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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 91 records · Page 5Linked to original sources

Rat fetuin: distribution of protein and mRNA in embryonic and neonatal rat tissues.

Fetuin is a serum protein widely distributed in the animal kingdom and found in all mammalian species so far investigated. It is mainly a fetal protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E 10Fetuin is a serum protein widely distributed in the animal kingdom and found in all mammalian species so far investigated. It is mainly a fetal protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E16-E18. Fetuin expression was present in germinal cell populations, e.g., in the basal layer in the skin, in the germinal cell populations in the brain anlage and the gonads, and it was heavily expressed in the fetal hemopoietic liver. Furthermore, fetuin was expressed in the gastrointestinal epithelium prior to the development of glands and crypts. Fetuin was widely distributed in mesenchymal derived tissues, e.g., bone and muscle. In the developing kidney fetuin was heavily expressed is both mesenchymal condensations and glomerular anlages. Thus, fetuin was located in cells or structures undergoing differentiation and transformation. As fetuin has been shown previously to interfere with hormone signaling of transforming growth factor-beta, insulin and hepatocyte-growth factor, fetuin might be involved in cell differentiation and tissue transformation during the initial histogenesis, i.e., the time period in which cellular phenotypic characteristics are established.

Animals↗

Group I-like ribozymes with a novel core organization perform obligate sequential hydrolytic cleavages at two processing sites.

A new category of self-splicing group I introns with conserved structural organization and function is found among the eukaryotic microorganisms Didymium and Naegleria. These complex rDNA introns contain two distinct ribozymes with different functions: a regular group I splicing-ribozyme and a small internal group I-like ribozyme (GIR1), probably involved in protein expression. GIR1 was found to cleave at two internal sites in an obligate sequential order. Both sites are located 3' of the catalytic core. GIR1-catalyzed transesterification reactions could not be detected. We have compared all available GIR1 sequences and propose a common RNA secondary structure resembling that of group I splicing-ribozymes, but with some important differences. The GIR1s lack most peripheral sequence components, as well as a P1 segment, and, at approximately 160-190 nt, they are the smallest functional group I ribozymes known from nature. All GIR1s were found to contain a novel 6-bp pseudoknot (P15) within their catalytic core region. Experimental support of the proposed structure was obtained from the Didymium GIR1 by RNA structure probing and site-directed mutagenesis. Three-dimensional modeling indicates a compactly folded ribozyme with the functionally essential P15 exposed in the cleft between the two principal domains P3-P8 and P4-P6.

Animals↗

Humerospinous distance measurements: accuracy and usefulness for predicting shoulder dystocia in delivery at term.

OBJECTIVE: To investigate if the humerospinous distance, as an indicator of shoulder width, could predict shoulder dystocia at term. DESIGN: Prospective cross-sectional study of a stratified reference group of healthy women and a test group of women with risk factors for shoulder dystocia. Measurements were not revealed. Outcome measures were difficulties with delivery of the shoulders and correlation with maternal body mass and birth weight. SUBJECTS: Seventy-two women with singleton pregnancies at a University Clinic: 32 women at 39-42 weeks for reference and 40 women in an at-risk test group (weight > 90 kg, weight gain > 20 kg, previous macrosomic baby, history of shoulder dystocia/difficult delivery, clinical suspicion of a large baby). Women with a breech fetus, twins and those not able to deliver vaginally were excluded. METHODS: Fetal shoulders were measured from the convergence of the cervical spinous processes at the approximate cervicothoracic vertebral junction to the medial border of the humeral head. Correlations were made with maternal body mass, birth weight, birth weight estimation, ultrasound and postnatal humerospinous measurements. RESULTS: One case of shoulder dystocia in a fetus with an average humerospinous measurement occurred in the reference group and there were no cases in the test group. There was no predictive value of a large humerospinous measurement and no correlation with maternal or fetal size. Movement of the fetal arm could change the humerospinous distance considerably, which could account for the difference between a normal and large measurement. CONCLUSION: The humerospinous distance cannot be used to predict shoulder dystocia.

Adult↗

Studies on mast cells and histamine release in psoriasis: the effect of ranitidine.

