Biomedical subjects

A S Hansen

Publications and source records attributed to A S Hansen.

14 recordsLinked to original sources

PubMed2000

Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases.

OBJECTIVE: To investigate the effect of a probiotic milk product containing the culture CAUSIDO(R) and of two alternative products on risk factors for cardiovascular disease in overweight and obese subjects. DESIGN: An 8 week randomized, double-blind, placebo- and compliance-controlled, parallel study. SUBJECTS: Seventy healthy, weight-stable, overweight and obese (25.0<BMI<37.5 kg/m2) males (n=20) and females (n=50), 18-55 y old, were randomly assigned into five groups. INTERVENTION: Four groups consumed 450 ml fermented milk products (yoghurt) daily. Group 1: a yoghurt fermented with two strains of Streptococcus thermophilus and two strains of Lactobacillus acidophilus (StLa). Group 2: a placebo yoghurt fermented with delta-acid-lactone (PY). Group 3: a yoghurt fermented with two strains of Streptococcus thermophilus and one strain of Lactobacillus rhamnosus (StLr). Group 4: a yoghurt fermented with one strain of Enterococcus faecium and two strains of Streptococcus thermophilus (CAUSIDO(R) culture), GAIO(R) (G). The dietary composition of the yoghurt was otherwise similar. The fifth group was given two placebo pills (PP) daily. RESULTS: When comparing all five treatment groups, unadjusted for changes in body weight, no statistical effects were observed in week 8 in the G-group on low density lipoproteins (LDL)-cholesterol (P=0.29). After adjustment for small changes in body weight, LDL-cholesterol decreased by 8.4% (0.26+/-0.10 mmol/l; P<0.05) and fibrinogen increased (0.74+/-0.32 mmol/l; P<0.05) after 8 weeks in the G-group. This was significantly different from the group consuming chemically fermented yoghurt and the group consuming placebo pills (P<0.05). After 8 weeks, systolic blood pressure was significantly more reduced in the StLa and G-group compared to StLr. No other differences were found. CONCLUSION: The CAUSIDO(R) culture reduced LDL-cholesterol and increased fibrinogen in the overweight subjects at a 450 ml consumption daily for 8 weeks. The effect on LDL-cholesterol confirms previous studies. An immunostimulation by one of the strains in the product might explain the effect on fibrinogen in the G-group. SPONSORSHIP: MD Foods A/S, Denmark.

Adult↗

PubMed1994

A quantitative assay to measure the interaction between immunogenic peptides and purified class I major histocompatibility complex molecules.

A direct and sensitive biochemical assay to measure the interaction in solution between peptides and affinity-purified major histocompatibility complex (MHC) class I molecules has been generated. Specific binding reflecting the known class I restriction of cytotoxic T cell responses was obtained. Adding an excess of beta 2-microglobulin (beta 2m) significantly increased the rate of peptide association, but it did not affect the rate of dissociation. Binding was complicated by a rapid and apparently irreversible loss of functional MHC class I at 37 degrees C which might limit the life span of empty MHC class I thereby preventing the inadvertent exchange of peptides at the target cell surface. All class I molecules tested bound peptides of the canonical octa- to nona-meric length. However, one class I molecule, Kk, also bound peptides, which were much longer suggesting that the preference of class I molecules for short epitopes is not absolute and may be caused by factors other than the peptide-MHC class I binding event itself.

Amino Acid Sequence↗

PubMed1994

The interaction between beta 2-microglobulin (beta 2m) and purified class-I major histocompatibility (MHC) antigen.

The function of MHC class-I molecules is to sample peptides from the intracellular environment and present them to CD8+ cytotoxic T lymphocytes. To understand the molecular details of the assembly (and disassembly) of peptide-beta 2m-class-I complexes a biochemical peptide-class-I binding assay has been generated recently and this paper reports on a similar assay for the interaction between beta 2m and class I. As a model system human beta 2m binding to mouse class I was used. The assay is strictly biochemical using purified reagents which interact in solution and complex formation is determined by size separation. It is specific and highly sensitive. The observed affinity of the interaction, KD, is close to 0.4 nM. The rate of association at 37 degrees C is very fast (the ka is around 5 x 10(4)/M/s) whereas the dissociation is slow (the kd is around 8 x 10(-6)/s); the ratio of dissociation to association yields a calculated KD close to the observed value. At 37 degrees C almost all of the purified class I participates in binding of the exogenously offered beta 2m showing that a considerable exchange of the endogenous beta 2m occurs. Finally, it was demonstrated that exogenous beta 2m enhances binding to MHC class-I of short perfectly-matching peptides as well as longer peptides.

Amino Acid Sequence↗

PubMed1993

A mouse aminopeptidase N is a marker for antigen-presenting cells and appears to be co-expressed with major histocompatibility complex class II molecules.

To analyze the expression of mouse aminopeptidase N (APN) on the cells of the immune system a panel of rat monoclonal antibodies against mouse intestinal APN was generated. These antibodies were used to affinity purify functional mouse APN from both intestine and kidney, and by flow cytometry to examine the APN expression of the cells of the mouse immune system. An APN closely related, perhaps identical, to the intestinal APN was expressed on a subpopulation of spleen cells and stimulated peritoneal exudate cells, primarily representing antigen-presenting cells, such as B cells, macrophages, dendritic cells, and veiled cells. In contrast this APN expression could not be detected on thymocytes or spleen T cells. As a corollary, APN was expressed on monocyte, macrophage, and B lymphoma cell lines, but not on T hybridoma or thymoma cell lines. The expression of APN showed a striking correlation with the MHC class II expression in all the cell populations studied. This apparent co-expression suggests a role for APN in antigen processing.

