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Biomedical subjects

M M Nielsen

Publications and source records attributed to M M Nielsen.

16 recordsLinked to original sources
PubMed2006

Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder.

Linkage studies suggest that chromosome 22q12-13 may contain one or more shared susceptibility genes for schizophrenia (SZ) and bipolar affective disorder (BPD). In a Faeroese sample, we previously reported association between microsatellite markers located at 22q13.31-qtel and both disorders. The present study reports an association analysis across five genes (including 14 single nucleotide and two microsatellite polymorphisms) in this interval using a case-control sample of 162 BPD, 103 SZ patients and 200 controls. The bromodomain-containing 1 gene (BRD1), which encodes a putative regulator of transcription showed association with both disorders with minimal P-values of 0.0046 and 0.00001 for single marker and overall haplotype analysis, respectively. A specific BRD1 2-marker 'risk' haplotype showed a frequency of approximately 10% in the combined case group versus approximately 1% in controls (P-value 2.8 x 10(-7)). Expression analysis of BRD1 mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection of BRD1 protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS. Quantitative mRNA analysis in developing fetal pig brain revealed spatiotemporal differences with high expression at early embryonic stages, with intense nuclear and cytosolar immunohistochemical staining of the neuroepithelial layer and early neuroblasts, whilst more mature neurons at later embryonic stages had less nuclear staining. The results implicate BRD1 with SZ and BPD susceptibility and provide evidence that suggests a role for BRD1 in neurodevelopment.

Animals↗
PubMed2005

Investigation of chromophore-chromophore interaction by electro-optic measurements, linear dichroism, x-ray scattering, and density-functional calculations.

Free-beam interferometry and angle-resolved absorption spectra are used to investigate the linear electro-optic coefficients and the linear dichroism in photoaddressable bis-azo copolymer thin films. From the first- and second order parameters deduced, the chromophore orientation distribution is calculated and displayed for several poling temperatures and chromophore concentrations. The influence of dipole-dipole interaction on the overall polymer dynamics is discussed. The first order parameter, and therefore the Pockels effect, peaks for a poling temperature of around 10 degrees C above the glass transition. The decrease of the Pockels effect above this temperature region is triggered by a head-to-tail chromophore orientation, i.e., a transition to a microcrystalline phase, increasing the second order parameter. Comparison of the experimentally observed absorption spectra and those obtained by density-functional calculations support the picture of differently aligned bis-azo dye molecules in a trans,trans configuration. Complementary wide-angle x-ray scattering is recorded to confirm the various kinds of ordering in samples poled at different temperatures.

Algorithms↗
PubMed2005

Characterization of the elastic properties of the nuclear envelope.

Underlying the nuclear envelope (NE) of most eukaryotic cells is the nuclear lamina, a meshwork consisting largely of coiled-coil nuclear intermediate filament proteins that play a critical role in nuclear organization and gene expression, and are vital for the structural stability of the NE/nucleus. By confocal microscopy and micromanipulation of the NE in living cells and isolated nuclei, we show that the NE undergoes deformations without large-scale rupture and maintains structural stability when exposed to mechanical stress. In conjunction with image analysis, we have developed theory for a two-dimensional elastic material to quantify NE elastic behaviour. We show that the NE is elastic and exhibits characteristics of a continuous two-dimensional solid, including connections between lamins and the embedded nuclear pore complexes. Correlating models of NE lateral organization to the experimental findings indicates a heterogeneous lateral distribution of NE components on a mesoscopic scale.

Elasticity↗
PubMed2001

Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients.

