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Biomedical subjects

B Andersen

Publications and source records attributed to B Andersen.

At least 37 records · Page 2Linked to original sources

NMR studies on metal complexes of DNA oligomers.

A short overview of NMR spectroscopic applications for the study of metal ion complexes of DNA oligomers is presented. One typical example is given to illustrate the scope of the methods: the NMR structure of a trans-DDP interstrand cross-linked duplex, d(CTCCTG*TGTCTC) x d(GAGATA*AGGAG). The solution structure of this double-stranded DNA oligonucleotide, containing a trans-diammineplatinum(II) interstrand cross-link, was determined using two-dimensional nuclear magnetic resonance (2D NMR) and NOE-restrained molecular dynamics and energy minimization refinement. The duplex is a non-palindromic 12/11-mer with a missing central residue in the lower strand and in addition it contains a GT mismatched base pair. The analysis indicated that an interstrand cross-link is established between G6-N7 of the upper strand and A18-N1 of the lower strand.

Base Sequence↗

Inhibition of glycogenolysis in primary rat hepatocytes by 1, 4-dideoxy-1,4-imino-D-arabinitol.

1,4-Dideoxy-1,4-imino-d-arabinitol (DAB) was identified previously as a potent inhibitor of both the phosphorylated and non-phosphorylated forms of glycogen phosphorylase (EC 2.4.1.1). In the present study, the effects of DAB were investigated in primary cultured rat hepatocytes. The transport of DAB into hepatocytes was dependent on time and DAB concentration. The rate of DAB transport was 192 pmol/min per mg of protein per mM DAB(medium-concentration). In hepatocytes, DAB inhibited basal and glucagon-stimulated glycogenolysis with IC(50) values of 1.0+/-0.3 and 1.1+/-0.2 microM, respectively. The primary inhibitory effect of DAB on glycogenolysis was shown to be due to inhibition of glycogen phosphorylase but, at higher concentrations of DAB, inhibition of the debranching enzyme (4-alpha-glucanotransferase, EC 2.4.1.25) may have an effect. No effects on glycogen synthesis were observed, demonstrating that glycogen recycling does not occur in cultured hepatocytes under the conditions tested. Furthermore, DAB had no effects on phosphorylase kinase, the enzyme responsible for phosphorylation and thereby activation of glycogen phosphorylase, or on protein phosphatase 1, the enzyme responsible for inactivation of glycogen phosphorylase through dephosphorylation.

Animals↗

Midlatency auditory-evoked potentials in the rat: effects of interventions that modulate arousal.

The vertex-recorded P13 midlatency auditory-evoked potential in the rat shows the same characteristics as the P1 potential in the human, namely, sleep-state dependence, rapid habituation and blockade by the cholinergic antagonist scopolamine. The P13 potential appears to be generated, at least in part, by projections of the pedunculopontine nucleus, the cholinergic arm of the reticular activating system. On the other hand, the auditory cortex-recorded P7 potential appears to be of primary cortical origin. Simultaneous recordings from the vertex and the auditory cortex showed that (1) the P13 potential was suppressed by administration of the anesthetics ketamine, pentobarbital or halothane in a dose-dependent manner, but the P7 potential was not; (2) the P13 potential was suppressed by intragastric injections of ethanol in a dose-dependent manner, but the P7 potential was not; (3) the amplitude of the P13 potential was negatively correlated with blood ethanol levels; (4) both the P13 and P7 potentials were still present following injections of the neuromuscular blocker pancuronium bromide; and (5) both the P13 and P7 potentials were decreased by diffuse brain injury induced by a weight-drop device in a weight-dependent manner. These findings suggest that the P13 potential is more sensitive than the P7 potential to changes in arousal and that the P13 and P7 potentials are not of myogenic but of neural origin.

Anesthetics↗

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.

Adult↗

Production of mycotoxins on artificially and naturally infested building materials.

