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D Goossens

Publications and source records attributed to D Goossens.

At least 19 recordsLinked to original sources
PubMed2006

Generation of mice with inactivated Rh or Rhag genes.

Mice carrying inactivated Rh and Rhag genes were generated by insertional targeting. KO animals exhibited normal growth, development and fertility and both types were indistinguishable at a gross phenotypic level from their wild type littermates. Preliminary analysis revealed that red cells from Rh-/- mice lack Rh protein and have a moderate decrease of Rhag protein, whereas those from Rhag-/- mice have a total absence of Rhag and Rh proteins. Studies are in progress to delineate the antigenic, biochemical and functional abnormalities of red cells from these animals as well as the impact on hematological parameters and erythropoiesis.

Animals↗
PubMed2006

Role of RhAG and AQP1 in NH3 and CO2 gas transport in red cell ghosts: a stopped-flow analysis.

To clarify the potential role Rh/RhAG and AQP1 proteins in erythrocyte gas transport, NH3 and CO2 transport was measured in erythrocyte ghost membrane vesicles from rare human variants (Rh(null), CO(null),) and knockout mice (homozygous AQP1-/-, Rh-/- and Rhag-/-) exhibiting well-characterized protein defects. Transport was measured from intracellular pH (pHi) changes in a stopped-flow fluorimeter. NH3 transport was measured in chloride-free conditions with ghosts exposed to 20 mM inwardly directed gradients of gluconate salts of ammonium, hydrazine and methylammonium at 15 degrees C. Alkalinization rates of control samples were 6.5+/-0.3, 4.03+/-0.17, 0.95+/-0.08 s(-1) for each solute, respectively, but were significantly reduced for Rh(null) and CO(null) samples that are deficient in RhAG and AQP1 proteins, respectively. Alkalinization rates of Rh(null) ghosts were about 60%, 83% and 94% lower than that in control ghosts, respectively, for each solute. In CO(null) ghosts, the lack of AQP1 resulted in about 30% reduction of the alkalinization rates as compared to controls, but the transport selectivity of RhAG for the three solutes was preserved. Similar observations were made with ghosts from KO mice Rhag-/- and AQP1-/-. These results confirm the major contribution of RhAG/Rhag in the NH3 conductance of erythrocytes and suggest that the reduction of transport rates in the absence of AQP1 would be better explained by a direct or indirect effect on RhAG/Rhag-mediated transport. When ghosts were preloaded with carbonic anhydrase and exposed to a 25 mM CO2/HCO3- gradient at 6 degrees C, an extremely rapid kinetics of acidification corresponding to CO2 influx was observed. The rate constants were not significantly different between controls and human variants (125+/-6 s(-1)), or between wild-type and KO mice, suggesting no major role of RhAG or AQP1 in CO2 transport, at least in our experimental conditions.

Ammonia↗
PubMed2006

Rh glycoproteins in epithelial cells: lessons from rat and mice studies.

Rhesus glycoproteins are a recently discovered family of ammonium transporters and a new branch of the Mep/AMT proteins superfamily that was identified more than 15 years ago in lower organisms and plants. Despite many ex vivo studies showing evidences that Rh glycoproteins can accelerate transmembrane NH3 or NH4+ transfer, their role in normal and disease physiology remains unknown. This review focuses on some of the different studies carried out in animal models to gain insight into Rh glycoprotein function. Immunolocalization studies have added new evidence that this protein family is related to ammonium transport or metabolism in epithelial cells. However, the absence of distal tubular acidosis or hyperammonemia in Rhbg KO mice have raised new questions about the physiological significance of these proteins.

Animals↗
PubMed2005

A novel susceptibility locus at 2p24 for generalised epilepsy with febrile seizures plus.

Generalised epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous epilepsy syndrome. Using positional cloning strategies, mutations in SCN1B, SCN1A, and GABRG2 have been identified as genetic causes of GEFS+. In the present study, we describe a large four generation family with GEFS+ in which we performed a 10 cM density genome-wide scan. We obtained conclusive evidence for a novel GEFS+ locus on chromosome 2p24 with a maximum two point logarithm of the odds (LOD) score of 4.22 for marker D2S305 at zero recombination. Fine mapping and haplotype segregation analysis in this family delineated a candidate region of 3.24 cM, corresponding to a physical distance of 4.2 Mb. Linkage to 2p24 was confirmed (p = 0.007) in a collection of 50 nuclear and multiplex families with febrile seizures and epilepsy. Transmission disequilibrium testing and association studies provided further evidence (p < 0.05) that 2p24 is a susceptibility locus for febrile seizures and epilepsy. Furthermore, we could reduce the candidate region to a 2.14 cM interval, localised between D2S1360 and D2S2342, based upon an ancestral haplotype. Identification of the disease gene at this locus will contribute to a better understanding of the complex genetic aetiology of febrile seizures and epilepsy.

