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H P Noteborn

Publications and source records attributed to H P Noteborn.

At least 19 recordsLinked to original sources
PubMed2001

Assessment of the food safety issues related to genetically modified foods.

International consensus has been reached on the principles regarding evaluation of the food safety of genetically modified plants. The concept of substantial equivalence has been developed as part of a safety evaluation framework, based on the idea that existing foods can serve as a basis for comparing the properties of genetically modified foods with the appropriate counterpart. Application of the concept is not a safety assessment per se, but helps to identify similarities and differences between the existing food and the new product, which are then subject to further toxicological investigation. Substantial equivalence is a starting point in the safety evaluation, rather than an endpoint of the assessment. Consensus on practical application of the principle should be further elaborated. Experiences with the safety testing of newly inserted proteins and of whole genetically modified foods are reviewed, and limitations of current test methodologies are discussed. The development and validation of new profiling methods such as DNA microarray technology, proteomics, and metabolomics for the identification and characterization of unintended effects, which may occur as a result of the genetic modification, is recommended. The assessment of the allergenicity of newly inserted proteins and of marker genes is discussed. An issue that will gain importance in the near future is that of post-marketing surveillance of the foods derived from genetically modified crops. It is concluded, among others that, that application of the principle of substantial equivalence has proven adequate, and that no alternative adequate safety assessment strategies are available.

Genetic Engineering↗
PubMed2000

Chemical fingerprinting for the evaluation of unintended secondary metabolic changes in transgenic food crops.

A common element in designed guidelines for assessment of the food safety of transgenic crops is centred on a comparative analytical analysis with conventionally bred crop plants, assuming that these products have a long history of safe use (i.e. OECD-principle of substantial equivalence). In this study we examine the utility of an off-line combination of 400 MHz proton (1H)-NMR spectroscopy and liquid chromatography (LC) for the multi-component comparison of low-molecular weight compounds (i.e. chemical fingerprinting) in complex plant matrices. The developed NMR-methodology can contribute to the demonstration of substantial equivalence by its ability to compare possible compositional alterations in a novel food crop with respect to related non-transgenic reference lines. In this respect a hierarchical approach is proposed by comparing the chemical fingerprints of the transgenic crop plant to those of: (1) isogenic parental or closely related lines bred at identical and multiple sites; (2) extended ranges of commercial varieties of that plant; and (3) downstream processing effects. This is of importance to assess the likelihood that some of the statistical differences in a transgenic crop plant may be false positives due to chance alone or arose from natural genetic and/or physiologic variations.

Animals↗
PubMed2000

Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diets containing purified genistein or genistein-rich soya protein.

The isoflavonoid genistein inhibits mitosis and increases apoptosis in a variety of tumour cell lines in vitro, and may exert anticarcinogenic effects in vivo. To assess its effects on the colon, rats were fed a semi-synthetic control diet, or similar diets enriched with genistein (0.25 g/kg), either as the pure isoflavone or as part of a soya protein isolate, for 7 days before receiving subcutaneous injections of saline or 1,2-dimethylhydrazine (DMH). After 48 h, rats given saline were killed and samples of their small and large intestinal mucosa were obtained for assessment of crypt cell mitosis and apoptosis by visual analysis of isolated intact crypts. Rats given DMH were fed control diet and killed after 48 h for assessment of crypt cytokinetics or maintained for 42 days then killed and their colonic mucosa analysed for aberrant crypt foci (ACF). Two further groups were given control diet before DMH, followed by the genistein or soya-based diet for 42 days before assessment of ACF. Neither genistein nor soya protein isolate had a significant effect on crypt cell mitosis or apoptosis in untreated rats, or on the proliferative response to treatment with DMH. However, consumption of pure genistein or the soya protein isolate before treatment with DMH was associated with a 3-fold (P < 0.001) or 2-fold (P < 0.05) increase, respectively, in ACF in the distal colon. There was no significant effect of genistein or soya protein isolate given after DMH treatment. We conclude that genistein has no detectable effect on colonic crypt mitosis or apoptosis in the rat in vivo, but that it promotes induction of ACF by an as yet undefined mechanism when fed immediately before treatment with DMH.

