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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

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

[Prevalence and incidence of dementia in Denmark. The Odense study].

Prevalence and incidence of dementia were determined for 65-84 year-old persons living in the municipality of Odense and randomly drawn from the Danish Civil Registration System (DCRS). All participants were examined with CAMCOG, the cognitive section of CAMDEX (The Cambridge Examination for Mental Disorders of the Elderly) and the follow-up period was two years. Individualized CAMCOG cut-off scores were determined by multiple linear regression. Possibly demented persons were further examined with the remaining part of CAMDEX and neuropsychological tests. Alzheimer's disease (AD) was diagnosed according to the NINCDS-ADRDA criteria for probable AD, and vascular dementia (VD) and dementias of other types according to the DSM-III-R criteria for dementia. The severity of dementia was determined according to the Clinical Dementia Rating scale. Of the 5,237 persons drawn from the DCRS, 3,346 participated in the prevalence study and 2,452 in the incidence study. The prevalence was 7.1% (66.7% AD, 18.3% VD, and 15.0% dementias of other types). Ninety-six (2.8%) were diagnosed as very mildly demented. The incidence rate was 29.5 new cases per 1,000 person-years and 20.9 for AD. Inclusion of cases with very mild dementia resulted in higher prevalence and incidence rates than generally reported.

Age Distribution↗
PubMed2000

The danish protease inhibitor study: a randomized study comparing the virological efficacy of 3 protease inhibitor-containing regimens for the treatment of human immunodeficiency virus type 1 infection.

The Danish Protease Inhibitor (PI) Study has enrolled 318 human immunodeficiency virus (HIV)-infected, PI-naive patients for the purpose of comparing 3 PI-containing regimens for the treatment of HIV infection. The regimens include 2 nucleoside analogues in combination with indinavir (Idr), ritonavir (Rtv), or Rtv and saquinavir (Rtv/Sqv). Similar percentages of patients in the 3 study arms achieved reduced levels (</=20 copies/mL) of HIV RNA. In the area under the curve minus baseline analyses, a better response was found in the Rtv/Sqv arm than in the Rtv arm. No difference was found when comparing Rtv/Sqv with Idr and Rtv with Idr. Patients in the 3 arms had comparable increases in CD4 cell counts. At 72 weeks of follow-up, there was no statistical difference between arms for the primary study end point (</=20 HIV RNA copies/mL); however, some of the additional analyses indicated an advantage for the Rtv/Sqv arm, especially when compared with the Rtv arm.

Adolescent↗
PubMed2000

Cloning and expression of a novel human antibody-antigen pair associated with Felty's syndrome.

An increasing number of studies suggest the importance of antibodies in the pathogenesis of most systemic and organ-specific autoimmune diseases, although there is considerable controversy over the precise role of the autoantibodies involved. In humans, a major obstacle to progress is the identification and cloning of the relevant autoantibodies and autoantigens. Here, an approach based on the sequential use of antibody phage display and antigen expression libraries is developed and applied to a donor suffering from rheumatoid arthritis (RA), splenomegaly, and peripheral destruction of neutrophils leading to neutropenia (Felty's syndrome). An antibody phage display library was constructed from bone marrow from the donor and a high-affinity human mAb, ANA15, selected by panning against fresh neutrophils and independently by panning against a fixed cell line. The antibody showed strong staining of neutrophils and a number of cell lines. Probing of a lambdagt11 expression library from an induced myelomonocytic cell line with the mAb ANA15 identified the eukaryotic elongation factor 1A-1 (eEF1A-1) as a novel autoantigen. The specificity of ANA15 was confirmed by reactivity with both purified and recombinant eEF1A-1. Screening of a large panel of sera revealed that 66% of patients with Felty's syndrome had elevated levels of anti-eEF1A-1 antibodies. The cloning of this antibody-antigen pair should permit rational evaluation of any pathogenicity resulting from the interaction and its significance in neutropenia.

Antigen-Antibody Complex↗
PubMed2000

Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.

A neural network-based tool, TargetP, for large-scale subcellular location prediction of newly identified proteins has been developed. Using N-terminal sequence information only, it discriminates between proteins destined for the mitochondrion, the chloroplast, the secretory pathway, and "other" localizations with a success rate of 85% (plant) or 90% (non-plant) on redundancy-reduced test sets. From a TargetP analysis of the recently sequenced Arabidopsis thaliana chromosomes 2 and 4 and the Ensembl Homo sapiens protein set, we estimate that 10% of all plant proteins are mitochondrial and 14% chloroplastic, and that the abundance of secretory proteins, in both Arabidopsis and Homo, is around 10%. TargetP also predicts cleavage sites with levels of correctly predicted sites ranging from approximately 40% to 50% (chloroplastic and mitochondrial presequences) to above 70% (secretory signal peptides). TargetP is available as a web-server at http://www.cbs.dtu.dk/services/TargetP/.

