Biomedical subjects

P Jordan

Publications and source records attributed to P Jordan.

At least 19 recordsLinked to original sources

PubMed2006

Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway.

The subfamily of WNK (with no K= lysine) protein kinases has four human members and germline mutations in the WNK1 and WNK4 genes were recently found to cause pseudohypoaldosteronism type II, a familial hypertension disease. Here, we describe cloning and functional analysis of a further WNK member, human WNK3. Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis. Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3. The mechanism of WNK3 action involves interaction with procaspase-3 and heat-shock protein 70. These results demonstrate a role for WNK3 in promoting cell survival and suggest a mechanism at the level of procaspase-3 activation.

Apoptosis↗

PubMed2006

[The art of horseshoeing--between empiricism and science].

To correctly shoe a horse requires the farriers to have a good working knowledge of postural anomalies and movement patterns, as well as of the different concepts of horseshoeing and to be able to apply the appropriate technique to every individual horse they shoe. The correct technique for specific problem cases is frequently a subject of debate amongst specialists and many theories would benefit from objective gait analyses. The case study presented examines the influence of different shoeing conditions on selected gait analysis parameters. The measurements were conducted on a Warmblood mare: (A) shod with long toes, (B) properly trimmed without shoes, (C) conventionally shod with rolled toes and finally (D) shod using the 4-point technique. Data on force-, time- and distance parameters were recorded using an instrumented treadmill. First contact and breakover of the hooves were documented using high-speed videography. A long toe resulted in a prolongation of the breakover time and, therefore, in a prolongation of the second half of the stance phase. Additionally, the prolonged stance duration associated with an unaltered force impulse, led to decreased force peaks. It was possible to objectively record differences between the trimmed, unshod foot, the shod long-toe and the shod rolled toe configurations. The differences between the rolled toe and the 4 point shoe however, were minimal. Gait analysis is a technique well suited for objective evaluation of different shoeing techniques under standardised conditions.

Animals↗

PubMed2006

Initiation of homologous chromosome pairing during meiosis.

Following pre-meiotic DNA replication, homologous chromosomes must be paired and become tightly linked to ensure reductional segregation during meiosis I. Therefore initiation of homologous chromosome pairing is vital for meiosis to proceed correctly. A number of factors contribute to the initiation of homologous chromosome pairing including telomere and centromere dynamics, pairing centres, checkpoint proteins and components of the axial element. The present review briefly summarizes recent progress in our understanding of initiation of homologous chromosome pairing during meiosis and discusses the differences that are observed between research organisms.

Animals↗

PubMed2006

Molecular genetic analysis of 1053 Danish individuals with clinical signs of familial hypercholesterolemia.

The lipid disorder familial hypercholesterolemia (FH) predisposes to cardiovascular disease. With a prevalence of approximately one in 500 in the general Caucasian population, FH is one of the most frequent single-gene disorders. As the mutational spectra vary between populations, it is crucial to identify the mutations in a given population in order to implement a molecular genetic screening strategy. A total of 1053 referred individuals with clinical signs of FH were investigated, and mutations were identified in 425 individuals. Fifty-four different mutations were identified, of which 13 are novel. The five most frequent mutations accounted for 56.3% of all disease-causing mutations. The majority of the remaining mutations were of a private nature only encountered in single families. In this study, a reliable molecular genetic screening protocol was established, and the relevance of performing presymptomatic genetic analysis as part of a preventive strategy was documented. We have acquired knowledge of the mutational spectra in the Danish population and thus will be able to trace mutations in their relatives through our index cases.

Apolipoprotein B-100↗

PubMed2005

[Nutrition in Switzerland 2002--results of the Swiss Health Survey].

The 2002 Swiss Health Survey is the third survey conducted by the Federal Office of Statistics in intervals of five years. Data are collected of a random sample (n = 19706) of persons aged 15 and over, living in Switzerland: 29% are overweight (BMI 25-29.9 kg/m2), and 8% are obese (BMI 30+ kg/m2). 31% do not care about their nutrition. Less than daily consumption is reported by 34% for fruit, by 18% for vegetable, by 64% for milk, by 39% for milk products. 20% eat every day meat or meat products, 38% do rarely or never consume fish. Inadequate nutritional habits are observed more often in men, young people, and in participants with a low level of education. According to the Swiss Health Surveys of 1992, 1997, and 2002 nutritional habits have hardly improved during the last ten years in Switzerland.

Adolescent↗

PubMed2005

Explicit solutions for a class of indirect pharmacodynamic response models.

