates of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, as identified by the conventional three-dimensional extract test, were used to evaluate the modified procedures. Whole bacterial cells and freeze-thaw preparations, as beta-lactamase sources, were strategically applied to culture plates near ceftazidime and cefoxitin discs on a lawn inoculum of E. coli ATCC 25922. Technical variations of the test included placing the beta-lactamase-containing inoculum into slits, wells and trenches, or onto the surface as spots at varying distances from the discs, and adding clavulanate or cloxacillin to the three-dimensional inoculum to confirm the presence of ESBLs and AmpC beta-lactamases, respectively. RESULTS: All the methods adopted for ESBL and AmpC detection by using the whole bacterial cells gave positive results. However, the best results were given by the spot-inoculation method. In modifications using the enzymic extracts, the enhanced growth of surface organisms was better appreciated in the designed modifications compared with the conventional methods. CONCLUSIONS: The method described here is simple and cost-effective. Furthermore, up to 16 isolates may be tested on a single culture plate, thus it is a less labour-intensive and more economic technique than other reported phenotypic methods. 相似文献
994.
995.
Robina Khan Niazi Mette Hollensted Christian Theil Have Niels Grarup Oluf Pedersen Asmat Ullah Gulbin Shahid Wasim Ahmad Asma Gul Torben Hansen 《BMC medical genetics》2018,19(1):199
Background
Mutations in the genes encoding leptin (LEP), the leptin receptor (LEPR), and the melanocortin 4 receptor (MC4R) are known to cause severe early-onset childhood obesity. The aim of the current study was to examine the prevalence of damaging LEP, LEPR, and MC4R mutations in Pakistani families having a recessive heritance of early-onset obesity.Methods
Using targeted resequencing, the presence of rare mutations in LEP, LEPR, and MC4R, was investigated in individuals from 25 families suspected of having autosomal recessive early-onset obesity. Segregation patterns of variants were assessed based on chip-based genotyping.Results
Homozygous LEPR variants were identified in two probands. One carried a deletion (c.3260AG) resulting in the frameshift mutation p.Ser1090Trpfs*6, and the second carried a substitution (c.2675C?>?G) resulting in the missense mutation p.Pro892Arg. Both mutations were located within regions of homozygosity shared only among affected individuals. Both probands displayed early-onset obesity, hyperphagia and diabetes. No mutations were found in LEP and MC4R.Conclusions
The current study highlights the implication of LEPR mutations in cases of severe early-onset obesity in consanguineous Pakistani families. Through targeted resequencing, we identified novel damaging mutations, and our approach may therefore be utilized in clinical testing or diagnosis of known forms of monogenic obesity with the aim of optimizing obesity treatment.996.
Ilhan Alcelik Zubair M. Saeed Ben A. Haughton Rizwan Shahid John C. Alcelik Craig Brogden Adam Budgen 《Foot and Ankle Surgery》2018,24(5):427-434
Background
Open Achilles tendon repairs (OATR) are associated with high complication rates. Minimally invasive surgery (MIS) techniques like the Achillon Achilles tendon repair (AATR) were developed to reduce this. We performed a systematic review and meta-analysis to compare OATR with AATR.Methods
We performed an extensive literature search including all studies that compared the two techniques. Outcomes assessed included overall complication rate, re-rupture rate, sural nerve injury, wound length, The American Orthopaedic Foot and Ankle Scores (AOFAS) scores and return to sports.Results
Eight studies were suitable for inclusion totalling 210 patients in the AATR group vs 233 patients in the OATR group. Total complication rates were significantly reduced in the Achillon patients with odd ratio of 0.14 (CI 95%, 0.08–0.27, P < 0.00001) in favour. There were no significant differences in re-rupture rate, sural nerve injury, return to sports and AOFAS scores following repair between the two groups.Conclusions
AATR has fewer overall complications compared with OATR. It should be considered as an alternative to open surgical repair. 相似文献997.
Javed Faqeeha Shafique Muhammad Rani Noshaba Rubab Aqsa Shahid Ahmad Ali 《International journal of legal medicine》2022,136(2):557-558
Fifteen autosomal STRs were evaluated using Identifiler plus kit in 121 Arain samples of Pakistan. The highly discriminatory locus was D2S1338 with value of 0.968. Allele 8 at TPOX was the most frequent with value of 0.467. No significant deviations from Hardy–Weinberg equilibrium were seen except D3S1358 and D18S51. Combined power of discrimination, combined power of exclusion, and combined matching probability were obtained as 0.9999999999999999925, 0.99999815, and 7.4897 × −18, respectively. Population differentiation test demonstrated significant differences between Arain and geographically distinct populations.
