Biomedical subjects

J Pedersen

Publications and source records attributed to J Pedersen.

At least 19 recordsLinked to original sources

PubMed2007

A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis.

Systemic sclerosis is a connective tissue disease that involves the gastrointestinal (GI) tract. Seventy-five per cent of systemic sclerosis patients experience symptoms arising from oesophagus. The intestine has less frequently been subject for studies than the oesophagus. When the small intestine becomes involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur. Previous studies have shown decreased and abnormal intestinal motility, dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic sclerosis patients using novel analysis of intestinal muscle contraction force-velocity and power. A volume-controlled duodenal ramp-distension protocol was used in nine patients and eight healthy controls. The wall stretch ratio, tension, shortening velocity and muscle power were computed from pressure and cross-sectional area data recorded by an impedance planimetry system. The tension-stretch ratio relation obtained in patients was shifted to the left, indicating a stiffer wall. The in vivo tension-shortening velocity relationship was quantified using Hill's equation. The maximum preload tension (tension at zero velocity) was lower in the patients than in the healthy controls (P < 0.001). The muscle power was lowest in the patients. An association was found between the duration of the disease and the maximum stretch ratio (P < 0.05). The study represents the first data with application of in vivo muscle force-velocity relations in patients with gastrointestinal diseases. Systemic sclerosis patients had increased stiffness and impaired muscle dynamics of the duodenum. Decreased muscle function and increased wall stiffness may explain the GI symptoms reported in this patient group.

Algorithms↗

PubMed2006

Evaluation of a non-targeted "omic" approach in the safety assessment of genetically modified plants.

Genetically modified plants must be approved before release in the European Union, and the approval is generally based upon a comparison of various characteristics between the transgenic plant and a conventional counterpart. As a case study, focusing on safety assessment of genetically modified plants, we here report the development and characterisation of six independently transformed ARABIDOPSIS THALIANA lines modified in the flavonoid biosynthesis. Analyses of integration events and comparative analysis for characterisation of the intended effects were performed by PCR, quantitative Real-time PCR, and High Performance Liquid Chromatography. Analysis by cDNA microarray was used as a non-targeted approach for the identification of potential unintended effects caused by the transformation. The results revealed that, although the transgenic lines possessed different types of integration events, no unintended effects were identified. However, we found that the majority of genes showing differential expression were identified as stress-related genes and that environmental conditions had a large impact on the expression of several genes, proteins, and metabolites. We suggest that the microarray approach has the potential to become a useful tool for screening of unintended effects, but state that it is crucial to have substantial information on the natural variation in traditional crops in order to be able to interpret "omics" data correctly within the framework of food safety assessment strategies of novel plant varieties, including genetically modified plant varieties.

Arabidopsis↗

PubMed2005

Multimodal pain stimulations in patients with grade B oesophagitis.

AIM: To obtain a better understanding of nociceptive processing in patients with oesophagitis. PATIENTS AND METHODS: Eleven patients with grade B oesophagitis were compared with an age and sex matched group of 16 healthy subjects. A probe was positioned in the lower part of the oesophagus. After preconditioning of the tissue, painful mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. Distensions were done before and after pharmacological impairment of distension induced smooth muscle contractions. Thermal stimulation was performed by recirculating water at 1 and 60 degrees C in the bag. The area under the temperature curve (AUC) represented caloric load. The referred pain area (being a proxy for the central pain mechanisms) to the mechanical stimuli was drawn at maximum pain intensities. RESULTS: Patients were hyposensitive to mechanical stimuli, as assessed by the distending volume (F=8.1, p=0.005). After relaxation of smooth muscle with butylscopolamine, the difference between the two groups was more evident (F=27.4, p<0.001). AUC for cold stimulation was 1048.6 (242.7) degrees Cxs in controls and 889.8 (202.6) degrees Cxs in patients (p=0.5). For heat stimuli, AUC values were 323.3 (104.1) and 81.3 (32.3) degrees Cxs in controls and patients, respectively (p=0.04). The referred pain area to the mechanical stimulations was larger and more widespread in patients (49.3 (6.2) cm2 compared with controls 23.9 (7) cm2; p=0.02). CONCLUSIONS: The data indicate that peripheral sensitisation of heat sensitive receptors and pathways combined with facilitation of central pain mechanisms may explain the symptoms in patients with oesophagitis.

