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K Sundberg

Publications and source records attributed to K Sundberg.

At least 19 recordsLinked to original sources
PubMed2006

First trimester Down syndrome screening: distribution of markers and comparison of assays for quantification of pregnancy-associated plasma protein-A.

OBJECTIVE: First trimester screening for fetal chromosomal disease is now possible using the maternal serological markers pregnancy-associated plasma protein-A (PAPP-A) and the free ss-form of human chorionic gonadotrophin (sshCG) in combination with the ultrasound marker nuchal translucency (NT) thickness. The availability of well-defined analytical methods and reference ranges for the involved parameters, and knowledge of the correlation between markers and clinical parameters, e.g. maternal weight, parity and age, are important for the design of efficient screening programs. MATERIAL AND METHODS: Women (n = 2702), with singleton pregnancies, participating in the Copenhagen First Trimester Screening Study had PAPP-A and sshCG values determined and NT measured at a gestational age of 11 to 14 weeks, as determined from crown rump length (CRL). The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and reference intervals established. Three methods for determination of PAPP-A, one manual in-house poly-monoclonal ELISA and two commercial semi-automatic double-monoclonal methods, i.e. PAPP-A for the AutoDelfia platform and PAPP-A for the Kryptor platform, were compared in 260 women. RESULTS: All markers had log-normally distributed MoMs. Gestational age independent reference intervals were established. Maternal weight should be included in risk algorithms. The semi-automated PAPP-A assays (AutoDelfia and Kryptor) gave similar values, mean difference 10.5 %, whereas the manual assay gave higher values, mean differences 50.4 % and 41.0 %, respectively, CONCLUSIONS: This calls for better standardization and a uniform quality control scheme that is focused on discriminatory ability rather than adherence to mean values from a large number of laboratories.

Biomarkers↗
PubMed2005

Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women.

OBJECTIVE: To determine the performance of screening for Down syndrome (DS) and other major chromosomal abnormalities using nuchal translucency (NT), free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a prospective study of a non-selected population. METHODS: Of 9941 women with an early ultrasound examination, NT was measured in 8622 singleton pregnancies with a gestational age between 10 + 3 and 13 + 6 weeks. beta-hCG and PAPP-A were analyzed in 6441 cases. Detection rates (DR) and false-positive rates (FPR) for the NT screening, the double test (beta-hCG and PAPP-A) and the combined test (NT and the double test) were calculated using a 1 : 250 cut-off. RESULTS: NT could be measured in 97.5% of cases. The DR for DS with NT screening alone was 75% with a FPR of only 1.8%. The double test detected 73% and the combined test 91%, for FPRs of 8.8% and 2.1%, respectively. We detected 80% of fetuses with other major chromosomal abnormalities with a combination of NT screening and other ultrasound findings. Low beta-hCG and PAPP-A values (below 0.4 MoM) were observed in 0.5% of the women including all cases of triploidy and trisomy 18 and 13. CONCLUSIONS: The performance of a screening strategy for DS using a combination of NT and the double test was superior to that using either NT or the double test alone due to a very low FPR and a higher DR.

Adult↗
PubMed2003

Amniocentesis and chorionic villus sampling for prenatal diagnosis.

BACKGROUND: A major disadvantage of second trimester amniocentesis is that the result is usually available only after 18 weeks' gestation. Chorionic villus sampling (CVS) and early amniocentesis can be done between 9 and 14 weeks and offer an earlier alternative. OBJECTIVES: The objective was to assess comparative safety and accuracy of second trimester amniocentesis, early amniocentesis, transcervical and transabdominal CVS. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2002). SELECTION CRITERIA: All randomised trials comparing amniocentesis and CVS. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality and performed data extraction. We analysed the data using RevMan software. MAIN RESULTS: A total of 14 randomised studies have been included. In a low risk population with a background pregnancy loss of around 2%, a second trimester amniocentesis will increase this risk by another 1%. This difference did not reach statistical significance, but the increase in spontaneous miscarriages following second trimester amniocentesis compared with controls (no amniocentesis) did (2.1% versus 1.3%; relative risk (RR) 1.02 to 2.52). Early amniocentesis is not a safe early alternative to second trimester amniocentesis because of increased pregnancy loss (7.6% versus 5.9%; RR 1.29, 95% CI 1.03 to 1.61) and higher incidence of talipes compared to CVS (1.8% versus 0.2%; RR 6.43, 95% CI 1.68 to 24.64).Compared with second trimester amniocentesis, transcervical CVS carries a significantly higher risk of pregnancy loss (14.5% versus 11%; RR 1.40, 95% CI 1.09 to 1.81) and spontaneous miscarriage (12.9% versus 9.4%; RR 1.50, 95% CI 1.07 to 2.11). One study compared transabdominal CVS with second trimester amniocentesis and found no significant difference in the total pregnancy loss between the two procedures (6.3% versus 7%). Transcervical CVS is more technically demanding than transabdominal CVS with more failures to obtain sample and more multiple insertions. REVIEWER'S CONCLUSIONS: Second trimester amniocentesis is safer than transcervical CVS and early amniocentesis. If earlier diagnosis is required, transabdominal CVS is preferable to early amniocentesis or transcervical CVS. In circumstances where transabdominal CVS may be technically difficult the preferred options are transcervical CVS in the first trimester or second trimester amniocentesis.