In this study, the ability to produce mycotoxins during growth on artificially infested building materials was investigated for Penicillium chrysogenum, Pen. polonicum, Pen. brevicompactum, Chaetomium spp., Aspergillus ustus, Asp. niger, Ulocladium spp., Alternaria spp., and Paecilomyces spp., all isolated from water-damaged building materials. Spores from the different isolates of the above mentioned species were inoculated on gypsum board with and without wallpaper and on chipboard with and without wallpaper. Fungal material was scraped off the materials, extracted, and analyzed using high performance liquid chromatography-diode array detection and thin layer chromatography. All six isolates of C. globosum produced the toxic chaetoglobosins A and C, at levels of up to 50 and 7 microg/cm2 respectively. The quantities of secondary metabolites produced by Penicillia were generally low, and no toxin production was detected from any of the five isolates of Pen. chrysogenum. Both isolates of Pen. polonicum produced 3-methoxy-viridicatin, verrucosidin, and verrucofortine. Two of five isolates of Pen. brevicompactum produced mycophenolic acid. From five out of six isolates of Alternaria spp., altenariol and alternariol monomethyl ether were detected. From Ulocladium spp., Paecilomyces spp., and Asp. ustus no known mycotoxins were detected, although the latter two are known mycotoxin producers. Asp. niger produced several naphtho-gamma-pyrones and tetra-cyclic compounds. All investigated species, especially Asp. ustus and Asp. niger produced many unknown secondary metabolites on the building materials. Analyses of wallpaper and glass-fibre wallpaper naturally infested with Asp. versicolor revealed sterigmatocystin and 5-methoxysterigmatocystin. Analyses of naturally infested wallpaper showed that C. globosum produced the chaetoglobosins A and C, and Pen. chrysogenum produced the antibiotic meleagrin.

Chromatography, High Pressure Liquid↗

RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex.

LIM domains are required for both inhibitory effects on LIM homeodomain transcription factors and synergistic transcriptional activation events. The inhibitory actions of the LIM domain can often be overcome by the LIM co-regulator known as CLIM2, LDB1 and NLI (referred to hereafter as CLIM2; refs 2-4). The association of the CLIM cofactors with LIM domains does not, however, improve the DNA-binding ability of LIM homeodomain proteins, suggesting the action of a LIM-associated inhibitor factor. Here we present evidence that LIM domains are capable of binding a novel RING-H2 zinc-finger protein, Rlim (for RING finger LIM domain-binding protein), which acts as a negative co-regulator via the recruitment of the Sin3A/histone deacetylase corepressor complex. A corepressor function of RLIM is also suggested by in vivo studies of chick wing development. Overexpression of the gene Rnf12, encoding Rlim, results in phenotypes similar to those observed after inhibition of the LIM homeodomain factor LHX2, which is required for the formation of distal structures along the proximodistal axis, or by overexpression of dominant-negative CLIM1. We conclude that Rlim is a novel corepressor that recruits histone deacetylase-containing complexes to the LIM domain.

Amino Acid Sequence↗

Impact of menstrual cycle on the diagnostic performance of LCR, TMA, and PCE for detection of Chlamydia trachomatis in home obtained and mailed vaginal flush and urine samples.

OBJECTIVES: To assess the impact of the menstrual cycle on the diagnostic performance of various assays for detection of Chlamydia trachomatis in home obtained and mailed vaginal flush and urine specimens. METHODS: A ligase chain reaction assay (LCR; Abbott Laboratories), a transcription mediated amplification assay (TMA; Gen-Probe), and an enzyme amplified immunoassay (PCE; Dako Diagnostics) were evaluated for their validity in detecting C trachomatis in vaginal flush, first void urine, and midstream urine specimens obtained by female high school students at home and mailed directly to the diagnostic laboratory. RESULTS: C trachomatis was detected in 45 of 889 females (5.1%). The vaginal flush material was positive by TMA and LCR in 84% and 82% of the chlamydia positive females, respectively. First void urine was positive by TMA in 73% and by LCR in 49% of the cases. Midstream urine was positive by TMA and LCR in 69% and 42% of the females, respectively. On a pool of first void and midstream urine, PCE detected 49% of the chlamydia positive females. The overall prevalence of C trachomatis increased with increasing time after the last menstrual bleeding. In urine samples, but not vaginal flush specimens, obtained 3 weeks after the last menstrual bleeding, the sensitivities of TMA, LCR, and PCE decreased markedly suggesting that inhibitors to the assays are excreted in the urine but not in vaginal secretions at this time. CONCLUSION: Vaginal flush samples are superior to urines for detection of chlamydia infections in females. In screening of young asymptomatic females, samples should be obtained in the latter part of the menstrual cycle.

Adolescent↗

Expression of LMO-4 in the central nervous system of the embryonic and adult mouse.

