Search PubMed⌕ Search

Biomedical subjects

K Poulsen

Publications and source records attributed to K Poulsen.

At least 55 records · Page 3Linked to original sources

Highly toxic clone of Actinobacillus actinomycetemcomitans in geographically widespread cases of juvenile periodontitis in adolescents of African origin.

The bacterium Actinobacillus actinomycetemcomitans has been implicated in the pathogenesis of juvenile periodontitis as the etiologic agent on the basis of several lines of circumstantial evidence. A matter of extensive debate is whether A. actinomycetemcomitans is an exogenous contagious pathogen or an opportunistic pathogen that resides in the normal oral microflora. Here we show evidence of a single clone of A. actinomycetemcomitans isolated from multiple patients with juvenile periodontitis in members of families of African origin living in geographically widespread areas. The clone is characterized by a 530-bp deletion in the leukotoxin gene operon, resulting in a significantly increased production of leukotoxin.

Adolescent↗

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.

Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Animals↗

Control of neuronal diversity by the floor plate: contact-mediated induction of midbrain dopaminergic neurons.

The notochord and floor plate contribute to patterning the ventral neural tube in part by expressing a diffusible factor that induces motoneurons. To determine the mechanisms that direct the development of other classes of ventral neurons, we studied the development of dopaminergic neurons that reside near motoneurons in the ventral midbrain. We provide evidence that dopaminergic neurons develop in the vicinity of the floor plate and that they can be specified by the floor plate in vitro and in vivo. Unlike motoneurons, efficient induction of dopaminergic neurons requires contact with floor plate cells. These results suggest that neuronal diversification along the dorsal-ventral axis may be achieved partly through the concerted action of diffusible and contact-dependent signals from a single organizing center, the floor plate.

Animals↗

Regulation of angiotensin II receptor expression in ovarian follicles. A review.

The regulation of angiotensin (Ang) II receptor expression in ovarian follicles was reviewed. Ang II receptor expression, assessed as the Ang II binding capacity, varied with the animal species and the developmental stage of the follicle. In cows, the expression correlated positively with follicular size and negatively with the active renin concentration in the follicular wall tissue. No relations were found to the follicular fluid concentrations of prorenin, estradiol or progesterone. In cell cultures, luteinizing hormone up-regulated Ang II receptor expression in cows, whereas it was decreased by follicle-stimulating hormone, Ang II and testosterone in rats. These data support the concept of an active and regulated RAS in ovarian follicles. The species differences in Ang II expression suggest varying functional roles of the RAS between species.

Angiotensin II↗

Evaluation of mass spectrometric techniques for characterization of engineered proteins.

Mass spectrometric characterization of engineered proteins has been examined using bovine recombinant Acyl-CoA-Binding Protein (rACBP), [15N]-labeled rACBP, and a number of sequence variants of ACBP produced by site-directed mutagenesis. The mass spectrometric techniques include ESIMS and MALDIMS for analysis of the intact protein. Peptide maps have been obtained either by direct analysis of enzymatically derived mixtures by PDMS, ESIMS, and MALDIMS or by off- and on-line HPLC-mass spectrometry. ESIMS was found to be most accurate for analysis of intact proteins. The best sequence coverage in mapping was obtained by LC-ESIMS and by direct mixture analysis by MALDIMS. The latter technique was favorable in terms of sensitivity and speed. A general strategy for mass spectrometric characterization of engineered proteins is suggested.