Adult↗

PubMed2005

High incidence of skewed X chromosome inactivation in young patients with familial non-BRCA1/BRCA2 breast cancer.

BACKGROUND: A higher frequency of skewed X chromosome inactivation has been reported in a consecutive series of young patients with breast cancer compared with controls of a similar age. OBJECTIVE: To investigate the X inactivation pattern in patients with familial non-BRCA1/BRCA2 breast cancer (n = 272), BRCA1/BRCA2 germline mutations (n = 35), and sporadic breast cancer (n = 292). METHODS: X inactivation pattern was determined by polymerase chain reaction analysis of the highly polymorphic CAG repeat in the androgen receptor (AR) gene. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially expressed one X chromosome. RESULTS: Young patients with familial breast cancer had a significantly higher frequency of skewed X inactivation (11.2%) than young controls (2.7%) (p = 0.001). There was also a strong tendency for middle aged patients with sporadic breast cancer to be more skewed than middle aged controls (13.6% v 4.4%) (p = 0.02). No association between skewed X inactivation and breast cancer was found for the BRCA1/BRCA2 patients . CONCLUSIONS: Skewed X inactivation may be a risk factor for the development of breast cancer in both sporadic and familial breast cancer and may indicate an effect of X linked genes.

Adult↗

PubMed2005

New analysis for the study of the muscle function in the human oesophagus.

The aim was to further develop a method for studying the active and passive tissue properties in the human oesophagus. An impedance planimetric probe with a bag for distension was placed in the distal oesophagus in 14 healthy volunteers. Distension was done at an infusion rate of 25 mL min(-1) with and without the administration of the antimuscarinic drug butylscopolamine. The flow was reversed when moderate pain was experienced by the subject. The total and the passive tension showed an exponential behaviour as function of the change in radius. The active tensions increased until they reached a maximum point. The active tension decreased after the maximum until the distension was stopped shortly after due to the pain. The change in tension during distension-induced contractions (the afterload) was plotted as function of the precontraction radius (the preload). The human oesophagus behaves in a manner known from in vitro studies on muscle strips and exhibits a muscle diagram similar to that in the heart, i.e. the larger the initial muscle length during distension (within limits), the greater the contraction force.

Adult↗

PubMed2004

Unintended effects and their detection in genetically modified crops.

The commercialisation of GM crops in Europe is practically non-existent at the present time. The European Commission has instigated changes to the regulatory process to address the concerns of consumers and member states and to pave the way for removing the current moratorium. With regard to the safety of GM crops and products, the current risk assessment process pays particular attention to potential adverse effects on human and animal health and the environment. This document deals with the concept of unintended effects in GM crops and products, i.e. effects that go beyond that of the original modification and that might impact primarily on health. The document first deals with the potential for unintended effects caused by the processes of transgene insertion (DNA rearrangements) and makes comparisons with genetic recombination events and DNA rearrangements in traditional breeding. The document then focuses on the potential value of evolving "profiling" or "omics" technologies as non-targeted, unbiased approaches, to detect unintended effects. These technologies include metabolomics (parallel analysis of a range of primary and secondary metabolites), proteomics (analysis of polypeptide complement) and transcriptomics (parallel analysis of gene expression). The technologies are described, together with their current limitations. Importantly, the significance of unintended effects on consumer health are discussed and conclusions and recommendations presented on the various approaches outlined.

Animals↗

PubMed2004

Trends in hospital admission for stroke in Calgary.

