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Biomedical subjects

H S Andersen

Publications and source records attributed to H S Andersen.

At least 19 recordsLinked to original sources
PubMed2006

Fetal programming: causes and consequences as revealed by studies of dietary manipulation in rats -- a review.

During pregnancy, the developing fetus is dependent on its mother for all nutritional requirements. It is not surprising, therefore, that variations in maternal nutrition can be reflected in alterations in fetal health and well-being. Interestingly, the changes can persist into adulthood and may result in increased risk of diseases such as diabetes, obesity and cardiovascular disease. The first observations of these phenomena resulted in the development of hypotheses collectively brought under the heading of "fetal" or, more recently, "developmental" programming. In this review, we will examine some of the animal models used to understand the mechanisms involved and attempt to determine whether there are common, "gatekeeper", pathways or genes, altered by the different nutritional stresses. We will concentrate primarily on nutrition related to post-natal development of hypertension and will restrict the review to studies in rodents, since that is where most of the mechanistic studies are being undertaken. Our conclusions are that, while there may well be some common gatekeeper pathways, there is also some diversity of mechanism which may contribute to the generation of the same or similar phenotypes.

Adaptation, Physiological↗
PubMed2005

Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling.

Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice. The present study was undertaken to investigate the mechanism by which PTP1B mediates the cessation of the leptin signal transduction. Leptin-induced activation of a STAT3 responsive reporter was dose-dependently inhibited by co-transfection with PTP1B. No inhibition was observed when a catalytically inactive mutant of PTP1B was used or when other PTPs were co-transfected. PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3.

Animals↗
PubMed2004

Effect of timing of iron supplementation on maternal and neonatal growth and iron status of iron-deficient pregnant rats.

We have previously shown that maternal iron (Fe) deficiency not only reduces fetal size, but also increases blood pressure in the offspring when they are adults. In this paper we examine whether there are critical periods when supplementation reverses or fails to reverse the effect both on size and on expression of genes of Fe metabolism. We made dams Fe deficient, mated them and provided supplements of Fe in the diet from the beginning of gestation (0.5 days), from 7.5 days or from 14.5 days. Within 12 h of birth, dams and neonates were killed and tissues taken and examined. Fe deficiency throughout pregnancy reduces neonatal size. Supplementation from the beginning of the first, second or third week all reduced the effect. Maternal haematocrit was restored to normal levels only in animals given supplements for at least 2 weeks. In contrast, the neonates' Fe levels were normal in all supplemented groups. These results were mirrored in liver Fe levels and in transferrin receptor mRNA. Iron-responsive element (IRE)-regulated divalent metal transporter 1 (DMT1) increased in maternal and neonatal liver. Non-IRE-regulated DMT1 levels did not change in the maternal liver, but decreased in the neonatal liver. H and L ferritin mRNA levels also showed different patterns in the mother and her offspring. Finally, the neonatal size correlated with maternal Fe stores, and not with those of the fetus. The data demonstrate that Fe supplementation during pregnancy is most effective when given early, rather than later, in gestation.

Animals↗
PubMed2004

Use of folic acid casei medium reveals trimethoprim susceptibility of Lactobacillus species.

AIM: Lactobacilli have been reported to have intrinsic resistance to trimethoprim. The susceptibility of lactobacilli to trimethoprim on different media was investigated in order to search for a phenotypic test method that could indicate the presence of acquired resistance genes. METHODS AND RESULTS: Strains of Lactobacillus acidophilus, Lact. paracasei, Lact. rhamnosus and Lact. plantarum were susceptibility tested with E-tests on folic acid casei medium (FACM), MRS and defined medium 1. The effects of addition or removal of nucleosides and thymidine phosphorylase were investigated. E-tests on FACM yielded reproducible minimal inhibitory concentrations (MICs) for trimethoprim but addition of nucleosides was necessary for growth of Lact. acidophilus. MICs for the tested strains were 0.125-0.19, 0.25-3 and 0.064-0.19 microg ml(-1) for Lact. paracasei, Lact. rhamnosus and Lact. plantarum, respectively. With the addition of deoxyuridine and deoxyadenosine to FACM the MICs of Lact. acidophilus were 0.064-1 microg ml(-1). CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacilli do not have intrinsic resistance to trimethoprim. The results show that trimethoprim susceptibility testing of the tested Lactobacillus species is possible and indicate that transferable resistance genes are absent in all the tested strains.

