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Biomedical subjects

J de Boer

Publications and source records attributed to J de Boer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Organochlorines in Greenland ringed seals (Phoca hispida).

Twenty-five ringed seals (Phoca hispida) were sampled in 1994 at each of four areas in Greenland, three on the west coast and one on the east coast. Seal blubber samples were analysed for polychlorinated biphenyls (PCBs, IUPAC Nos. 28, 31, 52, 101, 105, 118, 138, 153, 156 and 180), DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT), hexachlorocyclohexanes (alpha-, beta- and gamma-HCH), hexachlorobenzene (HCB) and trans-nonachlor. A number of the seals (n = 56) were also analysed for toxaphene (total toxaphene and single congeners: CHB Nos. 26, 32, 50 and 62). The overall geometric means (and ranges) found in seals were in microgram kg-1 wet wt. for sigma PCBs: 452 (85-4200), sigma DDTs: 607 (97-6040), sigma HCHs: 123 (51-382), HCB: 13 (3-27), trans-nonachlor: 83 (21-1236) and total toxaphene: 263 (71-950). The geometric means for HCB, trans-nonachlor, toxaphenes and the sums of PCBs and DDTs were higher for the east coast samples than for those from the west coast, and a decreasing trend in concentrations followed the east Greenland current. No geographical trend was apparent for HCHs. Differences in concentrations between females and males were only significant for HCB and HCH within certain age classes and sampling areas. A tendency for concentrations to increase with age was observed, but was not statistically significant. Principal component analyses for PCB congeners revealed that the proportion of higher chlorinated PCBs (Cl atoms > or = 6) decreased with decreasing concentrations of PCBs found for the four sampling areas. No differences between the higher and lower chlorinated PCBs were seen in females and males, but a higher proportion of CB-105 and CB-118 compared to CB-52 and CB-101 was seen in male seals compared to female seals.

Animals↗
PubMed2000

Organochlorines in Greenland lake sediments and landlocked Arctic char (Salvelinus alpinus).

Lake sediments and landlocked Arctic char (Salvelinus alpinus) were sampled in 1994 and 1995 at four different locations in Greenland, three at the west coast and one at the east coast. Sediments, char muscle and char liver were analysed for PCBs (10 congeners), DDTs (pp'), HCHs (alpha, beta, gamma), dieldrin, HCB and chlordanes (5) and char in addition to toxaphene (total and 4 congeners). All organochlorines in the sediment samples were below the detection limit of 0.1 microgram kg-1 dry wt., while the overall geometric means in Arctic char muscle were, in microgram kg-1 wet wt., for PCBs 11 (range 1-140), for DDTs 4.0 (1-35), for HCHs 0.4 (0.06-1.5), for dieldrin 0.7 (< 0.1-4.2), for HCB 0.7 (0.09-3.8), for chlordanes 4.8 (1-57) and for total toxaphene 13 (1-180). The sums of PCBs, DDTs, chlordanes and total toxaphene disclosed higher concentrations in muscle of char from the east coast compared to char from the west coast. Dieldrin and HCB showed the same tendency, but less pronounced, while the sum of HCHs were found in highest concentrations at the west coast. PCB, DDT, chlordane and toxaphene concentrations showed a decreasing trend following the East Greenland Current. Principal component analysis on PCB congeners showed that the proportion of higher chlorinated PCBs (Cl > 5) were higher in Qaqortoq in south Greenland compared to the three other sampling areas in Greenland. However, no correlation was seen either between degree of chlorination and latitude or between degree of chlorination and PCB concentrations.

Animals↗
PubMed2000

The tumor promoter TPA enhances benzo[a]pyrene and benzo[a]pyrene diolepoxide mutagenesis in Big Blue mouse skin.

The Big Blue mouse was used to investigate the role of cell proliferation in mutation fixation in the mouse back skin model of carcinogenesis. Phorbol 12-myristate 13 acetate (TPA) was applied to the dorsum of Big Blue mice to manipulate cell proliferation, and benzo[a]pyrene (BaP) or BaP-diolepoxide (BPDE) was applied to produce premutagenic DNA damage. Mutations in the lacI transgene of skin DNA were measured. BaP and BPDE elevated mutant frequency, DNA adducts, and cell damage over untreated and acetone-treated mice. BPDE-DNA adducts peaked within 30 min of exposure and DNA adducts, formed after application of both BaP and BPDE, declined rapidly with time. As the dose of BaP increased (4 to 64 microg), DNA adducts, mutant frequency, and cell damage increased in a dose-dependent manner. TPA applied after BaP and BPDE further increased mutant frequency, DNA adducts, and cell damage, while variably affecting mitotic index and other measures of cell proliferation. TPA became less effective at increasing mitotic index as the dose of BaP increased, although all measures of cell proliferation, taken together, increased. The most effective production of DNA adducts and mutations occurred when the carcinogen was applied simultaneously with or within 1 hr of TPA. Mutations induced by BPDE were predominantly base substitutions: of these base substitutions, 35% were G:C --> A:T transitions, and 36% were G:C --> T:A and 29% G:C --> C:G transversions. Approximately 88% of all mutations and 100% of base substitutions were at G:C sites; 60% of all mutations and 70% of the base substitution mutations occurred at CpG sites. A:T --> G:C transitions were not found. All of the single-base deletions were at G:C base pairs.