Explicit solutions for four, ordinary differential equation (ODE)-based, types of indirect response models are presented. These response models were introduced by Dayneka et al. in 1993 [J. Pharmacokinet. Biopharm. 21 (1993) 457] to describe pharmacodynamic responses utilizing inhibitory or stimulatory E(max) type functions. The explicit solutions are expressed in terms of hypergeometric 2F1 functions and their analytical continuations. A practical application is demonstrated for modeling the kinetics of drug action for ibandronate, a potent bisphosphonate that suppresses bone turnover resulting in a reduction in the markers of bone turnover. Ten times shorter model evaluation times, with the explicit solution compared with the differential equation implementation, may enhance situations where a large number of model evaluations are needed, such as clinical trial simulations and parameter estimation.

Bone Remodeling↗

PubMed2005

Isolation and characterization of a novel mouse lymphatic endothelial cell line: SV-LEC.

BACKGROUND: The lymphatic system regulates interstitial fluid and protein balance and modulates immune responses by regulating leukocyte and antigen traffic to lymph nodes. The present article describes a stable mouse lymphatic endothelial cell line from mesenteric adventitial tissue (SV-LEC) which is distinct from blood aortic (AEC) and venous (VEC) endothelial cells, based on expression of several lymphatic markers (e.g., Prox-1, LYVE-1, Flt-4). SV-LEC also expresses MAdCAM-1 in response to TNF-alpha, an effect seen in VEC, but not AEC. METHODS AND RESULTS: Lymphatic endothelial cells (SV-LEC) were isolated from mesenteric adventitia from mice expressing temperature-sensitive SV40 large T ('Immortomouse', H-2K(b)tsA58) selected with hypoxia culture in D-valine-substituted MEM supplemented with VEGFC in a low oxygen atmosphere (0% O2, 5% CO2, and 95% N2) with 5 mM thioglycolate. Expression of lymphatic-specific markers (Flt-4, LYVE-1, Prox-1) and the tight junction proteins (ZO-1) were examined by RT-PCR, immunoblotting, and fluorescent microscopy. MAdCAM-1 (a high endothelial venular marker) expression was also examined in response to TNF-alpha IL-1beta and IFN-gamma. RESULTS: Message for Flt-4 and LYVE-1 was detected on SV-LEC. Immunoblotting for LYVE-1 and Prox-1 showed strong expression on SV-LEC and VEC, but not AEC. Occludin expression was seen in all cell types, junctional ZO-1 was detected at SV-LEC and VEC junctions, not AEC. CONCLUSION: SV-LEC expresses several lymphatic endothelial markers, some of which are shared with VEC, but not AEC, and may represent a useful system for modeling lymphatic function in vitro.

Animals↗

PubMed2005

Homogeneity of mesothelial cells with lymphatic endothelium: expression of lymphatic endothelial markers by mesothelial cells.

BACKGROUND: Mesothelial cell monolayers cover the serous cavities and internal organs, and provide a protective low-friction interface between apposed organs and tissues. The mesothelium also regulates inflammation, fluid and cell exchange, and tissue repair in these compartments and possibly tumor metastasis. In the present study, a stable pleural mesothelial cell line (MIM) was isolated and characterized, and the expression of several lymphatic specific markers by these cells examined. METHODS AND RESULTS: MIM were isolated from mice stably expressing a temperature-sensitive SV40 large T antigen ('Immortomouse', strain: H-2K(b)-tsA58). These cells were compared with lymphatic endothelial cells (LEC) derived from the mesenteric adventitia of the Immortomouse. MIM and LEC expression of lymphatic-specific markers (Flt-4, LYVE-1, and Prox-1) was examined, and the tight junction protein (ZO-1) was studied by immunofluorescence and immunoblotting in these cells. RESULTS: LYVE-1, Prox-1, and Flt-4 were detected in both MIM and LEC, with Prox-1 and LYVE-1 more strongly expressed on LEC than MIM. Conversely, Flt-4 was more densely expressed on MIM than on LEC. Spatially, ZO-1 was prominent at MIM junctions, but was less well organized in LEC. CONCLUSION: MIM and LEC share several characteristic markers usually associated with lymphatic endothelium. MIM might be useful for studying the biology and pathology of mesothelial cells in vitro and help in the development of therapies for mesothelial-related diseases, such as mesothelioma and pleural effusion.

Animals↗

PubMed2005

MAdCAM-1 expression and regulation in murine colonic endothelial cells in vitro.

