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Biomedical subjects

P Jensen

Publications and source records attributed to P Jensen.

At least 19 recordsLinked to original sources

MicroRNA sequence motifs reveal asymmetry between the stem arms.

The processing of micro RNAs (miRNAs) from their stemloop precursor have revealed asymmetry in the processing of the mature and its star sequence. Furthermore, the miRNA processing system between organism differ. To assess this at the sequence level we have investigated mature miRNAs in their genomic contexts. We have compared profiles of mature miRNAs within their genomic context of the 5' and 3' stemloop precursor arms and we find asymmetry between mature sequences of the 5' and 3' stemloop precursor arms. The main observation is that vertebrate organisms have a characteristic motif on the 5' arm which is in contrast to the 3' arm motif which mainly show the conserved U at the position of the mature start. Also the vertebrate 5' arm motif show a semi-conserved G 13 nucleotides upstream from the first position. We compared the 5' and 3' arm profiles using the average log likelihood ratio (ALLR) score, as defined by Wang and Stormo (2003) [Wang T., Stormo, G.D., 2003. Combining phylogenetic data with co-regulated genes to identify regulatory motifs. Bioinformatics 2369-2380.] and computing a p-value we find that the two profiles differs significantly in their 3' end where the 5' arm motif (in contrast to the 3' arm motif) has a semi-conserved GU rich region. Similar findings are also obtained for other organisms, such as fly, worm and plants. The observed similarities and differences between closely and distantly related organisms are discussed and related to current knowledge of miRNA processing.

Animals↗

Increased urinary aquaporin-2 excretion in response to furosemide in patients with chronic heart failure.

OBJECTIVE: Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U-AQP2 increases after a single intravenous dose of furosemide in CHF patients. MATERIAL AND METHODS: In a randomized, single-blind, placebo-controlled, crossover study, we measured the effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U-AQP2 and hormones were determined by radioimmunoassays. RESULTS: Furosemide increased U-AQP2 (140 %), urine volume (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change. CONCLUSIONS: In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin-angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.

Adult↗

Quantitative trait loci analysis of egg and meat production traits in a red junglefowlxWhite Leghorn cross.

Egg and production traits are of considerable economic importance in chickens. Using a White Leghorn x red junglefowl F(2) intercross, standard production measures of liver weight and colour, egg size, eggshell thickness, egg taste and meat quality were taken. A total of 160 markers covering 29 autosomes and the Z chromosome were genotyped on 175-243 individuals, depending on the trait under consideration. A total of nine significant quantitative trait loci (QTL) and three suggestive QTL were found on chicken chromosomes 1, 2, 4, 5, 7, 8, 10, 12, E47W24 and E22C19W28.

Animals↗

Feather pecking in chickens is genetically related to behavioural and developmental traits.

Feather pecking (FP) is a detrimental behaviour in chickens, which is performed by only some individuals in a flock. FP was studied in 54 red junglefowl (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from an F(2)-intercross between these two lines. From all F(2)-birds, growth and feed consumption were measured. Age at sexual maturity and egg production in females, and corticosterone levels in males were also measured. From 333 F(2)-birds of both sexes, and 20 parental birds, body composition with respect to bone mineral content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray Absorptiometry (DXA). In femurs of the same birds, the bone density and structure were analysed using DXA and Peripheral Quantitative Computerized Tomography (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore, plumage condition was determined in all birds as a measure of being exposed to feather pecking. Using 105 DNA-markers in all F(2)-birds, a genome-wide scan for Quantitative Trait Loci (QTL), associated with the behaviour in the F(2)-generation was performed. FP was at least as frequent in the red junglefowl as in the White Leghorn strain studied here, and significantly more common among females both in the parental strains and in the F(2)-generation. In the F(2)-birds, FP was phenotypically linked to early sexual maturation, fast growth, weak bones, and, in males, also high fat accumulation, indicating that feather peckers have a different resource allocation pattern. Behaviourally, F(2) feather peckers were more active in an open field test, in a novel food/novel object test, and in a restraint test, indicating that feather pecking might be genetically linked to a proactive coping strategy. Only one suggestive QTL with a low explanatory value was found on chromosome 3, showing that many genes, each with a small effect, are probably involved in the causation of feather pecking. There were significant effects of sire and dam on the risk of being a victim of feather pecking, and victims grew faster pre- and post-hatching, had lower corticosterone levels and were less active in a restraint test. Hence, a wide array of behavioural and developmental traits were genetically linked to FP.

Aggression↗

Social interactions in Red Junglefowl (Gallus gallus) and White Leghorn layers in stable groups and after re-grouping.

