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Sökning: WFRF:(Widell K.)

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1.
  • Engel, Lawrence S., et al. (författare)
  • Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer : A case–control study nested within two prospective cohorts
  • 2019
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:9, s. 2360-2371
  • Tidskriftsartikel (refereegranskat)abstract
    • Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case–control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p’-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p’-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.
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2.
  • Meinander, K., et al. (författare)
  • Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity
  • 2013
  • Ingår i: Medchemcomm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:3, s. 549-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Pseudopeptides based on the kallikrein-related peptidase 3 (KLK3) activating bicyclic peptide “C-4” comprising hydrocarbon-based disulphide bridge mimetics have been synthesized. After investigating different synthetic approaches, the pseudopeptides were successfully cyclized from two L-allylglycine side chains via an alkene ring-closing metathesis reaction during the peptide synthesis. The alkene-linker was formed in a 1 : 1 E/Z isomer ratio. The resulting pseudopeptides were almost as potent as the parent peptide, increasing the activity of KLK3 over four-fold at 200 μg ml−1 (130–140 μM) concentrations.
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3.
  • Niehoff, Nicole M., et al. (författare)
  • Prediagnostic serum polychlorinated biphenyl concentrations and primary liver cancer : A case-control study nested within two prospective cohorts
  • 2020
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351. ; 187
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the 1970s, they are highly persistent in the environment and bioaccumulate. Whether PCBs are associated with liver cancer risk at general population levels is unknown. Methods: This study consisted of 136 incident liver cancer cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the Norwegian Janus cohort. Sera collected in the 1960s–1980s were measured for 37 PCB congeners and markers of hepatitis B (HBV) and C (HCV) infection. Odds ratios (OR) and 95% confidence intervals (CI) for tertiles of each lipid-adjusted PCB were estimated from conditional logistic regression. We also examined the molar sum of congeners in groups: total PCBs; low, medium, and high chlorination; and Wolff functional groups. Results: Concentrations of individual congeners from the 1960s/1970s sera ranged from 1.3-123.0 and 1.4–116.0 ng/g lipid among MHC cases and controls, respectively, and from 1.9-258.0 and 1.9–271.0 ng/g lipid among Janus cases and controls, respectively. Among MHC participants with sera from the 1960s, collected an average of 27 years before diagnosis among cases, the top tertile of PCBs 151, 170, 172, 177, 178, 180, and 195 was significantly associated with elevated odds of liver cancer (OR range = 2.01–2.38); most of these congeners demonstrated exposure-response trends. For example, ORtertile 3vs1 = 2.38 (95% CI: 1.22–4.64, p-trend = 0.01) for PCB 180. As a group, Wolff group 1b congeners, which are biologically persistent and weak phenobarbital inducers, were associated with increased odds. In MHC participants, ever vs. never HBV or HCV infection modified the PCB-liver cancer associations. There was little evidence of an association between PCBs and odds of liver cancer among the Janus cohort. Discussion: We observed associations between a number of PCB congeners and increased odds of liver cancer among MHC, but not Janus, participants with sera from the 1960s/1970s.
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4.
  • Allander, T, et al. (författare)
  • Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81
  • 2000
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 81:10, s. 2451-2459
  • Tidskriftsartikel (refereegranskat)abstract
    • The antibody response to the envelope proteins of hepatitis C virus (HCV) may play an important role in controlling the infection. To allow molecular analyses of protective antibodies, we isolated human monoclonal antibodies to the E2 envelope glycoprotein of HCV from a combinatorial Fab library established from bone marrow of a chronically HCV-infected patient. Anti-E2 reactive clones were selected using recombinant E2 protein. The bone marrow donor carried HCV genotype 2b, and E2 used for selection was of genotype 1a. The antibody clones were expressed as Fab fragments in E. coli, and as Fab fragments and IgG1 in CHO cells. Seven different antibody clones were characterized, and shown to have high affinity for E2, genotype 1a. Three clones also had high affinity for E2 of genotype 1b. They all bind to conformation-dependent epitopes. Five clones compete for the same or overlapping binding sites, while two bind to one or two other epitopes of E2. Four clones corresponding to the different epitopes were tested as purified IgG1 for blocking the CD81-E2 interaction in vitro; all four were positive at 0.3-0.5 microg/ml. Thus, the present results suggest the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2-CD81 interaction, of which one appeared immunodominant in this donor.
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5.
  • Buffoni Hall, Roberta, et al. (författare)
  • Water- and temperature-dependence of DNA damage and repair in the fruticose lichen Cladonia arbuscula ssp mitis exposed to UV-B radiation
  • 2003
  • Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317. ; 118:3, s. 371-379
  • Tidskriftsartikel (refereegranskat)abstract
    • The induction of cyclobutane pyrimidine dimers (CPDs) by ultraviolet-B radiation (UV-B, 280-315 nm) and repair mechanisms were studied in the lichen Cladonia arbuscula ssp. mitis exposed to different temperatures and water status conditions. In addition, the development and repair of CPDs were studied in relation to the different developmental stages of the lichen thallus podetial branches. Air-dried lichen thalli exposed to UV-B radiation combined with relatively high visible light (HL, 800 mumol m(-2) s(-1); 400-700 nm) for 7 days showed a progressive increase of CPDs with no substantial repair, although HL was present during and after irradiation with UV-B. Fully hydrated lichen thalli, that had not been previously exposed to UV-B radiation for 7 days, were given short-term UV-B radiation treatment at 25degreesC, and accumulated DNA lesions in the form of CPDs, with repair occurring when they were exposed to photoreactivating conditions (2 h of 300 mumol m(-2)s(-1), 400-700 nm). A different pattern was observed when fully hydrated thalli were exposed to short-term UV-B radiation at 2degreesC, in comparison with exposure at 25degreesC. High levels of CPDs were induced at 2degreesC under UV-B irradiation, without significant repair under subsequent photoreactivating light. Likewise, when PAR (300 mumol m(-2)s(-1) ) and UV-B radiation were given simultaneously, the CPD levels were not lowered. Throughout all experiments the youngest, less differentiated parts of the lichen thallus - namely 'tips', according to our arbitrary subdivision - were the parts showing the highest levels of CPD accumulation and the lowest levels of repair in comparison with the older thallus tissue ('stems'). Thus the experiments showed that Cladonia arbuscula ssp. mitis is sensitive to UV-B irradiation in the air-dried state and is not able to completely repair the damage caused by the radiation. Furthermore, temperature plays a role in the DNA damage repairing capacity of this lichen, since even when fully hydrated, C. arbuscula ssp. mitis did not repair DNA damage at the low temperatures.
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8.
  • Dawson, George J., et al. (författare)
  • Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction
  • 1996
  • Ingår i: Journal of Medical Virology. - 1096-9071. ; 50:1, s. 97-103
  • 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.
  • Fredlund, K.M, et al. (författare)
  • NADH-ferricyanide reductases in plant membranes
  • 1996
  • Ingår i: Plant Membrane Biology- Proceedings of the Phytochemical Society of Europe -38. ; , s. 143-151
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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