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Biomedical subjects

O Nielsen

Publications and source records attributed to O Nielsen.

At least 73 records · Page 4Linked to original sources
PubMed1991

Repression of a mating type cassette in the fission yeast by four DNA elements.

The fission yeast, Schizosaccharomyces pombe, expresses one of two alternative mating types. They are specified by one of two determinants (M or P) present at the mat1 locus. In addition, silent copies of M and P are present on the same chromosome. In the present work we demonstrate that the difference between the active and the silent stage of the P determinant is controlled by four repressive elements that are located at the silent locus. There are two elements to the left and two to the right of the mating type cassette. Both elements to the left and either one of the two elements to the right are required for an effective blockage of transcription. When they are combined, the four elements define a highly efficient silencer functionally similar to the HMRE and HMLE and HMLI silencers in Saccharomyces cerevisiae. In addition, the DNA surrounding the silent P locus confers symmetric partitioning in mitosis to Schizosaccharomyces pombe ars plasmids.

DNA, Fungal↗
PubMed1991

Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction.

This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot hybridization. It was not possible to detect any viral antigen production in the cultures, and attempts to recover virus by highly sensitive coculture techniques were unsuccessful, indicating that the infection was latent. The PCR technique provides a simple approach to the study of viral infection in cases where viral replication is absent, or where genomic copies are present at such low numbers that they are otherwise undetectable.

Brain Neoplasms↗
PubMed1990

The pat1 protein kinase controls transcription of the mating-type genes in fission yeast.

The developmental programme of fission yeast brings about a transition from mitotic cell division to the dormant state of ascospores. In response to nitrogen starvation, two cells of opposite mating type conjugate to form a diploid zygote, which then undergoes meiosis and sporulation. This differentiation process is characterized by a transcriptional induction of the mating-type genes. Conjugation can also be induced in pat1-ts mutants by a shift to a semi-permissive temperature. The pat1 gene encodes a protein kinase, which also functions further downstream in the developmental pathway controlling entry into meiosis. We have analysed transcriptional induction of mating-type genes in various strains--with and without a pat1-ts allele. In wild-type cells of P-mating type derepression occurs in two rounds. First, the mat1-Pc gene is induced in response to nitrogen starvation. Mutants in the map1 gene are defective in this process. In the following step the mat1-Pm gene is expressed in response to a pheromone signal generated by cells of M mating type. Both these controls are derepressed in the pat1-ts mutant at semipermissive temperature. Previous work has established that expression of the mating-type genes in the zygote leads to complete loss of pat1 protein kinase activity causing entry into meiosis. Thus, pat1 can promote its own inactivation. We suggest a model according to which a stepwise inactivation of pat1 leads to sequential derepression of the processes of conjugation and meiosis.

Conjugation, Genetic↗
PubMed1990

Sexual differentiation in fission yeast.

The regulation of sexual reproduction in yeast constitutes the highest level of differentiation observed in these unicellular organisms. The various ramifications of this system involve DNA rearrangement, transcriptional control, post-translational modification (such as protein phosphorylation) and receptor/signal processing. A few basic similarities are common to both fission and budding yeasts. The wiring of the regulatory circuitry, however, varies considerably between these divergent yeast groups.

Conjugation, Genetic↗
PubMed1990

Dust in buildings with man-made mineral fiber ceiling boards.

Man-made mineral fibers (MMMF) and other airborne dusts were measured in 105 rooms in a representative sample of public buildings, excluding rooms with physically damaged boards or buildings with notable indoor climate problems. There were no differences in the MMMF concentrations with respect to the type of binder. The average concentrations ranged from 17 to 210 respirable MMMF/m3. The average concentrations of the reference group was intermediate and therefore indicated that sources other than ceiling boards contributed to the obtained values. No grouping by concentration of MMMF on cupboards was possible. Airborne concentrations of respirable MMMF were 2.7 times lower in rooms with mechanical ventilation than in rooms with natural ventilation. For nonrespirable MMMF, the most important factor was the quality of the cleaning. The concentration in poorly cleaned rooms was 5.5 times that of well-cleaned rooms. Ventilation, quality of cleaning, and number of persons affected the non-MMMF and total dust concentrations.

Air Pollutants↗
PubMed1989

Mapping the double-strand breaks at the mating-type locus in fission yeast by genomic sequencing.

