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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 109 records · Page 6Linked to original sources
PubMed1997

Neural network prediction of translation initiation sites in eukaryotes: perspectives for EST and genome analysis.

Translation in eukaryotes does not always start at the first AUG in an mRNA, implying that context information also plays a role. This makes prediction of translation initiation sites a non-trivial task, especially when analysing EST and genome data where the entire mature mRNA sequence is not known. In this paper, we employ artificial neural networks to predict which AUG triplet in an mRNA sequence is the start codon. The trained networks correctly classified 88% of Arabidopsis and 85% of vertebrate AUG triplets. We find that our trained neural networks use a combination of local start codon context and global sequence information. Furthermore, analysis of false predictions shows that AUGs in frame with the actual start codon are more frequently selected than out-of-frame AUGs, suggesting that our networks use reading frame detection. A number of conflicts between neural network predictions and database annotations are analysed in detail, leading to identification of possible database errors.

Amino Acid Sequence↗
PubMed1996

[Is the new LAE 355 certificate useful for extended sick leave benefits?].

In Storstrøm county an investigation was carried out concerning certificates in connection with sickness benefit during a period of two months, and the general practitioners and the social-workers were asked about their opinion of and attitude to sickness-certificates. A total of 420 sickness benefit certificates were collected consecutively, and all the social-workers and 85% of the general practitioners participated. About half of the certificates were not completely filled out and only one fifth supplied constructive supplementary information. Forty-five percent of the social-workers and 33% of the general practitioners regarded the certificates as useless when dealing with social medical cases. A systematic followup of patients with long-term sickness is an important task in primary health care, and should be carried out in co-operation with other health- and social-workers.

Certification↗
PubMed1996

Defining a similarity threshold for a functional protein sequence pattern: the signal peptide cleavage site.

When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary threshold value for excluding redundant sequences. The impact of the choice of scoring matrix used in the alignments is examined. We demonstrate that the parameter determining the quality of the correlation is the relative entropy of the matrix, rather than the assumed (PAM or identity) substitution mode. Results are presented for the case of prediction of cleavage sites in signal peptides. By inspection of the false positives, several errors in the database were found. The procedure presented may be used as a general outline for finding a problem-specific similarity measure and threshold value for analysis of other functional amino acid or nucleotide sequence patterns.

Algorithms↗
PubMed1996

Human papillomavirus in oral premalignant lesions.

The aetiology of oral premalignant lesions is generally accepted to be multifactorial. Tobacco and alcohol are established as important cofactors in malignant development in the oral cavity, but in addition microorganisms, such as human papillomavirus (HPV), have gained much interest over the past decade. For many years, HPV has been accepted as an important cofactor in the development of cervical cancer, originating from a mucous membrane with similarities to the oral mucosa. 49 patients with oral premalignant lesions and 20 control patients with normal oral mucosa and no history of HPV infection were examined for the presence of HPV by immune histochemical staining using the peroxidase anti-peroxidase technique (PAP), DNA-DNA in situ hybridisation (ISH), and polymerase chain reaction (PCR) analysed by Southern blot hybridisation with an HPV 16 specific probe. The investigations revealed that HPV was found in 62.5% of the verrucous leucoplakias, 50.0% of the erythroplakias, 45.5% of the homogeneous leucoplakias, 33.3% of erythroleucoplakias and in 12.5% of the nodular leucoplakias. An overall HPV detection rate in the examined premalignant lesions was 40.8% and no patients in the control sample were positive. Concerning oral cancer development, it seems likely that HPV may be a cofactor, as 100% of patients who developed oral cancers within 4-12 years were all positive for HPV, one being positive for HPV 16.

Adult↗
PubMed1996

Specific neutrophil hyporesponsiveness in chronic Helicobacter pylori infection.