Animals↗
PubMed2000

Enantiomer fractions instead of enantiomer ratios.

The use of enantiomer ratios (ERs) to indicate the relative amounts of a pair of enantiomers in a sample has some disadvantages. Enantiomer fractions (EFs) are proposed as an alternative expression to eliminate the difficulties.

Chemistry Techniques, Analytical↗
PubMed2000

Toxaphene in standard solutions and cleaned biota extracts--results of the first QUASIMEME interlaboratory studies. Quality Assurance of Information for Marine Environmental Monitoring in Europe.

Two interlaboratory studies on individual toxaphene congeners have been organised by the project Quality Assurance of Information for Marine Environmental Monitoring in Europe (QUASIMEME). Fifteen laboratories analysed two standard solutions in the first study and 13 laboratories analysed a standard solution and two cleaned biota extracts in the second study. The coefficients of variation obtained for the standard solutions were 6-21% and for the cleaned extracts 16-39%. Although the results were comparable to those of other studies, further improvement in the level of agreement between the participating laboratories was considered possible.

Animals↗
PubMed2000

Toxaphene: a challenging analytical problem.

The analysis of toxaphene, a highly complex mixture of chlorinated bornanes, bornenes and camphenes, is a challenging problem, especially as individual congeners are present at trace levels in biota and other relevant samples. The complicated nomenclature of the compounds of interest is briefly discussed. Gas chromatographic techniques are the most important tools in toxaphene analysis because of their high resolution. The main focus of attention is devoted to important steps in the GC-based analytical procedure, such as sample preparation and injection, separation by single-column and multidimensional GC, both heart-cut and comprehensive, and detection by electron capture and, increasingly, MS-based detection/identification. The gradual shift from total toxaphene to individual compound analysis is discussed, and the growing interest in enantiomer-selective separations is highlighted. The problems encountered when selecting appropriate indicator compounds for rapid toxaphene screening are also addressed.

Environmental Monitoring↗
PubMed2000

Nucleotide excision repair and human syndromes.

DNA damage is implicated in cancer and aging, and several DNA repair mechanisms exist that safeguard the genome from these deleterious consequences. Nucleotide excision repair (NER) removes a wide diversity of lesions, the main of which include UV-induced lesions, bulky chemical adducts and some forms of oxidative damage. The NER process involves the action of at least 30 proteins in a 'cut-and-paste'-like mechanism. The consequences of a defect in one of the NER proteins are apparent from three rare recessive syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and the photosensitive form of the brittle hair disorder trichothiodystrophy (TTD). Sun-sensitive skin is associated with skin cancer predisposition in the case of XP, but remarkably not in CS and TTD. Moreover, the spectrum of clinical symptoms differs considerably between the three syndromes. CS and TTD patients exhibit a spectrum of neurodevelopmental abnormalities and, in addition, TTD is associated with ichthyosis and brittle hair. These typical CS and TTD abnormalities are difficult to comprehend as a consequence of defective NER. This review briefly describes the biochemistry of the NER process, summarizes the clinical features of the NER disorders and speculates on the molecular basis underlying these pleitropic syndromes.

Cockayne Syndrome↗
PubMed2000

LacI mutation spectra following benzo[a]pyrene treatment of Big Blue mice.