Anti-Infective Agents↗
PubMed2004

Mental health in prison populations. A review--with special emphasis on a study of Danish prisoners on remand.

OBJECTIVE: To review the literature on mental health and psychiatric morbidity in prison populations and relate findings to a Danish study on remand prisoners. METHOD: The literature is reviewed and subdivided in the following section: validity of psychometrics in prison populations, prevalence of psychiatric disorders prior to imprisonment, incidence of psychiatric disorders during imprisonment, psychopathy related to psychiatric comorbidity, dependence syndromes with special emphasis on different administrations of heroin use (smoke vs. injection). The results are compared with a longitudinal Danish study on remand prisoners in either solitary confinement (SC) or non-SC. RESULTS: Many factors must be taken into consideration when dealing with prisoners and mental health, e.g. international differences, the prison setting, demographics and methodological issues. The prison populations in general are increasing worldwide. Psychometrics may perform differently in prison populations compared with general populations with the General Health Questionnaire-28 having a low validity in remand prisoners. Psychiatric morbidity including schizophrenia is higher and perhaps increasing in prison populations compared with general populations with dependence syndromes being the most frequent disorders. The early phase of imprisonment is a vulnerable period with a moderately high incidence of adjustment disorders and twice the incidence in SC compared with non-SC. Prevalence of psychopathy is lower in European than North American prisons. Medium to high scores of psychopathy is related to higher psychiatric comorbidity. Opioid dependence is the most frequent drug disorder with subjects using injection representing a more dysfunctional group than subjects using smoke administration. Many mentally ill prisoners remain undetected and undertreated. CONCLUSION: There is a growing population of mentally ill prisoners being insufficiently detected and treated.

Adult↗
PubMed2002

Analysis of scenarios for sewerage, wastewater treatment and prioritised load on environment from the Greater City of Copenhagen.

The sewer system for the Greater Copenhagen area covers an area of 4460 ha contributing to the runoff. The total area serves in total 8 municipalities, however it is dominated by the areas in the City of Copenhagen proper. The catchments merge into interceptors, which feed two large treatment plants. The effluent from the two treatment plants discharges during dry weather to Oresund, the sound between Denmark and Sweden. This large system has been analysed for selected scenarios with respect to handling runoff in an optimal way in order to minimise the loads on the most sensitive receiving waters and optimising treatment plant performance.

Cities↗
PubMed2001

Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases.

Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position [Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300-10307]. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity [Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201-18209]. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.

Animals↗
PubMed2001

Post-traumatic stress disorder: a review of psychobiology and pharmacotherapy.

OBJECTIVE: To review the literature on the psychobiology and pharmacotherapy of PTSD. METHODS: Relevant studies were identified by literature searches (Pub-med, Web of Science) and through reference lists. The search was ended by May 2001. RESULTS: There is evidence of involvement of opioid, glutamatergic, GABAergic, noradrenergic, serotonergic and neuroendocrine pathways in the pathophysiology of PTSD. Medications shown to be effective in double-blind placebo-controlled trials includes selective serotonin reuptake inhibitors, reversible and irreversible MAO-inhibitors, tricyclic antidepressants and the anticonvulsant lamotrigine. Still more agents appear promising in open-label trials. CONCLUSION: The complexity of the psychobiology is reflected by the difficulties in treating the disorder. According to the present knowledge, suggestions for drug treatment of PTSD are made.

Glutamic Acid↗
PubMed2001

Ganser syndrome after solitary confinement in prison: a short review and a case report.