The release from mucosal neutrophils of reactive oxygen species (ROS) is believed to be an important part of the pathogenesis of Helicobacter pylori-associated gastritis and duodenal ulcer. In this study, bacterial sonicates prepared from 1 reference and 29 patient strains were used to stimulate ROS release from peripheral blood neutrophils. In 29 H. pylori-positive patients, the neutrophil response toward the homologous strain was absent. In contrast, a significant response was observed toward the reference strain. In addition, on stimulation of neutrophils from 29 patients without H. pylori infection, ROS release was significant. The stimulatory effect on neutrophils by FMLP was comparable in the 2 groups. It is concluded that a specific neutrophil hyporesponsiveness in ROS release toward the homologous R. pylori strain exists. This feature has, to our knowledge, not been described previously for neutrophil responses to any human pathogen.

Adult↗
PubMed1996

Immunological properties of meningococcal lipopolysaccharide from serogroups A, B & C.

The aim of the study was to measure and compare the oxidative burst, chemotaxis and cytokine production of human white blood cells, stimulated with meningococcal lipopolysaccharides (LPS) extracted from three different serogroups (A, B and C) of Neisseria meningitidis, and to evaluate whether convalescent sera from patients with meningococcal disease could modify cell stimulation of LPS. All three preparations of LPS from groups A, B and C were tested using the Limulus amoebocyte lysate assay (LAL), and the KDO concentrations of the LPS extracts were measured. Equivalent amounts of biologically active LPS, judged by LAL, and LPS with the same KDO concentration were assayed. IL-1alpha, IL-1beta, IL-6 and TNF-alpha production was stimulated by all three LPS preparations. All three preparations stimulated oxidative burst in monocytes (MNC). Only group A LPS stimulated neutrophil chemotaxis, while none of the three LPS stimulated superoxide production. Pooled convalescent sera from five patients with meningococcal disease suppressed the activity of neutrophils stimulated with LPS from groups B and C (p<0.05, Mann-Whitney U-test).

Cells, Cultured↗
PubMed1996

Priming of neutrophil and monocyte activation in human immunodeficiency virus infection. Comparison of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interferon-gamma.

Activation of human blood neutrophils and monocytes for enhanced release of toxic oxygen radicals may take place after priming with several cytokines including hematopoietic growth factors. The potential impact of human immunodeficiency virus (HIV) on this response and the relative potency of various cytokines remains unclear. Blood neutrophils and monocytes were isolated from 25 HIV outpatients with variable immunodeficiency. Oxidative burst response upon stimulation with N-formyl-methionyl-leucyl-phenylalanine was assessed in neutrophils after priming with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g), and in monocytes after priming with GM-CSF and IFN-g. Monocyte oxidative burst responses were not changed in patients or controls. In contrast, following priming with IFN-g, GM-CSF or medium (but not G-CSF) the neutrophils in HIV patients with CD4 counts > 200 x 10(9)/L exhibited a significantly higher chemiluminescence response than was seen in healthy age-matched controls, whereas the response in patients with lower CD4 counts was not different from controls. At comparable concentrations, GM-CSF induced a significantly higher priming than G-CSF and IFN-g. A significant positive correlation between CD4 counts and priming activity of GM-CSF and IFN-g on neutrophils was observed. We conclude that neutrophils in HIV infection have a normal or enhanced response to the oxidative metabolism priming activity of hematopoietic growth factors in vitro, whereas priming effect on monocytes was not seen.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The gntP gene of Escherichia coli involved in gluconate uptake.

The gntP gene, located between the fim and uxu loci in Escherichia coli K-12, has been cloned and characterized. Nucleotide sequencing of a region encompassing the gntP gene revealed an open reading frame of 447 codons with significant homology to the Bacillus subtilis gluconate permease. Northern (RNA) blotting indicated that the gntP gene was monocistronic and was transcribed as an mRNA with an apparent molecular size of 1.54 kb. The transcriptional start point was determined by primer extension analysis. The gntP gene was found to be under catabolite repression and was not induced by gluconate. Also, expression seemed to be stringently controlled. Several observations indicated that the GntP protein is an inner membrane protein; it contains characteristic membrane-spanning regions and was isolated predominantly from the inner-membrane fraction of fractionated host cells. A topology analysis predicted a protein with 14 membrane-spanning segments. The inability of a mutant strain to grow on gluconate minimal medium could be relieved by introduction of a plasmid encoding the gntP gene. Finally, the kinetics of GntP-mediated gluconate uptake were investigated, indicating an apparent Km for gluconate of 25 microM.