Although social behaviour is a major factor affecting the coping of poultry in production environments little is known about how it has been affected by intensive selection processes in fowl. We attempted to clarify selection effects on overall repertoire and occurrence of different social behaviours as well as on aggressive responses to re-grouping with unfamiliar birds by comparing high-producing White Leghorn layers to wild type Red Junglefowl. In the first experiment we observed 8 stable mixed sex groups/breed each consisting of four 24-week-old birds previously familiar to each other. During 9 consecutive days, a wide range of social signals, sexual and aggressive interactions as well as spacing behaviour and activity were recorded over a 12-h photoperiod. In the second experiment, starting at 19 weeks of age, 16 single sex groups of three birds from each breed were formed by mixing unfamiliar individuals. Aggressive behaviours were recorded 0, 5, 24 and 48 h after re-grouping. Results from the stable groups indicated that the repertoire of social behaviours has been preserved during selection with few changes in frequencies and intensities. However, Leghorns showed a more cohesive spacing pattern than junglefowl. In the second experiment, aggressive activity was higher immediately and after 24 h following re-grouping in Leghorns, but there was a drop in the aggressiveness at 5 h to the same level as junglefowl. We suggest that this may indicate poorer social learning capacity with a weaker ability to cope with group disruptions compared to the ancestral breed.

Animals↗

Planned inguinal herniorrhaphy but no hernia sac?

BACKGROUND: Planned inguinal herniorrhaphy may present a clinical dilemma when no hernia is found. No large-scale data are available on the incidence of this problem, and, therefore, no recommendations exist for choice of surgical intervention. MATERIAL AND METHODS: Data were extracted from the Danish Hernia Database covering the interval from 1 January 1998-5 April 2002, and included 42,356 groin hernia repairs. Results. No hernia was found in 313 cases (0.74%). These patients were divided into three groups (lipomas, no pathology, and a "weak abdominal wall") and analysed according to surgical technique. There were 11 reoperations (3.5%) of which three were femoral and eight inguinal hernias, without differences between type of initial operation (herniorrhaphy or no herniorrhaphy). CONCLUSION: This study of 42,356 groin hernia repairs showed that in 313 patients (0.74%), no hernia was found. Recurrences did not occur with higher frequency in patients receiving no repair. Based on these data and the risk of chronic postherniorrhaphy pain, we suggest that no repair be performed when no inguinal hernia is found during planned inguinal herniorrhaphy.

Denmark↗

Responses of young red jungle fowl (Gallus gallus) and White Leghorn layers to familiar and unfamiliar social stimuli.

Social preferences of familiar over unfamiliar social stimuli in chicks may be used to measure sociality, a characteristic important for the welfare of poultry in commercial production. We studied social preferences and reaction to strangers in young White Leghorns and red jungle fowl (Gallus gallus) in 3 tests. All chicks were raised and housed in 2 groups of 34 individuals per breed. At 24 to 29 d of age 38 chicks per breed were tested in 2 runway tests. In the first, chicks had a free choice between familiar and unfamiliar breed members, and in the second the choice was between unfamiliar chicks of their own breed and the other breed. On d 41 to 42, spacing and agonistic interactions of 28 pairs of chicks per breed (in half of the pairs, chicks were unfamiliar to each other) were observed in an open field for 10 min (pair test). In the first runway test, clear preference for familiar chicks and avoidance of unfamiliar social stimuli was found only in Leghorns, whereas both breeds showed a preference for their own breed members in the second runway test. Affiliation to the familiar breed, however, was more pronounced in Leghorns. In the pair test, Leghorns were significantly more involved in agonistic interactions than wild-type chicks. Avoidance of unfamiliar and preference for familiar conspecifics might suggest a weaker capacity of Leghorns to cope with novel social and environmental stimuli, which might have implications for the welfare of the birds in production environments when encountering unfamiliar individuals.

Animal Welfare↗

Prediction of mortality at age 40 in Danish males at high and low risk for alcoholism.

OBJECTIVE: This prospective high-risk study examined the influence of father's alcoholism and other archival-generated measures on premature death. METHOD: Sons of alcoholic fathers (n = 223) and sons of non-alcoholic fathers (n = 106) have been studied from birth to age 40. Archival predictors of premature death included father's alcoholism, childhood developmental data, and diagnostic information obtained from the Psychiatric Register and alcoholism clinics. RESULTS: By age 40, 21 of the 329 subjects had died (6.4%), a rate that is more than two times greater than expected. Sons of alcoholic fathers were not more likely to die by age 40. Premature death was associated with physical immaturity at 1-year of age and psychiatric/alcoholism treatment. No significant interactions were found between risk and archival measures. CONCLUSION: Genetic vulnerability did not independently predict death at age 40. Death was associated with developmental immaturities and treatment for a psychiatric and/or substance abuse problem.

