Mesenteric panniculitis as a presentation of Whipple's disease: case report and review of the literature.

BACKGROUND: Whipple's disease is a rare, multi-organ disease caused by Tropheryma Whipplei. A classic presentation is characterized by arthropathy, diarrhea and weight loss but a broad spectrum of manifestations is possible. We present a case of a patient with mesenteric panniculitis as a manifestation of WD. A comprehensive review of the literature is provided. PATIENT: A 50 year old male presented at the outpatient clinic after an episode of fever and abdominal pain abroad. CT scan showed mesenteric infiltration with associated lymphadenopathies consistent with mesenteric panniculitis. After receiving 6 months of antibiotic therapy abdominal and joint pains improved. CONCLUSION: Clinicians should be aware of Whipple's disease. Mesenteric panniculitis is a rare presentation of this possible lethal infection. The golden standard for diagnosing WD is a PAS positive small bowel biopsy. Adequate antibiotic therapy is the cornerstone of treatment and usually leads to an amelioration of symptoms.

A multicentre, observational study on demographic and disease characteristics of patients seeking care for chronic hepatitis C in Belgium in 2016.

BACKGROUND AND STUDY AIMS: Direct-acting antivirals provide interferon-free treatments for chronic hepatitis C (CHC) virus infection. In Belgium, in 2016, access to these agents was limited to patients with advanced liver fibrosis stages F3 and F4. This study is the first to describe Belgium's patient population ineligible for interferon-free treatment. PATIENTS AND METHODS: This was an observational, cross-sectional, multicentre study that enrolled adult patients with CHC ineligible for interferon-free treatment. Patient data recorded at a single visit included demographic data, disease characteristics, comorbidities, co-medications, treatment status, and laboratory data. RESULTS: Three hundred and three patients from 16 centres in Belgium were included in the statistical analysis. On average, patients were aged 53.5 years and 50.2% were women ; 94.1% had health insurance and 99.0% resided in Belgium. The current hepatitis C virus (HCV) infection was the first infection for 96.0% of patients and the mean time since infection was 20.0 years. Liver fibrosis stage was F0 for 23.7%, F0/F1 or F1 for 38.3%, F1/F2 or F2 for 25.8%, F3 for 7.1%, and F4 for 5.1% of patients ; 28.4% of patients were CHC treatment-experienced. The main reason for ineligibility for interferon-free treatment was lack of reimbursement (84.8%). Other reasons included no treatment urgency or medical decision to wait (27.1%), waiting for future treatment option (8.3%), and no social insurance coverage (3.6%). CONCLUSIONS: This study provides recent data on the CHC patient population and disease characteristics in Belgium that could help medical communities and government agencies manage CHC disease burden.

Construction and characterization of a BAC library for functional genomics in Xenopus tropicalis.

Large insert genomic DNA libraries are useful resources for genomic studies. Although the genome of Xenopus tropicalis stands as the amphibian reference genome because it benefitted from large-scale sequencing studies, physical mapping resources such as BAC libraries are lagging behind. Here we present the construction and characterization of a BAC library that covers the whole X. tropicalis genome. We prepared this BAC library from the genomic DNA of X. tropicalis females of the Adiopodoume strain. We characterized BAC clones by screening for specific loci, by chromosomal localization using FISH and by systematic BAC end sequencing. The median insert size is about 110kbp and the library coverage is around six genome equivalents. We obtained a total of 163,787 BAC end sequences with mate pairs for 77,711 BAC clones. We mapped all BAC end sequences to the reference X. tropicalis genome assembly to enable the identification of BAC clones covering specific loci. Overall, this BAC library resource complements the knowledge of the X. tropicalis genome and should further promote its use as a reference genome for developmental biology studies and amphibian comparative genomics.

A functional genomic approach to the study of the milking ability in dairy sheep.