BACKGROUND: Although the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is associated with the etiology of inflammatory bowel diseases, few studies have directly examined MAdCAM-1 using microvascular endothelium derived from the colon. This study measured the expression of MAdCAM-1 in a novel colon endothelial line MJC-1, as well as MAdCAM-1 regulation and function in vitro. METHODS: We cloned microvascular endothelial cells from primary colon cultures using ImmortoMice mice (whose cells express a temperature-sensitive SV40 large T antigen, H-2Kb-tsA58 mice). Expression of MAdCAM-1 after stimulation with cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, or interferon (IFN)-gamma] was determined by Western blotting. Signal paths regulating MAdCAM-1 expression were examined using pharmacological blockers before cytokines. We also examined lymphocyte adhesion using lymphocytes that constitutively express alpha4beta7 integrin. RESULTS: TNF-alpha induced MAdCAM-1 in a dose-dependent manner by 24 hours. MAdCAM-1 induction was protein kinase C, tyrosine kinase, p38 mitogen activated protein kinase, and nuclear-factor kappa-B/poly adenosine diphosphate ribose polymerase dependent. Lymphocyte adhesion was increased 2.6-fold after TNF-alpha stimulation and was inhibited by anti-MAdCAM-1 antibody before treatment (P < 0.05 control versus TNF-alpha). CONCLUSIONS: In vitro, MAdCAM-1 can be induced on colon endothelial cells by TNF-alpha stimulation and may represent a useful model to study microvascular injury in the large intestine.

Animals↗

PubMed2004

Three-dimensional optical trapping of partially silvered silica microparticles.

We demonstrate three-dimensional trapping of micrometer-diameter silica particles, partially coated with silver, within conventional optical tweezers. Although metallic particles are usually repelled from the beam focus by the scattering force, we show that transparent spheres partially coated with silver can be trapped with efficiencies comparable with dielectric particles. The trapping characteristics of these particles are examined as a function of metallic coverage, and the application of these particles to surface-enhanced resonance Raman scattering is investigated.

Coated Materials, Biocompatible↗

PubMed2004

Compensatory load redistribution of horses with induced weightbearing hindlimb lameness trotting on a treadmill.

REASONS FOR PERFORMING STUDY: The compensatory mechanisms of horses with weightbearing hindlimb lameness are still not fully understood. HYPOTHESIS: That weightbearing, unilateral hindlimb lameness would not only alter stride characteristics to diminish structural stress in the affected limb but also induce compensatory load adjustments in the other supporting limbs. OBJECTIVE: To document the load and time shifting mechanisms of horses with unilateral weightbearing hindlimb lameness. METHODS: Reversible lameness was induced in 8 clinically sound horses by applying a solar pressure model. Three degrees of lameness (subtle, mild and moderate) were induced and compared with the nonlame (sound) control measurement. Vertical ground reaction forces were recorded for all 4 limbs simultaneously on an instrumented treadmill. RESULTS: Compared to the sound situation, moderate hindlimb hoof lameness induced a decrease in stride duration (-3.3%) and stride impulse (-3.1%). Diagonal impulse decreased selectively in the lame diagonal stance (-7.7%). Within the diagonal limb pair, vertical impulse was shifted to the forelimb during the lame diagonal stance (+6.5%) and to the hindlimb during the sound diagonal stance (+3.2%). Peak vertical force and vertical impulse decreased in the lame limb (-15%), but only vertical impulse increased in the contralateral hindlimb (+5.7%). Stance duration was prolonged in both hindlimbs (+2.5%). Suspension duration was reduced to a greater extent after push-off of the lame diagonal limb pair (-21%) than after the sound diagonal limb pair (-9.2%). CONCLUSIONS: Four compensatory mechanisms could be identified that served to reduce structural stress, i.e. peak vertical force on the affected limb: 1) reduction of the total vertical impulse per stride; 2) diagonal impulse decreased selectively in the lame diagonal; 3) impulse was shifted within the lame diagonal to the forelimb and in the sound diagonal to the hindlimb; and 4) the rate of loading and peak forces were reduced by prolonging the stance duration. POTENTIAL RELEVANCE: Load shifting mechanisms are not only effective in diminishing peak forces in the affected limb, but also suppress compensatory overload in other limbs. Selected force and time parameters allow the unequivocal identification of the lame limb. Future studies have to examine how far these compensatory mechanisms may be generalised for other defined orthopaedic problems in the hindlimb.

Adaptation, Physiological↗

PubMed2003

Increased disease activity in eNOS-deficient mice in experimental colitis.

Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many features of human inflammatory bowel disease (IBD), (leukocyte extravasation, cachexia, and histopathology). Previous studies suggest that the inducible nitric oxide synthase (iNOS) in blood cells or in the endothelium contribute to this injury. However, until now no study has been performed to directly evaluate the role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease activity in wild-type (eNOS+/+) and eNOS-deficient (eNOS-/-) mice in the DSS model of colitis. Administration of DSS induced weight loss, stool blood, and overt histopathology in both mouse strains. Disease activity was dramatically increased in eNOS-/- mice compared to wild types. Histologically, eNOS-deficient mice had greater leukocyte infiltration, gut injury, and expressed higher levels of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an important role in limiting injury to the intestine during experimental colitis and altered eNOS content and/or activity may contribute to human IBD.

Animals↗

PubMed2003

Lake sedimentary evidence of phosphorus, iron and manganese mobilisation from intensively fertilised soils.