相似文献998.
Liran Levy Ella Huszti Jussi Tikkanen Rasheed Ghany William Klement Musawir Ahmed Shahid Husain Pierre O. Fiset David Hwang Shaf Keshavjee Lianne G. Singer Stephen Juvet Tereza Martinu 《American journal of transplantation》2020,20(1):241-249
Acute cellular rejection (ACR) is a significant risk factor for chronic lung allograft dysfunction (CLAD). Although clinically manifest and higher grade (≥A2) ACR is generally treated with augmented immunosuppression, management of minimal (grade A1) ACR remains controversial. In our program, patients with subclinical and spirometrically stable A1 rejection (StA1R) are routinely not treated with augmented immunosuppression. We hypothesized that an untreated first StA1R does not increase the risk of CLAD or death compared to episodes of spirometrically stable no ACR (StNAR). The cohort was drawn from all consecutive adult, first, bilateral lung transplantations performed between 1999 and 2017. Biopsies obtained in the first‐year posttransplant were paired with (forced expiratory volume in 1 second FEV1). The first occurrence of StA1R was compared to a time‐matched StNAR. The risk of CLAD or death was assessed using univariable and multivariable Cox proportional hazards models. The analyses demonstrated no significant difference in risk of CLAD or death in patients with a first StA1R compared to StNAR. This largest study to date shows that, in clinically stable patients, an untreated first A1 ACR in the first‐year posttransplant is not significantly associated with an increased risk for CLAD or death. Watchful‐waiting approach may be an acceptable tactic for stable A1 episodes in lung transplant recipients. 相似文献
999.
Khan SY Ahmed ZM Shabbir MI Kitajiri S Kalsoom S Tasneem S Shayiq S Ramesh A Srisailpathy S Khan SN Smith RJ Riazuddin S Friedman TB Riazuddin S 《Human mutation》2007,28(5):417-423
Ezrin, radixin, and moesin are paralogous proteins that make up the ERM family and function as cross-linkers between integral membrane proteins and actin filaments of the cytoskeleton. In the mouse, a null allele of Rdx encoding radixin is associated with hearing loss as a result of the degeneration of inner ear hair cells as well as with hyperbilirubinemia due to hepatocyte dysfunction. Two mutant alleles of RDX [c.1732G>A (p.D578N) and c.1404_1405insG (p.A469fsX487)] segregating in two consanguineous Pakistani families are associated with neurosensory hearing loss. Both of these mutant alleles are predicted to affect the actin-binding motif of radixin. Sequence analysis of RDX in the DNA samples from the original DFNB24 family revealed a c.463C>T transition substitution that is predicted to truncate the protein in the FERM domain (F for 4.1, E for ezrin, R for radixin, and M for moesin) (p.Q155X). We also report a more complete gene and protein structure of RDX, including four additional exons and five new isoforms of RDX that are expressed in human retina and inner ear. Further, high-resolution confocal microscopy in mouse inner ear demonstrates that radixin is expressed along the length of stereocilia of hair cells from both the organ of Corti and the vestibular system. 相似文献
1000.
Cotton leaf curl disease (CLCuD) is caused by one of seven begomoviruses in conjunction with a specific satellite; CLCuD DNA beta. Associated with some monopartite begomoviruses, DNA beta components encode a single gene (betaC1) which mediates satellite functions. We have investigated the contribution the satellite, specifically betaC1, makes to CLCuD symptoms in the absence of the helper begomovirus. Systemic expression of CLCuD-betaC1 from a Potato virus X (PVX) vector induces bona fide CLCuD disease symptoms in Nicotiana tabacum plants, including enations, swollen veins and vein darkening. These contrast with the mild symptoms of PVX in this host. Analysis of thin sections across enations induced by PVX expressing betaC1 shows the structure of the enation to be identical to those induced by CLCuD DNA beta in conjunction with a helper begomovirus. These results demonstrate that CLCuD betaC1 is the major determinant of symptoms for the CLCuD complex. 相似文献