In fission yeast mating-type switching is initiated by the formation of a double-strand DNA break at the mating-type locus. A prerequisite for generation of the break is some 'imprinting' of the DNA in the previous cell cycle. We have used the technique of genomic sequencing to map the position of the break directly on chromosomal DNA cleaved in vivo. On one strand the break is situated very close to the right-hand border of the expressed mat1 cassette. Cells of opposite mating type, P and M, have their breaks at slightly different positions on this strand. On the other DNA strand of both alleles the ends are probably masked by tightly bound proteins and therefore the precise nature of the break could not be determined. Since the break is stable throughout the cell cycle, these proteins may function in vivo to confer structural stability on the chromosomes having the break. The implications of these findings for models of mating-type switching are discussed.

Base Sequence↗
PubMed1989

The effects of metformin on adipocyte insulin action and metabolic control in obese subjects with type 2 diabetes.

To investigate the mechanisms of action of metformin, insulin receptor binding and the activity of several insulin-controlled metabolic pathways were measured in adipocytes taken from 10 obese Type 2 diabetic patients treated for 4 weeks with either metformin (0.5 g x 3 daily) or matching placebo using a double-blind crossover design. Metformin therapy was associated with a significant fall in serum fructosamine levels (3.1 +/- 0.4 vs 2.8 +/- 0.4 mmol l-1, p less than 0.02) as well as fasting (10.8 +/- 2.4 vs 9.4 +/- 2.1 mmol l-1) and daytime (11.5 +/- 2.4 vs 10.0 +/- 2.2 mmol l-1) plasma glucose concentrations (p less than 0.05). Fasting and postprandial plasma levels of C-peptide and insulin were unchanged. While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 +/- 0.1 to 1.8 +/- 0.2 mmol l-1, p less than 0.05). Adipocyte insulin receptor binding was unaffected by drug treatment. Moreover, no insulin-like effects or post-binding potentiation of insulin action could be found on adipocyte glucose transport, glucose oxidation, lipogenesis, glycolysis or antilipolysis. A complementary in vitro study using adipocytes from non-obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.

Adipose Tissue↗
PubMed1988

Light microscopical demonstration and zonal distribution of parasinusoidal cells (Ito cells) in normal human liver.

The parasinusoidal cells of the liver (Ito cells) were demonstrated light microscopically in autopsy specimens fixed in formalin and stained with Oil red O after dichromate treatment. The method allows examination of large samples containing numerous acini. Quantitative assessment showed a zonal gradient with 6.3 and 7.7 parasinusoidal cells per 62.5 X 10(3) micron2 in zone 1 and 3, respectively.

Aged↗
PubMed1988

Electrically-induced collagen calcification in pig skin. A histopathologic and histochemical study.

Deposition of calcium salts on collagen fibres in skin of fully anaesthetized pigs was induced by exposure to direct current (d.c.). In biopsies obtained from cathode areas successively from day 1 to day 7 after exposure the histopathologic and histochemical changes before and after the initial deposition of calcium salts have been examined. For comparison skin sites with intradermal injected calcium hydroxyapatite crystals were studied in addition. Small areas of calcified collagen and elastic fibres were noted in viable tissue 2 days after d.c. exposure. In succeeding days the calcified areas enlarged with new deposits always more superficial and closer to the epidermis than the original calcium deposits. Preconditions for calcification appear to be (1) a pH change in basic direction and/or the electrochemical processes specific to the cathode area and (2) a viable tissue. Elastic fibres appear to have a lower calcification threshold than collagen fibres. A positive staining for glycoproteins (PAS) and glycosaminoglycans (alcian blue pH 2.5) was noted in the calcified collagen fibres simultaneously with the calcification. In succeeding days the intensity of the staining reactions increased. Whether changes in the glycoproteins, collagen and its intimately bound glycosaminoglycans precede the calcification or the staining reactions develop secondarily to this deposition is not known. However, seven days after intradermal injections of Ca-apatite crystals in pig skin small and large crystals were observed ultrastructurally without any relation to collagen fibrils, but the calcified tissue presented a positive PAS and alcian blue reaction from day 2. Thus the PAS and alcian blue stainings in this model develop secondary to the deposition of calcium salts.

Animals↗
PubMed1988

The morphogenesis of electrically and heat-induced dermal changes in pig skin.

