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Biomedical subjects

J Christensen

Publications and source records attributed to J Christensen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cytotoxic activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum.

Two previously known phenanthroindolizidine alkaloids, (-)-10beta-antofine N-oxide (1) and (-)-10beta, 13aalpha-14beta-hydroxyantofine N-oxide (2), and a novel alkaloid, (-)-10beta,13aalpha-secoantofine N-oxide (3), were isolated from aerial parts of Cynanchum vincetoxicum. Their structures were established by means of NMR methods, including COSY, NOESY, HSQC, and HMBC experiments, as well as from their CD spectra. Cytotoxic activity of the alkaloids was assessed in vitro using both a drug-sensitive KB-3-1 and a multi-drug-resistant KB-V1 cancer cell line. The antofine derivatives (1 and 2) showed pronounced cytotoxicity against the drug-sensitive cell line (IC(50) values about 100 nM), whereas the secoantofine derivative (3) was considerably less active. The KB-V1 cell line showed a marginal resistance against all alkaloids, demonstrating that these compounds are poor substrates for the P-glycoprotein (P-170) efflux pump.

Alkaloids↗
PubMed2000

Leishmanicidal, antiplasmodial and cytotoxic activity of indole alkaloids from Corynanthe pachyceras.

Five indole alkaloids, corynantheidine, corynantheine, dihydrocorynantheine, alpha-yohimbine and corynanthine were isolated from bark of Corynanthe pachyceras K. Schum. (Rubiaceae). The structures were established by spectroscopic methods, including previously unreported assignment of all 1H-NMR resonances by COSY and NOESY experiments. These and related alkaloids showed pronounced activity against Leishmania major promastigotes (IC50 at the micromolar level) but no significant in vitro antiplasmodial activity (against chloroquine-sensitive Plasmodium falciparum). Cytotoxicity assessed with drug sensitive KB-3-1 and multidrug-resistant KB-V1 cell lines was low; the alkaloids are apparently not substrates for the P-glycoprotein (P-170) efflux pump.

Alkaloids↗
PubMed2000

Two widely spaced initiator binding sites create an HMG1-dependent parvovirus rolling-hairpin replication origin.

Minute virus of mice (MVM) replicates via a linearized form of rolling-circle replication in which the viral nickase, NS1, initiates DNA synthesis by introducing a site-specific nick into either of two distinct origin sequences. In vitro nicking and replication assays with substrates that had deletions or mutations were used to explore the sequences and structural elements essential for activity of one of these origins, located in the right-end (5') viral telomere. This structure contains 248 nucleotides, most-favorably arranged as a simple hairpin with six unpaired bases. However, a pair of opposing NS1 binding sites, located near its outboard end, create a 33-bp palindrome that could potentially assume an alternate cruciform configuration and hence directly bind HMG1, the essential cofactor for this origin. The palindromic nature of this sequence, and thus its ability to fold into a cruciform, was dispensable for origin function, as was the NS1 binding site occupying the inboard arm of the palindrome. In contrast, the NS1 site in the outboard arm was essential for initiation, even though positioned 120 bp from the nick site. The specific sequence of the nick site and an additional NS1 binding site which directly orients NS1 over the initiation site were also essential and delimited the inboard border of the minimal right-end origin. DNase I and hydroxyl radical footprints defined sequences protected by NS1 and suggest that HMG1 allows the NS1 molecules positioned at each end of the origin to interact, creating a distortion characteristic of a double helical loop.

Animals↗
PubMed1999

Developmental expression of an amn(+) transgene rescues the mutant memory defect of amnesiac adults.