PURPOSE: Few studies have examined the possible importance of biologic prognostic factors in breast cancer connected with differentiation and growth in predicting response to a specific adjuvant treatment. HER2, epidermal growth factor receptor (EGFR), and p53 have all been suggested as possible markers of tamoxifen resistance. The aim of this study was to investigate interactions between adjuvant treatment with tamoxifen and the content of EGFR, HER2, and p53 in steroid receptor-positive patients. PATIENTS AND METHODS: A total of 1,716 high-risk postmenopausal breast cancer patients were randomly assigned to treatment with tamoxifen (868 women) or to observation (848 women) in a prospective trial (Danish Breast Cancer Cooperative Group's 77c protocol). The content of the steroid receptors and expression of p53, EGFR, and HER2 were determined by immunohistochemical analysis of paraffin-embedded tissue. The length of follow-up was 10 years. The end point for this analysis was disease-free survival. RESULTS: Multivariate analysis demonstrated no increased risk of recurrence after treatment with tamoxifen for HER2-, EGFR-, and p53-positive, high-risk, steroid receptor-positive patients. Patients with steroid receptor-positive tumors and positive immunohistochemical staining for HER2, EGFR or p53 benefited from treatment with tamoxifen for 1 year, although the latter variable contained independent prognostic information by itself. CONCLUSION: With the statistical power of the present randomized study, we did not find support for the hypothesis that HER2/EGFR or p53 status predicts benefit from tamoxifen treatment in estrogen receptor-positive patients with early-stage breast cancer. Thus, neither HER2, EGFR, nor p53 overexpression/accumulation should be used as a contraindication for giving tamoxifen.

Aged↗
PubMed2000

Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways.

In an effort to clone novel tyrosine-phosphorylated substrates of the epidermal growth factor receptor, we have initiated an approach coupling affinity purification using anti-phosphotyrosine antibodies to mass spectrometry-based identification. Here, we report the identification of a signaling molecule containing a Src homology 3 domain as well as an immunoreceptor tyrosine-based activation motif (ITAM). This molecule is 55% identical to a previously isolated molecule designated signal transducing adaptor molecule (STAM) that was identified as an interleukin (IL)-2-induced phosphoprotein and is therefore designated STAM2. Tyrosine phosphorylation of STAM2 is induced by growth factors such as epidermal growth factor and platelet-derived growth factor as well as by cytokines like IL-3. Several of the deletion mutants tested except the one containing only the amino-terminal region underwent tyrosine phosphorylation upon growth factor stimulation, implying that STAM2 is phosphorylated on several tyrosine residues. STAM2 is downstream of the Jak family of kinases since coexpression of STAM2 with Jak1 or Jak2 but not an unrelated Tec family kinase, Etk, resulted in its tyrosine phosphorylation. In contrast to epidermal growth factor receptor-induced phosphorylation, this required the ITAM domain since mutants lacking this region did not undergo tyrosine phosphorylation. Finally, overexpression of wild type STAM2 led to an increase in IL-2-mediated induction of c-Myc promoter activation indicating that it potentiates cytokine receptor signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1994

[Chemotherapy in metastasing breast cancer--is it beneficial?].

Carcinoma of the breast is the most common type of cancer among women in Denmark (3,000 new cases a year). About half of the patients will at some time develop metastases. Treatment of extended disease is controversial. Public discussion has focused on whether it is desirable to treat these patients with chemotherapy or not. This case story describes four cases with long term survival (nine, ten, 14, 19 years after début of metastases). This underlines that it is possible within the existing types of treatment to achieve both extended survival and acceptable life quality. The doctor's dilemma is that he does not know whom treatment helps. We conclude that treatment should be offered to all patients. This will be of benefit to the whole group.

Adult↗
PubMed1992

Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones near a source of lead emissions.

The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones were identified by a multivariate statistical analysis. Within each zone, the total dietary intake of lead was estimated for adults and children as a percentage of the provisional tolerably weekly intake (PTWI), and as a result recommendation on restrictions in use of locally grown fruit and vegetables were given to the public. The pattern of lead deposition in the area during the period 1981-1988 was monitored and the amount of lead ingested via vegetables was toxically evaluated. Lead emission reduction measures introduced in the factory and in the traffic during the period produced significant reductions in lead deposition.

Adolescent↗
PubMed1992

Atmospheric deposition of trace elements around point sources and human health risk assessment. II. Uptake of arsenic and chromium by vegetables grown near a wood preservation factory.