Amniocentesis↗
PubMed2002

Self-reported hand eczema: symptom-based reports do not increase the validity of diagnosis.

BACKGROUND: Hand eczema is a common skin disease that affects about 10% of the general population of working age in Sweden. The resulting long sick-leave periods and need for changes of work and re-training put an economic burden on society, and there is an interest in developing cost-effective epidemiological surveillance instruments such as a screening questionnaire. OBJECTIVES: In a search for a simple screening questionnaire for hand eczema we compared the validity of a question about the presence of hand eczema with hand eczema diagnosis based on self-reported signs. METHODS: Consecutive patients (n = 95) referred for hand eczema and people in an ongoing epidemiological survey (n = 113) participated in the study. Before seeing an experienced dermatologist they had to: (1) answer a short questionnaire about current signs and symptoms from the hands; and (2) state whether they had hand eczema on the day of examination. The minimum criteria for hand eczema diagnosed by the dermatologist ('gold standard') were erythema and papules or vesicles, or erythema and scaling and fissures/lichenification. RESULTS: Of the 208 persons examined 93 fulfilled the criteria for hand eczema according to the 'gold standard'. Hand eczema diagnosis based on clinical signs reported in the questionnaire by the participants gave a sensitivity of 0.62 and a specificity of 0.87 in comparison with the dermatologists' diagnoses. Regarding the question about current hand eczema, agreement was good between the participants' and the dermatologists' judgements, giving a sensitivity of 0.87 and a specificity of 0.79. Comparing clinical signs reported by the participants and the findings by the dermatologists, the best agreement was for fissures, with a kappa-value of 0.65 (95% CI 0.55-0.75), and the poorest was for papules with 0.47 (95% CI 0.32-0.62). CONCLUSIONS: It was difficult for the individual to identify skin signs compatible with the clinical diagnosis of hand eczema. Asking 'Do you have hand eczema?' had high sensitivity and specificity compared to the suggested gold standard for hand eczema. However, the validity of a screening questionnaire depends on the type of population investigated.

Adolescent↗
PubMed2001

First trimester screening for Down syndrome and assisted reproduction: no basis for concern.

In pregnancies obtained after assisted reproduction the false-positive rate of second trimester Down syndrome (DS) screening is increased by 1.5-3-fold. This may cause an increase in the number of amniocenteses and the fetal loss rate. The present study for the first time examined whether assisted reproductive technologies affect the results of first trimester screening. The markers PAPP-A, free beta-hCG and the nuchal translucency (NT) thickness were examined at 12-14 weeks' gestation. Screening markers in 47 in vitro fertilisation (IVF), 63 ovulation induction (OI) and 3026 spontaneously conceived singleton pregnancies were compared. The MoM (multiples of the median) value in the IVF pregnancies was 1.02 (95% CI: 0.85-1.22) for PAPP-A, 1.14 (95% CI: 0.95-1.37) for beta-hCG and 0.97 (95% CI: 0.89-1.05) for NT; the MoM value in the OI pregnancies was 0.89 (95% CI: 0.76-1.05) for PAPP-A, 1.08 (95% CI: 0.93-1.25) for beta-hCG and 1.02 (95% CI: 0.95-1.11) for NT. The first trimester marker values in assisted reproductive pregnancies and spontaneously conceived pregnancies were not significantly different. Estimated false-positive rates for a risk cut-off of 1:400 varied from 4.7% in IVF pregnancies to 5.1% in OI pregnancies. Therefore the false-positive rate in Down syndrome screening should be independent of the method of conception.