Amino Acid Sequence↗

Activation of the renin-angiotensin system in dogs with asymptomatic and symptomatic dilated cardiomyopathy.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were assessed in 23 dogs, nine of which had asymptomatic dilated cardiomyopathy (DCM) (New York Heart Association [NYHA] class I), eight had symptomatic DCM (NYHA class III) and six had severe congestive heart failure due to DCM (NYHA class IV). None of the dogs had received any drugs before the study. PRA was increased in dogs with DCM (NYHA classes III and IV) (median values 3.8 and 30.8 ng ml-1 hour-1) compared with normal dogs (median 0.89 ng ml-1 hour-1). However, PRA was only marginally increased in dogs with DCM NYHA class I (P = 0.06). The PAC was also increased in dogs with DCM (NYHA classes III and IV) (median values 123 and 600 pg ml-1) compared with normal dogs (median 61 pg ml-1). The PAC was not significantly increased in the early stage of DCM (NYHA class I). It was concluded that in dogs with DCM, the activity of the renin-angiotensin system (RAS) was increased in NYHA functional classes III and IV, and that the increase was correlated with the severity of the disease. The fact that the RAS tended to be activated in dogs with asymptomatic DCM supports the rationale of early therapeutic intervention with inhibitors of the angiotensin-converting enzyme (ACE) as first line therapy in congestive heart failure.

Aldosterone↗

Differences in expression of angiotensin II receptors and renin in porcine and bovine ovaries.

The expression of angiotensin (Ang) II receptors, active renin and prorenin in porcine and bovine ovarian follicles and corpora lutea was investigated and compared. In the wall tissue of porcine follicles, the Ang II receptor density was 47 (range 19-97; n = 13) fmol/mg membrane protein. The active renin concentration was 1.32 (0.40-3.43; n = 23) GU/kg wet tissue. These values were about 35-fold and 15-fold lower, respectively, than previously found in bovine follicles. No prorenin could be detected in the porcine follicular wall tissue. Ang II receptors of subtype 2 (AT2 receptors) with a dissociation constant (Kd) of 1.01 (0.64-1.79; n = 8) nmol/l for [Sar1-Ile5-Ile8]-Ang II were demonstrated in the bovine corpus luteum. The receptor density was 22.7 (1.9-93; n = 26) fmol/mg membrane protein, which was about 10-fold higher than in porcine corpora lutea. The active renin concentration was 20.7 (2.2-60.0; n = 26) GU/kg tissue in bovine and 0.40 (0.16-1.09; n = 17) GU/kg tissue in porcine corpora lutea. No prorenin could be detected in corpora lutea from both species. The variation between species in expression of the ovarian renin-angiotensin system indicates the existence of species differences in the physiological role.

Animals↗

Confirmation of the species Prevotella intermedia and Prevotella nigrescens.

The elevation of the two genotypes of Prevotella intermedia to species rank as P. intermedia and Prevotella nigrescens has increased the need for reliable differentiation between the two taxa. In this study, 53 strains, including strains whose species affiliations were known as well as fresh dental plaque isolates, were subjected to a multilocus enzyme electrophoretic analysis, DNA analyses in which we used whole genomic DNA, rRNA sequences, and an oligonucleotide specific for the former P. intermedia genotype II (P. nigrescens) as probes, and a sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of soluble cellular proteins. All of these tests consistently separated the strains into the same two distinct groups corresponding to P. intermedia and P. nigrescens, confirming that the two species constitute two distinct populations of bacteria. Each of the tests used independently provided reliable identification to the species level. A previously reported heterogeneity in the pattern of human immunoglobulin A1 (IgA1) degradation was not confirmed. No differences between species were observed. All of the strains induced total degradation of IgA1 within 48 h, a property that may be a virulence factor in periodontal disease development. The enzymes responsible for IgA1 degradation were not inactivated by the physiological proteinase inhibitors alpha 2-macroglobulin and alpha 1-proteinase inhibitor.

Alleles↗

Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae.

