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Biomedical subjects

Per Jensen

Publications and source records attributed to Per Jensen.

25 records · Page 2Linked to original sources

Risk factors that predicted problem drinking in Danish men at age thirty.

OBJECTIVE: The Danish Longitudinal Study of Alcoholism utilized a prospective, high-risk research paradigm to identify putative markers of adult male alcoholism from a comprehensive database that began with the birth of the subject and extended over three decades. This article focuses on measures antedating abusive drinking that predicted lifetime alcohol abuse/dependence at age 30 years. METHOD: The original 330 subjects of this study were drawn from a large Danish birth cohort (N = 9,125) born between 1959 and 1961. The sample included 223 sons of treated alcoholic fathers (high-risk group) and 107 matched sons whose biological fathers had no record of treatment for alcoholism (low-risk group). This sample has been thoroughly investigated with a variety of methods representing multiple domains that included perinatal records, pediatric records, school records, teacher ratings, school physician records and a series of structured interviews and psychometric tests at ages 19-20 and 30 years. The present analysis focuses on the degree to which premorbid differences between the high- and low-risk groups later predicted lifetime drinking problems at age 30 (n = 241). RESULTS: As expected lifetime alcohol abuse/dependence by age 30 was reported significantly more often in the high-risk group. Of the 394 premorbid variables tested, 68 were found to distinguish the high- from the low-risk group before any subjects had developed a drinking problem. Of these 68 variables, 28 (41%) were also associated with DSM-III-R alcohol abuse/dependence at age 30. These 28 putative markers were reduced to 12 that were entered into a multiple regression analysis to search for the most powerful unique predictors of alcoholism. Four of the 28 putative markers were independently associated with problem drinking at age 30: low birth weight, number of life crises in childhood, ratings of childhood unhappiness and antisocial personality disorder. The regression model accounted for 46% of the drinking outcome variance. A father's alcoholism by itself no longer independently contributed to the prediction of his son's drinking and with one exception, did not systematically interact with the putative markers to facilitate the prediction of alcohol dependence at age 30. CONCLUSIONS: Risk itself. which significantly predicted problem drinking at age 30, was not uniquely associated with the development of alcoholism in adulthood. These findings, rather, provide broad support for the biopsychosocial model of alcoholism, especially for those models that emphasize the cumulative influence over time of internal and external variables in biologically vulnerable individuals.

Adult↗

Search for a shared segment on chromosome 10q26 in patients with bipolar affective disorder or schizophrenia from the Faroe Islands.

Previous linkage studies have suggested a new locus for bipolar affective disorder and possibly also for schizophrenia on chromosome 10q26. We searched for allelic association and chromosome segment and haplotype sharing on chromosome 10q26 among distantly related patients with bipolar affective disorder or schizophrenia and controls from the relatively isolated population of the Faroe Islands by investigating 22 microsatellite markers from a 35 cM region. We used a combined approach with both assumption free tests and tests based on genealogical relationships. The 6.5 cM region between D10S1230 and D10S2322, which has been implied in previous linkage analyses, received some support. A search for segment sharing yielded empirical P-values around 0.02 among patients with bipolar affective disorder and around 0.03 for patients with schizophrenia. For both disorders combined allelic association yielded empirical P-values around 0.003 at marker D10S1723. A haplotype data mining approach supported haplotype sharing in this region. In another, more distal, 11.5 cM region between markers D10S214 and D10S505, which has received support in previous linkage studies, increased haplotype sharing in patients with bipolar affective disorder was supported by Fisher's exact test, tests based on genealogy and by haplotype data mining. Our findings yield some support for a risk gene for bipolar affective disorder and possibly also for schizophrenia.

Alleles↗

The Renner effect in triatomic molecules with application to CH+, MgNC and NH2.

We have developed a computational procedure, based on the variational method, for the calculation of the rovibronic energies of a triatomic molecule in an electronic state that become degenerate at the linear nuclear configuration. In such an electronic state the coupling caused by the electronic orbital angular momentum is very significant and it is called the Renner effect. We include it, and the effect of spin-orbit coupling, in our program. We have developed the procedure to the point where spectral line intensities can be calculated so that absorption and emission spectra can be simulated. In order to gain insight into the nature of the eigenfunctions, we have introduced and calculated the overall bending probability density function f(p) of the states. By projecting the eigenfunctions onto the Born-Oppenheimer basis, we have determined the probability density functions f+(rho) and f-(rho) associated with the individual Born-Oppenheimer states phi(-)elec and phi(+)elec. At a given temperature the Boltzmann averaged value of the f(p) over all the eigenstates gives the bending probability distribution function F(rho), and this can be related to the result of a Coulomb Explosion Imaging (CEI) experiment. We review our work and apply it to the molecules CH2+, MgNC and NH2, all of which are of astrophysical interest.

Algorithms↗

QTL analysis of a red junglefowl x White Leghorn intercross reveals trade-off in resource allocation between behavior and production traits.