To understand the mechanisms underlying milk ability and more precisely the kinetics of milk emission, we compared teat transcriptome profiles from Lacaune ewes in the tails of the milk flow phenotypic distribution. Two different arrays containing respectively 1896 and 13 168 PCR products selected from several tissue-specific cDNA libraries, including mammary gland, allowed the identification of 73 differentially expressed genes between teats from high and low milk flow ewes. Genes involved in muscle contraction were identified as over-expressed, and genes encoding collagen were found to be under-expressed in teats from low milk flow ewes. We confirmed this underexpression of COL1A1 and COL1A2 in low-milk flow ewes using RT-qPCR. These results suggest that milking ability may be due to the capacity of the teat sphincter to relax during mechanical milking. We propose that an optimal condition for mechanical milking may require proper relaxation of the teats. To our knowledge, this is the first transcriptomic analysis studying milking ability, using udder tissue for gene expression profiling, which demonstrates that mechanical milking ability is not only determined by morphological features but also by tissue composition.

Terminal differentiation of goat mammary tissue during pregnancy requires the expression of genes involved in immune functions.

Terminal differentiation of mammary tissue into a functional epithelium that synthesizes and secretes milk occurs during pregnancy. The molecular mechanisms underlying this complex process are poorly understood, especially in ruminants. To obtain an overview of the ruminant mammary gland's final differentiation process, we conducted time-course gene expression analysis of five physiological stages: four during pregnancy (P46, P70, P90, and P110) and one after 40 days of lactation (L40). An appropriate loop experimental design was used to follow gene expression profiles. Using three nulliparous (pregnancy) or primiparous (lactation) goats per stage, we performed a comparison starting from nine dye-swaps and using a 22K bovine oligoarray. Statistical analysis revealed that the expression of 1,696 genes varied significantly at least once in the study. These genes fell into 19 clusters based on their expression profiles. Identification of biological functions with Ingenuity Pathway Analysis software revealed several similarities, in keeping with physiological stages described in mice. As in mice, expression of milk protein genes began at midpregnancy, and genes regulating lipid biosynthesis were induced at the onset of lactation. During the first half of pregnancy, the molecular signature of goat mammary tissue was characterized by the expression of genes associated with tissue remodeling and differentiation, while the second half was mainly characterized by the presence of messengers encoding genes involved in cell proliferation. A large number of immune-related genes were also induced, supporting recent speculation that mammary tissue has an original immune function, and the recruitment of migrating hematopoietic cells possibly involved in the branching morphogenesis of the mammary gland. These data hint that the induction of differentiation occurs early in pregnancy, very likely before P46. This period is therefore crucial for obtaining a healthy and productive mammary gland.

Fouling and its reversibility in relation to flow properties and module design in aerated hollow fibre modules for membrane bioreactors.

Nowadays, most membrane bioreactors are using membranes submerged in the biomass and aeration in the concentrate compartment to limit or to control fouling. An important issue for the design of modules or membrane bundles in MBRs is to understand how the air/liquid flow is behaving and influencing fouling and its reversibility in relationship to the module properties. This paper focuses on an innovative and very specific process, in which HF membranes are put in a cartridge outside the activated sludge tank and a recycling loop is associated to the cartridge in order to decrease concentration of foulant species at the membrane surface and mass transfer resistance. Recycling operates with a very low liquid velocity in the module (a few cm.s(-1)) which constitutes a specificity of this process in terms of filtration operation. The aim of this study is to characterise two-phase flow and its effects on fouling and fouling reversibility at the scale of a semi-industrial bundle of outside/in hollow fibres, and as a function of bundle properties (packing density, fibre diameter), using specific methods to characterise the flow and fouling effects. Two modules were used showing a different packing density. Filtration was operated at constant permeate flux with clay suspension at 0.65 g.l(-1) in the same hydrodynamic conditions. Fouling kinetics and irreversibility were characterised by an adapted step method, and gas and liquid flows were characterised at global scale by residence time distribution analyses and gas hold-up. Fouling velocities are clearly influenced by gas velocity. The proportion of dead to total volume in the module is mainly affected by the liquid flow velocity and module design. The module with the higher fibre diameter and the lower packing density showed better performances in terms of fouling which was correlated with better flow properties.

Effect of selenium and Ascaridia galli infection on antioxidant biomarkers in broiler chickens: a mathematical model for parasite reduction and host growth.