Kale, lettuce, carrots and potatoes were grown in 20 experimental plots surrounding a wood preservation factory, to investigate the amount and pathways for plant uptake of arsenic and chromium. Arsenate used in the wood preservation process is converted to the more toxic arsenite by incineration of waste wood and is emitted into the atmosphere. Elevated concentrations of inorganic arsenic and chromium were found both in the test plants and in the soil around the factory. Multivariate statistical analysis of the results indicated that the dominating pathway of arsenic and chromium from the factory to the leafy vegetables grown nearby was by direct atmospheric deposition, while arsenic in the root crops originated from both the soil and the atmosphere. Consumption of vegetables grown near the source would result in an increased intake of inorganic arsenic, but the intake via the total diet was estimated to be below the provisional tolerable daily intake for inorganic arsenic established by FAO/WHO.

Air Pollutants↗
PubMed1992

Facilitating postischemic reduction of cerebral lactate in rats.

BACKGROUND AND PURPOSE: Dichloroacetate facilitates a decrease in brain lactate during reperfusion after incomplete ischemia. This study examined the possible activation of pyruvate dehydrogenase enzyme by dichloroacetate to explain this effect. Because the duration of ischemia and hyperglycemia exacerbate ischemic brain damage, the effect of both of these factors on lactate reduction with and without dichloroacetate treatment after ischemia also was explored. METHODS: The two-vessel occlusion and controlled blood loss model of stroke was applied to anesthetized rats. Samples of cerebral cortex were analyzed for lactate by enzyme fluorometry and for pyruvate dehydrogenase activity by radioassay. RESULTS: Treatment with dichloroacetate produced no significant stimulation of pyruvate dehydrogenase after ischemia. When the duration of ischemia was increased or 50% glucose was infused before ischemia, brain lactate was significantly higher (p less than 0.01, Duncan's test). After 30 minutes of ischemia, treatment with a low dose of dichloroacetate (25 mg/kg) improved the reduction in lactate (p less than 0.01, Duncan's test). CONCLUSIONS: These results indicate that although dichloroacetate reduces brain lactate after cerebral ischemia, the mechanism of action does not involve dichloroacetate's known ability to stimulate pyruvate dehydrogenase. However, these data support the use of dichloroacetate to lower cerebral lactate, especially in cases where ischemia is greater than or equal to 30 minutes in duration. They also suggest that early restoration and maintenance of perfusion after ischemia and discontinuing the use of 50% glucose before impending ischemia likewise would facilitate reduction of postischemic brain lactate.

Animals↗
PubMed1991

Logistical implementation of cholesterol screening at the worksite. Appointment versus walk-in approach.

Worksite cholesterol screening programs providing initial cholesterol screening, dietary consultation, and follow up evaluation are an excellent way to assist individuals to know their cholesterol. Two methods for implementation of cholesterol screening at the worksite include walk-in and appointment. These methods can be tailored to accommodate any worksite population. Guidelines for planning, implementation, follow-up, and evaluation of cholesterol screening programs are discussed.

Appointments and Schedules↗
PubMed1989

[Liver transplantation undertaken on Danes abroad].

The indication for liver transplantation is the end stage of liver disease. Liver transplantations are not carried out in Denmark at present, one of the reasons being that it requires introduction of the brain death criterion, because the donor liver must be removed during maintained circulation. To date (November 1988), liver transplantations have been carried out abroad on seven Danes. One of these died after operation, one has chronic rejection and is to have retransplantation while the remaining five patients are well. In Europe (including Sweden, Norway and Finland) and USA, more than 5,000 patients have been liver transplanted. The one-year survival is approximately 75%. After this, only few liver-related deaths occur and the majority of patients can resume their previous activities. A total of 18 Danes have been assessed in transplantation centres abroad: Two are waiting for transplantation in the near future and seven have been accepted for transplantation at a later date, depending on the course of the disease. In a number of Danes, liver transplantation has been considered indicated but has not been effectuated because the disease was so advanced at the time of referral, that the patient died before transfer or the patient did not desire operation abroad.

Adolescent↗
PubMed1984

Toxic effect of scopolamine eye drops in children.

Five children, admitted with acute psychotic reactions after use of Scopolamine eye drops 0.2%, are presented. The predominant symptoms were visual hallucinations, strange behaviour, and restlessness. In one case peripheral symptoms were observed. Recovery was complete in 24 h. Prescription of Scopolamine eye drops should be followed by information of possible adverse effects. Cyclopentolate might be used instead.

Acute Disease↗