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Biomedical subjects

P Møller

Publications and source records attributed to P Møller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans.

The present study investigated the effect of a single bout of exhaustive exercise on the generation of DNA strand breaks and oxidative DNA damage under normal conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test; lymphocytes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was collected for 24 h periods for analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage. Urinary excretion of 8-oxodG increased during the first day in altitude hypoxia, and there were more endonuclease III-sensitive sites on day 3 at high altitude. The subjects had more DNA strand breaks in altitude hypoxia than at sea level. The level of DNA strand breaks further increased immediately after exercise in altitude hypoxia. Exercise-induced generation of DNA strand breaks was not seen at sea level. In both environments, the level of FPG and endonuclease III-sensitive sites remained unchanged immediately after exercise. DNA strand breaks and oxidative DNA damage are probably produced by reactive oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity to withstand oxidative stress produced by exhaustive exercise.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Duration of untreated psychosis: are we ignoring the mode of initial development?. An extensive naturalistic case study of phenomenal continuity in first-episode schizophrenia.

Duration of untreated psychosis (DUP) might affect the course and treatment outcome in schizophrenia significantly. Looking for potential determinants of DUP, researchers have mostly assessed the initial untreated psychosis in terms of plain duration, not developmental content. The present study provides empirical contributions to the discussion of phenomenal continuity throughout the entire untreated illness by pointing out continuous trajectories from prodrome to psychosis. In a series of 19 first-episode DSM-IV schizophrenia patients, we explore prodromal and untreated psychotic phenomena, and the data indicate that symptoms considered intrinsic to core psychosis phenomenology had attenuated antecedents in the prodromes, increasing continuously until treatment, whereas symptoms considered not intrinsic to core psychosis were characterized by fluctuations. Mode of initial psychosis development is proposed as a tentatively informative concept, comprising duration and content aspects of the initial prodrome and untreated psychosis.

Adolescent↗
PubMed2001

Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation.

This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D(2)-receptors are not involved in the hypoxia-induced decrease in the maximal heart rate. These data suggest that receptor uncoupling, and not down-regulation, of cardiac adrenoreceptors, is responsible for the early decrease in heart rate at maximal hypoxic exercise.

Adult↗
PubMed2000

A strong genotoxic effect in mouse skin of a single painting of coal tar in hairless mice and in MutaMouse.

The dorsal skin of C3H/Tif/hr hairless mice was painted with coal tar, pharmacological grade. Epidermal cells and hepatocytes were isolated after 4, 24, 48 and 96 h and DNA strand breaks were determined as tail moment by the alkaline comet assay. The tail moment of epidermal cells was significantly greater at the time points 4, 24, 48 and 96 h after exposure compared to the controls, with the most DNA strand breaks at 24 h. The DNA strand breaks in epidermal cells increased linearly with the dose of coal tar. In hepatocytes, no difference in DNA strand breaks was found between exposed animals and controls. DNA adducts were determined by the 32P-postlabeling assay. For epidermal cells, the mean DNA adduct level was 12-fold greater in coal tar painted mice after 24 h than in controls. Again, a linear dose/response relationship was seen 24 h after painting. For liver DNA, the mean DNA adduct level was 3-fold greater than for controls. The mutation frequency in epidermal and liver cells was examined in lambdalacZ transgenic mice (MutaMouse). Thirty-two days after painting, the mutation frequency in epidermal cells was 16-fold greater in coal tar treated mice compared to controls. No effect was detected in hepatocytes. We found that a single painting of coal tar resulted in strong genotoxic effects in the murine epidermis, evidenced by induction of DNA strand breaks and DNA adducts in hairless mice and lambdalacZ mutations in the MutaMouse. This demonstrates that it is possible to detect genotoxic effects of mixtures with high sensitivity in mouse skin by these end-points.

Administration, Cutaneous↗
PubMed2000

Psoriasis patients with basal cell carcinoma have more repair-mediated DNA strand-breaks after UVC damage in lymphocytes than psoriasis patients without basal cell carcinoma.

We have investigated the formation of strand-breaks following UVC irradiation in lymphocytes from psoriasis patients with or without basal cell carcinoma (BCC). Isolated lymphocytes were irradiated with UVC light at a dose of 3.6 J/m(2), and the level of DNA strand-breaks were measured 25 min after the irradiation by the alkaline comet assay. The generation of strand-breaks following UVC irradiation indicates DNA-repair-mediated incisions, as UVC light does not generate strand-breaks per se. We found that psoriasis patients with BCC had more DNA-repair incisions than non-cancer patients. The incision level correlated to two polymorphisms of the XPD gene. At present, it is not clear if the association is a primary effect that is related to differences of the XPD protein. Genes encoding for other repair proteins, namely XRCC1, ERCC1, and LIG1 are located close to the XPD gene, and it is possible that the association is due to a cosegregation with a polymorphism in one of these genes.