In order to establish pathological evidence in dermis for distinguishing between sequelae of electrical torture and those of other superficial injuries, the skin of eleven fully anaesthetized Danish Landrace pigs have been exposed to heat and electrical energy from either 50 Hz alternating current (a.c.) or direct current (d.c.) via 12 mm large contact knobs or via a pointed 0.5 mm large electrode (only 50 Hz a.c.). The lesions have been examined from 1 to 126 days after the injury. While heat lesions exposed to energy lower than 60 joule only gave minor changes, heat lesions exposed to more than 60 joule showed changes in both collagen fibres (basophilic or eosinophilic fibres without any birefringence or coarse cross-striation in polarized light, respectively) and dermal cells (granular cytoplasm). Areas exposed to 50 Hz a.c. via 0.5 mm. electrode showed basophilic collagen fibres and in a few biopsies on day 7 calcium salts on collagen fibres. Using 12 mm large electrodes the changes were minor, but basophilic and eosinophilic collagen fibres with no birefringence or with fine/coarse cross-striation respectively were seen. Even cells with 'vesicular nuclei' were seen on day 1 and 2 after the injury. The changes in the anode area showed resemblance to that of heat lesions (basophilic collagen fibres). Eosinophilic collagen fibres with fine densely spaced cross-striation in polarized light and 'vesicular nuclei' as well as collagen fibres with calcium salts were seen in the cathode lesions. It is concluded that the dermal changes in the cathode area are specific for electrical injury from day 1 to 14. However, earlier studies have demonstrated dermal changes specific for electrical injury at day 0 and the presence of calcified collagen fibres up to 2 months after injury. The dermal changes in anode lesions were non specific and could not be differentiated from those found in heat lesions. Alternating current lesions (50 Hz) were specific from day 1 to day 7, when the pointed electrode was used, but only in a few days when the energy was transferred via the 12-mm electrodes.

Animals↗
PubMed1988

The effect of sodium hydroxide and hydrochloric acid on pig dermis. A light microscopic study.

In order to compare the dermal changes after exposure to direct current (d.c.) with changes after influence of acid and base influence, the skin of fully anaesthetized Danish Landrace pigs were exposed to acid and basic solutions. Biopsies were obtained immediately after and up to day 7 after the injury. Collagen fibres with increased affinity for eosin and irregular cross-striation in polarized light together with shrunken cells with dark stained nuclei were found just beneath the epidermis immediately after application of 1 N HCl. Immediately after exposure to 1 N NaOH dispersed collagen fibres showed increased eosinophilia and a fine densely spaced cross-striation in polarized light and vesicular nuclei were present within dermal cells. During the following days a narrow demarcation zone of neutrophilic granulocytes separated the zone containing abnormal collagen fibres from normal tissue below. Calcified collagen fibres were not observed and no other abnormal histochemical reactions were present. It is concluded that the morphology of acid induced lesions and base induced lesions shows resemblance to the morphology of anode and cathode lesions, respectively, but not to heat lesions. The reason for not finding depositions of calcium salts on collagen fibres in skin exposed to basic solutions could be a non-optimal pH in the tissue or that other electrochemical processes than shift in pH are necessary for the calcification process.

Animals↗
PubMed1988

Ultrastructural changes in dermal pig skin after exposure to heat and electric energy and acid and basic solutions.

In order to describe the ultrastructure of the histopathological changes in dermis after exposure to electrical energy, heat energy and acid and basic solutions the skin of fully anaesthetized Danish Landrace pigs were exposed to direct current, heat (80 degrees C and 450 degrees C) and acid and basic solutions. Biopsies were obtained immediately after the exposure from all types of injury. Biopsies from the cathode areas biopsies were also taken on day 1 and day 2.5 in order to describe the initial calcium deposits. Homogeneous collagen fibres without any birefringence from heat exposed areas were ultrastructurally composed of filamentous materials. Collagen fibres with fine densely spaced cross-striation from cathode areas and areas exposed to basic solutions were shown ultrastructurally to consist of parallelly arranged collagen fibrils with regular waves. It is concluded that the cross-striation of the collagen fibres observed in polarized light are due to a periodic change in the orientation of the fibres seen as waves of the fibres. The ultrastructure of dermal cells were similar to that of epidermal cells following the different types of influence. Characteristically the nuclei were condensed following heat and more electron-lucent following direct current (d.c.) and acid and basic solutions. In cathode areas and areas influenced by basic solutions the electron-lucent nuclei contained fine fibrils. The ultrastructural study supports the suggestion from light microscopic studies that the morphology of anode and cathode lesions shows resemblance to acid induced and basic induced lesions, respectively. Apatite crystals were observed on day 2.5 at the periphery of the collagen fibrils and in the matrix of elastic fibres.

