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Biomedical subjects

J Hansen

Publications and source records attributed to J Hansen.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effects of intranasal cocaine on sympathetic nerve discharge in humans.

Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these excitatory and inhibitory neural influences determines the net effect of cocaine on sympathetic discharge targeted to the human skeletal muscle circulation.

Administration, Intranasal↗
PubMed1997

Siroheme biosynthesis in Saccharomyces cerevisiae requires the products of both the MET1 and MET8 genes.

Siroheme is a uroporphyrinogen III-derivative used by sulfite reductase as a prosthetic group. We investigated in Saccharomyces cerevisiae the possible involvement in siroheme biosynthesis of three genes, MET1, MET8 and MET20. The MET1 gene from S. cerevisiae was cloned and shown to be the same gene as MET20. Sequence similitudes as well as complementation studies indicate that Met1p and Met8p are both involved in siroheme biosynthesis. In addition, we show formally that S. cerevisiae does not need vitamin B12 for growth.

Amino Acid Sequence↗
PubMed1997

Temperature-sensitive mutants of Corynebacterium ammoniagenes ATCC 6872 with a defective large subunit of the manganese-containing ribonucleotide reductase.

Chemical mutagenesis of the nucleotide-producing strain Corynebacterium ammoniagenes ATCC 6872 with N-methyl-N-nitro-N-nitrosoguanidine followed by an enrichment protocol yielded 46 temperature-sensitive (ts) clones. A rapid assay for the allosterically regulated Mn-ribonucleotide reductase (RRase) was developed with nucleotide-permeable cells of C. ammoniagenes in order to screen for possible defects in DNA precursor biosynthesis at elevated temperature. Three mutants (CH 31, CH 32, and CH 33) grew well at 30 degrees C but did not proliferate at 40 degrees C because they did not reduce ribonucleotides to 2'-deoxyribonucleotides. They were designated nrdts (nucleotide reduction defective). When the cultures were shifted from 30 to 40 degrees C, the nrdts mutants immediately ceased to incorporate radiolabeled nucleic acid precursors into the DNA fraction, while DNA chain elongation was barely affected. Thus, exhaustion of the deoxyribonucleotide pool ultimately inhibited cell division, leading to a filamentous growth morphology. In contrast to the wild-type, all three nrdts mutants displayed a distinctly enhanced sensitivity of ribonucleotide reduction towards hydroxyurea (in permeabilized cells and in vitro) at 30 degrees C. The results from assays for biochemical complementation of heat-inactivated (2 min, 37 degrees C) mutant enzyme with either the small or the large subunit of wild-type Mn-RRase located the mutational defect on the large subunit.

Brevibacterium↗
PubMed1997

Image quality and dose in computed tomography.

Radiation exposure to the patient during CT is relatively high, and it is therefore important to optimize the dose so that it is as low as possible but still consistent with required diagnostic image quality. There is no established method for measuring diagnostic image quality; therefore, a set of image quality criteria which must be fulfilled for optimal image quality was defined for the retroperitoneal space and the mediastinum. The use of these criteria for assessment of image quality was tested based on 113 retroperitoneal and 68 mediastinal examinations performed in seven different CT units. All the criteria, except one, were found to be usable for measuring diagnostic image quality. The fulfillment of criteria was related to the radiation dose given in the different departments. By examination of the retroperitoneal space the effective dose varied between 5.1 and 20.0 mSv (milli Sievert), and there was a slight correlation between dose and high percent of "yes" score for the image quality criteria. For examination of the mediastinum the dose range was 4.4-26.5 mSv, and there was no significant increment of image quality at high doses. The great variation of dose at different CT units was due partly to differences regarding the examination procedure, especially the number of slices and the mAs (milli ampere second), but inherent dose variation between different scanners also played a part.

Humans↗
PubMed1997

Comparison of information on occupation and lifestyle habits obtained from European man-made vitreous fibre production workers and their relatives.

BACKGROUND: Studies of the aetiology of fatal diseases often rely on data obtained from relatives, which can cause loss of precision and introduce bias. We assessed the quality of such information on demographics, occupation, smoking and alcohol habits. METHODS: We compared contemporary interviews, based on a structured questionnaire, with male workers from the man-made vitreous fibre production industry in four European countries and their relatives. The participation rate was 63% (74 pairs of workers and relatives). RESULTS: Only minor differences in the ability to answer the questions appeared among workers and relatives, except for specific occupational questions. There was moderate to excellent agreement for demographics, residential and work history (kappa or intraclass correlation range: 0.44-0.98). For smoking habits, beer and wine consumption the agreement was good to excellent (range: 0.59-0.99). In particular, number of different residential areas, jobs, industries, and duration of wine drinking were significantly underreported by the relatives. No general determinant for reduced agreement appeared. CONCLUSIONS: In general, the quality of information obtained from relatives appeared good. However, information on specific occupational exposures may be improved by supplementing the information from relatives with details obtained from colleagues, occupational hygiene experts or occupation-exposure matrices.