Amino Acid Sequence↗
PubMed2000

Flanking sequences with an essential role in hydrolysis of a self-cleaving group I-like ribozyme.

DiGIR1 is a group I-like ribozyme derived from the mobile twin ribozyme group I intron DiSSU1 in the nuclear ribosomal DNA of the myxomycete Didymium iridis. This ribozyme is responsible for intron RNA processing in vitro and in vivo at two internal sites close to the 5'-end of the intron endo-nuclease open reading frame and is a unique example of a group I ribozyme with an evolved biological function. DiGIR1 is the smallest functional group I ribozyme known from nature and has an unusual core organization including the 6 bp P15 pseudoknot. Here we report results of functional and structural analyses that identify RNA elements critical for hydrolysis outside the DiGIR1 ribozyme core moiety. Results from deletion analysis, disruption/compensation mutagenesis and RNA structure probing analysis all support the existence of two new segments, named P2 and P2.1, involved in the hydrolysis of DiGIR1. Significant decreases in the hydrolysis rate, k (obs), were observed in disruption mutants involving both segments. These effects were restored by compensatory base pairing mutants. The possible role of P2 is to tether the ribozyme core, whereas P2.1 appears to be more directly involved in catalysis.

Animals↗
PubMed2000

The prognostic value of pretherapeutic tetranectin and CA-125 in patients with relapse of ovarian cancer.

OBJECTIVE: The aim of the study was to examine the prognostic values of, respectively, tetranectin (TN) and CA-125 measured in serum from patients presenting with relapse of ovarian cancer (OC). METHODS: TN and CA-125 were measured in serum samples from 75 patients with relapse of OC before the start of second-line chemotherapy. The endpoint used was death of OC. The variables were analyzed by univariate life table analysis and multivariate Cox analysis. RESULTS: A significantly shortened survival was found for patients with low serum TN values compared to patients with serum TN levels above one of the cutoff levels. The survivals are illustrated by life tables. No prognostic function was found for CA-125. TN and relapse </=12 months after primary treatment were the only significant independent prognostic variables among the following variables tested in the Cox analyses: primary and second-line treatment, CA-125, age, histology, performance score, tumor localization, and size. CONCLUSION: Serum TN determination may be valuable in the selection of patients with relapse of OC for new treatment strategies in future studies.

Biomarkers, Tumor↗
PubMed2000

4. Preliminary Findings of a Prospective Study of FDG-PET in Patients with Possible Lung Cancer.

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest CT of thorax/upper abdomen, and c) by whole-body PET (GE Advance, visual analysis). The CT and PET studies were performed within 2 weeks of admission and read blinded to all information except the chest X-ray report. The decision to refer to mediastinoscopy/thoracotomy was made by a tumor board using clinical information, CT and PET findings. In principle, suspected metastatic lesions were biopsied before surgery. The gold standard was histology from biopsy or thoracotomy, or resolution of the X-ray findings and symptoms.Results: One patient was excluded because of uncertain diagnosis. In 3 (15%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused by granuloma, pneumonia and BOOP. These nodules were only 1 to <3 cm, while malignant nodules were 2-8 cm. There were no false negative PET or CT studies.Conclusion: FDG-PET is valuable in patients suspected for pulmonary malignancy, since thoracotomy was avoided in 15% of patients and in 10% of patients more extensive disease was found which changed the chemotherapy regime.

Journal Article↗
PubMed2000

CAMCOG as a screening instrument for dementia: the Odense study. Cambridge Cognitive Examination.

OBJECTIVE: The Cambridge Cognitive Examination (CAMCOG) score is correlated with age and sociodemographic variables. The aim of the study was to determine an individualized CAMCOG cut-off score for dementia, taking such correlates into account. METHOD: From the general population 150 people aged 65-84 years were examined with CAMDEX which includes CAMCOG, and a neuropsychological test battery. Data from 130 non-demented people were entered in setwise multiple regression analyses to identify variables predicting the CAMCOG score. RESULTS: The variables age, social class, matrimonial status, general knowledge and intellectual level explained 66% of the variance of the CAMCOG scores. A cut-off defined as a difference between actual and predicted CAMCOG score < or = -4.41 resulted in a sensitivity of 88.2% and a specificity of 89.2% for very mild to moderate dementia. CONCLUSION: It is possible to determine an individualized CAMCOG cut-off score for dementia in its early stages.

Age Factors↗
PubMed2000

Bacterial contamination of bath-water from spinal cord lesioned patients with pressure ulcers exercising in the water.