A study of historical P inputs to Friary Lough, Co. Tyrone, Northern Ireland used a multi-sediment core approach. One of the sediment cores taken from the littoral zone at 2.5m water depth showed exceptionally high P, Fe and Mn concentrations below 20 cm sediment depth. Concentrations increased to 14 mg Pg(-1), 238 mg Feg(-1) and 35 mg Mng(-1) in the sediment profile and compared with deep basin maxima of 7 mg Pg(-1), 70 mg Feg(-1) and 2 mg Mng(-1) in surface sediments at 8.5m water depth. It is proposed that the high concentrations in the littoral zone core are due to post-depositional intrusion of chemical-rich local groundwater from soils in adjacent fields that are excessively fertilised with organic slurry. Soil analyses showed Olsen-P concentrations in these fields up to 125 mgkg(-1) at the soil surface (0-7.5 cm) and 39 mgkg(-1) in the sub-soil at 20 cm depth. We suggest that the mobilisation of P, Fe and Mn is due to leaching following P saturation and/or the loss of P absorbing chemicals due to prolonged reduction and complexing in wet soils. Further work will explore this relationship and the nature of the hydrological pathways through soil.

Adsorption↗

PubMed2002

TNF-alpha -induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent.

It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-alpha, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-alpha induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

Animals↗

PubMed2001

Structure of photosystem I.

In plants and cyanobacteria, the primary step in oxygenic photosynthesis, the light induced charge separation, is driven by two large membrane intrinsic protein complexes, the photosystems I and II. Photosystem I catalyses the light driven electron transfer from plastocyanin/cytochrome c(6) on the lumenal side of the membrane to ferredoxin/flavodoxin at the stromal side by a chain of electron carriers. Photosystem I of Synechococcus elongatus consists of 12 protein subunits, 96 chlorophyll a molecules, 22 carotenoids, three [4Fe4S] clusters and two phylloquinones. Furthermore, it has been discovered that four lipids are intrinsic components of photosystem I. Photosystem I exists as a trimer in the native membrane with a molecular mass of 1068 kDa for the whole complex. The X-ray structure of photosystem I at a resolution of 2.5 A shows the location of the individual subunits and cofactors and provides new information on the protein-cofactor interactions. [P. Jordan, P. Fromme, H.T. Witt, O. Klukas, W. Saenger, N. Krauss, Nature 411 (2001) 909-917]. In this review, biochemical data and results of biophysical investigations are discussed with respect to the X-ray crystallographic structure in order to give an overview of the structure and function of this large membrane protein.

Crystallography, X-Ray↗

PubMed2001

Fenestration of the abaxial hoof wall and implantation of gentamicin-impregnated collagen sponges for the treatment of septic arthritis of the distal interphalangeal joint in cattle.

A novel surgical approach to the distal interphalangeal joint of cattle, through the abaxial hoof wall, for the treatment of septic arthritis is described. In seven cattle a rectangular piece of horn (15 x 40 mm) was excised from the abaxial hoof wall and the joint was lavaged with Ringer's solution. Infected and/or necrotic tissue was removed from the joint and gentamicin-impregnated collagen sponges were introduced. The piece of horn was reattached, a rubber block was glued to the contralateral claw, and a bandage applied. Aftercare consisted of changes of bandage, systemic administration of antimicrobial drugs and box rest. At follow-up, six of the cattle were sound but one cow which had been slaughtered five months after surgery had remained slightly lame.

Animals↗

PubMed2001

WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.

We have cloned and characterized a novel human serine/threonine protein kinase gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, the catalytic domain sequence contains a cysteine in place of a lysine residue conserved in subdomain II of most kinases. The same amino acid alteration was recently described for rat WNK1 (with no K=lysine) in which another nearby lysine residue was shown to confer kinase activity to the protein. Rat WNK1 is 85% identical to a splice variant lacking exons 11 and 12 of the described human kinase which we have called human WNK1. The WNK1 catalytic domain has closest homology with human PAK2, MEKK3, and Raf-1. Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1. These genes differ both in chromosomal location and tissue-specific expression. Moreover, we have identified in the database a total of 18 WNK-related genes, all exclusively from multi-cellular organisms, which share a WNK kinase sequence signature within subdomains I and II of the catalytic domain. We suggest that they constitute a novel subfamily of protein kinases that evolved together with cell adhesion and tissue-formation.

Amino Acid Motifs↗

PubMed2001

TNF-alpha induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide.

BACKGROUND: MAdCAM-1 is an adhesion molecule expressed in Peyer's patches and lymphoid tissues which is mobilized by cytokines like TNF-alpha and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-alpha. METHODS: To examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-alpha, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-alpha-stimulation, and measured MAdCAM-1 induction at 24 h. RESULTS AND DISCUSSION: DETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-alpha-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-alpha regulated MAdCAM-1 expression. CONCLUSIONS: Exogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines.

Amidines↗