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101.
Joanna Wiszniewska Weimin Bi Chad Shaw Pawel Stankiewicz Sung-Hae L Kang Amber N Pursley Seema Lalani Patricia Hixson Tomasz Gambin Chun-hui Tsai Hans-Georg Bock Maria Descartes Frank J Probst Fernando Scaglia Arthur L Beaudet James R Lupski Christine Eng Sau Wai Cheung Carlos Bacino Ankita Patel 《European journal of human genetics : EJHG》2014,22(1):79-87
In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60 000 SNP probes, referred to as Chromosomal Microarray Analysis – Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner. 相似文献
102.
Justin Pham Chad Shaw Amber Pursley Patricia Hixson Srirangan Sampath Erin Roney Tomasz Gambin Sung-Hae L Kang Weimin Bi Seema Lalani Carlos Bacino James R Lupski Pawel Stankiewicz Ankita Patel Sau-Wai Cheung 《European journal of human genetics : EJHG》2014,22(8):969-978
Somatic chromosomal mosaicism arising from post-zygotic errors is known to cause several well-defined genetic syndromes as well as contribute to phenotypic variation in diseases. However, somatic mosaicism is often under-diagnosed due to challenges in detection. We evaluated 10 362 patients with a custom-designed, exon-targeted whole-genome oligonucleotide array and detected somatic mosaicism in a total of 57 cases (0.55%). The mosaicism was characterized and confirmed by fluorescence in situ hybridization (FISH) and/or chromosome analysis. Different categories of abnormal cell lines were detected: (1) aneuploidy, including sex chromosome abnormalities and isochromosomes (22 cases), (2) ring or marker chromosomes (12 cases), (3) single deletion/duplication copy number variations (CNVs) (11 cases), (4) multiple deletion/duplication CNVs (5 cases), (5) exonic CNVs (4 cases), and (6) unbalanced translocations (3 cases). Levels of mosaicism calculated based on the array data were in good concordance with those observed by FISH (10–93%). Of the 14 cases evaluated concurrently by chromosome analysis, mosaicism was detected solely by the array in 4 cases (29%). In summary, our exon-targeted array further expands the diagnostic capability of high-resolution array comparative genomic hybridization in detecting mosaicism for cytogenetic abnormalities as well as small CNVs in disease-causing genes. 相似文献
103.
Ramina Nabiee Basir Syed Jesus Ramirez Castano Rukhsana Lalani Jennifer E. Totonchy 《Viruses》2020,12(12)
The virion proteins of Kaposi sarcoma-associated herpesvirus (KSHV) were initially characterized in 2005 in two separate studies that combined the detection of 24 viral proteins and a few cellular components via LC-MS/MS or MALDI-TOF. Despite considerable advances in the sensitivity and specificity of mass spectrometry instrumentation in recent years, leading to significantly higher yields in detections, the KSHV virion proteome has not been revisited. In this study, we have re-examined the protein composition of purified KSHV virions via ultra-high resolution Qq time-of-flight mass spectrometry (UHR-QqTOF). Our results confirm the detection of all previously reported virion proteins, in addition to 17 other viral proteins, some of which have been characterized as virion-associated using other methods, and 10 novel proteins identified as virion-associated for the first time in this study. These results add KSHV ORF9, ORF23, ORF35, ORF48, ORF58, ORF72/vCyclin, K3, K9/vIRF1, K10/vIRF4, and K10.5/vIRF3 to the list of KSHV proteins that can be incorporated into virions. The addition of these proteins to the KSHV virion proteome provides novel and important insight into early events in KSHV infection mediated by virion-associated proteins. Data are available via ProteomeXchange with identifier PXD022626. 相似文献
104.
Measurement of vasoactivity in the guinea-pig choroid 总被引:1,自引:0,他引:1
SJ Cringle PhD D-Y Yu PhD VA Alder PhD E-N Su PhD PK Yu BSc 《Clinical & experimental ophthalmology》1997,25(4):82-84
Purpose: A perfusion system for studying the vasoactive properties of the guinea-pig choroid is described. Methods :The principle of operation is that the vascular resistance of the entire vascular network of an isolated, perfused eye can be monitored by recording the pressure required to deliver a constant flow of perfusate through the network. Delivery of the pharmacological agent of interest into the perfusate stream and the subsequent determination of the magnitude of any induced pressure changes allows the vasoactive potency of various agonists to be assessed. Results: The baseline vascular resistance was 1.35 ± 0.16 mmHg. min/μL (mean ± SEM; n=10) and the mean response to intraluminal delivery of 124 mmol/L K+ Krebs was an increase in resistance of 297±67%. Vasoactive responses were sustainable for more than 8 h. Conclusions: This system will now be used to study the vasoactive properties of the guinea-pig choroid in greater detail. 相似文献
105.
Q. Davies A. C. Perkins M. Frier S. Watson E. -N. Lalani E. M. Symonds 《European journal of nuclear medicine and molecular imaging》1997,24(2):206-209
Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered
human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present
study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice
bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which
expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but dit
not shed into the ciruclation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody,
imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour
and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver
uptake of the secreting cell line. 相似文献
106.