BACKGROUND: Stroke incidence has fallen since 1950. Recent trends suggest that stroke incidence may be stabilizing or increasing. We investigated time trends in stroke occurrence and in-hospital morbidity and mortality in the Calgary Health Region. METHODS: All patients admitted to hospitals in the Calgary Health Region between 1994 and 2002 with a primary discharge diagnosis code (ICD-9 or ICD-10) of stroke were included. In-hospital strokes were also included. Stroke type, date of admission, age, gender, discharge disposition (died, discharged) and in-hospital complications (pneumonia, pulmonary embolism, deep venous thrombosis) were recorded. Poisson and simple linear regression was used to model time trends of occurrence by stroke type and age-group and to extrapolate future time trends. RESULTS: From 1994 to 2002, 11642 stroke events were observed. Of these, 9879 patients (84.8%) were discharged from hospital, 1763 (15.1%) died in hospital, and 591 (5.1%) developed in-hospital complications from pneumonia, pulmonary embolism or deep venous thrombosis. Both in-hospital mortality and complication rates were highest for hemorrhages. Over the period of study, the rate of stroke admission has remained stable. However, total numbers of stroke admission to hospital have faced a significant increase (p=0.012) due to the combination of increases in intracerebral hemorrhage (p=0.021) and ischemic stroke admissions (p=0.011). Sub-arachnoid hemorrhage rates have declined. In-hospital stroke mortality has experienced an overall decline due to a decrease in deaths from ischemic stroke, intracerebral hemorrhage and sub-arachnoid hemorrhage. CONCLUSIONS: Although age-adjusted stroke occurrence rates were stable from 1994 to 2002, this is associated with both a sharp increase in the absolute number of stroke admissions and decline in proportional in-hospital mortality. Further research is needed into changes in stroke severity over time to understand the causes of declining in-hospital stroke mortality rates.

Alberta↗

PubMed2004

Genetic parameters for stillbirth in Danish Holstein cows using a Bayesian threshold model.

The objective of this study was to make an inference about the direct and maternal genetic variation of stillbirth for first-calving Holstein cows and to estimate the effect of breed and heterosis for original Danish black and white and Holstein-Friesian. A Bayesian threshold model, which included correlated genetic effects of sires and maternal grandsires was used. Marginal posterior distributions of effects were obtained using Gibbs sampling. Point estimates were compared with results from a linear model using REML. Data with and without twins were analyzed and models with and without effects of breed and heterosis were fitted, but estimates of genetic parameters were almost identical. In all the analyses with threshold models, the marginal posterior mean (and standard deviation) was 0.10 (0.014) for the direct heritability, 0.13 (0.015) for the maternal heritability, and 0.05 (0.10) for the genetic correlation between direct and maternal effects. The stillbirth rate tended to increase with a higher proportion of Holstein-Friesian in the calf and in the dam, but no effects of breed and heterosis were significant. Joint sampling of all location parameters was found superior to univariate sampling in terms of much better mixing properties of the fixed effects. Based on the results showing genetic variation for stillbirth at first calving, both the direct and the maternal effect could be included in the breeding program.

Animals↗

PubMed2004

Undesired phenotypic and genetic trend for stillbirth in Danish Holsteins.

The primary aim of this study was to evaluate the phenotypic and genetic trends for stillbirth in Danish Holsteins. Trends of calving difficulty and calf size were also evaluated. The second aim was to compare predicted transmitting abilities (PTA) of sires for stillbirth using a linear and a threshold model. Direct and maternal genetic effects were modeled by fitting correlated additive genetic effects of the sire and the maternal grandsire (MGS). For both the calf and the dam, covariates of breed proportions of Holstein-Friesian (HF) and the heterozygosity between HF and the original Danish Black and White (ODBW) were included. Records from 1.8 million first-calving Danish Holstein cows calving from 1985 to 2002 were used. In this period, the overall frequency of stillbirth increased from 0.071 to 0.090. An unfavorable genetic trend of stillbirth was found for both the direct and maternal effect. The background for the genetic trends was an intense use of HF sires as sires of sons, which increased the proportion of HF genes to 94% in the Danish Holstein calves born in 2002. The effect of the imported HF genes was higher direct effects of calf size, calving difficulty, and stillbirth compared with the ODBW genes. The maternal effect of stillbirth was poorer for HF than for ODBW even though HF had a better maternal calving performance than ODBW. The threshold and the linear models showed almost similar predictions of transmitting abilities of sires.