Amino Acid Sequence↗
PubMed1996

Human SP-A locus: allele frequencies and linkage disequilibrium between the two surfactant protein A genes.

Two surfactant protein A (SP-A) genes and several alleles for each SP-A locus have been previously described. In this report we investigate the potential usefulness of the SP-A loci as markers for genetic studies. We establish conditions that allow the identification of alleles with very similar sequences; We also determine the degree of polymorphism for each SP-A locus: The heterozygosity and polymorphism information content (PIC) values for the SP-A1 locus are 0.63 and 0.55, respectively, and for the SP-A2 locus are 0.50 and 0.56. In the course of these studies, we identify one new SP-A2 allele and show that the SP-A1 and SP-A2 loci are in linkage disequilibrium (P < 0.000001). We also identify 19 of the 20 possible haplotypes in a population of n = 239. Nine of the observed haplotypes reach statistical significance (P < 0.01) in this population, and the segregation of two haplotypes (6A2/1A0 and 6A4/1A) without recombination is verified in a family pedigree. These data together indicate that both SP-A loci are sufficiently polymorphic to be good markers for use in genetic studies. Furthermore, the finding of one novel allele suggests that additional unknown SP-A alleles are yet to be found.

Adult↗
PubMed1996

Assessments of plasma HIV RNA and CD4 cell counts after combined Pneumovax and tetanus toxoid vaccination: no detectable increase in HIV replication 6 weeks after immunization.

The influence of simultaneous vaccination with Pneumovax and tetanus toxoid on plasma human immunodeficiency virus (HIV) RNA and CD4 cell counts was assessed in patients with HIV infection. Six weeks after immunization plasma HIV RNA did not differ significantly from baseline values. A slight decline in CD4 cell counts after vaccination was detected. There was no correlation between the serological responses to pneumococcal vaccination and baseline CD4 cell counts, changes in HIV RNA or CD4 cell counts. In conclusion, immunization did not induce an increase in viral replication detectable 6 weeks after immunization.

Bacterial Vaccines↗
PubMed1996

Invasive Candida norvegensis infection in immunocompromised patients.

Invasive infection with Candida norvegensis has previously been reported only once. Three new cases of invasive infection with C. norvegensis are described. One patient with acute myeloid leukaemia and neutropenic septicaemia had positive blood cultures with C. norvegensis, and 2 patients with AIDS and prolonged unexplained febrile cachexia had positive cultures of C. norvegensis from multiple sites, including pericardium, liver, kidneys lymph nodes and bone marrow, on autopsy. In severely immunocompromised patients, C. norvegensis appears to be an emerging new pathogen.

AIDS-Related Opportunistic Infections↗
PubMed1996

Malignant melanoma among lithographers.

OBJECTIVES: Mortality studies have suggested that workers in the printing industry may have a higher incidence of malignant melanoma. The aim of this study was to assess the incidence of malignant melanoma among lithographers. METHODS: A cohort of 837 lithographers, born in 1933-1942, was followed in the Danish Cancer Register from 1974 to 1989. RESULTS: Five cases of malignant melanoma were found, with 1.5 expected (relative risk 3.4, 95% confidence interval 1.2-7.5). CONCLUSIONS: Many known and suspected carcinogens are used in the printing industry. Hydroquinone, used for photographic development, may be implicated in the observed increase in risk, as it causes depigmentation and changes in melanocytes in the skin.

Carcinogens↗
PubMed1996

Some pharmacological and elastic characteristics of isolated subcutaneous small arteries from patients with essential hypertension.