Adult↗

Melanocortin 1-receptor (MC1R) mutations are associated with plumage colour in chicken.

The co-segregation of plumage colour and sequence polymorphism in the melanocortin 1-receptor gene (MC1R) was investigated using an intercross between the red junglefowl and White Leghorn chickens. The results provided compelling evidence that the Extended black (E) locus controlling plumage colour is equivalent to MC1R. E/MC1R was assigned to chromosome 11 with overwhelming statistical support. Sequence analysis indicated that the E92K substitution, causing a constitutively active receptor in the sombre mouse, is the most likely causative mutation for the Extended black allele carried by the White Leghorn founders in this intercross. The MC1R sequence associated with the recessive buttercup (ebc) allele indicated that this allele evolved from a dominant Extended black allele as it shared the E92K and M71T substitutions with some E alleles. It also carried a third missense mutation H215P which thus may interfere with the constitutive activation of the receptor caused by E92K (and possibly M71T).

Amino Acid Sequence↗

The twofold difference in adult size between the red junglefowl and White Leghorn chickens is largely explained by a limited number of QTLs.

A large intercross between the domestic White Leghorn chicken and the wild ancestor, the red junglefowl, has been used in a Quantitative Trait Loci (QTL) study of growth and egg production. The linkage map based on 105 marker loci was in good agreement with the chicken consensus map. The growth of the 851 F2 individuals was lower than both parental lines prior to 46 days of age and intermediate to the two parental lines thereafter. The QTL analysis of growth traits revealed 13 loci that showed genome-wide significance. The four major growth QTLs explained 50 and 80% of the difference in adult body weight between the founder populations for females and males, respectively. A major QTL for growth, located on chromosome 1 appears to have pleiotropic effects on feed consumption, egg production and behaviour. There was a strong positive correlation between adult body weight and average egg weight. However, three QTLs affecting average egg weight but not body weight were identified. An interesting observation was that the estimated effects for the four major growth QTLs all indicated a codominant inheritance.

Alleles↗

Lambda spectra in 11.6A GeV/c Au-Au collisions.

E896 has measured Lambda production in 11.6A GeV/c Au-Au collisions over virtually the whole rapidity phase space. The midrapidity p(t) distributions have been measured for the first time at this energy and appear to indicate that the Lambda hyperons have different freeze-out conditions than protons. A comparison with the relativistic quantum molecular dynamics model shows that while there is good shape agreement at high rapidity the model predicts significantly different slopes of the m(t) spectra at midrapidity. The data, where overlap occurs, are consistent with previously reported measurements.

Journal Article↗

Risk factors in HIV-associated diarrhoeal disease: the role of drinking water, medication and immune status.

In a cross-sectional survey of 226 HIV-infected men, we examined the occurrence of diarrhoea and its relationship to drinking water consumption patterns, risk behaviours, immune status and medication use. Diarrhoea was reported by 47% of the respondents. Neither drinking boiled nor filtered water was significantly associated with diarrhoea (OR = 0.5 [0.2, 1.6], 1.2 [0.6, 2.5] respectively), whereas those that drank bottled water were at risk for diarrhoea (OR = 3.0 [1.1, 7.8]). Overall, 47% always or often used at least one water treatment. Of the 37% who were very concerned about drinking water, 62% had diarrhoea, 70% always or often used at least one water treatment. An increase in CD4 count was protective only for those with a low risk of diarrhoea associated with medication (OR = 0.6 [0.5, 0.9]). A 30% attributable risk to diarrhoea was estimated for those with high medication risk compared to those with low medication risk. The significant association between concern with drinking water and diarrhoea as well as between concern with drinking water and water treatment suggests awareness that drinking water is a potential transmission pathway for diarrhoeal disease. At the same time we found that a significant portion of diarrhoea was associated with other sources not related to drinking water such as medication usage.

Adult↗

Associations between water-treatment methods and diarrhoea in HIV-positive individuals.

This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we employed logistic regression and marginal structural modelling of the data. The relative risk of diarrhoea for 'always' vs. 'never' drinking boiled water was 0.68 (95% CI 0.45-1.04) and for 'always' vs. 'never' drinking bottled water was 1.22 (95 % CI 0.82-1.82). Drinking filtered water was unrelated to diarrhoea (1.03 (95% CI 0.78, 1.35) for 'always' vs. 'never' drinking filtered water]. Adjustment for confounding did not have any notable effect on the point estimates (0.61, 1.35 and 0.98 for boiled, bottled, and filtered water respectively, as defined above). The risk of diarrhoea was lower among those consuming boiled water but this finding was not statistically significant. Because of these findings, the importance of diarrhoea in immunocompromised individuals, and the limitations of cross-sectional data further prospective investigations of water consumption and diarrhoea among HIV-positive individuals are needed.

