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| 3. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 4. |
- Charakida, M., et al.
(författare)
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Endothelial dysfunction in childhood infection
- 2005
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Ingår i: Circulation. - 1524-4539. ; 111:13, s. 1660-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.
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| 5. |
- Johnson, Katherine, et al.
(författare)
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Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression : Diagnostic and mechanistic relevance
- 2022
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2-4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5-8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2-4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p.Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
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| 7. |
- Budde, M., et al.
(författare)
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Identification of the hydrogen-saturated self-interstitials in silicon and germanium
- 1998
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 57:18, s. 4397-4412
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Tidskriftsartikel (refereegranskat)abstract
- Silicon and germanium single crystals are implanted with protons. The infrared-absorption spectra of the samples contain sharp absorption lines due to the excitation of hydrogen-related local vibrational modes. The lines at 743.1, 748.0, 1986.5, and 1989.4 cm-1 in silicon and at 700.3, 705.5, 1881.8, and 1883.5 cm-1 in germanium originate from the same defect in the two materials. Measurements on samples coimplanted with protons and deuterons show that the defect contains two equivalent hydrogen atoms. Uniaxial stress measurements are carried out and a detailed analysis of the results is presented. It is shown that the defect has monoclinic-II symmetry, and the orientations of the Si-H and Ge-H bonds of the defect are determined. Ab initio local-density-functional theory is used to calculate the structure and local vibrational modes of the self-interstitial binding one and two hydrogen atoms in silicon and germanium together with the structure of the self-interstitial itself. The observed properties of the defect are in excellent agreement with those calculated for the self-interstitial binding two hydrogen atoms.
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| 8. |
- Budde, M., et al.
(författare)
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The hydrogen-saturated self-interstitial in silicon and germanium
- 1997
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Ingår i: Defects in semiconductors. - : Trans Tech Publications Inc.. ; , s. 35-40
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Konferensbidrag (refereegranskat)abstract
- Infrared absorption spectroscopy is used to study H-related point defects in H+-implanted Si (Si:H) and Ge (Ge:H). The absorption lines at 743.1, 748.0, 1986.5 and 1989.4 cm-1 in Si:H and at 700.3, 705.5, 1881.8 and 1883.5 cm-1 in Ge:H are shown to originate from the same defect containing two equivalent H atoms. Uniaxial stress experiments show that the defects have monoclinic-II symmetry, and the orientations of the two Si-H or Ge-H bonds are determined. The structure and the local vibrational modes of the self-interstitial binding two H atoms (IH2) are calculated with LDF cluster theory. The symmetry, bond-orientations and isotopic frequency-shifts calculated for IH2 are in excellent agreement with those observed for the 743.1-, 748.0-, 1986.5- and 1989.4-cm-1 modes in Si:H and for the 700.3-, 705.5-, 1881.8- and 1883.5-cm-1 modes in Ge:H.
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| 9. |
- Dawson, George J., et al.
(författare)
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Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction
- 1996
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Ingår i: Journal of Medical Virology. - 1096-9071. ; 50:1, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Among the three recently described GB viruses (GBV-A, GBV-B, and GBV-C), only GBV-C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV-C proteins, the prevalence of GBV-C RNA in human sera was studied using reverse transcription-polymerase chain reaction (RT-PCR). The prevalence of GBV-C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV-C was frequently detected in residents of West Africa, where the prevalence was > 10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV-C RNA. In addition, GBV-C RNA sequences were detected in individuals diagnosed with non-A-E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV-C RNA more than 1 year after the initial positive result.
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| 10. |
- Hoffmann, L., et al.
(författare)
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Substitutional carbon in Ge and Si1-xGex
- 1997
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Ingår i: Defects in semiconductors. - : Trans Tech Publications Inc.. ; , s. 97-102
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Konferensbidrag (refereegranskat)abstract
- In the present work, carbon is implanted into monocrystalline Ge and into relaxed epitaxial MBE-grown Si1-xGex. The samples are studied with infrared absorption spectroscopy along with ion-channeling studies on the Ge samples. Finally, ab-initio local density functional cluster theory is applied to calculate the structure and the local vibrational modes of substitutional carbon, Cs, in Ge. After implantation of 12C+ in Ge at room temperature and subsequent annealing at 350°C, a sharp absorption line is observed at 531 cm-1. By isotope substitution, it is concluded that the 531 cm-1 line represents a local vibrational mode of a single carbon atom. From ion-channeling measurements on samples annealed at 450°C, it is found that 31±3 % of the carbon atoms are located at substitutional sites. The population of the substitutional site and the intensity of the 531 cm-1 mode have identical annealing behavior and it is concluded that the 531 cm-1 mode is the three-dimensional T2 stretch mode of Cs in Ge. The calculated frequency and isotope shift for this mode are in good agreement with the observations. In Si0.65Ge0.35, two broad absorption lines are observed at ∼551 and ∼592 cm-1 after implantation of 12C+ and subsequent annealing at 550°C. From measurements on samples implanted with 13C+ and coimplanted with 12C+ and 13C+ we conclude that these lines represent local vibrational modes of defects containing a single carbon atom. In 13C+ implanted Si1-xGex samples that contain 15 to 50 % Ge a number of modes are observed in a frequency range from ∼510 to ∼610 cm-1, i.e., in the range of Cs in Ge and in Si. From the experimental findings it is concluded that substitutional carbon in Si1-xGex binds to both Si and Ge.
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