Adolescent↗
PubMed1997

Expression of the H2-E molecule mediates protection to collagen-induced arthritis in HLA-DQ8 transgenic mice: role of cytokines.

Transgenic mice expressing DQA1*0301 and DQB1*0302 (HLA-DQ8) molecules in class II-deficient Ab degree mice are susceptible to collagen-induced arthritis (CIA). To evaluate the role of the H2-E molecule (a homolog of HLA-DR) in DQ-restricted arthritis, the H2-E gene was introduced into DQ8.Ab degree mice to generate DQ8/E+.Ab degree mice. Expression of the E molecule protects DQ8.Ab degree mice against arthritis. In vitro studies using draining lymph nodes from mice primed with bovine type II collagen (BII) showed that the response to BII in both transgenics is DQ and CD4 restricted. Challenge with BII in vitro leads to production of high levels of IFN-gamma in DQ8 and IL-4 in DQ8/E+ mice. We have hypothesized that the H2-E molecule modulates the T cell repertoire and changes the cytokine balance, resulting in protection of disease.

Animals↗
PubMed1997

Protein distance constraints predicted by neural networks and probability density functions.

We predict interatomic Calpha distances by two independent data driven methods. The first method uses statistically derived probability distributions of the pairwise distance between two amino acids, whilst the latter method consists of a neural network prediction approach equipped with windows taking the context of the two residues into account. These two methods are used to predict whether distances in independent test sets were above or below given thresholds. We investigate which distance thresholds produce the most information-rich constraints and, in turn, the optimal performance of the two methods. The predictions are based on a data set derived using a new threshold which defines when sequence similarity implies structural similarity. We show that distances in proteins are predicted more accurately by neural networks than by probability density functions. We show that the accuracy of the predictions can be further increased by using sequence profiles. A threading method based on the predicted distances is presented. A homepage with software, predictions and data related to this paper is available at http://www.cbs.dtu.dk/services/CPHmodels/.

Amino Acids↗
PubMed1997

Cancer mortality among man-made vitreous fiber production workers.

We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.

Aged↗
PubMed1997

Relation between phylogeny of African green monkey CD4 genes and their respective simian immunodeficiency virus genes.

An apparent species-specific relatedness of SIVagm suggests a coevolution with their natural hosts. However, the exact species or subspecies classification of African green monkeys, AGM, is uncertain because current classification schemes rely on phenotype markers, while more definitive genetic data are lacking. In this study, the CD4 protein involved in tissue type recognition was genetically cloned and sequenced from PBMC RNA from all AGM species, including Barbados green monkeys (BGM). Phylogenetic trees were constructed that also included genomic CD4 nucleotide sequences from patas, sooty mangabeys, rhesus and pig-tail macaques, chimpanzees, and humans. Chimpanzees and humans consistently clustered together. Monkeys within the Cercopithecus genus formed a separate cluster which included pata monkeys, supporting its grouping as a member of Cercopithecus. Surprisingly, sooty mangabeys were genetically more closely related to Asian macaques than to other African species, which might explain why macaques are more susceptible to infection by the SIVsm group than to infection by SIVagm or HIV-1 and why patas, on the other hand, are highly susceptible to SIVagm infection. Based on CD4 genetic data, tantalus, vervets, grivets, and sabaeus formed separate subgroups with BGM grouping closely with vervets. The branching order of the AGM species was related to that of their respective SIVagm env sequences. The study suggests a strong correlation between CD4 phylogeny and the susceptibility of the host species to infection by a specific lentivirus and supports the assumption of a coevolution of SIVagm and AGM. CD4 sequencing is suggested as a relevant method for genetic determination of primate species.

Amino Acid Sequence↗
PubMed1997

Epitope mapping and functional characterization of monoclonal antibodies specific for herpes simplex virus type I DNA polymerase.

Three monoclonal antibodies (MAbs 1051a, 1051b and 1051c) were raised against a surface region (residues 597-686) of the herpes simplex virus type 1 (HSV-1) DNA polymerase (HSV pol), and their epitopes were mapped. The MAbs reacted serotype specifically with the native and denatured HSV pol, as shown by Western blot analysis, immunoprecipitation and immunofluorescence microscopy, indicating their usefulness for biochemical studies and clinical diagnosis of HSV-1 infections, MAb 1051c, displaying the least cross-reactivity with cellular proteins in the Western blot analysis, was successfully utilized not only for coimmunoprecipitation, but also for the analysis and three-dimensional modeling of the cellular sites of HSV pol interaction by confocal laser immunofluorescence microscopy.

Amino Acid Sequence↗
PubMed1997

The sympathetic nervous system is involved in the maintenance but not initiation of the hypertension induced by N(omega)-nitro-L-arginine methyl ester.