The activity of selenium-dependent glutathione peroxidase (GPX), liver concentration of vitamin E, and plasma and liver selenium levels were used for estimation of the antioxidant status of broiler chickens infected with Ascaridia galli. These biomarkers were recorded in an experiment covering 70 days p.i. At the same time the establishment rate of A. galli in chicken intestines, gain in the host body weight and chicken survival were studied. Broiler chickens (Cobb hybrids) were infected with 1450 embryonated A. galli eggs and treated with Sel-plex. A mathematical model was applied to determine the rate of nematode reduction and the relative rate of gain of host body weight, which are essential kinetic parameters of parasite-host interaction. The activity of GPX increased with both elevated selenium and reduced infection levels. The concentrations of selenium and vitamin E, and the GPX activity in the infected chickens demonstrated a similar pattern of change with time after day 30 p.i. The supplementation of the broilers with dietary selenium in the form of Sel-plex improved their antioxidant status. Increases by 29% in vitamin E concentration, 15% in GPX activity, and 22% in liver selenium concentration, respectively, were recorded in the infected and treated, compared to infected and untreated broilers.

The olig family: phylogenetic analysis and early gene expression in Xenopus tropicalis.

The olig genes form a small subfamily of basic helix-loop-helix transcription factors. They were discovered in 2000 as genes required for oligodendrocyte lineage specification. Since then, olig genes have been identified in various vertebrate species and corresponding sequences accumulated within genomic databases. Until now, three groups of olig genes have been characterized. Our phylogenetic analysis demonstrates the existence of a fourth group, which we named olig4. Genes of the four olig groups are present in actinopterygians and amphibians, whereas mammals only possess olig1, 2, and 3. We also found one olig gene in hemichordates, urochordates, and cephalochordates. Our expression study during Xenopus tropicalis embryogenesis shows that the four olig genes have very distinct expression patterns. Olig1 is very faintly expressed before the tadpole stage, whereas olig2, 3, and 4 are expressed from the gastrula stage onward. The olig3 expression during neurulation suggests a role in early anteroposterior patterning of the brain. All these results indicate that olig genes are involved in several developmental processes during early development.

Influence of subcutaneous injection of essential fatty acids on the stress-induced modifications of rat platelet aggregation and membrane lipid composition.

Membrane lipids play an important role in the function of blood platelets but the mechanisms by which the lipid composition of the platelet membrane is adjusted remain unclear. It has been shown that stress and poly-unsaturated fatty acids modified the lipid composition of blood plasma and platelet lipids, but very little is known about the effect of stress and fatty acids on membrane platelet lipid composition. The purpose of the present investigation was to study the influence of the essential fatty acids: linoleic, linolenic and arachidonic acids on the composition of the platelet membrane lipids of rats assigned to heat and restraint stress. It was shown that injections of polyunsaturated fatty acids decrease or suppress the stress-induced increase in platelet aggregation, suppress the stress-induced modification of the composition of the platelet membrane lipids and modify the fatty acid composition of the platelet membrane phospholipids.

A cDNA macroarray resource for gene expression profiling in ruminant tissues involved in reproduction and production (milk and beef) traits.

cDNA arrays have proven to be useful tools to screen gene expression in many animal species including livestock species. A collaborative program was launched to construct a ruminant cDNA collection, representative of three tissues: Muscle, Embryo and Mammary gland, named MEM. This collection gathers clones mainly arising from 3 non-normalised cDNA libraries: a directed bovine muscle library, a 14-day-old bovine embryo library and a goat lactating mammary library. It is made up of 1896 clones (637 muscle, 882 embryo and 377 mammary cDNAs), selected after sequencing and bioinformatic analyses. Amplification products yielded from these clones as well as controls were printed onto Nylon membranes to generate macroarrays. Hybridisation with relevant cDNA targets allowed checking the location of about 50 cDNAs and the specificity of each sub-set of the repertoire. Macroarrays were hybridised with radiolabelled cDNA complex targets from five different tissues (muscle, embryo, mammary gland, adipose tissue and oocyte). Both somatic and germinal complex targets gave valid hybridisation signals with 45 to 80% of the printed probes. This specific cDNA collection now provides a powerful tool for transcriptomic studies with the ultimate objective to better understand physiological and metabolic functions in ruminants. It will be subsequently included into a forthcoming larger collection.