The Drosophila memory gene amnesiac (amn) has been proposed to encode a neuropeptide protein, which includes regions homologous to vertebrate pituitary adenylyl cyclase-activating peptide (PACAP; Feany and Quinn, 1995). Definitive experiments to link this gene to memory formation, however, have not yet been accomplished (Kandel and Abel, 1995). The experiments described here demonstrate that the putative amn transcript is involved in adult memory formation. With the use of a UAS-amn(+) transgene, we show complete rescue of memory defects in amn(28A), a mutant allele caused by the insertion of a GAL4 enhancer trap transposon (Moore et al., 1998). Study of the amn(28A) reporter reveals widespread expression in the adult brain but also enriched expression in the embryonic and larval nervous systems. To begin addressing the temporal requirement of amn in memory, we asked whether the memory defects could be rescued by restricting transgenic expression to the adult stage. A heat-shock regimen shown previously to rescue fully the amn ethanol sensitivity defect (Moore et al., 1998) failed to rescue the memory defect. These results, coupled with previous genetic and anatomical studies, suggest that adult memory formation and ethanol sensitivity have different temporal and spatial requirements for amn.

Aging↗
PubMed1999

Numerical simulation of motility patterns of the small bowel. II. Comparative pharmacological validation of a mathematical model.

A model of a locus of the small bowel, described earlier by the authors (Miftakhov et al., 1999) was validated in a comparison of the results of numerical simulations of pharmacological compounds to their effects in biological studies. The actions of the following four classes of drugs were simulated, those: (i) acting on the sarcoplasmic reticulum, (ii) altering the permeability of L- and T-type Ca(2+)channels on the smooth muscle membrane, (iii) motilides, and (iv) benzodiazepines. The strong qualitative resemblance between the theoretical and experimental results supports the robustness of the model.

Benzodiazepines↗
PubMed1999

Change in lameness risk estimates in piglets due to the modelling of herd-level variation.

In a previous study (Christensen, 1996. Prev. Vet. Med. 26, 107-118), an effect parameter changed from positive to negative depending on the model used. The study considered lameness in suckling piglets and the dataset included 7632 litters from 35 herds from the Health and Production Surveillance (HEPS) system database. To further investigate the change in the effect parameter, we performed a simple test to demonstrate the presence of herd-level variation. Finding substantial herd-level variation, we have re-analysed the data with special attention to the herd-level variation, and how to account for it. When herd-level variation was not accounted for in the model, a detrimental effect of prior treatment of the sow was seen but this turned into a beneficial effect when we accounted for the herd-level variation. The treatment of sow refers to any therapeutic treatment given to the sow after farrowing but before lameness or weaning occurred. This is, therefore, an example where not only the variances but also the effect parameters changed when we accounted for herd-level variation.

Animal Husbandry↗
PubMed1999

Salmonella level of Danish swine herds based on serological examination of meat-juice samples and Salmonella occurrence measured by bacteriological follow-up.

Analyses of data collected in the Danish Salmonella Control Program in swine herds were conducted to assess the association between bacteriological and serological findings (including the degree to which changing serological status over time modulated the relationship) and to assess the degree to which type of swine operation and age group affected the relationship between bacteriological and serological findings. Although serological status was significantly associated with bacteriological prevalence of salmonella enterica in swine herds, the association was clarified by adding information on the change in serological status over time and the age group being tested. Salmonella infection assessed by serological tests at a single time-point and data on age group tested would allow better targeting and managing control programs.

Animals↗
PubMed1999

Numerical simulation of motility patterns of the small bowel. 1. formulation of a mathematical model.

A complete mathematical model of the periodic myoelectrical activity of a functional unit of the small intestine is presented. Based on real morphological and electrophysiological data, the model assumes that: the functional unit is an electromyogenic syncytium; the kinetics of L-type Ca2+, T-type Ca2+, Ca2+-activated K+, voltage dependent K+and Cl-channels determine the electrical activity of the functional unit; the enteric nervous system is satisfactorily represented by an efferent cholinergic neuron that provides an excitatory input to the functional unit through receptor-linked L-type Ca2+channels and by an afferent pathway composed of the primary and secondary sensory neurons; the dynamics of propagation of the wave of depolarization along the unmyelinated nerve axons satisfy the Hodgkin-Huxley model; the electrical activity of the neural soma reflects the interaction of N-type Ca2+channels, Ca2+-activated K+and voltage dependent Na+, K+and Cl-channels; the smooth muscle syncytium of the locus is a null-dimensional contractile system. With the proposed model the dynamics of active force generation are determined entirely by the concentration of cytosolic calcium. The model describes: the mechanical excitation of the free nerve endings of the mechanoreceptor of the receptive field of the pathway; the electrical processes of the propagation of excitation along the afferent and efferent neural circuits; the chemical mechanisms of nerve-pulse transmission at the synaptic zones; the slow wave and bursting type electrical activity; cytosolic calcium concentration; the dynamics of active force generation. Numerical simulations have shown that the model can display different electrical patterns and mechanical responses of the locus. The results show good qualitative and quantitative agreement with the results of experiments conducted on the small intestine.