LMO (LIM-only) proteins constitute a family of coregulators thought to act as adapters in transcriptionally active complexes. In this manuscript, we describe in situ hybridization studies to elucidate the expression of the recently identified LMO-4 in embryonic and adult mouse brain. We found that LMO-4 expression was very widespread at early (E10.5-11.5) embryonic stages with more intense hybridization signal in certain regions. The expression became more regionalized over mid (E14.5-15.5) and late (E17.5-P0) embryonic stages. Throughout development the ventricular zone, consisting of less differentiated cells, showed less intense signal than the subventricular and marginal zones. Further, expression of LMO-4 in and surrounding myelinating axons, representing Schwann cells, was seen at late embryonic stages. In the adult brain, a restricted number of regions displayed significant LMO-4 expression. Interestingly, these were the same regions that showed most consistent and intense hybridization signal during embryonic development. These regions included the cerebral cortex (layer 2-6), the hippocampus (e.g., the CA3 layer), the dentate gyrus, the basal ganglia, the lateral amygdala, olfactory structures, the paraventricular, dorsomedial and ventromedial hypothalamic nuclei, zona incerta, intralaminar and reticular nuclei of the ventral thalamus, medullary motor structures and the cerebellum. In summary, the regionalized expression of LMO-4 during development suggest a role for this gene in differentiation and specification of specific brain regions involved in various functions, such as autonomic, motor and neuroendocrine regulation.

Adaptor Proteins, Signal Transducing↗

Appendicitis in pregnancy: diagnosis, management and complications.

BACKGROUND: Acute appendicitis is the most common surgical emergency in pregnancy. The purpose of this study is to investigate the clinical presentation, management and outcome in patients who underwent appendectomy during pregnancy. MATERIAL AND METHODS: The case records of 56 women who underwent appendectomy during pregnancy between January 1985 and December 1997 were reviewed and analyzed. RESULTS: The incidence of appendicitis in pregnancy was one in 766 births. The preoperative diagnosis was correct in 75% of the cases. Uterine contractions and a history of diffuse or periumbilical pain migrating to the right lower abdominal quadrant were significantly more frequent among women with appendicitis compared to those patients where the appendectomy revealed a normal appendices. Abdominal pain, nausea, vomiting, leukocyte count, CRP and body temperature were not helpful in establishing the correct diagnosis. There was no maternal morbidity related to the appendectomy. Pregnancy complications were found to be considerable: 4/12 (33%) who underwent appendectomy for appendicitis during the first trimester aborted spontaneously. Second trimester appendectomy for appendicitis was followed by premature delivery in 4/28 (14%). However, no pregnancy complications were observed following third trimester appendectomy for appendicitis. We found no increase in pregnancy complications in cases with perforated appendicitis. CONCLUSION: Appendicitis in pregnancy should be suspected when a pregnant woman complains of new abdominal pain. No laboratory finding was found to be diagnostic for acute appendicitis during pregnancy. Considerable fetal loss was found after appendectomy during pregnancy in the first and second trimester. No increase in pregnancy complications in cases with perforated appendicitis was observed. The combination of symptoms and clinical judgement is still vital in deciding which patient needs surgical treatment. Based on the results in the present study we recommend prophylactic antibiotic treatment in all laparotomies during pregnancy when appendicitis is suspected.

Abortion, Spontaneous↗

Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators.

Nuclear LIM domains interact with a family of coregulators referred to as Clim/Ldb/Nli. Although one family member, Clim-2/Ldb-1/Nli, is highly expressed in epidermal keratinocytes, no nuclear LIM domain factor is known to be expressed in epidermis. Therefore, we used the conserved LIM-interaction domain of Clim coregulators to screen for LIM domain factors in adult and embryonic mouse skin expression libraries and isolated a factor that is highly homologous to the previously described LIM-only proteins LMO-1, -2, and -3. This factor, referred to as LMO-4, is expressed in overlapping manner with Clim-2 in epidermis and in several other regions, including epithelial cells of the gastrointestinal, respiratory and genitourinary tracts, developing cartilage, pituitary gland, and discrete regions of the central and peripheral nervous system. Like LMO-2, LMO-4 interacts strongly with Clim factors via its LIM domain. Because LMO/Clim complexes are thought to regulate gene expression by associating with DNA-binding proteins, we used LMO-4 as a bait to screen for such DNA-binding proteins in epidermis and isolated the mouse homologue of Drosophila Deformed epidermal autoregulatory factor 1 (DEAF-1), a DNA-binding protein that interacts with regulatory sequences first described in the Deformed epidermal autoregulatory element. The interaction between LMO-4 and mouse DEAF-1 maps to a proline-rich C-terminal domain of mouse DEAF-1, distinct from the helix-loop-helix and GATA domains previously shown to interact with LMOs, thus defining an additional LIM-interacting domain.