Animals↗

PubMed2003

Time after surgery, symptoms and well-being in survivors of urinary bladder cancer.

OBJECTIVE: To evaluate how an increasing burden of symptoms influences well-being, anxiety and depression at different intervals after a radical cystectomy with urostomy for bladder cancer, as this therapy can induce long-term distressful symptoms. PATIENTS AND METHODS: Patients with bladder cancer undergoing radical cystectomy in Stockholm between 1969 and 1995 were matched with 434 controls from the normal population; all 404 patients operated on between 1985 and 1995 at three other hospitals in Sweden were invited to enter the study. The final analysis included 306 patients and 310 controls, all assessed for symptoms and well-being. RESULTS: A low or moderate level of well-being was reported by 35% of the patients having none or one of the symptoms studied, by 39% with two symptoms, by 45% with three symptoms and by 66% of those with four or more symptoms. The values, irrespective of symptom burden, were 45% after 2-5 years of follow-up, 58% after 6-10 years and 38% at>10 years after surgery. The total symptom burden also influenced the risk of anxiety and depression. Symptom prevalence remained largely unaffected by the duration of follow-up, except for defecation urgency. CONCLUSIONS: The number of long-term symptoms after radical surgery with a urostomy for urinary bladder cancer affects the risk of anxiety, depression and low or moderate well-being.

Adult↗

PubMed2003

Genetic parameters of postnatal mortality in Danish Holstein calves.

The objective of this study was to estimate genetic parameters of postnatal mortality (PM) in dairy cattle. Data originated from 841,921 Danish Holstein calves. Four binary traits of mortality were considered: D1-14, D15-60, D61-180, and D1-180 with numbers indicating the period of risk in days after birth. The unadjusted frequency of D1-14, D15-60, D61-180, and D1-180 were 0.027, 0.018, 0.020, and 0.066, respectively. A linear sire-model was fitted to the data, and average information-REML was used to estimate (co)variance components. Estimates of direct heritabilities for the four mortality traits ranged from 0.001 to 0.008 but were all significant. D61-180 and D1-180 had the highest direct heritabilities. Maternal heritabilities were very low, ranging from 0.0002 to 0.0015 and significant for D1-14 and D1-180 only. The direct genetic correlation between D1-14 and D15-60, between D15-60 and D61-180, and between D1-14 and D61-180 was 0.73, 0.54, and 0.34, respectively. It indicates that different genes are responsible for early PM (D1-14) and late PM (D61-180). When D61-180 was treated as a different trait for females, males not transferred, and transferred males, the direct heritability was 0.004, 0.008, and 0.034, respectively, but the direct genetic correlations between these three traits were very high. If transfers of calves are getting more common, the importance of including PM in a breeding program will increase, as the genetic variation of PM was considerably higher for transferred calves than for calves that were not transferred.

Aging↗

PubMed2003

Bayesian estimates of covariance components between lactation curve parameters and disease liability in Danish Holstein cows.