Cloning and sequencing of the IgA1 protease gene (iga) from Neisseria meningitidis strain HF13 showed an overall structure equivalent to iga genes from Neisseria gonorrhoeae and Haemophilus influenzae, although no region corresponding to the gonococcal alpha-peptide was evident. An additional 18 N. meningitidis and 3 H. influenzae iga genes were amplified by the polymerase chain reaction technique and sequenced corresponding approximately to the N-terminal half of the mature enzyme. Comparative analyses of a total of 29 iga genes showed that pathogenic Neisseria have iga genes with a significantly lower degree of heterogeneity than H. influenzae iga genes. Recombinational events indicated by mosaic-like structures corresponding to those found among N. gonorrhoeae protease genes were detected among N. meningitidis iga genes. One region showed characteristic differences in sequence and length which correlated with each of the different cleavage specificities. Meningococci were extremely conserved in this region with no evidence of recombination between isolates of different cleavage specificities. Sequences further downstream showed no obvious relationship with enzyme cleavage type. This region consisted of conserved areas interspersed with highly variable areas. Amino acid sequence homologies in the variable regions of meningococci reflected the antigenic types defined by using polyclonal neutralizing antibodies.

Amino Acid Sequence↗

Evidence for absence in northern Europe of especially virulent clonal types of Actinobacillus actinomycetemcomitans.

Genetic analysis of an Actinobacillus actinomycetemcomitans population consisting of 88 clinically well characterized Finnish isolates performed by multilocus enzyme electrophoresis confirmed that the five serotypes divide into two phylogenetic lineages, one comprising serotypes b and c and one comprising serotypes a, d, and e. There was no association between any subpopulation and the periodontal health status of the subject from whom the isolates originated, suggesting that the role of A. actinomycetemcomitans in periodontitis is largely opportunistic in the population examined. Southern blot analyses of genomic DNA digested with each of the restriction endonucleases MspI, RsaI, and TaqI revealed extremely limited genetic polymorphism of the structural leukotoxin gene, ltxA, and its associated promoter. All isolates hybridized to a 530-bp DNA fragment derived from the promoter region of the leukotoxin gene operon of a minimally leukotoxic A. actinomycetemcomitans strain. Deletion of the 530-bp sequence has been associated with significantly increased toxin production detected among isolates from patients with juvenile periodontitis in North America but was detected neither among the 88 isolates in the present collection analyzed nor among more than 60 strains in another population of northern European A. actinomycetemcomitans isolates analyzed previously.

Actinobacillus Infections↗

Neurotrophin-4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures.

Parkinson's disease is a prevalent neurological disease characterized by profound and incapacitating movement disorders. A common pathology in Parkinson's patients is degeneration of substantia nigra dopaminergic neurons that innervate the striatum and a corresponding decrease in striatal dopamine content. We now report that NT-4/5 can prevent the death of rat embryonic substantia nigra dopaminergic neurons in low density, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT-4/5 and transcripts for NT-4/5 are present in their environment. In addition, we demonstrate that NT-4/5 protects embryonic dopaminergic neurons from the toxic effects of the neurotoxin MPP+. Thus, NT-4/5 could be a physiological survival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

The uteroplacental renin-angiotensin system: a review.

Evidence has accumulated for the existence of local tissue renin-angiotensin systems in the reproductive tissues. In the ovary the local renin-angiotensin system (RAS) has been shown to influence ovulation and steroidogenesis. In this review we focus on aspects of a local RAS in the uteroplacental unit. High renin concentrations have been found in all tissues of the uteroplacental unit. The presence of renin mRNA in the endometrium, choriodecidua and the fetal part of the placenta indicates local renin synthesis. Angiotensin (Ang) II, formed by the enzymatic action of tissue renin and Ang I converting enzyme, acts by interaction with its receptors. These receptors have been demonstrated in high densities in the placenta and uterus, indicating an autocrine or paracrine action of Ang II. Several probable effects of the uteroplacental RAS can be defined. It is very likely that the uteroplacental RAS plays an important role during implantation and placentation by stimulation of decidualization and angiogenesis. Furthermore, Ang II may regulate synthesis and secretion of other hormones formed locally in the uteroplacental unit. During labour the action of Ang II may be important for contraction of the uterine musculature, Ang II is also involved in the complex regulation of the uteroplacental blood flow. Species difference in the expression of the uteroplacental RAS exists, and one may speculate that the physiological and pathophysiological roles vary between species.