AIM: To evaluate the bacterial contamination of the water from the microflora of pressure ulcers in para- and tetraplegic patients, when they were exercising in water at 36 degrees C for half an hour. MATERIAL: Twelve spinal cord lesioned (SCL) patients with ulcers participated, and six of the 12 SCL patients with healed ulcers constituted a control group. METHODS: The evaluation was performed both with and without the ulcer covered with a moisture reactive occlusive dressing, DuoDERM. Bacterial samples were taken from the bath-water before and after the exercise programmes and additionally specimens were obtained from the ulcer, the patients skin and urine, and from the skin of the physiotherapist who exercised the patient. A similar procedure was carried out in the controls. RESULTS: The bacteriologic analyses showed no significant difference in the contamination of the bath-water after exercising with or without DuoDERM covering the ulcers. In half of the patients DuoDERM loosened. After all exercise programmes with or without DuoDERM dressing the water was contaminated with facultative aerobic intestinal bacteria, ie E. faecalis and Enterobacteriaceae (E. coli, Klebsiella species, Proteus species, Enterobacter species). In nearly one-third of the exercise sessions the bath-water was contaminated with P. aeruginosa before starting, and after the exercise programmes one fourth of the ulcers were colonized with these pathogens. CONCLUSION: The water specimen showed the bacteria from the intestine to be much more prominent than the bacteria coming from the ulcers. Thus the pressure ulcers were of minor importance for the bath-water and ought not to prohibit patients from the potential benefits of water exercise, but chlorination of the water in the training pool seems appropriate.

Adult↗
PubMed2000

Assessing the accuracy of prediction algorithms for classification: an overview.

We provide a unified overview of methods that currently are widely used to assess the accuracy of prediction algorithms, from raw percentages, quadratic error measures and other distances, and correlation coefficients, and to information theoretic measures such as relative entropy and mutual information. We briefly discuss the advantages and disadvantages of each approach. For classification tasks, we derive new learning algorithms for the design of prediction systems by directly optimising the correlation coefficient. We observe and prove several results relating sensitivity and specificity of optimal systems. While the principles are general, we illustrate the applicability on specific problems such as protein secondary structure and signal peptide prediction.

Algorithms↗
PubMed1999

Distribution of metallothionein I + II and vesicular zinc in the developing central nervous system: correlative study in the rat.

Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essential for brain development. However, because excess Zn may cause neuronal injury, cerebral mechanisms for Zn regulation must operate. The metallothionein isoforms I and II (MT I + II) are putative candidates for chelating unbound Zn released from Zn-containing nerve terminals or transported into the brain. Whether vesicular Zn and MT I + II occur in identical regions of the developing brain is unknown. Accordingly, the developmental distribution of MT I + II and vesicular Zn was mapped. By using double-labeling fluorescence histochemistry, MT I + II immunoreactivity (ir) was attributed to astrocytes and cells of myelomonocytic lineage. The cells of the myelomonocytic lineage shared the morphology of monocytes and macrophages but not of microglia and occurred primarily around vessels and ventricles in the brainstem. By contrast, astrocytes were widespread throughout the developing brain. In embryonic and neonatal brain, MT I + IIir astrocytes were almost selectively observed in the septum and fascia dentate hilus (hi) of the hippocampus. With increasing postnatal age, they also occurred in hippocampal cortex, basal forebrain, neocortex, cerebellar cortex, and cranial nerve nuclei. MT I + II mRNAs were detected in regions of the brain that also displayed MT I + IIir, indicating transcriptional events. Vesicular Zn was recorded in neonatal brain solely in the dentate hi of the hippocampus. With increasing age, the amount of vesicular Zn increased in the hippocampus and other forebrain regions. The presence of MT I + II proteins in the developing brain was confirmed by radioimmunoassay. The regional distribution of astrocytic MT I + IIir and vesicular Zn suggests that MT I + II are implicated in Zn metabolism in the developing forebrain.

Aging↗
PubMed1999

Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?

BACKGROUND: In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after the introduction of highly active antiretroviral therapy (HAART). OBJECTIVES: To assess incidences of opportunistic infections after discontinuation of chemoprophylaxis in HIV-infected patients, who have experienced a HAART-induced increase in CD4 cell count. METHODS: The Danish guidelines for chemoprophylaxis against opportunistic infections in HIV-infected patients were revised in late 1997, allowing discontinuation of chemoprophylaxis after initiation of HAART if the CD4 cell count remained above a specified limit for more than 6 months. Consecutive patients were followed, and incidences of opportunistic infections after discontinuation of chemoprophylaxis were assessed. RESULTS: A total of 219 patients discontinued Pneumocystis carinii pneumonia (PCP)-chemoprophylaxis (12% maintenance therapy). One case of PCP was diagnosed within 174 person-years (PY) of follow-up, resulting in an incidence of 0.6 cases/100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. CONCLUSION: PCP-chemoprophylaxis can be safely discontinued after HAART-induced increase in CD4 cell count to more than 200 x 10(6) cells/l. Among consecutive patients who discontinue chemoprophylaxis according to well-defined guidelines, the observed incidence of PCP is below those reported earlier in patients with similar CD4 cell count.