Enteric Nervous System↗
PubMed1999

[Effects of admission qualifications on medical education].

We investigated the relationship between admission qualifications and the course and result of university medical education. In the period 1981-1983 685 medical students started at Aarhus University, and 501 (73%) obtained a medical degree within 13 years. The completion rate was heavily influenced by the type of admission qualifications. Students with a science background did best (79%), languages background somewhat worse (62%) whereas the completion rate was 44% for students with a Higher Preparatory Examination. After stratifying for type and grades obtained at admission qualification, gender did not influence the outcome. A positive correlation was found between grade at the admission qualification and the completion rate, but when the grades were above average (8.0) this correlation was weak and insignificant. A delay of more than two years from the admission exam to admission was associated with a significantly increased drop-out rate.

Adult↗
PubMed1999

Early postnatal development of the rat corticostriatal pathway: an anterograde axonal tracing study using biocytin pellets.

UNLABELLED: The ontogenetic development of the neocortical projections to the striatum was studied in postnatal rats by sensitive anterograde tracing with biocytin. The developmental status of this mainly glutamatergic pathway is important as it plays a major role in regulation of striatal maturation and induction of excitotoxic striatal neurodegeneration resembling the type found in Huntington's disease. Biocytin pelletts were injected into the motorcortex caudal forelimb area of newborn rats and of rats aged 3, 6, 13, 27 and 61 days followed by sacrifice and visualisation of the tracer 24 h later, at P1, P7, P14, P28 and P62, respectively. Biocytin pellets were also injected into the motorcortex jaw-lip-tongue area and into the cingulate cortex of newborn and 6-day-old rats. The biocytin pellets produced intense anterograde labelling of corticofugal projection fibres from the injection sites, as well as a local Golgi-like labelling of neurons. From postnatal day 1 into adult age efferent fibres from the motorcortex caudal forelimb area displayed a progressively denser innervation of the ipsilateral and contralateral, dorsolateral striatum. The terminating fibres were most dense in the ipsilateral striatum. In the dorsolateral striatum the corticostriatal fibres displayed a patch/matrix-like arrangement from postnatal day 14 onwards. Injections into the motorcortex jaw-lip-tongue area at postnatal days 0 and 6 displayed a progressive, denser innervation of the ipsilateral and contralateral ventrolateral striatum. The cingulate corticostriatal fibre projection, was more developed at birth than the projection from the motorcortex and increased its fibre density in the ipsilateral dorsomedial striatum up to at least day 7. IN CONCLUSION: the ipsilateral corticostriatal projections from the rat motorcortex and cingulate areas are present in newborn rats. During postnatal life the pathway develops further and specialisation of the terminating fibres into a patch/matrix like arrangement can be identified by postnatal day 14.

