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Biomedical subjects

L Jacobsen

Publications and source records attributed to L Jacobsen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Whey hydrolysate compared with cow's milk-based formula for weaning at about 6 months of age in high allergy-risk infants: effects on atopic disease and sensitization.

Ninety-one high atopy-risk infants were prospectively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization. They were randomized into one of two feeding groups, i.e., a hydrolyzed, ultrafiltered cow's milk whey formula, Profylac (n = 32), or an ordinary cow's milk formula (n = 39), for 12 months, started after exclusive breast-feeding for 0-9 (median 6.0) months. Lactating mothers avoided milk, egg, and fish, as did the infants up to 12 months of age. Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group. All infants were followed-up by questionnaires, physical examinations, skin prick tests, and determination of serum total IgE and cow' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups. However, all three infants who developed cow's milk allergy with skin symptoms belonged to the cow's milk formula group. The skin prick test with whey hydrolysate was negative in all, while with cow's milk it was positive in eight infants. Growth was similar in the three groups. The study comprises too few infants to allow us to make statistically based statements. However, the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden.

Animals↗
PubMed1995

Crystallisation and preliminary X-ray analysis of the receptor-binding domain of human and bovine alpha 2-macroglobulin.

The receptor-binding domains (RBDs) of human and bovine alpha 2-macroglobulin (alpha 2M) have been isolated after limited proteolysis of methylamine-treated alpha 2M with papain. Single crystals of the RBDs have been grown by vapour diffusion. Crystals of human RBD are very thin plates unsuited for data collection. However, crystals of RBD from bovine alpha 2M give diffraction patterns suitable for X-ray analysis, and a complete dataset with a maximum resolution of 2.3 A has been collected with synchrotron radiation at cryogenic temperature. The crystals belong to spacegroup P3(1)21 or P3(2)21 with cell parameters a = b = 106.8 A, c = 72.2 A.

Amino Acid Sequence↗
PubMed1995

The chicken oocyte receptor for yolk precursors as a model for studying the action of receptor-associated protein and lactoferrin.

Receptor-associated protein (RAP) was originally described as a 39-kDa intracellular protein copurifying with mammalian low density lipoprotein (LDL) receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR). RAP has a high affinity for LRP/alpha 2MR and interferes with the receptor's ability to bind a variety of ligands. The laying hen expresses, in a tissue-specific manner, at least four different proteins which belong to the same family of receptors as LRP/alpha 2MR. Here we show that the chicken also produces RAP, so far thought to be expressed only in mammals. Studies on the interaction of recombinant human RAP with the LDL receptor family in the chicken revealed that RAP binds with high affinity to the abundant oocyte receptor for yolk precursors (OVR) as well as to the somatic cell-specific LRP/alpha 2MR. Significantly, RAP interacts with a lower affinity with the LDL receptor, but does not bind to the oocyte-specific form of LRP. Binding of RAP to OVR inhibits the interaction of the receptor with all known physiological ligands, i.e. the yolk precursors very low density lipoprotein, vitellogenin, and alpha 2-macroglobulin. In COS cells transfected with OVR, RAP is internalized and degraded in a concentration-dependent and saturable manner. Lactoferrin, another protein with a high affinity for mammalian LRP/alpha 2MR, also binds to OVR and abolishes its interaction with yolk precursors. Cross-competition experiments show that RAP and lactoferrin recognize sites different from those involved in yolk precursor binding. The availability of pure OVR and LDLR enable us to determine kinetic parameters for the binding of RAP and lactoferrin to these receptors by surface plasmon resonance. Taken together, our results strongly suggest that chicken OVR, which is easily accessible and highly abundant in growing oocytes, represents a superior system for studying mechanistic and structural aspects of the interaction of ligands and modulating proteins with members of the LDL receptor gene family.

Amino Acid Sequence↗
PubMed1995

The chicken oocyte receptor for lipoprotein deposition recognizes alpha 2-macroglobulin.

alpha 2-Macroglobulin (alpha 2M), a major plasma component in all vertebrates, is proposed to function as a broad spectrum protease inhibitor. The alpha 2M-proteinase complex (activated alpha 2M; alpha 2M*) is removed rapidly by receptor-mediated endocytosis in the liver. Here we demonstrate by Western blotting that alpha 2M is also present in the yolk of chicken oocytes. Plasma levels of alpha 2M are increased by estrogen, and yolk alpha 2M is partially proteolyzed, consistent with the action of cathepsin D on endocytosed alpha 2M. Two known estrogen-induced ligands of the oocyte-specific 95-kDa very low density lipoprotein/vitellogenin receptor (OVR) are also fragmented by yolk cathepsin D (Retzek, H., Steyrer, E., Sanders, E. J., Nimpf, J., and Schneider, W. J. (1992) DNA Cell Biol. 11, 661-672). Since these findings suggested a common uptake mechanism for lipoproteins and alpha 2M by oocytes, we investigated whether OVR, a member of the low density lipoprotein receptor family, functions in the metabolism of alpha 2M. Ligand blotting of oocyte membrane extracts with chicken alpha 2M* revealed that it binds to OVR. Surprisingly, the oocyte receptor also recognizes native alpha 2M, in sharp contrast to the hepatic receptor, which only binds alpha 2M*. Receptor interaction of both forms requires Ca2+; however, competition experiments suggest that alpha 2M and alpha 2M* interact with slightly different, or overlapping, sites on the receptor. Colocalization of alpha 2M and OVR in coated vesicles isolated from growing oocytes, and internalization and degradation of methylamine-activated alpha 2M by COS-7 cells transfected with OVR, strongly suggest that alpha 2M is transported into growing oocytes via OVR. We propose that this multifunctional receptor mediates pathways at the metabolic crossroads of lipoproteins and protease inhibitor complexes.