Aminopeptidases↗

PubMed1992

MHC molecules protect T cell epitopes against proteolytic destruction.

There is a subtle duality in the role of proteolytic enzymes in Ag processing. They are required to fragment protein Ag ingested by APC. However, prolonged exposure to proteolytic enzymes may lead to a complete degradation of the Ag, leaving nothing for the T cell system to recognize. What ensures that some of the Ag is salvaged? Using a cell-free system we demonstrate that an Ag fragment, once bound to a MHC class II molecule, is effectively protected against proteolytic destruction by cathepsin B and pronase E. The bound fragment, however, can be modified by aminopeptidase N. We suggest that MHC class II molecules play an important regulatory role in the physiologic processing of Ag.

Amino Acid Sequence↗

PubMed1992

pH dependence of the interaction between immunogenic peptides and MHC class II molecules. Evidence for an acidic intracellular compartment being the organelle of interaction.

The pH dependence of the interaction between immunogenic peptide and MHC class II was studied both in a direct biochemical binding assay and in a functional Ag presentation assay. The two approaches yielded similar results. All of the peptides tested bound optimally to their relevant MHC class II restriction element at around pH 4.5. Indeed, several of the peptides did not bind at neutral pH. These results demonstrate that Ag under physiologic conditions meet MHC class II in a quite acidic environment. The very acidic pH optimal for peptide-MHC class II interaction is only found intracellularly and most notably in the endosome-lysosome compartment in which Ag processing is thought to occur. Thus, Ag processing and interaction with MHC class II molecules can potentially happen in the very same compartment. This yet undefined acidic compartment would have to contain proteolytic enzymes and MHC class II molecules.

Amino Acid Sequence↗

PubMed1992

Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice.

The toxicity and efficacy of two oximes, HLö-7 and pyrimidoxime, were evaluated in mice and compared to those obtained with HI-6. HLö-7 and pyrimidoxime produced 24 h LD50 values of 356 and 291 mg/kg (i.p.), respectively. In combination with atropine (17.4 mg/kg, i.p.), HLö-7 was a very efficient therapy against poisoning by 3 x LD50 dose of soman, sarin and GF and 2 x LD50 dose of tabun with ED50 values of 12.4, 0.31, 0.32 and 25.2 mg/kg, respectively. In contrast, pyrimidoxime was a relatively poor therapy which resulted in ED50 values of greater than 150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLö-7 produced significant (p less than 0.05) reactivation of phosphorylated acetylcholinesterase, in vivo, resulting in 47, 38, 27 and 10% reactivation of sarin, GF, soman and tabun inhibited mouse diaphragm acetylcholinesterase, respectively. HLö-7 also antagonized sarin-induced hypothermia in mice suggesting that it reactivated central acetylcholinesterase. The potential of HLö-7 as a replacement oxime for the treatment of nerve agent poisoning is discussed.

Animals↗

PubMed1992

Comparison of several oximes against poisoning by soman, tabun and GF.

Three oximes currently being evaluated for adoption as replacement nerve agent therapy by various countries were compared for therapeutic efficacy against the toxic organophosphate inhibitors soman and tabun under a standard set of conditions. These oximes together with PAM-Cl and toxogonin, were also compared for efficacy against GF, an agent weaponized by Iraq. The order of effectiveness against soman was HI-6 greater than HLö-7 greater than pyrimidoxime. HLö-7 was very effective against tabun poisoning while HI-6 and pyrimidoxime were of moderate value. Against GF, HI-6 and HLö-7 were extremely effective, toxogonin was moderately effective, and PAM-Cl and pyrimidoxime were the least effective. HI-6 provided a high level of protection against all of the agents tested as did HLö-7 to a slightly lesser degree. The other oximes suffered from their lack of effects against one or more of the organophosphates.

Animals↗

PubMed1991

Toxicity of organophosphate nerve agents and related phosphonylated oximes compared to their anticholinesterase activity in neuron cultures.

Oximes, such as pralidoxime and toxogonin, are important therapeutic agents for the treatment of organophosphate (OP) nerve agent poisoning. Oximes can react with these nerve agents to give intermediates, phosphonylated oximes, which may be equally toxic to the parent OP. The sc LD50s of a series of phosphonylated 2-butanone and 2,3-butanedione monoximes were compared to the sc LD50s of their parent OPs (tabun, sarin, and VX) in CD-1 mice. In every case the derivatives were significantly less toxic than their parent nerve agents. Times to death, and to signs of poisoning, were inversely proportional to the dose of test compound, and in all mortalities, blood serum acetylcholinesterase (AChE) was severely inhibited. The relative potencies of these compounds, as well as soman, cyclohexyl methylphosphonofluoridate, and diisopropyl fluorophosphate, as inhibitors of AChE in primary cultures of mouse embryo neurons, correlated with their in vivo toxicities. The results indicate that mouse embryo neuron cultures may be a useful model with which to study this class of compounds.

Animals↗

PubMed1982