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B Norgaard-Pedersen

Publications and source records attributed to B Norgaard-Pedersen.

At least 19 recordsLinked to original sources
PubMed2006

The relation of germ cells per tubule in testes, serum inhibin B and FSH in cryptorchid boys.

At bilateral orchiopexy bilateral biopsies may be indicated to determine fertility potential. It is currently unknown if the serum inhibin B levels at time of orchiopexy reflect the testicular status of the bilaterally cryptorchid child. The aim of this study was to relate the results of inhibin B and FSH measurements with testicular biopsy parameters in bilateral cryptorchid boys. Included were 25 boys with bilateral cryptorchidism, median 2.5 years (9 months to 5.5 years) at surgery for bilateral cryptorchidism with simultaneous testicular biopsies, and blood sample for inhibin B and FSH. The number of spermatogonia and gonocytes was measured in 100 tubular transverse sections, the S/T and the mean-S/T of the patient was found, and expressed as percent of lowest normal value. Inhibin B and FSH were measured and related to age-specific values. Forty percent (10/25) of the patients had very low mean-S/T (mean-S/T<10% of lowest normal-value). Inhibin B was decreased in 24% (6/25) of the patients, all with decreased mean-S/T, predominantly with a mean-S/T<10% of lowest normal-value (p<0.05). There was a negative correlation between inhibin B and FSH (p<0.05). In cases of mean-S/T<10% of lowest normal-value and decreased inhibin B, we found increased FSH in 9% (2/22) of the patients and hypergonadotropic hypogonadism was suspected. Low FSH was found in 5% (1/22) of the patients and hypogonadotropic hypogonadism was suspected. Low inhibin B predicts a serious condition in respect of infertility. Low FSH and inhibin B indicates examination for hypogonadotropic hypogonadism. In bilateral cryptorchid boys inhibin B levels correlated negatively to FSH.

Child, Preschool↗
PubMed1999

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome.

The proform of eosinophil major basic protein (proMBP), the most abundant protein in the eosinophil specific granule, is synthesized by the placenta and secreted into the maternal circulation, where it is found complex-bound to pregnancy-associated plasma protein-A (PAPP-A) and other proteins. We examined the potential of proMBP as a maternal serum marker for fetal Down syndrome (DS) by determining its maternal serum concentration (MSpMBP) in 25 Down syndrome (DS) pregnancies and 152 control pregnancies in the first trimester, and in 105 DS pregnancies and 156 control pregnancies in the second trimester. The median (95 per cent confidence interval) MSpMBP MoM in DS pregnancies (n=15) was 0.66 (0.49-0.79) in gestational weeks 5-9; 1.06 (0.71-1.97) in weeks 10-12 (n=10) and 1.62 (1.18-1.98) in weeks 14-20 (n=105). Using parameterized receiver operator characteristics analysis for proMBP as a single marker for DS, detection rates (DRs) of 22 per cent and 38 per cent, for false-positive rates (FPRs) of 5 per cent, were found in weeks 5-9 (using MSpMBP</=cut-off) and weeks 14-20 (using MSpMBP>/=cut-off), respectively. When age and MSpMBP were used as markers in combination, a DR of 36.8 per cent for an FPR of 5.5 per cent was obtained in weeks 5-9 using a risk cut-off of 1:250. In weeks 14-20 the DR was 48.4 per cent for an FPR of 5.3 per cent using the same risk cut-off. This makes proMBP a marker comparable in diagnostic efficiency to human chorionic gonadotrophin (hCG), and exceeding that of alpha-fetoprotein (AFP) and unconjugated oestriol (uE3), in the second trimester.

Aging↗
PubMed1999

SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. International Prenatal Screening Research Group.