The purpose of this study was to investigate histamine and skin mast cells in psoriasis before and during 6 months of treatment with high-dose ranitidine. Sixteen psoriasis patients, presenting a mean PASI score of 15.4, were compared with 13 age- and sex-matched healthy controls. Resting extracellular skin levels of histamine and histamine release to mast cell secretagogues, as measured by the microdialysis technique, were increased in involved psoriasis skin compared to normal skin in the controls. Plasma histamine, but not basophil histamine release, was significantly increased in the patients. Mast cells and lymphocytes were significantly increased in numbers in involved versus non-involved skin in the patients, the lymphocytes being predominantly T-lymphocytes expressing HLA-DR activation. During 6 months of ranitidine treatment, mean PASI score of 15.4 decreased to 5.8. The lymphocyte infiltration, but not mast cell numbers, was significantly reduced during treatment, and histamine release to mast cell secretagogues was normalized. These observations suggest that skin mast cells in active psoriasis are functionally hyperreactive. The biochemical findings together with the clinical effect of ranitidine indicate that histamine may be involved in the pathophysiology of psoriasis.

CD4-CD8 Ratio↗

Hen age and fatty acid composition of egg yolk lipid.

1. Total lipid, total cholesterol, and phospholipid contents per gram of egg yolk were found to be the same for eggs from 21 and 57 week-old hens. 2. In contrast, fatty acid composition of total egg yolk lipid was different for the 2 groups of hens. The contents of long-chain (20 C and 22 C) polyunsaturated fatty acids of n-6 and n-3 series were 20% to 25% higher in egg yolks from the younger hens. 3. This finding is discussed with respect to the nutritional value of eggs from hens of different ages regarding the use of egg yolk lipid in the production of infant formulae.

Aging↗

Rapid loss of specific antibodies after pneumococcal vaccination in patients with human immunodeficiency virus-1 infection.

Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.

Acquired Immunodeficiency Syndrome↗

Fluconazole therapy in Candida albicans spondylodiscitis.

A case of Candida albicans spondylodiscitis in a 20-year-old female liver transplant recipient is reported. The patient was successfully treated with sequential therapy with liposomal amphotericin B and fluconazole. A review of the literature showed 10 cases of Candida albicans spondylodiscitis successfully treated either with fluconazole alone or a sequential therapy with amphotericin B and fluconazole. If long-term amphotericin B therapy is not feasible, a prolonged course of fluconazole in a daily dose of 200-400 mg may be considered as an alternative.

Adult↗

Improvement in long-term prognosis of elderly patients with acute myocardial infarction after the introduction of intravenous thrombolytic therapy.

Survival rate from a "thrombolytic" period of 351 patients above 66 years of age with acute myocardial infarction (AMI) was compared with that of 289 patients from a "prethrombolytic" period. The two groups were comparable regarding sex, age, previous AMI, cerebrovascular events, morbidity and mortality during admission. Survival rates after four years were 45.0% in the "thrombolytic" group and 38.4% in the "prethrombolytic" group (p = 0.047, log rank test). Using the Cox proportional hazard analysis, thrombolytic therapy was shown to be an independent prognostic predictor in "the thrombolytic population" with a relative risk of death from day 30 to end of follow-up of 0.4 (95% confidence interval 0.2-0.8). No interaction was found between age and thrombolysis. Although only one-fifth of the patients with AMI were eligible for thrombolysis, this treatment may have contributed to the improved long-term survival.

Aged↗

Age-associated memory impairment--pathological memory decline or normal aging?

The aim of the study was to determine whether the memory capacity of individuals with age-associated memory impairment (AAMI) over a period of approximately 3 1/2 years declines more, if at all, than the memory capacity of persons without AAMI. Four computerized and three non-computerized memory tests, a naming test, and a test of visuo-motor speed were administered twice. Two estimates of intellectual capacity were made, one at the first examination and the other 3 1/2 years later. One person in the AAMI group (n = 44) developed vascular dementia. The group of AAMI subjects did less well on two of the seven memory tests after 3 1/2 years than they did initially; the control group (n = 18) had lower scores on one memory test at follow-up than they had previously. The data suggest that the memory capacity of subjects with AAMI is not pathologically impaired. The general intellectual level significantly influences whether an individual with memory complaints will be classified AAMI or not. People with high intelligence are less likely than people with lower intellectual capacity to fulfill the AAMI criteria. This suggests that AAMI lacks in construct validity.