Adult↗
PubMed2001

Quality assessment in prospective nuchal translucency screening for Down syndrome.

OBJECTIVES: To develop and apply a quality control system in a Down syndrome screening study using nuchal translucency as an interventional marker. METHODS: In a prospective Down syndrome screening study fetal nuchal translucency thickness was measured in 9236 of the 10 045 examined pregnancies. For quality assessment two models were introduced: firstly, image-scoring evaluation of the nuchal translucency thickness measurements and secondly, establishment of the distributions of nuchal translucency multiples of the median over time and the influence of intervention. RESULTS: The observer variability in the image-scoring evaluation was high with a kappa value of 0.48 in the overall validation. A revised model showed better interobserver agreement with a kappa value of 0.58; however, comparing the individual criteria the differences were still unsatisfactory, i.e. we found highly significant differences in the criteria "position of the fetus" (P = 0.0026) and "magnification of the image" (P = 0.0001). Regarding the distributions of the nuchal translucency multiples of the median, the median stabilized after a short learning phase representing the practical part of the sonographer's certification to nuchal translucency screening. In groups of medians of 50 nuchal translucency multiples of the median the intergroup standard deviation decreased from 0.100-0.060 after the learning phase to 0.046 after intervention. CONCLUSIONS: When well-trained certified examiners perform nuchal translucency screening, continuous evaluation of the distribution of the nuchal translucency multiples of the median seems to be a good method to assess the quality for a center and may also be used to identify individual examiners deviating from the mean performance. The image-scoring methods we introduced cannot be recommended for quality control in a nuchal translucency screening program.

Down Syndrome↗
PubMed2000

Studies on the differential inhibition of glutathione conjugate formation of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide and 1-chloro-2,4-dinitrobenzene in V79 Chinese hamster cells.

V79 Chinese hamster cells have previously been shown to lack the capacity to detoxify the mutagenic and carcinogenic compound (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide [(+)-anti-BPDE] by Pi class glutathione transferase (GSTPi)-catalysed conjugation with GSH, although these cells contain such an enzyme [Romert, Dock, Jenssen and Jernström (1989) Carcinogenesis 10, 1701-1707; Swedmark, Romert, Morgenstern and Jenssen (1992) Carcinogenesis 13, 1719-1723; Swedmark and Jenssen (1994) Gene 139, 251-256]. Previous findings also indicate that these results do not depend on an inactive GSTPi enzyme, since V79 cells conjugate 1-chloro-2, 4-dinitrobenzene (CDNB) with GSH, but more likely on (a) factor(s) that inhibit(s) V79 GSTPi selectively [Swedmark, Jernström and Jenssen (1996) Biochem. J. 318, 533-538]. The present study demonstrates that both human and V79 recombinant GSTPi enzymes are inhibited with respect to conjugating (+)-anti-BPDE, but not CDNB, after pre-incubation with V79-cell extract, but not with MCF-7-cell extract. In addition, it was found that the inhibition is dependent on the amount of cell extract present and that the factor(s) is heat-resistant and has a molecular mass of less than 10 kDa, suggesting that the factor(s) is (are) non-proteinaceous in nature.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Comparison of cell cultures, chromosome quality and karyotypes obtained after chorionic villus sampling and early amniocentesis with filter technique.

548 cell cultures and karyotypes obtained by early amniocentesis with filtration technique (EAF) at a mean gestational age of 12 1/2 weeks were compared with 555 obtained by transabdominal chorionic villus sampling (CVS) at a mean gestational age of 11 weeks. The number of abnormal karyotypes, culture failure rate and harvest time were evaluated. The results were then compared with three similar studies from the literature evaluating early amniotic fluid cultures obtained with conventional techniques compared with chorionic villus cultures. Further, the quality of the chromosome preparations from chorionic villi and early amniotic fluid respectively was compared. More abnormal karyotypes were found among the CVS cultures, which was expected due to earlier sampling and presence of confined placental mosaicism. No ambiguous results were present after EAF. The lowest culture failure rate of 0.2 per cent was found after EAF compared with 0.9 per cent among CVS. EAF also showed a significantly lower culture failure rate when compared with the literature, where early amniocentesis (EA) had been carried out by standard techniques. The time from sampling to harvest was longer in the EAF group (mean 9.5 days) compared with CVS (mean 6.1 days), in accordance with the literature. Nevertheless, the culture time of EAF was significantly shorter than the mean of EA from the comparative studies, whereas CVS culture times showed no differences. Rates of pseudomosaicism, maternal cell contamination, single cell aberrations, number of chromosome bands, mitoses counted and number of primary cultures needed for each karyotype were also compared. We concluded that EAF carried out around 12 1/2 weeks of gestation is a successful method with a lower culture failure rate compared with CVS cultures from 11-week gestations and with a significantly lower culture failure rate when compared with EA from similar studies. EAF provides chromosome preparations of high quality, and the risk of ambiguous karyotypes is very low.