We conducted a study to determine the value of serum pregnancy-specific beta-1-glycoprotein (Schwangerschafts protein 1, SP1) as an antenatal screening test for Down syndrome in the first trimester. Serum samples collected from women at 8 to 14 weeks of pregnancy, immediately prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from 96 women with Down syndrome pregnancies (cases) and from 480 women with unaffected pregnancies (controls). Cases and controls were ascertained at 21 obstetric centres in nine countries. Each case was matched with five controls for maternal age (same five-year age groups), duration of storage of the serum sample (same calendar year) and gestational age (usually the same week of pregnancy). The levels of SP1 were lower in pregnancies associated with Down syndrome: the median level was 0.86 multiples of the median level in the controls (95 per cent confidence interval 0.76 to 0.97). This difference, though statistically significant, was not large enough for SP1 to be a useful marker in screening, at least from 10 weeks onwards where most of our data lie.

Biomarkers↗
PubMed1995

Successive organophosphate inhibition and oxime reactivation reveals distinct responses of recombinant human cholinesterase variants.

To explore the molecular basis of the biochemical differences among acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and their alternative splicing and allelic variants, we investigated the acylation phase of cholinesterase catalysis, using phosphorylation as an analogous reaction. Rate constants for organophosphate (DFP) inactivation, as well as for oxime (PAM)-promoted reactivation, were calculated for antibody-immobilized human cholinesterases produced in Xenopus oocytes from natural and site-directed variants of the corresponding DNA constructs. BuChE displayed inactivation and reactivation rates 200- and 25-fold higher than either product of 3'-variable AChE DNAs, consistent with a putative in vivo function for BuChE as a detoxifier that protects AChE from inactivation. Chimeric substitution of active site gorge-lining residues in BuChE with the more anionic and aromatic residues of AChE, reduced inactivation 60-fold but reactivation only 4-fold, and the rate-limiting step of its catalysis appeared to be deacylation. In contrast, a positive charge at the acyl-binding site of BuChE decreased inactivation 8-fold and reactivation 30-fold. Finally, substitution of Asp70 by glycine, as in the natural 'atypical' BuChE variant, did not change the inactivation rate yet reduced reactivation 4-fold. Thus, a combination of electrostatic active site charges with aromatic residue differences at the gorge lining can explain the biochemical distinction between AChE and BuChE. Also, gorge-lining residues, including Asp70, appear to affect the deacylation step of catalysis by BuChE. Individuals carrying the 'atypical' BuChE allele may hence be unresponsive to oxime reactivation therapy following organophosphate poisoning.

Acetylcholinesterase↗
PubMed1994

Overexpressed monomeric human acetylcholinesterase induces subtle ultrastructural modifications in developing neuromuscular junctions of Xenopus laevis embryos.

Formation of a functional neuromuscular junction (NMJ) involves the biosynthesis and transport of numerous muscle-specific proteins, among them the acetylcholine-hydrolyzing enzyme acetylcholinesterase (AChE). To study the mechanisms underlying this process, we have expressed DNA encoding human AChE downstream of the cytomegalovirus promoter in oocytes and developing embryos of Xenopus laevis. Recombinant human AChE (rHAChE) produced in Xenopus was biochemically and immunochemically indistinguishable from native human AChE but clearly distinguished from the endogenous frog enzyme. In microinjected embryos, high levels of catalytically active rHAChE induced a transient state of over-expression that persisted for at least 4 days postfertilization. rHAChE appeared exclusively as nonassembled monomers in embryos at times when endogenous Xenopus AChE displayed complex oligomeric assembly. Nonetheless, cell-associated rHAChE accumulated in myotomes of 2- and 3-day-old embryos within the same subcellular compartments as native Xenopus AChE. NMJs from 3-day-old DNA-injected embryos displayed fourfold or greater overexpression of AChE, a 30% increase in postsynaptic membrane length, and increased folding of the postsynaptic membrane. These findings indicate that an evolutionarily conserved property directs the intracellular trafficking and synaptic targeting of AChE in muscle and support a role for AChE in vertebrate synaptogenesis.

Acetylcholinesterase↗
PubMed1990

Maternal serum alpha-fetoprotein screening for open neural tube defects in twin pregnancies.