Aged↗

Association of pulmonary surfactant protein A (SP-A) gene and respiratory distress syndrome: interaction with SP-B.

Deficiency of the lipoprotein complex, surfactant, can lead to respiratory distress syndrome (RDS) in the prematurely born infant. The surfactant proteins (SP) play important roles in the function of surfactant. Previously, we have characterized four allelic variants of the SP-A1 gene (6A, 6A2, 6A3, and 6A4) and five allelic variants of the SP-A2 gene (1A, 1A0, 1A1, 1A2, and 1A3). We hypothesized that specific SP-A alleles/genotypes are associated with increased risk of RDS. Because race, gestational age (GA), and sex are risk factors for RDS, we first studied the distribution and frequencies of SP-A alleles/genotypes while adjusting for these factors as confounders or effect modifiers in control (n = 86 white and 12 black subjects) and RDS (n = 106 white and 37 black subjects) populations with GAs ranging from 24 wk to term. Although the odds ratios of several alleles and genotypes were in the opposite directions for black and white subjects, the homogeneity of odds ratio reached statistical significance only in the case of 6A3/6A3. Although differences were observed in subgroups with different GAs (< or =28 and >28 wk) of the RDS white population, definitive conclusions cannot be made regarding the effect of modification by GA. No differences were observed as a function of sex. Second, we compared the frequencies of SP-A genotypes and alleles between control (n = 83) and RDS (n = 82) patients in the >28-wk white population. Differences between the two groups were observed for the 1A0 allele and 1A0 genotypes. Moreover, a significant synergistic positive association was observed between 1A0 allele + SP-B polymorphic variant and RDS. We conclude that 1) the genetic analyses of RDS and SP-A locus should be performed separately for black and white populations and 2) SP-A alleles/genotypes and SP-B variant may contribute to the etiology of RDS and/or may serve as markers for disease subgroups.

Alleles↗

Prediction of signal peptides and signal anchors by a hidden Markov model.

A hidden Markov model of signal peptides has been developed. It contains submodels for the N-terminal part, the hydrophobic region, and the region around the cleavage site. For known signal peptides, the model can be used to assign objective boundaries between these three regions. Applied to our data, the length distributions for the three regions are significantly different from expectations. For instance, the assigned hydrophobic region is between 8 and 12 residues long in almost all eukaryotic signal peptides. This analysis also makes obvious the difference between eukaryotes, Gram-positive bacteria, and Gram-negative bacteria. The model can be used to predict the location of the cleavage site, which it finds correctly in nearly 70% of signal peptides in a cross-validated test--almost the same accuracy as the best previous method. One of the problems for existing prediction methods is the poor discrimination between signal peptides and uncleaved signal anchors, but this is substantially improved by the hidden Markov model when expanding it with a very simple signal anchor model.

Artificial Intelligence↗

Effect of genetic variation on the fatty acid-binding properties of human serum albumin and proalbumin.

In the circulation, non-esterified fatty acids are transported by albumin which also facilitates their removal from donor cells and uptake into receptor cells. We have studied whether genetic variations in the albumin molecule can affect its in vivo fatty acid-binding properties. The fatty acids bound to 25 structurally different variants and to their wildtype counterparts, isolated from heterozygous carriers, were determined gas chromatographically. The variants were proalbumins, albumins with single amino acid substitutions and glycosylated or truncated albumins. In eight cases the total amount bound to the variants was diminished (0.4-0.8-fold), and in seven cases the load was increased to 1.3 or more of normal. Twenty-one fatty acids were quantitated, and for 19 alloalbumins significant deviations from normal were found. Usually, changes in total and individual fatty acid binding were of the same type, but several exceptions to this rule was found. The glycosylated albumin Casebrook showed the largest changes, the total load and the amount of bound palmitate was 8.6 and 14 times, respectively, the normal. The most pronounced changes and the majority of cases of increased binding were caused by molecular changes in domain III. Mutations in domain I, II and the propeptide resulted in smaller effects, if any, and these were often reductions in binding.