El-Nasir M.A. Lalani Philip J. Weatherill Sue M.E. Kennedy Brian Burchell 《Biochemical pharmacology》1980,29(17):2367-2371
More than 18 compounds have been tested for their ability to stimulate defective UDP-glucuronyltransferase activity of Gunn rat liver homogenates towards 2-aminophenol, up to levels of transferase activity in similarly treated Wistar rat liver homogenates. The minimum structural requirements of an effective compound are a combination of the presence of an electron-attracting atom or group and a sparing solubility in water. The activation of defective UDP-glucuronyltransferase towards 2-aminophenol by pentan-3-one is reversible. The possible mechanism of action of alkyl ketone activators is discussed. 相似文献
107.
Zahid Lalani Mark Wong Eric M Brey Antonios G Mikos P J Duke 《Journal of oral and maxillofacial surgery》2003,61(9):1061-1072
PURPOSE: The purpose of this study was to test the hypothesis that spatial and temporal localization of growth factors transforming growth factor (TGF)-beta1, bone morphogenetic protein (BMP)-2, and platelet derived growth factor (PDGF)-A in a rabbit tooth extraction model correlate with the histologic events contributing toward healing. MATERIALS AND METHODS: Twenty-four male New Zealand White rabbits were used in the study. Incisor teeth were extracted from both jaws, and the healing extraction socket with the surrounding jaw bone was harvested at 48 hours, 4 days, and 1, 2, 4, 8, 12, and 16 weeks. Tissues were fixed, decalcified, and processed for hematoxylin and eosin and immunohistochemical staining. The sections were stained to detect TGF-beta1, BMP-2, and PDGF-A. Stained sections were then imaged, and an automated computer program was used to detect the brown 3,3'-diaminobenzidine regions representing the location of growth factors of interest. The data were collected in terms of percentage area and intensity of stain, and an analysis of variance was conducted (Tukey-Kramer and Scheffe's test) for statistical comparison between different time points, jaws, and growth factors. These results were also compared with hematoxylin and eosin-stained histologic specimens obtained at similar time points. RESULTS: Spatial and temporal differences in localization of TGF-beta1, BMP-2, and PDGF-A were observed across all time frames in both jaws. Statistically significant differences in percentage area and intensity of brown diaminobenzidine stain were detected temporally between TGF-beta1, BMP-2, and PDGF-A (P < or =.0001). CONCLUSION: The results of this study showed positive correlation between histologic events and the spatial and temporal localization of TGF-beta1, BMP-2, and PDGF-A in a rabbit tooth extraction model. 相似文献
108.
Ayoub AF Lalani Z Moos KF Wood GA 《The International journal of adult orthodontics and orthognathic surgery》2001,16(2):138-144
The aim of this study was to assess complications following various orthognathic surgical procedures that required early surgical intervention. This study was carried out on 821 patients who had undergone surgical treatment for correction of dentofacial deformities between 1985 and 2000. Only patients who required a second procedure to deal with immediate or early postoperative complications (i.e., those occurring within 4 weeks of surgery) were investigated in this study. Twelve patients underwent a second surgical procedure; 9 had undergone conventional osteotomy surgery, and 3 had undergone distraction osteogenesis. Three Le Fort I cases had to be further impacted and repositioned, and 4 vertical subsigmoid osteotomies had to be reexplored. The details of the complications are presented, and possible methods by which these problems could be reduced and/or prevented are discussed. 相似文献
109.
Spatial and temporal localization of FGF-2 and VEGF in healing tooth extraction sockets in a rabbit model. 总被引:1,自引:0,他引:1
Zahid Lalani Mark Wong Eric M Brey Antonios G Mikos P J Duke Michael J Miller Carol Johnston Dina Montufar-Solis 《Journal of oral and maxillofacial surgery》2005,63(10):1500-1508
PURPOSE: The purpose of this study was to test the hypothesis that spatial and temporal localization of growth factors FGF-2 and VEGF in a rabbit tooth extraction socket model correlate with the histologic events of healing. MATERIALS AND METHODS: Twenty-four male New Zealand white rabbits divided into 8 groups of 3 were used in the study. Incisor teeth were extracted from both jaws and the healing extraction socket with surrounding jaw bone was harvested at 48 hours, 4 days, 1, 2, 4, 8, 12, and 16 weeks. Tissues were fixed, decalcified, and processed for hematoxylin-eosin and immunohistochemical staining. The sections were stained to detect FGF-2 and VEGF. The stained sections were then imaged and an automated computer program was used to detect the brown diaminobenzidine stain that represented the growth factors of interest. Data was obtained in the form of percentage area and intensity of stain and analyzed using the analysis of variance (ANOVA - Tukey Kramer and Scheffe's post-test). RESULTS: Spatial and temporal differences in localization of FGF-2 and VEGF were observed across all time frames in both jaws. Statistically significant differences in percentage area and intensity of brown diaminobenzidine stain were seen temporally between FGF-2 and VEGF (P < .05). CONCLUSION: The results of this study showed positive correlation of histologic events to spatial and temporal localization of FGF-2 and VEGF in a rabbit tooth extraction model. 相似文献