Amniocentesis↗
PubMed1999

Maternal age- and gestation-specific risk for trisomy 21.

OBJECTIVE: To provide estimates of maternal age- and gestational age-related risks for trisomy 21. METHODS: The prevalence of trisomy 21 was examined in 57,614 women who had fetal karyotyping at 9-16 weeks of gestation for the sole indication of maternal age of 35 years or more. On the basis of the maternal age distribution and the reported maternal age-related risk for trisomy 21 at birth, the expected number of trisomy 21 cases was calculated for each gestational age subgroup (9-10 weeks, 11-14 weeks and 15-16 weeks). The ratio of the observed to expected number of cases of trisomy 21 was then calculated and regression analysis was applied to derive a smoothened curve. The formula for maternal age- and gestational age-related risk was then applied to a population of 96,127 pregnancies that were examined at 10-14 weeks to calculate the expected number of trisomy 21 pregnancies, and this number was compared to the observed number of 326. RESULTS: In the 57,614 pregnancies there were 538 cases of trisomy 21. The relative prevalences of trisomy 21, compared to a prevalence of 1.0 at 40 weeks, was 10 exp(0.2718 x log(10)(gestation)2 - 1.023 x log10(gestation) + 0.9425). On the basis of the estimated maternal age- and gestational age-related risks, the expected number of trisomy 21 cases at 10-14 weeks of gestation in the 96,127 pregnancies was 329 (95% confidence interval 291-361), which was not significantly different from the observed number of 326 cases (chi2 = 0.02). CONCLUSION: The risk for trisomy 21 increases with maternal age and decreases with gestation. The prevalence of trisomy 21 at 12 and 16 weeks of gestation is higher than the prevalence at 40 weeks by 30% and 21%, respectively.

Adult↗
PubMed1998

Detoxication of carcinogenic fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1-1 variants and glutathione.

Epidemiological studies suggest that individuals differing in the expression of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polycyclic aromatic hydrocarbons (PAH). This study reports the catalytic efficiencies (k(cat)/Km) of two naturally occurring variants, GSTP1-1/I-105 and GSTP1-1/ V-105, towards a series of fjord-region diol epoxides representing potent biologically active PAH metabolites, and two GSTP1-1 mutants with Ala105 and Trp105 in the active site. The results indicate that individuals who are homozygous for the allele encoding GSTP1-1/V-105 might be more susceptible to PAH carcinogenesis due to other reasons than a reduced capacity for detoxifying diol epoxides.

Carcinogens↗
PubMed1998

Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons.

Previous studies have identified allelic variants of the human glutathione transferase (GST) Pi gene and showed that the two different encoded proteins with isoleucine (GSTP1-1/I-105) or valine (GSTP1-1/V-105) at position 105, respectively, differ significantly in their catalytic activities with model substrates. Moreover, recent epidemiological studies have demonstrated that individuals differing in the expression of these allelic variants also differ in susceptibility to tumour formation in certain organs, including such in which polycyclic aromatic hydrocarbons (PAH) may be etiological factors. In the present study the catalytic efficiencies (kcat/Km) of these GSTP1-1 variants were determined with a number of stereoisomeric bay-region diol epoxides, known as the ultimate mutagenic and carcinogenic metabolites of PAH, including those from chrysene, benzo[a]pyrene and dibenz[a,h]anthracene. In addition, GSTP1-1 mutants in which amino residue 105 is alanine (GSTP1-1/A-105) or tryptophan (GSTP1-1/W-105) have been constructed and characterized. GSTP1-1/V-105 was found to be more active than GSTP1-1/I-105 in conjugation reactions with the bulky diol epoxides of PAH, being up to 3-fold as active towards the anti- and syn-diol epoxide enantiomers with R-absolute configuration at the benzylic oxiranyl carbon. Comparing the four enzyme variants, GSTP1-1/A-105 generally demonstrated the highest kcat/Km value and GSTP1-1/W-105 the lowest with the anti-diol epoxides. A close correlation was observed between the volume occupied by the amino acid residue at position 105 and the value of kcat/Km. With the syn-diol epoxides, such a correlation was observed with alanine, valine and isoleucine, whereas tryptophan was associated with increased kcat/Km values. The mutational replacement of isoleucine with alanine or tryptophan at position 105 did not alter the enantio selectivity of the GSTP1-1 variants compared with the naturally occurring allelic variants GSTP1-1/I-105 and GSTP1-1/V-105. Since the amino acid at position 105 forms part of the substrate binding site (H-site) the effect of increasing bulkiness is expected to cause restricted access of the diol epoxide and proper alignment of the two reactants for efficient glutathionylation. In conclusion, the present study indicates that individuals who are homozygous for the allele GSTP1* B (coding for GSTP1-1/V-105) display a higher susceptibility to malignancy because of other factors than a decreased catalytic efficiency of GSTP1-1/V-105 in the detoxication of carcinogenic diol epoxides of benzo[a]pyrene or structurally related PAH.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Overexpression of stably transfected human glutathione S-transferase P1-1 protects against DNA damage by benzo[a]pyrene diol-epoxide in human T47D cells.