A short review of the Ganser syndrome is given. The condition is a rare, probably dissociative, disorder with transient Vorbeireden as the central symptom. The case of a middle-aged man developing a transient Ganser syndrome after long-term solitary confinement in a remand prison is presented. Systematic investigation of 268 remand prisoners confirms the rarity of the syndrome, as only the case subject had this disorder.

Attention↗
PubMed2001

Psychosis and pregnancy: five cases of severely ill women.

An increasing number of patients with chronic mental disease are now integrated in society. As a consequence, women with severe psychiatric illness may become pregnant and wish to complete the pregnancy and to give birth to a child. The lack of sensation of reality in these patients and their social situation may result in particular problems in their treatment, and it may be necessary to admit them to a psychiatric ward before delivery. In this paper five cases of pregnant women with severe and chronic psychosis are described. These patients had many problems in common. Thus, they were all schizophrenics with very severe psychopathology, had poor understanding of their own situation, and lacked social networks. All the fathers were non-Danish. Coercion was used in all cases. To help women with severe mental illness to go through pregnancy and childbirth requires close collaboration between psychiatric and obstetric staff and social workers, and this should be organized in an institution with experience in the treatment of this type of patient.

Adult↗
PubMed2000

Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha.

The aim of this study was to define the structural elements that determine the differences in substrate recognition capacity of two protein-tyrosine phosphatases (PTPs), PTP1B and PTPalpha, both suggested to be negative regulators of insulin signaling. Since the Ac-DADE(pY)L-NH(2) peptide is well recognized by PTP1B, but less efficiently by PTPalpha, it was chosen as a tool for these analyses. Calpha regiovariation analyses and primary sequence alignments indicate that residues 47, 48, 258, and 259 (PTP1B numbering) define a selectivity-determining region. By analyzing a set of DADE(pY)L analogs with a series of PTP mutants in which these four residues were exchanged between PTP1B and PTPalpha, either in combination or alone, we here demonstrate that the key selectivity-determining residue is 259. In PTPalpha, this residue is a glutamine causing steric hindrance and in PTP1B a glycine allowing broad substrate recognition. Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme. By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)). Both effects may indicate that PTPalpha regulates highly selective signal transduction processes.

Animals↗
PubMed2000

Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B.

Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. Recent studies have shown increased insulin sensitivity and resistance to obesity in PTP1B knockout mice, thus pointing to this enzyme as a potential drug target in diabetes. Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. This was achieved by addressing residue 48 as a selectivity determining residue. By introducing a basic nitrogen in the core structure of the inhibitor, a salt bridge was formed to Asp-48 in PTP1B. In contrast, the basic nitrogen causes repulsion in other PTPs containing an asparagine in the equivalent position resulting in a remarkable selectivity for PTP1B. Importantly, this was accomplished while retaining the molecular weight of the inhibitor below 300 g/mol.

Animals↗
PubMed2000

2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases.

Protein-tyrosine phosphatases (PTPs) are critically involved in regulation of signal transduction processes. Members of this class of enzymes are considered attractive therapeutic targets in several disease states, e.g. diabetes, cancer, and inflammation. However, most reported PTP inhibitors have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore embarked on identifying a general, reversible, competitive PTP inhibitor that could be used as a common scaffold for lead optimization for specific PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid (OBA) as a classical competitive inhibitor of several PTPs. X-ray crystallography of PTP1B complexed with OBA and related non-phosphate low molecular weight derivatives reveals that the binding mode of these molecules to a large extent mimics that of the natural substrate including hydrogen bonding to the PTP signature motif. In addition, binding of OBA to the active site of PTP1B creates a unique arrangement involving Asp(181), Lys(120), and Tyr(46). PTP inhibitors are essential tools in elucidating the biological function of specific PTPs and they may eventually be developed into selective drug candidates. The unique enzyme kinetic features and the low molecular weight of OBA makes it an ideal starting point for further optimization.

Binding Sites↗
PubMed2000

A longitudinal study of prisoners on remand: psychiatric prevalence, incidence and psychopathology in solitary vs. non-solitary confinement.