Studies in anesthetized animals have advanced the theory that there is an important neurogenic component to the hypertension caused by pharmacological inhibition of nitric oxide, but studies in conscious animals have produced conflicting evidence for and against this theory. To try to reconcile the seemingly contradictory data, we hypothesized that the neurogenic component of this hypertension is time dependent such that the sympathetic nervous system is involved primarily in the maintenance, rather than the initiation, of the hypertension. We measured intra-arterial pressure in conscious, unrestrained rats with and without guanethidine-induced sympathectomy during varying durations of intravenous N(omega)-nitro-L-arginine methyl ester (L-NAME). The major new finding is that sympathectomy had no effect on the hypertensive response to bolus injections of L-NAME but in the same rats it produced a greater than 50% attenuation in the hypertension seen after 6 days of continuous L-NAME (change in mean arterial pressure, 23+/-4 versus 55+/-4 mm Hg, P<.01, sympathectomy versus control). Using 8-hour infusions of L-NAME, we found that 60 minutes was the minimum time required for detecting a sympathectomy-sensitive component of L-NAME-induced hypertension. Furthermore, we demonstrate that the magnitude of this component increases further between 8 hours to 6 days of continuous L-NAME: it accounted for only 18% of the total hypertensive response at 8 hours but 61% after 6 days. From these experiments, we conclude that the importance of the sympathetic system in the pathogenesis of L-NAME-induced hypertension accrues slowly over hours and days, and thus its importance can be overlooked by focusing on the initial phase of the hypertension.

Analysis of Variance↗
PubMed1997

Clinically silent microemboli in patients with artificial prosthetic aortic valves are predominantly gaseous and not solid.

BACKGROUND AND PURPOSE: Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood. METHODS: Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber. RESULTS: Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa). CONCLUSIONS: The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.

Aged↗
PubMed1997

Evaluation of pretransplant donor anti-recipient cytotoxic and helper T lymphocyte responses as correlates of acute graft-vs.-host disease and survival after unrelated marrow transplantation.

We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) responses separately in two cohorts of unrelated marrow transplant recipients. Donors and recipients were typed for HLA-A and -B antigens by serologic methods, and for HLA-DRB1 by molecular methods. A single mismatch for a cross-reactive HLA-A or -B antigen or the -DRB1 allele was accepted in patients younger than 36 years if an HLA-A, -B, or -DRB1-matched donor could not be identified. The combination of methotrexate and cyclosporine was used for graft-vs.-host disease (GVHD) prophylaxis, and marrows were not T cell depleted. Donor anti-recipient CTL precursor frequencies showed no correlation with the severity of acute GVHD or with survival after transplantation. HTL responses were detected in the presence of HLA-class II disparity and showed weak correlations with the severity of acute GVHD (p = 0.054) and with survival after transplantation (p = 0.08). These results suggest that testing donor anti-recipient CTL responses before unmodified marrow transplantation does not predict clinically important events and is not likely to help select unrelated donors. With the current availability of molecular genetic methods for assessing HLA-class II compatibility, testing donor anti-recipient HTL responses is not likely to add information that would help select unrelated donors.

Acute Disease↗
PubMed1996

HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.

MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs. These mice developed spontaneous arthritis and nail changes in the rear paws. Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area. Transgenic mice expressing HLA-B27 with mouse beta2m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease. Our data demonstrate specific involvement of HLA-B27 'free' HCs in the disease process.

Animals↗
PubMed1996

Inactivation of MET2 in brewer's yeast increases the level of sulfite in beer.

Brewer's yeasts sometimes produce inadequate or excessive amounts of sulfite, an antioxidant and flavour stabilizer, so means of controlling the sulfite production are desired. Understanding the physiology and regulation of the sulfur assimilation pathway of Saccharomyces yeasts is the key to change sulfite production. The MET2 gene of Saccharomyces yeasts encodes homoserine O-acetyl transferase, which catalyzes the conversion of homoserine to O-acetyl homoserine which in turn combines with hydrogen sulfide to form homocysteine, the immediate precursor of methionine. We expected that inactivation of MET2 would lead to accumulation of sulfide and derepression of the entire sulfur assimilation pathway and, therefore, possibly also to sulfite accumulation. Brewer's yeasts were constructed in which several of the four MET2 gene copies were inactivated. Sulfite production was increased in strains with one remaining MET2 gene and even more so when no active MET2 was present. In both cases, hydrogen sulfide production was also increased. To the extent that excess sulfide can be removed, this strategy may be applied to control sulfite accumulation by brewer's yeast in beer production.

Beer↗
PubMed1996

Modification of biochemical pathways in industrial yeasts.

Yeasts have many applications in industrial food and beverage production. While these uses are often of ancient origin, modern demands for control of the amounts of process-derived compounds and for cost-effective processing can make it desirable to modify metabolic pathways of production yeasts. While the genetics of standard laboratory strains of Saccharomyces cerevisiae are well described, industrial strains and species are less characterized, and many of them have a complicated genetic constitution. Nevertheless, their biochemical pathways can be modified, and the knowledge becoming available on the physiology of genetic reference strains of S. cerevisiae is a great help in directing the modifications of the industrial yeasts towards practical goals.

Amino Acids↗
PubMed1996

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia.

Adult↗