The (+)-anti enantiomer of benzo[a]pyrene-7,8-dihydrodiol-9, 10-epoxide (BPDE) is a potent mutagenic and carcinogenic metabolite of benzo[a]pyrene (BP), and a major fraction is conjugated with glutathione in vivo. The chemopreventive role of glutathione S-transferases (GSTs) in protecting against covalent modification of DNA and other cellular macromolecules by BPDE was modeled in human T47D and MCF-7 cell lines previously stably transfected with human GSTpi1 (hGSTP1). Cells were exposed to [3H]BPDE (30-600 nM). Dose-response experiments indicated that the high level of expression of hGSTP1-1 in the T47Dpi cell line (4411 +/- 183 milliunits/mg of cytosolic protein, using 1-Cl-2,4-dinitrobenzene as substrate), resulted in 70-90% reduction in the covalent 3H-adduct formation in DNA or RNA isolated from the GSTP1-transfected T47Dpi cell line. The lower level of hGSTP1-1 expression in the transfected MCF-7 cell line (91 milliunits/mg) provided only marginal protection against [3H]BPDE adduct formation and did not affect sensitivity to BPDE-induced cytotoxicity. Protection against BPDE-induced cytotoxicity was observed only in the T47Dpi cell line, which had an IC50 value 5.8-fold greater than that of the T47Dneo control cell line. Measurement of glutathione conjugates of BPDE indicated that the total conjugation was 5-fold higher in the GSTpi-transfected T47D line, most of which was exported into the culture medium over the 20-min exposure period. These results indicate that hGSTP1-1 protects effectively against DNA and RNA modification by BPDE, but moderate to high level expression may be required for strong protection against BPDE-induced genotoxicity and cytotoxicity.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1997

Randomised study of risk of fetal loss related to early amniocentesis versus chorionic villus sampling.

BACKGROUND: Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS. METHODS: We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal. FINDINGS: We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01). INTERPRETATION: Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion.

Abortion, Spontaneous↗
PubMed1997

Glutathione conjugation of bay- and fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferases M1-1 and P1-1.