AIDS-Related Opportunistic Infections↗
PubMed1999

Competition between Sec- and TAT-dependent protein translocation in Escherichia coli.

Recently, a new protein translocation pathway, the twin-arginine translocation (TAT) pathway, has been identified in both bacteria and chloroplasts. To study the possible competition between the TAT- and the well-characterized Sec translocon-dependent pathways in Escherichia coli, we have fused the TorA TAT-targeting signal peptide to the Sec-dependent inner membrane protein leader peptidase (Lep). We find that the soluble, periplasmic P2 domain from Lep is re-routed by the TorA signal peptide into the TAT pathway. In contrast, the full-length TorA-Lep fusion protein is not re-routed into the TAT pathway, suggesting that Sec-targeting signals in Lep can override TAT-targeting information in the TorA signal peptide. We also show that the TorA signal peptide can be converted into a Sec-targeting signal peptide by increasing the hydrophobicity of its h-region. Thus, beyond the twin-arginine motif, the overall hydrophobicity of the signal peptide plays an important role in TAT versus Sec targeting. This is consistent with statistical data showing that TAT-targeting signal peptides in general have less hydrophobic h-regions than Sec-targeting signal peptides.

Amino Acid Sequence↗
PubMed1999

Structural characterization, stability and fatty acid-binding properties of two French genetic variants of human serum albumin.

Four bisalbuminemic, unrelated persons were found in Bretagne, France, and their variant and normal albumins were isolated by DEAE ion exchange chromatography, reduced, carboxymethylated and treated with CNBr. Comparative two-dimensional electrophoresis of the CNBr digests showed that three of the variants were modified in fragment CB4, whereas the fourth had an abnormal fragment CB1. These fragments were isolated, digested with trypsin and mapped by reverse-phase HPLC. Sequencing of altered tryptic peptides showed that the three variants modified in CB4 were caused by the same, previously unreported, amino acid substitution: Asp314-->Val (albumin Brest). The fourth, however, was a proalbumin variant with the change Arg-2-->Cys (albumin Ildut). Both amino acid substitutions can be explained by point mutations in the structural gene: GAT-->GTT (albumin Brest) and CGT-->TGT (albumin Ildut). The proalbumin Ildut is very unstable and already in vivo it is to a large extent cleaved posttranslationally to Arg-Albumin and normal albumin. Furthermore, we observed that during a lengthy isolation procedure the remaining proalbumin was changed to Arg-Albumin or proalbumin lacking Arg-6. In addition, part of normal albumin had lost Asp1. Gas chromatographic investigations using isolated proteins indicated that albumin Brest has improved in vivo fatty acid-binding properties, whereas the structural modification(s) of albumin Ildut does not affect fatty acid binding.

Fatty Acids↗
PubMed1999

Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain.

In non-neuronal tissue, ferritin subunit mRNAs are regulated by post-transcriptional mechanisms leading to decreased ferritin protein synthesis during iron deficiency. Biochemical studies have demonstrated that the cerebral ferritin concentration declines during iron deficiency, suggesting that expression of ferritin subunit mRNAs in the brain may be regulated by mechanisms similar to those of non-neuronal tissue. However, as ferritin expression has been only vaguely studied in brain, this hypothesis remains to be tested. We investigated the influence of dietary iron deficiency on the cellular distribution of ferritin protein using immunohistochemistry and H- and L-ferritin subunit mRNAs by non-radioactive in situ hybridization. Pregnant rats were subjected to an iron depleted diet (6.4 mg/kg) from the day of conception. Litters were kept on the same diet until euthanized at the postnatal age of 10 weeks. This treatment reduced brain iron levels from approximately 57 to 26 microgram/g. Reducing the iron stores reduced histochemical detectable iron and the expression of ferritin immunoreactivity in neurons, oligodendrocyte-like and microglia-like cells. In normal rats, H- and L-ferritin subunit mRNAs were expressed in virtually all neurons and non-neuronal cells. The cerebral expression of the ferritin subunit mRNAs was not affected by iron deficiency. The levels of ferritin subunit mRNAs in the brain were also unaltered from iron deficiency when examined by Northern blotting. In conclusion, brain levels of iron and ferritin protein are highly susceptible to dietary iron deficiency, whereas the cerebral expression of H- and L-ferritin subunit mRNAs remains unchanged.

Animals↗