Afferent Pathways↗
PubMed1999

Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and permeability factor that is potently angiogenic in vivo. We report here studies that suggest that VEGF potentiates angiogenesis in vivo and prolongs the survival of human dermal microvascular endothelial cells (HDMECs) in vitro by inducing expression of the anti-apoptotic protein Bcl-2. Growth-factor-enriched and serum-deficient cultures of HDMECs grown on collagen type I gels with VEGF exhibited a 4-fold and a 1.6-fold reduction, respectively, in the proportion of apoptotic cells. Enhanced HDMEC survival was associated with a dose-dependent increase in Bcl-2 expression and a decrease in the expression of the processed forms of the cysteine protease caspase-3. Cultures of HDMECs transduced with and overexpressing Bcl-2 and deprived of growth factors showed enhanced protection from apoptosis and exhibited a twofold increase in cell number and a fourfold increase in the number of capillary-like sprouts. HDMECs overexpressing Bcl-2 when incorporated into polylactic acid sponges and implanted into SCID mice exhibited a sustained fivefold increase in the number of microvessels and a fourfold decrease in the number of apoptotic cells when examined 7 and 14 days later. These results suggest that the angiogenic activity attributed to VEGF may be due in part to its ability to enhance endothelial cell survival by inducing expression of Bcl-2.

Animals↗
PubMed1999

Extensive and symptomatic cranial pneumatization: caused by frequent performance of Valsalva's manoeuvre?

Pneumocranium and spontaneous pneumocephalus are very rare disorders. We report a case in which the patient had suffered for some time from neck pain and neurological symptoms which originated from an extensively pneumatized cranium. The symptoms and the abnormal bone pneumatization disappeared after normalization of a high middle-ear pressure. The history and the findings suggest that the pathological pneumatization was caused by the patient's habit of frequently performing Valsalva's manoeuvre, in combination with the Eustachian tube functioning as a valve.

Adult↗
PubMed1999

Epitope mapping of Aleutian mink disease parvovirus virion protein VP1 and 2.

Six overlapping fragments of the Aleutian Mink Disease parvoVirus (AMDV) virion protein VP1 and 2 (VP1/2) gene were inserted into the expression vector pMAL-c2. Four of the clones carried large overlapping fragments covering the entire VP1/2 gene. The remaining two clones covered specifically chosen regions within the VP1/2 gene. Using a Western blotting detection system, sera from AMDV-infected mink were tested against the recombinant polypeptides. These studies showed reactions primarily directed against the two AMDV polypeptides ranging from amino acids 297 to 518. Weaker reactions against other regions of the VP1/2 were also observed. The small fusion protein designed to cover the presumed AMDV VP1/2 loop 4 was purified by affinity chromatography and used to develop solid-phase immunoassays. Twelve small synthetic peptides were constructed and used as inhibitors. A peptide covering amino acids S428 to T448 was shown to block the reactivity of a pool of positive mink sera, indicating the presence of one dominant linear epitope.

Aleutian Mink Disease↗
PubMed1999

Three-dimensional structure of Aleutian mink disease parvovirus: implications for disease pathogenicity.

The three-dimensional structure of expressed VP2 capsids of Aleutian mink disease parvovirus strain G (ADVG-VP2) has been determined to 22 A resolution by cryo-electron microscopy and image reconstruction techniques. A structure-based sequence alignment of the VP2 capsid protein of canine parvovirus (CPV) provided a means to construct an atomic model of the ADVG-VP2 capsid. The ADVG-VP2 reconstruction reveals a capsid structure with a mean external radius of 128 A and several surface features similar to those found in human parvovirus B19 (B19), CPV, feline panleukopenia virus (FPV), and minute virus of mice (MVM). Dimple-like depressions occur at the icosahedral twofold axes, canyon-like regions encircle the fivefold axes, and spike-like protrusions decorate the threefold axes. These spikes are not present in B19, and they are more prominent in ADV compared to the other parvoviruses owing to the presence of loop insertions which create mounds near the threefold axes. Cylindrical channels along the fivefold axes of CPV, FPV, and MVM, which are surrounded by five symmetry-related beta-ribbons, are closed in ADVG-VP2 and B19. Immunoreactive peptides made from segments of the ADVG-VP2 capsid protein map to residues in the mound structures. In vitro tissue tropism and in vivo pathogenic properties of ADV map to residues at the threefold axes and to the wall of the dimples.

Aleutian Mink Disease↗