Behaviors with high energetic costs may decrease in frequency in domestic animals as a response to selection for increased production. The aim of this study was to quantify production traits, foraging behavior, and social motivation in F2 progeny from a White Leghorn x red junglefowl intercross (n = 751-1046) and to perform QTL analyses on the behavioral traits. A foraging-social maze was used for behavioral testing, which consisted of four identical arms and a central box. In two arms there was ad libitum access to the birds' usual food, and in the other two there was novel food (sunflower seeds) mixed with cat litter. In one arm with each of the two food sources, social stimuli were simulated by the presence of a mirror. Each bird could therefore feed on novel or well known food either alone or in the perceived company of a conspecific. Egg production, sexual maturity (females), food intake, and growth were measured individually, and residual food intake and metabolic body weight were estimated using standard methods. A genome scan using 104 microsatellite markers was carried out to identify QTLs affecting behavioral traits. Phenotypic growth rates at different ages showed weak associations in both sexes. Sexual maturity and egg weight were not strongly correlated to growth, indicating that these traits are not genetically linked. Time spent in each arm and in the central part of the maze was analyzed using principal component analyses. Four principal components (PC) were extracted, each reflecting a pattern of behavior in the maze. Females with early onset of sexual maturity scored higher on the PC1 reflecting preference for free food without social stimuli, and females with higher egg production scored higher on the PC2 reflecting exploration. Males with an overall higher growth rate and higher residual food intake scored higher on the PC3, which possibly reflected fear of the test situation, and tended to score higher on the PC4 reflecting low contrafreeloading. Significant QTLs were found for PC1 and PC4 scores on chromosomes 27 and 7, respectively. The location of the QTLs coincided with known QTLs for growth rate and body weight. The results suggest a trade-off between energy-demanding behavior and high production and that some of this may be caused by genetic linkage or pleiotropic gene effects.

Animals↗

The Near Ultraviolet Band System of Singlet Methylene.

In a classic paper by G. Herzberg and J. W. C. Johns entitled "The Spectrum and Structure of Singlet CH(2)" (Proc. Roy. Soc. A 295, 107-128 (1966)) the analysis of the &btilde;(1)B(1)<--ã(1)A(1) red absorption band system of CH(2) is discussed in detail for the first time. In addition to that band system the observation of a fragment of a weak near ultraviolet absorption band system is reported. The three observed bands of the system could not be vibrationally assigned or rotationally analyzed but it was pointed out that they probably involve absorption into the second excited singlet state, &ctilde;(1)A(1). We show this supposition to be true here by simulation. In order to simulate the spectrum we have calculated ab initio the &ctilde;-ã and &ctilde;-&btilde; transition moment surfaces and used the MORBID and RENNER program systems with previously determined potential energy surfaces for the ã, &btilde;, and &ctilde; states in a calculation of the energy levels and wavefunctions. We find that the three bands seen by Herzberg and Johns are part of the &ctilde;<--(ã/&btilde;) system but that all of the bands of the system above about 31 000 cm(-1) are missing as a result of &ctilde; state predissociation. We vibrationally assign the bands but the weakness of the spectrum, and the presence of perturbations, make it impossible for us to analyze the rotational structure fully. Further experimental and theoretical studies are suggested. Copyright 2001 Academic Press.

Journal Article↗

Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung.

The leading cause of mortality in patients with cystic fibrosis (CF) is respiratory failure due in large part to chronic lung infection with Pseudomonas aeruginosa strains that undergo mucoid conversion, display a biofilm mode of growth in vivo and resist the infiltration of polymorphonuclear leukocytes (PMNs), which release free oxygen radicals such as H2O2. The mucoid phenotype among the strains infecting CF patients indicates overproduction of a linear polysaccharide called alginate. To mimic the inflammatory environment of the CF lung, P. aeruginosa PAO1, a typical non-mucoid strain, was grown in a biofilm. This was treated with low levels of H2O2, as if released by the PMNs, and the formation of mucoid variants was observed. These mucoid variants had mutations in mucA, which encodes an anti-sigma factor; this leads to the deregulation of an alternative sigma factor (sigma22, AlgT or AlgU) required for expression of the alginate biosynthetic operon. All of the mucoid variants tested showed the same mutation, the mucA22 allele, a common allele seen in CF isolates. The mucoid mucA22 variants, when compared to the smooth parent strain PA01, (i) produced 2-6-fold higher levels of alginate, (ii) exhibited no detectable differences in growth rate, (iii) showed an unaltered LPS profile, (iv) were approximately 72% reduced in the amount of inducible-beta-lactamase and (v) secreted little or no LasA protease and only showed 44% elastase activity. A characteristic approximately 54 kDa protein associated with alginate overproducing strains was identified as AlgE (Alg76) by N-terminal sequence analysis. Thus, the common phenotype of the mucoid variants, which included a genetically engineered mucA22 mutant, suggested that the only mutation incurred as a result of H2O2 treatment was in mucA. When a P. aeruginosa biofilm was repeatedly exposed to activated PMNs in vitro, mucoid variants were also observed, mimicking in vivo observations. Thus, PMNs and their oxygen by-products may cause P. aeruginosa to undergo the typical adaptation to the intractable mu- coid form in the CF lung. These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence by the bacteria. This is the first report to show that PMNs and their oxygen radicals can cause this phenotypic and genotypic change which is so typical of the intractable form of P. aeruginosa in the CF lung. These findings may provide a basis for the development of anti-oxidant and anti-inflammatory therapy for the early stages of infection in CF patients.

Alginates↗