In the present work, covariance components for milk yield and disease liability were estimated with bivariate random regression test-day sire models using a Bayesian approach and implemented via the Gibbs sampler. The data consist of 8075 first-parity Danish Holstein (DH) cows, from 1259 sires, performing in 57 herds from 1992 to 1997. Treatments associated with five different type of diseases were pooled into a single general disease liability for each cow. Two models were fitted to the data. First, using a bivariate model, milk yield is modeled via a random regression, and disease liability via a repeatablility model. Second, using a bivariate model, both milk yield and disease liability are modeled using random regressions. A comparison based on a Bayes factor provides very strong support for the bivariate random regression model. Posterior means of heritabilities for each of the traits were estimated for five different points in time throughout lactation. Across models, heritabilities for milk yield are lowest in the beginning of the lactation (0.19) and highest at the end of the lactation (0.35). Posterior means of heritabilities of disease liability range from 0.04 to 0.10 for test days, and is equal to 0.20 for the whole lactation. Heritability of persistency measures estimated from the two models are 0.20 and 0.21. Estimates of posterior means of genetic correlations between single test-day milk yield and single test-day disease liability are in the range of 0.31 to 0.57. The estimates of posterior mean and of the 95% posterior interval of the genetic correlation between persistency and (total) disease liability using the model with the highest posterior probability are -0.12 and (-0.44; 0.20), respectively. Even though the largest proportion of the posterior probability mass is spread along negative values of the correlation (indicating that individuals with a flatter lactation curve tend to have lower disease liability), a value of zero of the genetic correlation falls comfortably within the 95% posterior interval. Thus the prospects of reducing incidence of disease by manipulating persistency as defined in this work remain inconclusive.

Animals↗

PubMed2003

Controlled mechanical distension of the human oesophagus: sensory and biomechanical findings.

BACKGROUND: The relation between mechanical distension of the gut and the sensory response is poorly understood. The current experimental study aimed to examine the sensory response in the human oesophagus during on-line recording of the luminal pressure, cross-sectional area (CSA) and sensory rating using different distension rates before and during relaxation of the smooth muscle. METHODS: An impedance planimetric probe for bag distension of the oesophagus was used in 13 healthy subjects aged 43 +/- 15 years. Ramp distensions were done with an electromechanical pump using infusion rates of 10, 25 and 50 ml/min, with and without relaxation of the smooth muscle with butylscopolamine. The sensory intensity was measured using a 0-10 visual analogue scale (VAS), with 5 as the pain threshold. The pump was reversed at 8 on the scale, corresponding to medium pain intensity, and the pressure, volume, tension and CSA were evaluated. Finally, three isovolumetric experiments where the CSA was held constant for 2 min at initial VAS ratings of 3, 5 and 7 were performed. RESULTS: A total of 104 distension profiles were investigated. The volume at maximal pain intensity (VAS = 8) increased as a function of the distension rate (P < 0.001), whereas the pressure, tension and CSA were not affected. When the smooth muscle was relaxed, there was a 29% fall in pressure at maximal pain intensity (P = 0.004), a 27% fall in tension (P = 0.003), whereas CSA did not change (P = 0.3). When the pressure was recorded as a function of the sensory intensity, there was an exponential increase after the pain threshold was reached, whereas the stimulus-response functions for tension, volume and CSA were nearly linear. In the isovolumetric experiments the ratings during the three sensory intensities were the same in the individual subjects, but the between-individual pain response was variable, probably reflecting individual differences in adaptation/central integration. CONCLUSIONS: The study allowed us to assess the strain-rate dependency of both perception and biomechanical properties in the oesophagus. It was demonstrated that the pain response was related to the CSA (and hence strain), independently of the contractile state of the muscle and biomechanical behaviour of the tissue. The findings support the fact that the pain-sensitive mechanoreceptors in the human oesophagus depend on circumferential wall stretch rather than on pressure, tension and volume. The model should be used in future studies to investigate whether changes in strain are responsible for the oesophageal sensation in health and disease.

Adult↗

PubMed2002

PCR identification of dermatophyte fungi Trichophyton rubrum, T. soudanense and T. gourvilii.