Metabolism of polycyclic aromatic hydrocarbons in mammalian cells results in the formation of vicinal diol epoxides considered as ultimate carcinogens if the oxirane ring is located in a bay- or fjord-region of the parent compound. In the present study, individual stereoisomers of the bay-region diol epoxides of chrysene, dibenz[a,h]anthracene, and benzo[a]pyrene as well as of the fjord-region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene, and benzo[g]-chrysene have been incubated with GSH in the presence of human glutathione transferases GSTM1-1 (a mu-class enzyme) and GSTP1-1 (a pi-class enzyme). As previously shown with GSTA1-1 (an alpha-class enzyme) both M1-1 and P1-1 demonstrate considerable activity toward a number of the diol epoxides studied, although a great variation in catalytic efficiency and enantioselectivity was observed. With GSTM1-1, the bay-region diol epoxides, in particular the syn-diastereomers were in most cases more efficiently conjugated with GSH than the fjord-region analogues. GSTM1-1 demonstrated an enantioselectivity ranging from no preference (50%) to high preference (> or = 90%) for conjugation of the enantiomers with R-configuration at the benzylic position of the oxirane ring. With GSTP1-1, the enzyme demonstrated appreciable activity toward both bay- and fjord-region diol epoxides and, in most cases, a preference for the anti-diastereomers. In contrast to GSTM1-1 and as previously shown for GSTA1-1, GSTP1-1 showed an exclusive preference for conjugation of the enantiomers with R-configuration at the benzylic oxirane carbon. With both GSTM1-1 and GSTP1-1, the chemically most reactive diol epoxide, the (+)-syn-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,-10-tetrahydrobenzo[a]pyrene (BPDE), was the best substrate. As for GSTA1-1, no obvious correlation between chemical reactivity or lipophilicity of the compounds and catalytic efficiencies was observed. Molecular modeling of diol epoxides in the active sites of GSTP1-1 and -A1-1 is in agreement with the assumption, based on functional studies, that the H-site of GSTA1-1 [Jernström et al. (1996) Carcinogenesis 17, 1491-1498] can accommodate stereoisomers of different sizes. Further, modeling of the enantiomers of anti- and syn-BPDE in the active site of GSTP1-1 provides an explanation for the exclusive preference for the enantiomers with R-configuration at the benzylic oxirane carbon. These isomers could be snuggly fitted in the H-site close to the GSH sulfur, whereas those with opposite stereochemistry could not.

Bay-Region, Polycyclic Aromatic Hydrocarbon↗
PubMed1996

Early filtration amniocentesis for further investigation of mosaicism diagnosed by chorionic villus sampling.

In 44 pregnancies where chorionic villus sampling (CVS) had shown mosaicism, early amniocentesis using a filter technique was carried out with the purpose of clarifying the fetal karyotype and reducing the waiting time for a final karyotype. Since the filter technique increases the cell yield of the amniotic fluid sample, it was hypothesized that this technique could be applied as soon as the mosaic CVS result was available, without compromising the culturing of the amniotic fluid cells. The mean gestational age at amniocentesis was 12.5 weeks and the mean gestational age at the time of the final karyotype was 13.9 weeks. All amniotic fluid sampling procedures and cultures were successful. Four pregnancies were terminated due to abnormal karyotypes (9.1 per cent). Two spontaneous abortions occurred in the second trimester (5.0 per cent), and one infant was lost at term due to unexplained intrapartum death. The total fetal loss rate was 7.5 per cent. This loss rate is concordant with other reported series where the outcome of pregnancies with placental mosaicism has been evaluated. We conclude that early amniocentesis with the filtration technique is a useful method for follow-up on CVS, mosaicism, providing results prior to 14 weeks of gestation.

Adult↗
PubMed1995

Alpha-fetoprotein and acetylcholinesterase activity in first- and early second-trimester amniotic fluid.

Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase activity (AChE) are described for gestational weeks 11-14 using rocket gel immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19) enzyme antigen immunoassay for AChE activity measurement. The normal ranges were established by the examination of 281 amniotic fluid samples from 281 normal pregnancies. AFP was found to increase from a median level of 14.0 MIU/l at 11 weeks to a maximum at 13 weeks (median = 18.0 MIU/l) (P < 0.05), thereafter falling (not significant). No AChE test result exceeded 4.8 nkat/l. In addition, AFP and AChE values for three cases of fetal malformation, identified by the biochemical analyses of amniotic fluid, are given. These cases included two fetuses with a neural tube defect and one fetus with an abdominal wall defect. Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and AChE values were all high.

Abdominal Muscles↗
PubMed1995

Early amniocentesis.

Amniocentesis before 15 weeks has been introduced in many prenatal diagnosis centres. There are, however, major anatomical differences between the appearance of fetus at 15-16 weeks, when amniocentesis has normally been performed, and in the first and early second trimester. This is mainly because of the presence of extraembryonic coelome and the relatively small amount of amniotic fluid in early pregnancy. Several small cohort studies have indicated no increased fetal loss rate with early amniocentesis. Others have suggested an increased risk of respiratory distress among the newborn. The only randomized study published, however, found a significantly increased rate of fetal losses after early amniocentesis. This incomplete study indicates the urgency of further randomized studies of early amniocentesis. A randomized study comparing early amniocentesis with transabdominal chorionic villus sampling is being undertaken at our centre in Copenhagen using a filter method that reduces the volume of fluid needed for karyotyping.

Amniocentesis↗