OBJECTIVE: To compare two levels of stress (solitary confinement (SC) and non-SC) among remand prisoners as to incidence of psychiatric disorders in relation to prevalent disorders. METHOD: Longitudinal repeated assessments were carried out from the start and during the remand phase of imprisonment. Both interview-based and self-reported measures were applied to 133 remand prisoners in SC and 95 remand prisoners in non-SC randomly selected in a parallel study design. RESULTS: Incidence of psychiatric disorders developed in the prison was significantly higher in SC prisoners (28%) than in non-SC prisoners (15%). Most disorders were adjustment disorders, with depressive disorders coming next. Incident psychotic disorders were rare. The difference regarding incidence was primarily explained by level of stress (i.e. prison form) rather than confounding factors. Quantitative measures of psychopathology (Hamilton Scales and General Health Questionnaire) were significantly higher in subjects with prevalent and incident disorders compared to non-disordered subjects. CONCLUSION: Different levels of stress give rise to different incidence of psychiatric morbidity among remand prisoners. The surplus of incident disorders among SC prisoners is related to SC, which may act as a mental health hazard.

Adult↗
PubMed1999

Peroxyvanadium compounds inhibit glucose-6-phosphatase activity and glucagon-stimulated hepatic glucose output in the rat in vivo.

The present investigation was undertaken to characterize the direct inhibitory action of the peroxyvanadium compounds oxodiperoxo(1, 10-phenanthroline) vanadate(V) (bpV(phen)) and oxodiperoxo(pyridine-2-carboxylate) vanadate(V) (bpV(pic)) on pig microsomal glucose-6-phosphatase (G-6-Pase) activity and on glucagon stimulated hyperglycemia in vivo. Both bpV(phen) and bpV(pic) were found to be potent competitive inhibitors of G-6-Pase with Ki values of 0.96 and 0.42 microM (intact microsomes) and 0.50 and 0.21 microM (detergent-disrupted microsomes). The corresponding values for ortho-vanadate were 20.3 and 20.0 microM. Administration of bpV(phen) to postprandial rats did not affect the basal glucose level although a modest and dose-dependent increase in plasma lactate levels was seen. Injection of glucagon raised the plasma glucose level from 5.5 mM to about 7.5 mM in control animals and this increase could be prevented dose-dependently by bpV(phen). The inhibition of the glucagon-mediated blood glucose increase was accompanied by a dose-dependent increase in plasma lactate levels from 2 mM to about 11 mM. In conclusion, the finding that vanadate and bpV compounds are potent inhibitors of G-6-Pase suggests that the blood-glucose-lowering effect of these compounds which is seen in diabetic animals may be partly explained by a direct effect on this enzyme rather than, as presently thought, being the result of inhibition of phosphoprotein tyrosine phosphatases and thereby insulin receptor dephosphorylation.

Animals↗
PubMed1999

Psychopathy and psychopathological profiles in prisoners on remand.

A total of 178 Danish male remand prisoners were examined using comprehensive interviews and questionnaires on psychopathological, personality and social measures, and file data. These data were compared with scores on the Hare Psychopathy Checklist - Revised (PCL-R). Subjects were divided into four groups according to quartile PCL-R scores. In general there were high rates of psychiatric morbidity in all PCL-R quartile groups. The medium-high scorers represent a more vulnerable group with a high prevalence of dependence disorders, relatively high neuroticism score and relatively high prevalence of neurotic and stress-related disorders. The high scorers were more psychosocially maladjusted, had more often made previous suicidal attempts, and had a higher psychoticism score. Chronic psychotic disorders did occur, mostly in the high-scoring group. The population had lower scores on the PCL-R than in most previous studies, suggesting a lower prevalence of psychopathic features among Danish criminals and possibly a lower cut-off point when using the PCL-R as a categorical measure. Both findings are consistent with the results of other European studies. Further studies on cross-cultural differences with regard to PCL-R psychopathic features and on psychic vulnerability related to PCL-R scores and factor 1/factor 2 of the PCL-R are suggested.

Adolescent↗