Administration of Zn-Co-Mn basic salt to chickens with ascaridiosis. II. Sex ratio and microelement levels in Ascaridia galli and in treated and untreated chickens.

Hisex chickens were infected with 1,450 embryonated Ascaridia galli eggs and treated with a new synthesized basic mixed salt (Zn(x)Co(y)Mn(1-x-y)) x (OH)6SO4 x 2H2O). The worm burden was determined and sex ratios for A. galli of M:F = 1.4 and M:F = 2 in untreated and treated chickens, respectively, were found. A decrease in the mean establishment rate of A. galli in treated chickens was observed. The levels of zinc, cobalt and manganese were determined in liver and muscle of the host and in male and female A. galli. The survival of the chickens and gain in body weight were improved, and the restoration of microelement content was observed by treatment with the salt. A positive effect of the basic Zn-Co-Mn salt was also observed in the nematode microelement levels. Significant differences were found between the levels of zinc, cobalt and manganese in male and female A. galli.

[The Rel/NF-kappa-B transcription factors: complex role in cell regulation]. / Les facteurs de transcription Rel/NF-kappa B: rôle complexe dans les régulations cellulaires.

The transcription factor NF-kappa B has attracted widespread attention among researchers. NF-kappa B displays some original characteristics including rapid regulation, the wide range of genes that it controls and its probable involvement in several diseases. In resting cells, NF-kappa B is kept in an inactive form in the cytoplasm where it is bound to a member of the I kappa B family of inhibitory proteins. NF-kappa B can be activated by exposure of cells to physiological as well as non physiological stimuli. Upon cell activation, the inhibitors are modified through site specific phosphorylations which target them for subsequent ubiquitination and proteolytic degradation by the proteasome. Removal of the inhibitor unmasks the nuclear localization signals on subunits of NF-kappa B. Free NF-kappa B moves to the nucleus where it binds to target DNA elements and activate transcription of genes encoding proteins involved in immune responses, inflammation or cell proliferation. NF-kappa B could be considered as a co-ordinating element in the body's responses to situations of stress, infection or inflammation. A tight regulation of NF-kappa B seems to be crucial since a dysfunction could promote pathogenic processes including AIDS (acquired immunodeficiency syndrome), rheumatoid arthritis and cancer. Additionally, it will be important to understand the exact roles for NF-kappa B in regulating apoptosis. NF-kappa B is now regarded as a good therapeutic target and the development of specific inhibitors should lead in the next future to novel therapeutics.

Insight into some of the signaling pathways triggered by a lipid immunomodulator.

The use of non specific immunomodulatory agents takes an important place in the aspecific host response to invading microorganisms. In this context, antimicrobial properties of royal jelly have been ascribed to organic acids (mainly 10 hydroxy-2-decenoic acid or 10-HDA) and proteins. We synthesized a derivative of 10-HDA, the 1-(2-methoxyethoxymethyl)2,3-(10-hydroxy2-decenoyl)(E) glycerol referred as diHDA-glycerol which was previously found to protect mice against virulent Salmonella typhimurium challenge through more adequate immune regulations. This study was conducted to further investigate some of the signaling pathways followed by diHDA-glycerol in cell transduction. Members of NF-kappaB transcription factors are key regulators of many cytokines acting on immunity and they control genes involved in responses to numerous signals such as bacterial products. Therefore, we investigated some parameters acting on NF-kappaB translocation in U937 cells after diHDA-glycerol treatment. Due to the chemical structure of the molecule we also investigated the sphingomyelinase pathway. Our results showed that diHDA-glycerol induced a rapid NF-kappaB translocation as a consequence of IkappaB-alpha proteolysis. An intracellular production of reactive oxygen species (ROS) may also account for NF-kappaB activation, without de novo protein synthesis. DiHDA-glycerol induced a strong activation of neutral sphingomyelinase, suggesting an important role of sphingolipids in the regulatory responses induced by diHDA-glycerol.

Effect of a synthetic lipid immunomodulator on the regulation of the transcription factor NF-kappaB.