Animals↗
PubMed1994

Chicken oocyte growth is mediated by an eight ligand binding repeat member of the LDL receptor family.

Deposition of the yolk mass components of chicken oocytes, very low density lipoprotein (VLDL) and vitellogenin (VTG), is mediated by a 95 kDa plasma membrane protein, termed VLDL/VTG receptor (VLDL/VTGR). Molecular characterization of the VLDL/VTGR revealed that it is a member of the LDLR gene superfamily, and harbours eight complement-type, cysteine-rich ligand binding repeats at the N-terminus. This ligand binding domain structure is the hallmark of the recently discovered mammalian so-called VLDLRs, whose true physiological function remains to be elucidated. Northern blot analysis revealed that this receptor is expressed almost exclusively in oocytes, with very much lower levels of hybridizing transcripts present in heart and skeletal muscle. Heterologous expression of the cloned receptor demonstrated its ability to bind both VLDL and VTG. The receptor gene is located on the avian sex chromosome Z, in agreement with the sex linkage of a single-gene defect in animals that fail to reproduce because of the lack of expression of functional VLDL/VTGR. In situ hybridization analysis of oocytes suggested that VLDL/VTGR mRNA may relocalize during oocyte growth. Thus, the current study has identified and characterized the first non-mammalian VLDLR. Its key role in avian reproduction and extremely high evolutionary conservation shed new light on VLDLR function in mammals, which also express the gene in ovaries.

Amino Acid Sequence↗
PubMed1994

[Quality development at an emergency unit--an intervention study based on consumer satisfaction].

A study among the users of an emergency department was carried out to assess user satisfaction, based upon a questionnaire. The study was split into two periods, before and after a change in procedure in the emergency department, namely that a nurse was to give information about waiting time, make coordinations and fix an order of priority of patients (triage) in the waiting room. Fourteen hundred and twenty-six answers were received, 794 before and 632 after the change. The users questioned after this change of procedure felt that they had been better received, that they had waited for a shorter time and described a better general experience as compared to the users questioned before the change, these differences were significant. There were no difference between the two groups concerning opinions on information about diagnosis, treatment and outcome, whether there was enough time for examination, treatment and information, whether the staff were obliging or whether their expectations had been fulfilled. It is concluded that such changes in procedure in the emergency department are to be recommended.

Denmark↗
PubMed1993

Localization of epsilon-lysyl-gamma-glutamyl cross-links in alpha 2-macroglobulin-plasmin complex.

The major epsilon-lysyl-gamma-glutamyl cross-links present in the largely covalent 1:1 alpha 2-macroglobulin-(alpha 2M)-plasmin complex have been localized. Cross-linking engaged Lys607, -708, and -750 of the plasmin light chain, Lys550, -556, and -557 of the heavy chain-light chain connecting strand, Lys258 and -298 of the kringle 3 region, and Lys473 of the kringle 5 region of the plasmin heavy chain. Lys607, -708, and -750 accounted for 75% of all cross-linking, Lys550, -556, and -557 accounted for 20%, and Lys258, -298, and -473 accounted for 5%. Hence, cross-linking engaged only nine of the 41 Lys residues of plasmin, showing that, probably due to their large size, individual plasmin molecules become deposited in the large elongated binding cavity in alpha 2M in a relatively uniform way. The cross-linking of Lys residues in the heavy chain-light chain connecting strand to alpha 2M explains earlier findings that a substantial portion of the heavy chain is cross-linked to alpha 2M [Pizzo et al. (1986) Biol. Chem. Hoppe-Seyler 367, 1177-1182]. Although located in the heavy chain, Lys550, -556 and -557 should be considered part of the serine proteinase domain. That part of plasmin must be deeply buried in the alpha 2M structure in close vicinity to the four thiol esters, while most of the elongated heavy chain is protruding from the binding cavity. The pattern of cross-linked species seen in sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that individual plasmin molecules are bound to alpha 2M through one or two cross-links. Bivalent cross-linking can take place within or between 360-kDa alpha 2M dimers, pointing to the tetrameric alpha 2M structure as the functional proteinase binding unit.

Amino Acid Sequence↗
PubMed1993

A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects.