1,2-Dimethylhydrazine↗
PubMed1997

Oral absorption and metabolism of quercetin and sugar-conjugated derivatives in specific transport systems.

The intestinal transport and metabolism of quercetin and various sugar-conjugates were quantified in in vitro and in vivo model systems. The nature of the sugar moiety at the C3 and C4' position had no significant effect on the rate of transport. At the 10 microM level, quercetin and glycosides with sugars at position 3 were determined to be glucose transport carrier inhibitors.

Absorption↗
PubMed1994

Preparation and characterization of albumin-heparin microspheres.

Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsphere stabilization in one step. The first technique was superior since it allowed better control over the composition and the homogeneity of the microspheres. Microspheres could be prepared with a diameter of 5-35 microns. The size could be controlled by adjusting the emulsification conditions. The degree of swelling of the microspheres was sensitive to external stimuli, and increased with increasing pH and decreasing ionic strength of the medium.

Albumins↗
PubMed1994

A reversed-phase high-performance liquid chromatographic method for the determination of Clanfenur in rat and human plasma.

A selective and specific high-pressure liquid chromatographic (HPLC) method for the simultaneous assay of Clanfenur and its metabolites in biological fluids of interest has been developed which is suitable for routine analysis, using micro volumes (0.1 ml) of plasma samples only. After protein precipitation the extract is analysed by reversed-phase HPLC with UV detection. Excellent recovery, linearity, accuracy and precision (less than 5% for plasma) are achieved by the assay which is able to quantify Clanfenur and its metabolites in plasma at concentrations between 0.025 and 5.0 mg l-1.

Animals↗
PubMed1993

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland.

The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M(r) range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [125I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (Ka of 4.7 +/- 0.2 x 10(9) M-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M(r) 24,000. The functional status of PRL- and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.

Animals↗
PubMed1992

Identification of luteinizing hormone-like proteins in the ovine pineal gland.

A chemical analysis was instigated to investigate the identity of the luteinizing hormone (LH)-like immunoactivity present in ovine pineal protein homogenates. Isolation of pineal LH-like material was accomplished using a 0.1 M ammonium sulphate (pH 4.0) extraction followed by anion-exchange chromatography. The resulting 3.0 M ammonium sulphate precipitate containing 70% of the LH-like immunoactivity was refractionated by cation-exchange and Sephadex G-100 chromatography. Analysis of the pattern of recovered LH-like immunoactivity in the Sephadex G-100 eluate indicated the presence of molecular weight (MW) less than 60,000 besides MW 21,000 species of LH-like proteins. Bioactivity was tested in the rat Leydig cell steroidogenesis assay. In terms of steroid production, the activity was associated with the MW 21,000 LH-like proteins only. Further purification by CM-Sephadex chromatography and gel permeation HPLC was conducted in order to determine whether the physicochemical properties of pineal LH-like material represented endogenous LH, synthesized and released by the ovine pituitary. It is concluded by a variety of means, including polyacrylamide gel electrophoresis, and amino acid and carbohydrate analyses, that at least two molecular forms of immunoactive LH-like proteins occur in ovine pineal tissue. The MW 21,000 forms showed much similarity with ovine adenohypophyseal LH or with a complex mixture of its subunits. These observations contribute to the understanding of endocrine-endocrine transducing events that may occur in this organ.

Animals↗
PubMed1991

Cellular pharmacokinetics of carboplatin and cisplatin in relation to their cytotoxic action.