Adaptor Proteins, Signal Transducing↗

The human D1A dopamine receptor: heterologous expression in Saccharomyces cerevisiae and purification of the functional receptor.

Functional human D1A dopamine receptor has been expressed in Saccharomyces cerevisiae. The primary sequence of the receptor was modified to include two affinity tags at the C-terminus of the protein, a FLAG tag (DYKDDDDK), and a His6 tag (HHHHHH). These modifications allowed for purification to near homogeneity using immobilized metal affinity chromatography and immunoaffinity chromatography. Radioligand binding demonstrated that the purified and reconstituted receptor binds the antagonist [3H]SCH23390 with an affinity (KD = 8.0 +/- 3.2 nM) comparable to that of the native receptor.

Amino Acid Sequence↗

Methylergometrine during the early puerperium; a prospective randomized double blind study.

BACKGROUND: The purpose of the study was to determine the efficacy of 72-hour prophylactic oral methylergometrine in reducing postpartum hemorrhage and endometritis during the early puerperium, and the effect of methylergometrine on lochia and requests for analgesics. MATERIAL AND METHODS: A prospective randomized double-blind study was undertaken; a total of 217 women received 0.2 mg methylergometrine intravenously after delivery of the placenta and randomized to either tabl. Methergin 0.125 mg or placebo three times a day for three days. The main measures were weight of sanitary towels, temperature, consumptions of analgesics and length of hospital stay. RESULTS: We found no significant difference in the median amount of lochia, the need for analgesics or length of hospital stay between the two groups. Incidence of infection and postpartum hemorrhage were low in both groups. CONCLUSION: We conclude that prophylactic use of methylergometrine during early puerperium has no effect on lochia. Endometritis and postpartum hemorrhage were rare in both groups. There was no increase in requests for analgesics among women given oral methylergometrine.

Administration, Oral↗

Urogenital Chlamydia trachomatis infections in general practice: diagnosis, treatment, follow-up and contact tracing.

BACKGROUND: Patients with urogenital Chlamydia trachomatis infection are frequently seen in general practice. It is, therefore, important to assess GPs' management of these patients in order to ensure adequate control of the disease. OBJECTIVE: We aimed to evaluate the GPs' routines in diagnosis, medical treatment, follow-up and contact tracing according to knowledge/attitude (criteria) and actual performance. METHODS: The study comprised the 388 GPs in the County of Aarhus. Two questionnaires were used. The first questionnaire was mailed to each of 252 GPs who had attended a patient with urogenital C. trachomatis infection 4 weeks previously. Each GP was asked about his/her actual performance for that particular patient. In order to elucidate the GPs' criteria, the second questionnaire was mailed to each of the 388 GPs in the County of Aarhus, asking about their usual intended routines (criteria) for managing urogenital C. trachomatis infections. The questionnaires covered the same topics. RESULTS: Great variations among the GPs' management of urogenital C. trachomatis infection according to sampling-site, medical treatment, follow-up and contact tracing were found. Furthermore, a discrepancy between criteria and actual performance for obtaining an urethral swab-sample in women and for contact tracing of previous partners were demonstrated. The GPs stated that they had intended to obtain more urethral swab-samples and do more contact tracing than they actually did. CONCLUSIONS: We conclude that increasing the collection of urethral samples from women combined with greater emphasis on contact tracing procedures might limit the prevalence of the infection. In order to achieve this, continuous medical education and auditing procedures on urogenital chlamydial infections may be helpful.

Anti-Bacterial Agents↗

[Self-collected and mailed samples for diagnosis of urogenital Chlamydia trachomatis infection in women].

The study compared urine and vaginal flush samples, collected by women at home by endocervical and urine swabs obtained from their general practitioners, for their efficacy in the diagnosis of Chlamydia trachomatis infection. The study was a multipractice study in 33 general practices. A total of 222 women aged 18-25 years, who attended the general practitioner for a gynaecological examination, were included. Diagnostic tests-eight per woman-were performed by the polymerase chain reaction and the ligase chain reaction. A test was considered true positive if two tests or more were positive The prevalence of infection was 11.2% (23/205). Test sensitivity in samples obtained by general practitioners, samples obtained at home subjected to polymerase chain reaction, and samples obtained at home subjected to ligase chain reaction were 91%, 96%, and 100% respectively. The corresponding specificities were 100%, 92.9% and 99.5%. It is concluded that the diagnostic efficacy of samples obtained at home is as good as tests obtained by the general practitioner.

Adolescent↗