Alleles↗
PubMed2000

[Endoscopic treatment of colorectal obstruction with self-expandable metal endoprosthesis].

Relief of colo-rectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death (33-175 days, four patients) or are still patent (follow-up 35-80 days). These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomized trials can be initiated.

Aged↗
PubMed2000

Genotoxic hazards of azo pigments and other colorants related to 1-phenylazo-2-hydroxynaphthalene.

Azo pigments are used extensively as coloring agents in inks, paints and cosmetics. We have surveyed the literature for genotoxic and cancer data on nine colorants, which are structurally related to 1-phenylazo-2-hydroxynaphthalene (C.I. Solvent yellow 14). C.I. Solvent yellow 14 is metabolized by oxidative and peroxidative enzymes. Metabolically activated C.I. Solvent yellow 14 forms both RNA and DNA adducts. It induces liver nodules in rats upon oral administration. Although there is a mixture of negative and positive findings in short-term tests and in animal cancer studies, C.I. Solvent yellow 14 should be considered genotoxic. C.I. Pigment red 3 should be considered carcinogenic but is only weakly genotoxic. C.I. Solvent yellow 7, C.I. Pigment orange 5, C.I. Pigment red 4, and C.I. Pigment red 23 should be considered genotoxic. C.I. Pigment red 53:1 is not genotoxic, and observations of spleen tumors in male rats but not in female rats or mice seem to be related to toxic effects of high doses of C.I. Pigment red 53:1 in this organ. The data in the literature indicate that Pigment red 57:1 is not genotoxic or carcinogenic. We did not find sufficient data for a relevant evaluation of C.I. Pigment red 2 and C.I. Pigment red 64:1. Some of the colorants have in common the 2-amino-1-naphthol structure. This compound is not genotoxic. On the other hand, reductive cleavage of the azo bonds or hydrolysis of anilido bonds would produce aromatic amines, most of which have been under suspicion for genotoxicity or carcinogenicity. For C.I. Pigment red 53:1 and 57:1, sulphonated aromatic amines would be formed that are not genotoxic.

Animals↗
PubMed2000

Lasting auditory attention impairment after persistent middle ear infections: a dichotic listening study.

Dichotic listening performance was studied in children who at an early age had undergone a myringotomy with insertion of ventilating tubes for persistent middle ear infections (otitis media with effusion; OME) and compared with age-equivalent children who had no history of otitis media or hearing problems. The OME group consisted of 19 children with a median age of 9 years; 15 of whom were right-handed, and 14 were boys. The comparison sample comprised 18 children with a median age was 9 years 4 months. Hand preference and sex were matched with the OME group. Both groups were tested with dichotic listening to consonant-vowel syllables and additional forced-attention tasks. The comparison sample showed a weak right-ear advantage, and age-adequate attentional modulations. The children in the OME group showed a strong right-ear advantage, but were not able to modulate the ear advantage during directed-attention tasks. Models for interpreting the result are discussed.

Attention↗
PubMed2000

Sensitivity to nitrogen mustard relates to the ability of processing DNA damage in Chinese hamster ovary cells.

The hallmark of the excision repair pathways is the removal of DNA adducts by excision of the damaged nucleotides. In the course of repair, transient DNA strand breaks occur, which can be measured by the Comet assay. We have investigated the processing of DNA damage, mediated by nitrogen mustard, in wild-type AA8 Chinese hamster ovary cells, and in UV5, UV20 and UV41 DNA repair deficient cell lines. Whereas DNA repair could not be detected by unscheduled DNA synthesis at nitrogen mustard doses below 10 microM, processing of nitrogen mustard-mediated DNA damage was observed by the Comet assay at a 100-times lower concentration. Wild-type Chinese hamster ovary AA8 cells were able to process nitrogen mustard-mediated DNA damage within 4-24 hr depending on the dose of nitrogen mustard (0.1-10 microM). None of the repair-deficient cell lines was able to completely process the DNA damage induced by 10 microM nitrogen mustard. At nitrogen mustard doses that conferred 10% colony forming ability, the repair-deficient cells had an altered processing of nitrogen mustard-mediated DNA damage: In the AA8, UV20, and UV41 cells, the amplitude of strand breaks peaked early (within 4 hr), the level of strand breaks in the nitrogen mustard exposed UV20 and UV41 cells did not return to the baseline of the unexposed reference culture, and the peak in strand breaks in the UV5 cell line occurred after 4 hr. Our results indicate that the single cell gel electrophoresis (Comet) assay is suitable for assessing repair capability of DNA alkylations.