Diagnosis of dermatophytosis employing conventional laboratory procedures has been complicated by the slow growth and varied morphological features shown by dermatophytes. After analysis of the nucleotide base sequences of a 1.2-kb fragment amplified from a dermatophyte fungus Trichophyton rubrum by arbitrarily primed PCR with random primer OPD18, a pair of primers (TRIF and TR1R) was designed and evaluated for specific identification of T. rubrum. The sensitivity of the primers TR1F and TR1R was high, as a specific PCR band of c. 600 bp was detected from as little as 7 pg of T. rubrum DNA. By examining 92 dermatophyte strains and clinical isolates, it was found that this pair of primers reacted in PCR with T. rubrum, T. soudanense and T. gourvilii through formation of the specific fragment of 600 bp, but not with any other of the dermatophyte species or varieties, fungi, yeasts or bacteria tested. As T rubrum is one of the most frequently isolated dermatophyte fungi, and T. soudanense and T. gourvilii are relatively uncommon in many parts of the world, these primers can be used for rapid, sensitive and specific identification and differentiation of T. rubrum from other fungi and micro-organisms.

DNA, Fungal↗

PubMed2002

The influence of consanguineous marriage on infant and child mortality among Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria.

OBJECTIVES: The purpose of this paper is to explore the characteristics of mortality differences associated with consanguineous marriage among Palestinians in the Middle East. METHODS: The data came from five surveys of Palestinians living in the West Bank and Gaza, Syria, Jordan and Lebanon, conducted during the period 1995-2000. Infant and child mortality was estimated for the offspring of consanguineous and non-consanguineous parents using the synthetic cohort method. RESULTS: The data showed an increase in infant mortality of 15.0 additional deaths per 1,000 births among the offspring of first cousins, and a corresponding increase of 6.1 deaths per 1,000 for the progeny of parents from the same patrilineal clan. CONCLUSION: In populations where marriage within kin groups is common, both first cousin marriage and intra-group marriage carries an added risk of infant and child mortality.

Journal Article↗

PubMed2002

Genetic parameters for milk production and persistency for Danish Holsteins estimated in random regression models using REML.

(Co)variance components for milk, fat, and protein yield of 8075 first-parity Danish Holsteins (DH) were estimated in random regression models by REML. For all analyses, the fixed part of the model was held constant, whereas four different functions were applied to model the additive genetic effect and the permanent environment effect. Homogeneous residual variance was assumed throughout lactation. Univariate models were compared using a minimum of -2 ln(restricted likelihood) as the criterion for best fit. Heritabilities as a function of time were calculated from the estimated curve parameters from univariate analyses. Independent of the function applied and the trait in question, heritabilities were lowest in the beginning of the lactation. Heritabilities for persistency of fat yield were slightly higher than heritabilities for persistency of milk and protein yield. Genetic correlations between persistency and 305-d production were higher for protein and milk yield than for fat yield. Bivariate analyses between the production traits were carried out in sire models using the models with the best 3-parameter curve fit in the univariate analyses. Correlations between traits were calculated from covariance components for curve parameters estimated in bivariate analyses. Genetic correlations between milk and protein yield were higher than between milk and fat yield.

Algorithms↗

PubMed2001

Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor. The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.

Amino Acid Sequence↗

PubMed2001

Tetrameric dipeptidyl peptidase I directs substrate specificity by use of the residual pro-part domain.

The crystal structure of mature dipeptidyl peptidase I reveals insight into the unique tetrameric structure, substrate binding and activation of this atypical papain family peptidase. Each subunit is composed of three peptides. The heavy and light chains form the catalytic domain, which adopts the papain fold. The residual pro-part forms a beta-barrel with the carboxylate group of Asp1 pointing towards the substrate amino-terminus. The tetrameric structure appears to stabilize the association of the two domains and encloses a 12700 A3 spherical cavity. The tetramer contains six chloride ions, one buried in each S2 pocket and two at subunit interfaces.

Animals↗