The mutation spectrum of the lacI gene from the liver of C57Bl6 Big Blue transgenic mice treated with benzo[a]pyrene (B[a]P) has been compared with the spectrum of spontaneous mutations observed in the liver of untreated Big Blue mice. Mice were treated with B[a]P for 3 days followed by a partial hepatectomy one day after the last injection. Liver tissue was removed for analysis at hepatectomy and, again, 3 days later at the time of sacrifice. Earlier, we reported that the lacI mutant frequency in these B[a]P-treated mice was elevated in the liver both at the time of hepatectomy and at sacrifice; however, a statistically significant increase in the mutant frequency was observed only at sacrifice. In this study, the DNA sequence spectra of lacI mutations observed in the liver of B[a]P-treated Big Blue mice at hepatectomy and at time of sacrifice were compared with each other and with the spectrum of spontaneous liver mutations. No differences were observed between the two B[a]P-treatment spectra. However, mutation frequencies of both GC-->TA and GC-->CG at the time of hepatectomy and at sacrifice were significantly elevated compared with the spontaneous frequency of these same transversions. Also, the frequency of AT-->TA transversions was significantly higher than the spontaneous frequency at the time of hepatectomy but not at sacrifice. The frequency of all other classes of mutations scored was not significantly different from the frequency of these same events in the spontaneous spectra. These data support the view that B[a]P treatment results in the induction of GC-->TA and GC-->CG transversions within 1 day of the last injection and they provide insights regarding the relative roles of benzo[a]pyrene-7,8-diol-9, 10-epoxide and radical cations of B[a]P in B[a]P-induced mutagenesis in vivo. Finally, these data provide evidence for B[a]P-induced mutagenesis under conditions where no statistical increase in mutant frequency could be shown.

Animals↗
PubMed2000

Chromium(VI)-induced mutagenesis in the lungs of big blue transgenic mice.

The mutagenic activity of the hexavalent chromium [Cr(VI)] compound potassium dichromate was examined in the Big Blue transgenic mouse lung, the target organ for Cr(VI) carcinogenesis in humans. Mice were exposed to Cr(VI) by intratracheal instillation of a potassium dichromate (K2Cr2O7) solution. Analysis of the deposition of Cr in mouse lungs revealed that the procedure reproducibly resulted in about 5% retention of the Cr in the lung. Lower but measurable levels were detected in kidney and liver. We found a dose-dependent and time-dependent increase in the mutant frequency in the mouse lung. A significant elevation of the mutant frequency above the spontaneous background was observed two weeks after Cr(VI) intratracheal instillation and at doses above 3 mg/kg. Depletion of tissue glutathione (GSH) levels by buthionine sulfoximine (BSO) before Cr(VI) treatment led to a decrease in the Cr(VI)-induced mutant frequency, compared to that in the animals with normal GSH levels, suggesting a role for GSH in the generation of reactive intermediates during the intracellular reduction of Cr(VI). Sequence analysis for the Cr(VI)-induced mutants revealed a similarity to the spontaneous mutational spectrum observed in mouse lungs, consistent with the generation of oxidative-type DNA damage by Cr(VI). These results demonstrate that Cr(VI) is mutagenic in mouse lung, the target organ for human carcinogenesis.

Animals↗
PubMed1999

Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition.

Patients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD encodes a helicase subunit of the dually functional DNA repair/basal transcription complex TFIIH. The pleiotropic disease phenotype is hypothesized to be, in part, derived from a repair defect causing UV sensitivity and, in part, from a subtle, viable basal transcription deficiency accounting for the cutaneous, developmental, and the typical brittle hair features of TTD. To understand the relationship between deficient NER and tumor susceptibility, we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline. Like the fibroblasts from the patient, mouse cells exhibit a partial NER defect, evident from the reduced UV-induced DNA repair synthesis (residual repair capacity approximately 25%), limited recovery of RNA synthesis after UV exposure, and a relatively mild hypersensitivity to cell killing by UV or 7,12-dimethylbenz[a]anthracene. In accordance with the cellular studies, TTD mice exhibit a modestly increased sensitivity to UV-induced inflammation and hyperplasia of the skin. In striking contrast to the human syndrome, TTD mice manifest a dear susceptibility to UV- and 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis, albeit not as pronounced as the totally NER-deficient XPA mice. These findings open up the possibility that TTD is associated with a so far unnoticed cancer predisposition and support the notion that a NER deficiency enhances cancer susceptibility. These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins.

The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW: 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33% of either HTK-(n = 105) or UW-(n = 99) preserved kidneys (P = NS), and in 29% of the HTK-(n = 85) and in 43% of the EC-(n = 119) preserved kidneys (P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73%, compared to 68% for UW-preserved kidneys in the UW-HTK study (P = NS); while the 3-year graft survival of HTK preserved kidneys was 70% compared to 67% for EC-preserved kidneys in the EC-HTK study (P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided.

Adenosine↗
PubMed1999

Auxiliary versus orthotopic liver transplantation for acute liver failure. EURALT Study Group. European Auxiliary Liver Transplant Registry.