Animals↗
PubMed1988

The occurrence of calcium salt deposition on dermal collagen fibres following electrical injury to porcine skin.

Deposition of calcium salts on collagen fibres has been shown to occur in cathode areas from 2 days to 2 months after exposure to direct current (d.c.) via contact knobs measuring 12 mm in diameter using energy level from 0.5 to 96 J and on day 7 after exposure to alternating current (a.c.) via pointed electrodes using energy level from 30 to 50 J. In order to determine the statistical relation of this histological observation to the type of energy applied 1095 biopsies from 49 pigs including biopsies from skin areas exposed to heat, 50 Hz a.c., 100 kHz a.c. and d.c. as well as from unexposed skin were examined. The specificity was 1.0 using calcium deposition as the test criterium. The sensitivity for cathode areas was found to vary from 0.52 to 1.0 depending on the biopsy technique and the number of days after exposure. Calcium salts on collagen fibres seem uniformly to be present in the cathode area from day 4 to 7, the positive test answer being depending on the biopsy technique. For 50 Hz a.c. the sensitivity using a pointed electrode was found to vary from 0.08 to 0.27 dependent on the number of days after exposure. For all other types of energy the sensitivity was 0.

Animals↗
PubMed1986

Immediate dermal changes in pig skin after exposure to moderate amounts of heat and electrical energy.

Pig skin was exposed to approximately 80 joules of heat and electrical energy [50 Hz alternating current (a.c.) and direct current (d.c.)], respectively, under controlled conditions in order to find methods to document electrical torture. Biopsies were obtained immediately after exposure, and the morphology of the electrical lesions was compared with that of heat lesions and unexposed skin by using normal and polarized light microscopy. In areas exposed to 50 Hz a.c. and in cathode areas after d.c., where calcified collagen fibers have been found 2 days after injury, the collagen fibers showed a regular, densely spaced, cross-striation. This type of cross-striation was not found in heat or anode lesions. It was possible to blindly group all biopsies correctly with regard to influence of heat, 50 a.c. and d.c.

Animals↗
PubMed1984

Epidermal hyperplasias of northern pike (Esox lucius) associated with herpesvirus and C-type particles.

Northern pike from several locations in central Canada were observed to have two different types of hyperplastic epidermal lesions on the body and fins. One type of epidermal hyperplasia consisted of flat lesions, bluish-white in color with a granular or "gritty" appearance. Histological examination of this granular lesion showed the presence of grossly hypertrophied cells surrounded by normal sized epidermal cells. The enlarged nuclei in thin section contained many typical herpesvirus capsids measuring 100 nm in diameter. A large proportion of the cytoplasmic mass consisted of many dark staining inclusions in which were embedded numerous herpes-like virions. For this herpesvirus of pike the name esocid herpesvirus 1 is proposed in keeping with the herpesvirus nomenclature of Roizman et al. (19). The second type of epidermal hyperplasia was a smooth convex whitish translucent tissue mass consisting largely of a population of randomly oriented normal sized undifferentiated cells. Electron microscopic examination showed them to be associated with clusters of C-type retrovirus measuring 150 nm in diameter. The formation of these virus particles was by budding from the cytoplasmic membrane into the inter-cellular spaces. Neither the herpesvirus nor the C-type particles could be isolated in fish cell cultures.

Animals↗
PubMed1984

Tracing the use of electrical torture.

With the aim of being able to trace skin sequelae to electrical torture, an interdisciplinary group of scientists (the "electrical group" of Anti-Torture Research, ATR) has performed controlled morphological studies on skin biopsies from experiments with fully anesthetized pigs. "Vesicular nuclei" in epidermis and a characteristic pattern of collagen calcification in dermis were found to be typical of electrical damage. These alterations were produced by alternating current as well as by direct current.

Calcinosis↗