Macrophage activation plays a central role in host defense against a variety of pathogens via inducible messengers. The transcription factor NF-kappaB controls the synthesis of cytokines involved in immune responses. In quiescent cells, NF-kappaB is located in the cytosol bound to an inhibitor IkappaB. Upon appropriate signal, NF-KB translocates to the nucleus and binds to DNA. The present study investigated the involvement of an immunomodulator, (diHDA-glycerol) on the NF-kappaB/IkappaB complex. Results were compared to those obtained with lipopolysaccharide (LPS) as a major virulence factor in bacterial sepsis. Data showed that exposure of J774.1 cells either to LPS or diHDA-glycerol substantially increased with time the nuclear levels of NF-kappaB complexes. Antibodies to various NF-kappaB proteins supershifted p50, p65 and to a lesser extent c-rel. Western blot analyses showed a rapid cytosolic IkappaB-alpha turn over following LPS exposure in contrast to diHDA-glycerol treatment. Further experiments investigated the involvement of protein kinase C (PKC) by using two inhibitors, staurosporine and H7. Pretreatment of J774.1 with either inhibitor prior to diHDA-glycerol or LPS exposure decreased NF-kappaB activation. Our results indicate that diHDA-glycerol was acting on NF-kappaB through IkappaB regulative mechanisms differing from those used by LPS. DiHDA-glycerol is likely acting on many other transcription factors targeting distinct genes implied in up regulation of the immune system.

Human and mouse XAP-5 and XAP-5-like (X5L) genes: identification of an ancient functional retroposon differentially expressed in testis.

Although most retroposons that arose by reverse transcription of cellular mRNAs and by reintegration into the genome are nonfunctional, several examples exist in which the retroposon acquired a novel function and became fixed in the genome as a functional gene. We identified another such case: the ubiquitously expressed X-linked XAP-5 gene with unknown function gave rise to its retroposed counterpart, XAP-5-like (X5L), which has an intronless open reading frame and is autosomal in human. Phylogenetic analysis of the human and mouse XAP-5 and X5L genes shows that the retroposition most likely took place before the radiation of eutherian mammals. The XAP-5 and X5L genes are expressed in a wide range of tissues but are differentially expressed in testis. The ancient origin and broad expression of the X5L retroposon indicate that the XAP-5 and X5L genes may have assumed different functions in somatic cells. In addition to this, because of its autosomal location and its high level and particular pattern of expression in spermatogenic cells, the X5L expression in testis may compensate for the X-linked XAP-5 gene, which may be silenced during spermatogenesis.

Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome.

BACKGROUNDS & AIMS: Mutations in the JAGGED1 gene are responsible for the Alagille syndrome, an autosomal dominant disorder characterized by neonatal jaundice, intrahepatic cholestasis, and developmental disorders affecting the liver, heart, vertebrae, eyes, and face. We screened a large group of patients for mutations in JAGGED1 and studied transmission of the mutations. METHODS: The coding sequence of the JAGGED1 gene was searched by single-strand conformation polymorphism and sequence analysis for mutations in 109 unrelated patients with the Alagille syndrome and their family if available. RESULTS: Sixty-nine patients (63%) had intragenic mutations, including 14 nonsense mutations, 31 frameshifts, 11 splice site mutations, and 13 missense mutations. We identified 59 different types of mutation of which 54 were previously undescribed; 8 were observed more than once. Mutations were de novo in 40 of 57 probands. CONCLUSIONS: Most of the observed mutations other than the missense mutations in JAGGED1 are expected to give rise to truncated and unanchored proteins. All mutations mapped to the extracellular domain of the protein, and there appeared to be regional hot spots, although no clustering was observed. Thus, the sequencing of 7 exons of JAGGED1 would detect 51% of the mutations. Transmission analysis showed a high frequency of sporadic cases (70%).

Changes in myosin heavy chain profile of mature regenerated muscle with endurance training in rat.