Data on maternal serum alpha-fetoprotein (AFP) levels at 13-24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2.5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent. Using a 5.0 MoM cut-off level to maintain a similar false-positive rate to that found among singleton pregnancies at 16-18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.

Anencephaly↗
PubMed1988

An enzyme antigen immunoassay for the determination of neuron-specific enolase in serum samples.

A method is presented for the detection and quantification of neuron-specific enolase (NSE) in serum samples. It is an enzyme antigen immunoassay (EAIA), relying on specific antibodies to 'catch' the enzyme on a solid support (ELISA-plate) whereafter the enzymatic activity of the immunocaptured enzyme is determined, by coupling the reaction to lactate dehydrogenase. The oxidation of NADH to NAD is followed at 340 nm in an ELISA photometer. The method is proven to work well and is able to measure the low amounts of NSE present in serum samples from normal individuals. It does not require labelling of neither antigen nor antibody, and is therefore superior to the commercially available radioimmunoassay (RIA). The method will also work with monoclonal antibodies towards the enzyme as demonstrated by preliminary observations.

Animals↗
PubMed1987

Immunochemical determination of acetylcholinesterase in amniotic fluid--an evaluation of eleven monoclonal antibodies.

Eleven monoclonal antibodies and a polyclonal rabbit antiserum were evaluated with respect to reactivity with acetylcholinesterase (AChE, EC 3.1.1.7) from erythrocytes and brain. Employing our enzyme antigen immunoassay for AChE five selected antibodies were evaluated with regard to their clinical usefulness in the prenatal diagnosis of neural tube defects (NTD). Of these, one antibody preferentially bound the enzyme from human brain, and discerned better than the others pathological samples (anencephaly, spina bifida and encephalocele) from normal ones. With this antibody no false positive values were obtained even if amniotic fluid samples were blood contaminated.

Acetylcholinesterase↗
PubMed1987

An inhibitory monoclonal antibody to human acetylcholinesterases.

The monoclonal antibody AE-2 raised against acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) from human erythrocytes is shown to inhibit the enzyme activity. The reaction of the antibody with a structural epitope is investigated further. The epitope resides on monomeric, dimeric and tetrameric species of the enzyme. The rate of phosphorylation of the enzyme by diisopropylfluorophosphate was not affected by the antibody. On the other hand, inhibitors directed towards the anionic site(s) competed with antibody binding, suggesting that one of these is the epitope. The titration with antibody is biphasic and yields about 80% inhibition even in the presence of a large excess of antibody. Inhibition is fully reversible upon dilution, in a time-dependent manner. AE-2 also inhibited human adult and fetal brain acetylcholinesterase (to the same extent). However bovine brain acetylcholinesterase was inhibited to a lesser extent and rat brain acetylcholinesterase did not interact with the antibody. Butyrylcholinesterase (EC 3.1.1.8) also showed no reactivity towards the antibody.

Acetylcholinesterase↗
PubMed1987

Determination of maternal serum acetylcholinesterase in pregnancies with fetal neural tube defects.

We have investigated the occurrence of acetylcholinesterase (AChE) (E.C. 3.1.1.7) in fetal serum, amniotic fluid and maternal serum using an immuno-chemical assay-technique employing both polyclonal and monoclonal antibodies. Fetal serum had increased amounts of AChE, which is due to an increase in the 10.5S form of the enzyme. This form was also found in amniotic fluids of pregnancies with a fetal neural tube defect (NTD), but not in normal amniotic fluid. The increase in amniotic fluid AChE was however, not reflected in the maternal serum.

Acetylcholinesterase↗
PubMed1986

Normal human serum contains two forms of acetylcholinesterase.

We have produced antibodies (polyclonal and monoclonal) against acetylcholinesterase, and used them for immuno-chemical demonstration and quantification of the enzyme in serum. The concentration was 1.2 IU/l. The antibodies were shown not to cross-react with human butyrylcholinesterase, using pure preparations of the enzymes. The serum acetylcholinesterase could be purified using affinity chromatography. The resulting preparation was analyzed using sucrose density gradient centrifugation. Two forms of the enzyme with sedimentation constants of 10.9S and 7.6S were observed, both reacted equally well with monoclonal antibodies towards acetylcholinesterase indicating a common epitope.