We have studied the cellular pharmacokinetics of carboplatin (CBDCA), as part of the evaluation of the antitumor activity of CBDCA in cancers limited to the peritoneal cavity in comparison with cisplatin (cDDP). The uptake of CBDCA into L1210 (lymphosarcoma), CC531 (colonic carcinoma), COV413.B (human ovarian carcinoma) and NB1 (human neuroblastoma) cells was 1.5 to 13 times lower than the uptake of cDDP. The uptake of CBDCA into human ovarian carcinoma cells, taken directly from patients, was also 8-20 times lower than cDDP. Platinum concentrations, expressed as a percentage of the total intracellular Pt concentration, were similar for CBDCA and cDDP in cytosol and nucleus/membrane fractions. A second major difference between the drugs was their binding to DNA. Less CBDCA-DNA than cDDP-DNA adducts were formed after incubation at equimolar amounts of drug with isolated salmon sperm DNA (5-25 times less). A 16-69 times higher concentration of CBDCA than cDDP was needed to induce similar changes in cell growth activity (50% [3H]thymidine inhibition) in CC531 and COV413.B cells, indicating that equitoxicity can only be achieved when tumor cells are exposed to higher concentrations of CBDCA than cDDP. Similar toxicity was achieved in CC531 cells after incubation with a 16-fold higher CBDCA dose than cDDP. Comparable intracellular platinum concentrations, however, were obtained with a 10-fold higher CBDCA dose, suggesting that cellular pharmacokinetics of the drugs are different. Regarding drug uptake and pharmacokinetics the mechanism of action of CBDCA differed from cDDP at a cellular level.

Animals↗
PubMed1989

Partial purification of a polypeptide extract derived from ovine pineal that suppresses the growth of human melanoma cells in vitro.

A combination of gelfiltration and reverse-phase high performance liquid chromatography with postcolumn antitumour assay has been developed. A melatonin insensitive human melanoma cell strain was used to guide the purification of the antitumour effect of an ovine pineal aqueous extract (MW 1,000 to 10,000) that possessed the ability to decrease the hypophysiotropic activity of rat and mice hypothalami in vitro. This allows a specific identification of a pineal factor (MW 2,000 to 6,000) that inhibits the growth of human melanoma cells at a dose of 0.47 mg/ml medium. It was shown that the activity of this pineal compound differs from structures known to be present in the pineal, such as melatonin, pteridines, and beta-carbolines. There appears to be evidence for a peptidic nature of this pineal antitumour factor.

Animals↗
PubMed1988

Partial purification of (a) low molecular weight ovine pineal compound(s) with an inhibiting effect on the growth of human melanoma cells in vitro.

An in vitro human melanoma cell assay was used to work up the partial purification of (a) low molecular weight (MW) substance(s) from aqueous extracts of ovine pineal tissue shown to contain a growth-inhibiting activity. A combination of paper chromatography, ion-exchange and reverse-phase high performance liquid chromatography with post-column antitumor assay has been developed. This allows a specific identification of an ovine pineal factor (MW less than 500) which inhibits the growth of human melanoma cells in vitro. The substance was partially purified to about 1,000 times as compared to the IC100-value of the starting material (retentate 5). The growth inhibition of human melanoma cells in culture was complete at a dose of 0.1 microgram/ml of purified pineal factor(s). It was demonstrated that the activity of this pineal compound differs from some substances known to be present in the pineal, such as melatonin, serotonin, peridines and beta-carbolines. The activity was not destroyed by treatment with proteolytic enzymes.

Animals↗
PubMed1988

Studies on a high molecular weight luteinizing hormone release stimulating factor of the ovine pineal gland.

Former work has shown that crude extracts of ovine pineal glands probably exert a stimulating activity on the release of gonadotropins of anterior pituitaries in vitro. By aqueous extraction followed by ultrafiltration through anisotropic membranes high Mr (above 100,000 daltons) fractions were obtained, which exhibit a stimulating effect on the levels of gonadotropins in the medium of either cultured pituitary cells or anterior hemipituitaries in short-term culture. Partial purification of a pineal luteinizing hormone release stimulating factor was accomplished by Sephadex G-150 filtration with a biopotency of 226 +/- 23 micrograms LH-RP-1 equivalents per mg protein and without an affinity for binding to anti-LHRH or anti-LH antibodies. The present data substantiate that high Mr forms, slightly heavier than authentic pituitary LH (Mr 23,000 daltons) and therefore not identical to the hypothalamic decapeptide LH-RH, represent ovine pineal factors which can increase the concentration of LH in the medium of cultured anterior pituitaries, but does not influence the secretion of prolactin in vitro.