Allantois↗

Population structure of Actinobacillus actinomycetemcomitans: a framework for studies of disease-associated properties.

The Actinobacillus actinomycetemcomitans population consists of a large number of clones among which the ubiquitous leukotoxin gene operon appears very homogeneous. Population genetic analyses performed by multilocus enzyme electrophoresis together with DNA fingerprinting and analyses of genomic DNA restriction fragment length polymorphisms (RFLP) on 97 strains isolated over a period of 45 years revealed that each of the serotypes a, b, c, d and e comprise genetically isolated subpopulations and that successful horizontal transfer of genomic DNA between strains of different serotypes appears to be extremely rare in vivo. In contrast, recombination between strains of the same serotype in general appears to take place in nature. The results provide evidence that non-serotypeable strains are serotype antigen-deficient variants originating from strains of the known serotypes. Serotype b and c strains may contain transmittable DNA sequences not found in strains of the other serotypes.

Actinobacillus Infections↗

Short term effects of acute inhibition of the angiotensin-converting enzyme on the renin-angiotensin system and plasma atrial natriuretic peptide in healthy dogs fed a low-sodium diet versus a normal-sodium diet.

The purpose of the present study was to quantify some of the short term responses of the renin-angiotensin system (RAS) to a recommended dosage of the angiotensin-converting enzyme inhibitor enalapril in clinically healthy dogs fed a normal-sodium and a low-sodium diet. A single dose of enalapril (0.5 mg/kg PO) was given to eight clinically healthy male Beagle dogs after a period where the dogs were fed a normal-sodium diet and low-sodium diet, respectively. Serum angiotensin-converting enzyme activity (ACE), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma atrial natriuretic peptide (ANP) concentration were measured during the following twenty-four hour period. The data indicate that enalapril induced a potent blockade of the renin-angiotensin system (RAS) for at least twenty-four hour. Specifically, enalapril during low-sodium diet elicited an exaggerated increase in PRA and a diminished decrease in ACE and ANP when compared to the results of the drug during normal-sodium diet. Long term controlled studies of enalapril in dogs with congestive heart failure (CHF) are warranted in order to determine the duration of action and optimal dose of enalapril.

Aldosterone↗

Angiotensin II receptor density in bovine ovarian follicles relates to tissue renin and follicular size.

1. The purpose of this study was to investigate angiotensin II (AII) receptors in isolated bovine ovarian follicles and the relationship of their density to follicular concentrations of prorenin, active renin, oestradiol and progesterone. 2. Displacement of [125I]-[Sar1-Ile5-Ile8]-AII binding by the AII receptor antagonists PD 123319 and Losartan (DuP 753) confirmed that follicular AII receptors are of subtype 2 (AT2 receptor). 3. The dissociation constant (Kd) for [Ile5]-AII (human AII) was 0.84 (range 0.51-1.47) nmol/L. The receptor density varied between 90 and 5990 (mean 1640) fmol/mg membrane protein. 4. The follicular AII receptor density correlated positively with follicular diameter (Spearman's rho = 0.518; P < 0.003) and tissue weight (Spearman's rho = 0.636; P < 0.0001), and negatively with the active renin concentration in the follicular wall (Spearman's rho = -0.399; P < 0.02). The AII receptor density did not correlate with the follicular fluid concentrations of prorenin, active renin, oestradiol (E2), progesterone (P4) or the E2/P4 ratio. The follicular fluid concentrations of prorenin correlated negatively with the E2/P4 ratio (Spearman's rho = -0.716; P < 0.0001). 5. The inverse relationship between AII receptor density and the high active renin concentrations in the follicular wall suggests an active regulated tissue renin-angiotensin system. A high AII receptor density is a general feature of large bovine ovarian follicles.

Angiotensin II↗