OBJECTIVE: To investigate the elastic characteristics of the wall of isolated subcutaneous resistance arteries from patients with essential hypertension, the response of the vessels to endothelium-dependent and -independent vasodilators and the dependence on calcium. METHODS: Subcutaneous resistance arteries were isolated from 16 patients with never-treated essential hypertension and from 16 normotensive controls matched for age and sex. The vessels were mounted in a myograph for isometric force development. The passive elastic characteristics were determined and then the response to acetylcholine, nitroprusside, felodipine, caffeine and calcium (in the presence of noradrenaline and prazosin or yohimbine) were determined. RESULTS: Young's elastic modulus as a function of wall stress was similar in the two groups of vessels. The relaxation of vessels from hypertensive and normotensive in response to acetylcholine, nitroprusside and felodipine was also similar. However, the response to caffeine was increased in vessels from the hypertensive patients, although the relationship between the dependence on the effect of calcium on the behaviour of arteries from hypertensives and controls was similar in the presence of prazosin and yohimbine. CONCLUSIONS: The altered morphology of subcutaneous resistance arteries from hypertensives is not caused by a change in the elastic characteristics of the wall material. The data support our previous observation of abnormal calcium handling in vessels from hypertensives, although they do not support the hypothesis that a generalized abnormality in endothelium-dependent or endothelium-independent relaxation is of importance in essential hypertension.

Acetylcholine↗
PubMed1995

[Shore-term stimulation with myeloid growth factors expands bone marrow hematopoiesis. A magnetic resonance spectroscopic study].

The present study is intended to investigate the expansion of haematopoiesis by localised volume selective proton magnetic resonance spectroscopy (MRS) during treatment with myeloid growth factors. Six consecutive patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for five days before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76. x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow "relative water content" day 12, one week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93) (p < 0.05). Haematopoiesis was concommittantly detected in new areas of femur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Tissue culture supernatants from human islets of Langerhans activate the oxidative burst response of human monocytes in vitro.

Macrophages play a major role in the pathogenesis of insulin-dependent diabetes mellitus in animals. These cells are the first to invade the pancreas and macrophage-eradicating treatments reduce the incidence of the disease. In humans, however, their role is less clear. In this study we investigated the hypothesis that the pancreatic environment per se could activate macrophages. Tissue culture supernatants from human islets of Langerhans were tested for chemotactic activity and oxidative burst response in monocytes isolated from healthy adults. Preincubation with the supernatants enhanced the oxidative burst response evoked by fMLP (up to 379%) and opsonized zymosan (up to 173%). The activity decreased by dilution and was no longer detectable at 1:16. No increased activity was seen in supernatants from a number of other human endocrine and non-endocrine primary cells, suggesting a factor specific for islet tissue. The increased oxidative burst response could partially be eliminated by heat- and proteinase K treatment, suggesting that the activity could be of polypeptide nature. The factor could not be absorbed by polyvalent rabbit antibodies directed towards a variety of cytokines not by a mixture of high-titer anti-cytokine antibodies. It is possible that islet factors could also promote such monocyte activation in vivo in monocytes attracted to the islets of Langerhans by other means. This could contribute to the development of insulin-dependent diabetes in humans.

Adolescent↗
PubMed1995

[Attitudes to autopsy among critically ill patients and the general population].

Attitudes towards autopsy were investigated by a questionnaire given to 60 cancer patients, 30 patients with severe cardiac disease and 132 healthy people without known disease. Eighty-five percent of the patients and 82% of the healthy people had a positive attitude towards autopsy. A majority (65-72%) found that permission should be given by the patient rather than the family. Only 6% of patients and 13% of the healthy people would refuse to give permission to autopsy, 71% and 47% would give permission and 10% and 25% would consent to autopsy under certain conditions. both groups were more reluctant to give consent to the performance of an autopsy on a relative. It is concluded that hospital routine should be changed so that patients should be asked whether they would permit an autopsy to be performed in event of their decease.

Autopsy↗