Animals↗
PubMed1988

Purification and characterization of DSIP-like material from ovine pineal glands: possible peptide-protein interaction.

The nonapeptide delta-sleep-inducing peptide (DSIP) has been isolated from venous blood of rabbits induced to sleep. Numerous reports have described sleep as well as extra-sleep effects. Radiochemical and immunochemical data suggest a relationship of DSIP with the pineal gland supported by interactions of this peptide with pineal functions such as the serotonin N-acetyltransferase activity. In order to demonstrate the natural occurrence of DSIP-like material associated with high Mr proteins in the ovine pineal, organs were water-extracted and fractionated by ultrafiltration and gel filtration. Radioimmunoassay (RIA) for DSIP-like fragments of the fractions revealed considerable amounts of pineal DSIP-like immunoreactivity (DSIP-LI) apparently existing in small as well as large molecular forms. Acidification of large DSIP-LI forms resulted in the elution from Sephadex G-50 of Mr less than or equal to 1,000 DSIP-like material. This free DSIP-LI form coeluted with the synthetic DSIP nonapeptide from microBondapak C18 on high-performance liquid chromatography. The results, therefore, appear to indicate the presence of a (biospecific) noncovalent intermolecular interaction of DSIP (1-9) with proteins (Mr greater than or equal to 10,000) of the ovine pineal gland.

Animals↗
PubMed1988

Characterization of a neurohypophyseal hormone-like activity isolated from ovine pineal glands.

The milk-ejecting response of lactating mouse mammary gland tissue to ovine pineal extracts indicated the presence of a neurohormone-like bioactivity in this tissue. After successive fractionation on gel permeation chromatography and reversed-phase liquid chromatography (HPLC) in conjunction with radioimmunoassays (RIA), it was demonstrated that the milk-ejection response to ovine pineal components with an Mr less than 1,000 corresponded to a biologically active peptide sequence that probably differs from that of arginine vasopressin, arginine vasotocin, and oxytocin and from peptides with a COOH-terminal Pro-Arg-Gly-amide ending. Gel permeation chromatography in formic acid appeared also to indicate the presence of a noncovalent interaction of the neurohormone-like bioactivity with proteins (Mr greater than 25,000) of the pineal.

Animals↗
PubMed1987

Modified forms of vasopressin and oxytocin in a bovine pineal preparation.

A bovine pineal acid extract displays a vasotocin-like bioactivity in several bioassays, and is recognized by antibodies against the Pro-Arg-Gly-amide ending common to vasopressin and vasotocin. By using molecular sieve filtration and reversed-phase HPLC, a vasopressin- and oxytocin-like peptide was isolated from this pineal preparation, while no evidence for a vasotocin-like peptide was obtained. The isolated neuropeptides contain a modified amino acid at position 2. This structural difference with authentic pituitary vasopressin and oxytocin may alter their biological and immunological properties, which have been interpreted as vasotocin-like, and thus underlies the controversy concerning the existence of vasotocin in the mammalian pineal gland.

Amino Acid Sequence↗
PubMed1987

Growth-inhibiting effect of crude pineal extracts on human melanoma cells in vitro is different from that of known synthetic pineal substances.

The effect was studied of a number of synthetic indoleamines, pteridines, beta-carbolines, of AVT and of crude extracts from rat and ovine pineal glands on human melanoma cells in vitro. The identified pineal substances as well as some of their analogues showed an inhibitory effect only at non-physiologically high concentrations. However, crude pineal extracts were more active than the synthetic pineal substances tested. They contain a compound which may have a tumor-inhibiting potency comparable to that of methotrexate but a different mechanism of action.

Animals↗