BACKGROUND/AIMS/METHODS: We report 1-year results after auxiliary liver transplantation for acute liver failure in a cohort of 47 patients transplanted in 12 European centers as compared with those of 384 consecutive patients undergoing orthotopic liver transplantation for acute liver failure in the Eurotransplant area. RESULTS: One-year patient survival resp. retransplant-free patient survival did not differ between orthotopic (61%, 232/384 resp. 52%, 200/384) and auxiliary liver transplantation (62%, 29/47 resp. 53%, 25/47). One-year patient survival resp. retransplant-free patient survival after auxiliary partial orthotopic liver transplantation was 71% (25/35) resp. 60% (21/35), not significantly different from orthotopic liver transplantation (61%, 232/384 resp. 52%, 200/384), while both transplantation techniques had better 1-year patient survival resp. retransplant-free patient survival than after heterotopic auxiliary liver transplantation (33%, 4/12) (p < 0.05). Primary nonfunction was more frequent after heterotopic auxiliary liver transplantation (3/12, 25%) than after orthotopic liver transplantation (21/384, 5.5%), while the incidence did not differ between orthotopic liver transplantation and auxiliary partial orthotopic liver transplantation (3/35, 8.5%). Portal vein thrombosis was more frequent after both heterotopic auxiliary liver transplantation (5/12, 42%) and auxiliary partial orthotopic liver transplantation (5/35, 14%) than after orthotopic liver transplantation (2/384, 0.5%) (p < 0.001). Of the patients, 65% (17/26) surviving auxiliary liver transplantation for 1 year without retransplantation by orthotopic liver transplantation were free of immunosuppression within 1 year, compared with none of the patients transplanted by orthotopic liver transplantation (p < 0.01). CONCLUSIONS: Auxiliary liver transplantation, especially auxiliary partial orthotopic liver transplantation, offers an advantage over orthotopic liver transplantation in acute liver failure in terms of a chance of a life free of immunosuppression, apparently without jeopardizing chances of survival. Reduction of the incidence of primary nonfunction and vascular complications should be a focus of research in auxiliary liver transplantation. These findings need to be confirmed in a prospective study.

Adolescent↗
PubMed1999

Environmental occurrence, analysis, and toxicology of toxaphene compounds.

Toxaphene production, in quantities similar to those of polychlorinated biphenyls, has resulted in high toxaphene levels in fish from the Great Lakes and in Arctic marine mammals (up to 10 and 16 microg g-1 lipid). Because of the large variabiliity in total toxaphene data, few reliable conclusions can be drawn about trends or geographic differences in toxaphene concentrations. New developments in mass spectrometric detection using either negative chemical ionization or electron impact modes as well as in multidimensional gas chromatography recently have led researchers to suggest congener-specific approaches. Recently, several nomenclature systems have been developed for toxaphene compounds. Although all systems have specific advantages and limitations, it is suggested that an international body such as the International Union of Pure and Applied Chemistry make an attempt to obtain uniformity in the literature. Toxicologic information on individual chlorobornanes is scarce, but some reports have recently appeared. Neurotoxic effects of toxaphene exposure such as those on behavior and learning have been reported. Technical toxaphene and some individual congeners were found to be weakly estrogenic in in vitro test systems; no evidence for endocrine effects in vivo has been reported. In vitro studies show technical toxaphene and toxaphene congeners to be mutagenic. However, in vivo studies have not shown genotoxicity; therefore, a nongenotoxic mechanism is proposed. Nevertheless, toxaphene is believed to present a potential carcinogenic risk to humans. Until now, only Germany has established a legal tolerance level for toxaphene--0.1 mg kg-1 wet weight for fish.

Animals↗
PubMed1999

[Mutant mice as a model of human diseases of aging. Defective transcription and premature aging].

Mouse mutants as model for human ageing disorders. Defective transcription and premature ageing. DNA damage has been implicated in carcinogenesis and ageing. Our group examines the nucleotide excision DNA repair (NER) process, which can detect and repair various UV- and chemically-induced DNA damages, in addition to some types of oxidative DNA damage. Recently, two mouse models were generated with a defect in one of the NER genes (XPD and CSB), displaying distinctive symptoms of premature ageing. Remarkably, in both cases the NER gene plays an additional role in transcription. Research using these mouse models aims to investigate the link between premature ageing and molecular defects in NER and transcription.

Aging, Premature↗
PubMed1998

Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient mice.

To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair-deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand-break repair, and AAG-mediated base excision repair.

Animals↗