Adolescent↗

Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes: Maintenance of differentiated phenotype under defined culture conditions.

OBJECTIVE: To establish an immortalized normal human articular chondrocyte line which could be useful for a better understanding of cell molecular mechanisms relevant for the development of new therapeutic approaches in rheumatic diseases. DESIGN: Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 (HPV-16) early function genes: E6 and E7, using the highly efficient cationic liposome-mediated (lipofection) procedure. The transfection was verified by reverse transcriptase-polymerase chain reaction analysis of E7 mRNA and by immunofluorence localization of the E7 protein in the cell cytoplasm. The established chondrocyte cell line was examined in monolayer and in two culture conditions that were described to re-induce differentiated characteristics: culturing in a serum-free defined medium supplemented with an insulin-containing serum substitute and seeding on a hyaluronan-based non-woven structured biomaterial. The expression of markers characteristic of cartilage was shown in the mRNA by reverse transcriptase-polymerase chain reaction. Immunohistological staining and Western blotting analysis were performed to evaluate type II collagen synthesis. Proteoglycans deposition was detected by Alcian Blue staining. A Field Emission In Lens Scanning Microscopy was used to look at the morphology of the immortalized cells at very high magnification. RESULTS: Normal human articular chondrocytes were efficiently transfected leading to the establishment of an immortalized cell line as confirmed by HPV-16 E7 mRNA and protein detection. These cells were able to re-express type II collagen both at mRNA and protein levels under the two defined cultured conditions we used, still maintaining type I collagen expression. Collagen IX mRNA was present only in early primary culture while collagen type X and aggrecan transcripts were always detected. Alcian Blue staining showed a proteoglycan-rich matrix production. The ultrastructural analysis of the immortalized cells revealed that their morphology strictly resembled that of normal chondrocytes. CONCLUSIONS: The cell line that we obtained may be a useful tool for increasing our knowledge of the genetic and biochemical events involved in the processes of cartilage growth and differentiation. Moreover, it appears to be a suitable model for pharmacological and toxicological studies related to rheumatic diseases relevant to humans.

Blotting, Western↗

Longer term effects of stimulant treatments for Attention-Deficit/Hyperactivity Disorder.

Of pharmacological options available for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulant medications are the most studied, the most commonly used, the most effective, and the first-line choice for treatment. Evidence of the short-term efficacy of methylphenidate (MPH) and other stimulants as well as behavioral treatments in the management of symptoms of ADHD is abundant This paper reviews therapeutic trials with a duration or follow-up period of 12 months or more and evaluates the longer term outcomes of available treatments for ADHD. The trials were reported by Ialongo et al. (1993), Horn et al. (1991), Schachar, Tannock, Cunningham, and Corkum (1997), Gillberg et al. (1997), Hechtman and Abikoff (1995), and the National Institute of Mental Health (MTA Cooperative Group, 1999a, 1999b).

Attention Deficit Disorder with Hyperactivity↗

Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder.

OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.

Adolescent↗

Occupational risk from ultraviolet germicidal irradiation (UVGI) lamps.

The recommended role of ultraviolet germicidal irradiation (UVGI) is to reduce the risk of tuberculosis (TB) transmission in health care facilities. However, excess exposure may result in dermatosis and photokeratitis. In one hospital setting in Botswana, two nurses and one housekeeper complained of eye discomfort, 'like sand in the eyes', after working in an administrative office. The following day, one employee noted facial skin peeling. All symptoms resolved over 2-4 days without sequelae. Six weeks later, the syndrome recurred for all three employees. A workplace investigation revealed that the office had been converted from a hospital sputum induction room, and that an unshielded 36-W UVGI lamp was still installed and operational. The on/off switch for the UVGI lamp was immediately adjacent to the fluorescent bulb on/off switch, and did not have a locking mechanism. The US National Institute for Occupational Safety and Health recommends that exposure to UVGI (254 nm) be less than 6000 microJ/cm2 (6000 microW approximately = sec/cm2) over a daily 8-hour period on unprotected skin or eyes. In the office, UVGI measurements at eye level and looking directly at the UVGI lamp ranged from a low of 20.0 microW approximately = sec/cm2 when seated to a high of 49.9 microW approximately = sec/cm2 when standing. These irradiance levels result in allowable exposure times of 300 and 120 seconds, respectively, and are the most likely cause of the clinical syndrome described.

Disinfection↗