BACKGROUND: Seventy-four asthmatic patients allergic to house dust mite were included in a double-blind, controlled study to establish the optimal maintenance dose of a standardized extract of Dermatophagoides pteronyssinus (Der p I) during 24 months of immunotherapy (IT). METHODS: The patients were given the following maintenance doses: 19 patients 10,000 standardized quality units (SQ-U) (group 10, 0.7 microgram Der p I), 20 patients 100,000 SQ-U (group 100, 7 micrograms Der p I), 16 patients 300,000 SQ-U (group 300, 21 micrograms Der p I), and 19 control patients (group 0) had no injections. After 24 months bronchial challenge demonstrated a dose-related increased tolerance to Der p I, group 10 (p = 0.003), group 100 (p = 0.0005), group 300 (p = 0.0007), with no change in group 0 (p = 0.6). Patients given IT had a decrease in medication and peak expiratory flow score. In total, 2104 injections were given, and 3.5% were followed by a systemic reaction, defined as a fall 15% or greater in forced expiratory volume in 1 second within 30 minutes. A dose-response relation was demonstrated, with rates of systemic reactions in percent of injections; group 10, 0.56%; group 100, 3.30%; and group 300, 7.10% (p < 0.0001). No anaphylactic reactions occurred, and no late systemic reactions were observed. This study demonstrated a dose dependence of efficacy and side effects of IT in asthmatic patients. We suggest a maintenance dose of 100,000 SQ-U (7 micrograms Der p I) as an appropriate guideline for IT with house dust mite extract.

Adolescent↗
PubMed1992

Comparison between two different assays for measurements of allergen-specific IgE and skin prick test in the diagnosis of insect venom allergy.

Forty-one patients stung by wasp and 29 by bee were evaluated by comparing the correlation between skin prick test (SPT), Phadebas radioallergosorbent test (P-RAST) and Magic Lite SQ Specific IgE assay (LIA). All patients had had a systemic reaction to insect sting. In the patients stung by bee we found agreement between SPT and P-RAST, and SPT and LIA. Similarly, there were no significant differences in sensitivity between P-RAST and LIA (p > 0.05). In patients stung by wasp, SPT was found to be more sensitive than P-RAST. There were no differences between SPT and LIA or between P-RAST and LIA.

Allergens↗
PubMed1992

The polycationic compound gentamicin inhibits the calcium paradox in guinea-pig hearts.

The polycationic drug gentamicin and two calcium antagonists were studied with respect to their protecting action against the calcium paradox in perfused guinea-pig hearts. Besides the mechanograms the release of creatine kinase was recorded; in parallel experiments the Na(+)-content of the hearts was measured before and at the end of the Ca(2+)-lack period, and during re-exposure to normal [Ca2+]0. The calcium paradox was induced by perfusion, for 50 s, with Ca(2+)-free solution containing EGTA (3 x 10(-4) M). Nifedipine and verapamil in concentrations which reduced the equilibrium contractile force by 50%, only mitigated the extent of the calcium paradox, whereas gentamicin applied in a concentration also reducing the contractile amplitude by 50% was able to suppress the calcium paradox completely. The dose-response curves for nifedipine, with respect to the reduction of contractile force and contracture, were identical. In contrast, gentamicin was more effective in attenuating the contracture of the paradox than in reducing the equilibrium contractile force. The large gain of Na+ during the Ca(2+)-lack period was diminished by both nifedipine and gentamicin. The partial protection of calcium antagonists can be related to their interference with the uptake of Na+ through L-type Ca(2+)-channels during the Ca(2+)-lack period, whereas gentamicin seems to act by an additional inhibition of the Na/Ca exchange during the re-exposure to normal [Ca2+]0.

Animals↗
PubMed1992

Relative bioavailability in man of noscapine administered in lozenges and mixture.

The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture.

Adult↗
PubMed1991

Crystallization and preliminary X-ray analysis of methylamine-treated alpha 2-macroglobulin and 3 alpha 2-macroglobulin-proteinase complexes.

Crystals of methylamine-treated alpha 2-macroglobulin (alpha 2M-MA), alpha 2-macroglobulin in complex with two molecules of trypsin, alpha 2M-T2, one molecule of plasmin, alpha 2M-PL, and one molecule of plasmin followed by methylamine-treatment, alpha 2M-PL(MA), have reproducibly been obtained using ammonium sulfate or magnesium sulfate as precipitants. The crystals are fragile tetragonal bipyramids of up to 1.5 mm in length. Crystals of alpha 2M-MA diffracted to at least 9 A resolution, crystals of alpha 2M-T2 diffracted to 10 A resolution and crystals of alpha 2M-PL and alpha 2M-PL(MA) diffracted to 11 A resolution. For alpha 2M-MA the cell parameters were determined as: a=b=257 A, c=555 A; and for alpha 2M-T2 as: a=b=247 A, c=559 A. For both preparations the space group was I4(1)22. As estimated from density measurements, the crystals of alpha 2M-MA and alpha 2M-T2 contain one 360 kDa alpha 2M dimer per asymmetric unit. The volume of the asymmetric unit/molecular weight, Vm, was estimated at 5.6 A3/Da. The crystal parameters of alpha 2M-PL and alpha 2M-PL(MA) were not determined.

Crystallization↗