Acetylcholinesterase↗
PubMed1983

Radiocrossed immunoelectrophoretical heterogeneity of beta 2-microglobulin in blood from patients with germ cell tumors and with colorectal cancer.

A new sensitive radiocrossed immunoelectrophoretic method has been used to analyse beta 2-microglobulin heterogeneity in serum samples from 20 healthy controls, 127 patients with germ cell tumors (GCT) (102 testicular, 15 mediastinal and 10 infantile GCT) and 90 patients with colorectal cancer. Overall, 95% of cancer patients showed an abnormal beta 2-microglobulin pattern (precipitate with beta 1 or alpha 2 mobility before treatment) whereas all healthy controls only had one normal precipitate in the beta 2 region, The beta 2-microglobulin heterogeneity was correlated with disease stage in both GCT and colorectal cancer, and to some extent also with the outcome. The exact clinical relevance of beta 2-microglobulin heterogeneity in cancer patients is still unknown. The phenomenon may be due to proteolytic enzymes, increased turnover of surface membrane constituents, complex formation between tumor antigen and beta 2-microglobulin, polymers of beta 2-microglobulin or activation of the reticuloendothelial system.

Colonic Neoplasms↗
PubMed1977

Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein.

Extracts of glioblastomas and meningiomas were analysed by quantitative immunoelectrophoresis for the presence of foetal brain antigens and tumour-associated antigens, and levels of 2 normal brain-specific proteins were also determined. The following antibodies were used: monospecific anti-S-100 (glia specific); monospecific anti-GFA (glial fibrillary acidic protein), (astroglia specific); polyspecific anti-foetal brain (12-16th week of gestation); a polyspecific anti-glioblastoma antiserum, absorbed with insolubilized serum, haemolysate and normal brain extract; polyspecific anti-alpha-foetoprotein; and monospecific anti-ferritin. Using the antibodies raised against the tumours, several antigens not present in foetal or adult normal brain were found in the glioblastomas and the meningiomas. These antigens cross-reacted with antigens present in normal liver and were therefore not tumour-associated. S-100 was found in glioblastomas in approximately one tenth the amount in whole brain homogenate, whereas GFA was found 2-4 times enriched. The 2 proteins were absent in meningiomas. The possible use of the GFA protein as a marker for astroglial neoplasia is discussed. Five foetal antigens were found in foetal brain, but none in the tumours. alpha-Foetoprotein could only be demonstrated in foetal tissue extracts, including foetal brain, but not in tumours. Ferritin was detected in all tumour extracts, although the amounts determined were unrelated to histological tumour type.

Antigens, Neoplasm↗
PubMed1976

Serum alpha-fetoprotein as a marker for the effect of post-operative radiation therapy and/or chemotherapy in eight cases of ovarian endodermal sinus tumour.

The clinical pathological findings of eight cases of ovarian endodermal sinus tumour (yolk sac tumour) are presented. Histological exmination in all eight cases showed a typical endodermal sinus tumour pattern, and in six of the patients other tumour elements such as dysgerminoma, choriocarcinoma, malignant teratoma, endometriosis, and a dermoid cyst were also found. Six patients had increased serum alpha-fetoprotein concentration in the post-operative period, and two patients had a normal concentration 27 and 35 days after operation, respectively. In all cases except one, a close correlation between serum alpha-fetoprotein and progression or regression of tumour was found. Serum alphafetoprotein was thus found to be a reliable parameter in post-operative radiation and/or chemotherapy (VAMBLE). In one patient who died 10 months after operation with widespread endodermal sinus tumour growth, only a small terminal increase in serum alpha-fetoprotein concentration was found. Four of the eight women are still alive with normal alpha-fetoprotein concentration, and without clinical evidence of tumour disease.

Adolescent↗