Amino Acid Sequence↗

Increased in vivo antibody activity against interferon alpha, interleukin-1alpha, and interleukin-6 after high-dose Ig therapy.

High-avidity antibodies against interferon alpha (IFN alpha), interleukin-1alpha (IL-1alpha), and IL-6 have been demonstrated in preparations of normal human IgG, and in vivo modulation of these cytokines may therefore account for immunomodulatory and anti-inflammatory effects of high-dose intravenous IgG therapy. We have investigated the in vivo recovery and the effect on serum cytokine levels of antibodies to IFN alpha, IL-1alpha, and IL-6 infused with IgG preparations. Fifteen treatment series of 0.4 g IgG/kg/d were administered over 3 days to eight patients with autoimmune diseases. All IgG preparations contained variable amounts of antibodies binding to 125I-labeled human IFN alpha2A, -IL-1alpha, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti-IL-1alpha antibody activity was fully recovered, whereas the recovery of anti-IFN alpha2A antibodies was significantly reduced. Serum antiviral activities were significantly reduced after IgG therapy (before, 0 to 5.6 IU/mL; after, 0 to 0.6 IU/mL). In contrast, enzyme-linked immunosorbent assay (ELISA) showed no significant reduction in the serum levels of IL-6 (before, 1 to 70 pg/mL; after, 2 to 55 pg/mL), and the levels of IL-1alpha were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFN alpha2A, IL-1alpha, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.

Adult↗

[Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology].

The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.

Anesthesiology↗

Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.

We have developed a new method for the identification of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome-wide data sets. Discrimination between cleaved signal peptides and uncleaved N-terminal signal-anchor sequences is also possible, though with lower precision. Predictions can be made on a publicly available WWW server.

Algorithms↗

Prevalence of very mild to severe dementia in Denmark.

OBJECTIVES: The prevalence of dementia has been estimated in several countries and a meta-analysis has shown moderate and severe dementia in people aged 65 years and older to be between 4% and 6%. The Odense study is aiming to estimate the prevalence and incidence of dementia and to identify risk factors. MATERIAL AND METHODS: A total of 3346 persons, equivalent to 64.5% of a random sample of 5237 persons aged 65-84 years living in the municipality of Odense, Denmark, underwent a two phase diagnostic procedure including a screening with CAMCOG, the cognitive section of The Cambridge Examination for Mental Disorders of the Elderly, seven neuropsychological tests, medical examination, and CT scan. The severity of dementia was assessed by the CDR (Clinical Dementia Rating). RESULTS: The prevalence rate was 7.1%, including the very mildly demented, defined as persons rated questionably demented according to the CDR scale. The prevalence rate of very mild dementia was 2.8%. The proportion of cases with very mild dementia decreased with increasing age while the prevalence rate increased. CONCLUSION: Inclusion of very mild cases of dementia resulted in a higher prevalence rate than generally reported, and the prevalence rate increased exponentially with age which was mainly due to Alzheimer's disease.

Age Factors↗

Change in minimal cross sectional area using the new nasal dilator, "Airplus".

In 36 persons without nasal complaints nasal cavities were investigated using acoustic rhinometry (Rhin 2000), to study the effect of a nasal dilator (ND) named "Airplus". The minimal cross sectional area (MCA) of both the right and left side was assessed before and after application of the ND, and the total MCA was calculated as the sum of the right and left side. In 8 persons the MCA was measured before and after 2 applications of the ND. In 8 persons the MCA was measured before, immediately after and 2 hours after application of the ND. In trial one the median total MCA was 1.37 cm2 before and 1.96 cm2 after application of the ND. This corresponds to an increase of 43%, p < 0.000-01. In trial two the median total MCA was increased from 1.37 cm2 respectively 1.35 cm2 to 1.98 cm2 respectively 2.01 cm3, an increase of 45% respectively 49%, p < 0.008 in both. In trial three the median total MCA was 1.21 cm2 before and 1.95 cm2 immediately after application and 1.93 cm2 after 2 hours. The increase was 61 and 59%, p < 0.008 in both. The results show that the "Airplus" nasal dilator improves significantly the MCA, it was possible to reproduce the effect and it was stable in the recorded period.

Acoustics↗