Alkylating Agents↗
PubMed2000

Concurrent disruption of p16INK4a and the ARF-p53 pathway predicts poor prognosis in aggressive non-Hodgkin's lymphoma.

The INK4a/ARF locus at chromosome 9p21 encodes two structurally and functionally distinct molecules with tumor-suppressive properties. p16INK4a controls cell cycle progression by inhibiting phosphorylation of the retinoblastoma protein (Rb), while ARF prevents MDM2-mediated degradation of p53. By using a panel of PCR-based methods, we have examined the status of the p16INK4a, ARF and p53 genes in 123 cases of non-Hodgkin's lymphoma (NHL) at diagnosis. Alterations of one or more of these genes were detected in seven of 36 (19%) cases with low- to intermediate-grade histology, and in 35 of 87 (40%) cases with aggressive histology. For the aggressive lymphomas, the Kaplan-Meier estimate of overall survival for cases with disruption of either p16INK4a or the ARF-p53 pathway was not different from cases with retention of both pathways (5 year survival 45% vs 35%; P= 0.85), suggesting that selective inactivation of one of the pathways does not significantly influence overall survival. By contrast, the 5-year survival was only 7% for cases with concurrent disruption of p16INK4a and the ARF-p53 pathway vs 38% for cases with retention of one or both pathways (P = 0.005). Similar results were obtained when the analysis was confined to diffuse large B cell lymphomas (P= 0.019). On stepwise multivariate regression analysis including factors from the international prognostic index, concurrent disruption of p16INK4a and the ARF-p53 pathway was an independent negative prognostic factor in NHL with aggressive histology (P = 0.006). Our results suggest that the compound status of the p16INK4a and ARF-p53 pathways is a major determinant of outcome in NHL.

ADP-Ribosylation Factors↗
PubMed2000

Lasting effects of otitis media with effusion on language skills and listening performance.

Otitis media with effusion (OME) and its related hearing loss has been associated with delayed language development, particularly if the disease is recurrent or of long duration. To find out more about the long-term effects of OME on language skills and listening performance we performed a retrospective study. A group of 19 otherwise healthy 9-year-old children with an earlier history of long lasting bilateral OME were compared with an age-matched control group of 19 children with no history of OME or hearing impairment and normal otoscopy, tympanometry and audiometry. The children in the OME group had an average of 1.4 treatments with ventilation tubes. Mean hearing levels for 500, 1,000 and 2,000 Hz in the OME group were 13 dB in the right ear and 11.3 dB in the left ear. All children were examined with the Illinois test of psycholinguistic abilities (ITPA), test for articulation, Boston naming test, dichotic listening tests with additional tasks of directed attention and tests for word and sound discrimination. In the OME group we found significant lower scores in the articulation test and small, but significant, lower scores in the test regarding sound discrimination. No significant differences on other language skills were detected in the ITPA test or Boston naming test. We found a significantly higher degree of right ear advantage and lower attentional effectiveness in the OME-group.

Attention↗
PubMed2000

The initial prodrome in schizophrenia: searching for naturalistic core dimensions of experience and behavior.

The scientific exploration of prepsychotic detection and intervention in psychosis has just commenced. To identify developing psychosis at prodromal stages, it is important to learn how patients and families perceive initial prodromes naturalistically. We must understand better what we are going to detect, because the essential components of this phase, particularly the subjective experiences, remain unsettled. In a series of 19 first episode DSM-IV schizophrenia patients, we explore prodromal phenomena in depth and identify potential core dimensions. On the basis of our findings, we describe experiences and behaviors that appear to be essential components of initial prodromes. The subjects reported serious difficulties interpreting and talking about prodromal experiences at the time these occurred, causing delayed identification. We report detailed reasons for this, pointing out vulnerable aspects of at-risk assessments. From eight proposed groups of experiences, two are highlighted as tentative core dimensions: "disturbance of perception of self" and "extreme preoccupation by and withdrawal to overvalued ideas." Four potential dimensions of prodromal behavior are also identified: (1) quit school, university, or job, or major school truancy, (2) marked and lasting observable shift of interests, (3) marked and lasting social passivity, withdrawal, or isolation, and (4) marked and lasting change in global appearance or behavior. We argue that the findings, the phenomena, and their significance in prodromes are valid because they are logical and coherent in light of clinical experience as well as the empirical literature of a full century.

Adolescent↗