The objective of the present study was to examine the response of fast-twitch muscle to endurance training long after the muscle had regenerated from toxin injury. Seventeen male Wistar rats were randomly assigned to a sedentary (S, n = 10) or a trained group (T, n = 7). Endurance training by treadmill running (5 days week(-1), 30 m min(-1), 7% grade, 2 h day(-1) for 5 weeks) was initiated 5 weeks after myofibre degeneration was induced in the right extensor digitorum longus muscle (EDL) by two injections of 0.2 mL of the unfractionated venom from Naja nigricollis snake. Gel electrophoresis analyses showed that training alone resulted in a 140% increase in type IIX myosin heavy chain (MHC) (P < 0.01) and a slight decrease in type IIB MHC (-14% P < 0.05). Regeneration alone induced an increase in both type IIA and IIX MHC expression (103%, P < 0.05, and 131%, P < 0.01, respectively), and a concomitant decrease in the percentage of type IIB MHC (P < 0.05). The shift from type IIB toward type IIA MHC composition observed in regenerated muscles of T rats resulted not only from an additive, but from a cumulative effect of training and regeneration. Immunohistochemical analysis of MHC content in individual fibres showed similar changes. These data suggest that the impact of endurance training on fast-type MHCs was more marked in mature regenerated muscles than in regenerating ones, and provide evidence of the heightened plasticity of fully regenerated muscles to repeated exercise.

Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.

The chromosomal band 17p11.2 is associated with a number of neurological disorders and malignant diseases. This region is also characterized by the presence of complex repeat elements that are probably responsible for the frequent occurrence of interstitial deletions, duplications, and isochromosome formation. In the course of the molecular analysis of this interval, an integrated map with YACs, PACs, and cosmids covering approximately 6 Mb was established. Focusing on the 1.4-Mb interval containing the Smith-Magenis syndrome critical region and the breakpoint region for medulloblastomas, we constructed a detailed transcript map between the marker PS2 and the proximal CMT1A repeat. FISH analysis of the PACs allowed determination of the position of the transcripts with respect to the SMS critical region and the presumptive chromosomal breakpoint in medulloblastomas. One PAC (G21100) provided evidence for the presence of a novel complex repeat unit, indicating that there are at least three independent repeat elements within 2 Mb. Five genes were mapped to clone G21100 and are likely to form part of this novel complex sequence repeat. In summary, 53 new transcripts were isolated by using cDNA selection and exon trapping. This included 8 known but previously unmapped genes and 45 novel transcripts. The expression profile of 21 transcripts was determined by RT-PCR. Based on their homologies to known genes or proteins, some of the novel genes are considered candidate genes either for malignant diseases or for the Smith-Magenis syndrome.

Construction of an integrated physical and gene map of human chromosome 20p12 providing candidate genes for Alagille syndrome.

Physical mapping and localization of eSTS markers were used to generate an integrated physical and gene map covering a approximately 10-Mb region of human chromosome 20p12 containing the Alagille syndrome (AGS) locus. Seventy-four STSs, 28 of which were derived from cDNA sequences, mapped with an average resolution of 135 kb. The 28 eSTS markers define 20 genes. Six known genes, namely CHGB, BMP2, PLCB1, PLCB4, SNAP, and HJ1, were precisely mapped. Among the genes identified, one maps in the smallest region of overlap of the deletions associated with AGS and could therefore be regarded as a candidate gene for Alagille syndrome.

Zinc and DNA fragmentation in keratinocyte apoptosis: its inhibitory effect in UVB irradiated cells.

Zinc has been shown to have antioxidant properties and to exhibit inhibitory effects on apoptosis. In this work we investigated the effect of zinc on DNA integrity and on apoptosis of HaCaT keratinocytes. Cells were submitted to zinc deprivation by a diffusible zinc chelator, (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine) (TPEN) or supplied with zinc chloride and submitted to UVB radiation. After cell exposure to TPEN for 2 h, strand breaks significantly impaired DNA resistance to alkaline denaturation. DNA strand breaks induced by a 6 h TPEN application were significantly prevented if zinc chloride was supplied together with the chelator. TPEN also generated, after 4-6 h of application, cytoplasmic histone-associated DNA fragments (mononucleosomes and oligonucleosomes), features of cell death by apoptosis. Moreover, UVB irradiation led to early DNA strand breaks and to an increase in cytoplasmic nucleosomes which was maximum 10 h after irradiation. These effects were prevented by the supply of zinc chloride (0.1 mM) in the culture medium. These results suggest that zinc ions interfere with the apoptosis process at an early stage, by decreasing DNA damage able to trigger apoptosis.