Chromosomes, Human, Pair 2↗
PubMed2005

Survival of the probiotic, L. plantarum 299v and its effects on the faecal bacterial flora, with and without gastric acid inhibition.

INTRODUCTION: Probiotic bacteria have to survive passage through the gastrointestinal tract. In this placebo-controlled double-blind study, the effect of Lactobacillus plantarum 299v on the faecal flora was studied with and without gastric acid inhibition. METHODS: Thirty-two healthy volunteers were given pantoprazole (40 mg/day) or placebo for 3 weeks from week 2 until week 4. In addition, from week 3 until week 4, L. plantarum 299v in an oatmeal-fermented drink (10(9) CFU/ml) was given twice daily to both groups. From each healthy volunteer, faecal samples were collected at the end of week 1, 2, 4 and 8 (4 weeks after cessation of L. plantarum 299v and pantoprazole/placebo). Several aerobically and anaerobically growing bacteria were counted and short chain fatty acid concentrations were determined. RESULTS: In both the pantoprazole and the placebo group, median lactobacilli counts increased significantly in week 4 compared to week 1 (from log 4.5 to 8.0 CFU/g faeces in pantoprazole and from log 4.2 to 7.7 CFU/g faeces in placebo group) and decreased significantly in week 8 (to log 4.5 CFU/g faeces in pantoprazole and log 4.3 CFU/g faeces in placebo group). These lactobacilli were identified as L. plantarum 299v. No significant differences were observed in all other bacterial counts and short chain fatty acid concentrations. CONCLUSIONS: The comparable increase of faecal lactobacilli counts in both the pantoprazole and the placebo-treated group demonstrates that L. plantarum 299v survives passage through the gastrointestinal tract irrespective of gastric acidity. The increment of the intra-gastric pH in combination with L. plantarum 299v did not modulate bacterial composition and/or the production of short chain fatty acids.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

[Palatal myoclonus and dysphagia].

INTRODUCTION: Post brainstem lesion dysphagia is frequently associated with palatal myoclonus (PM) but the correlation between these two symptoms is still unclear. OBJECTIVE: The aim of this study was to verify the relationship between PM and dysphagia, and if PM could itself induce dysphagia. PATIENTS AND METHODS: Twelve patients suffering from post brainstem lesion PM and dysphagia; 10 male and two female, mean aged of 50.5 years, were assessed using clinical examination, radiological and endoscopic examination of deglutition. RESULTS: In three cases, PM were associated with pharyngeal area decreasing, laryngeal aspiration, and dysphagia. DISCUSSION: This study confirms the hypothesis of close relationship between PM and dysphagia. In these cases, specific dysphagia therapy should be recommended. CONCLUSION: Post brainstem lesion dysphagia is sometimes associated with PM and in some cases, there is probably a relationship between PM and swallowing disorders of these patients.

Adult↗
PubMed2003

The effect of Lactobacillus plantarum 299v on the bacterial composition and metabolic activity in faeces of healthy volunteers: a placebo-controlled study on the onset and duration of effects.

AIM: To study the onset and duration of a possible effect of a fermented oatmeal drink containing Lactobacillus plantarum 299v on the composition of the faecal flora of healthy volunteers in a placebo-controlled, double-blind study. METHODS: Twenty-two participants consumed a fermented oatmeal drink with or without L. plantarum 299v for 4 weeks. Faecal samples were collected weekly: two samples before, four during and four after the consumption of the drink. Several bacterial species were counted and enzyme activities, short-chain fatty acid concentrations, endotoxin concentration and pH were determined. L. plantarum 299v was identified using randomly amplified polymorphic DNA. RESULTS: In contrast with the placebo group, median lactobacilli counts increased significantly from 4.2 (3.4-6.3) to 8.2 (7.3-8.5) log colony-forming units/gram faeces (P = 0.005) after 1 week of consumption of L. plantarum 299v, thereafter remaining stable during the treatment period. One week after cessation, a significant decrease in lactobacilli [to 4.4 (2.2-6.5) log colony-forming units/gram faeces] was observed (P = 0.003). These lactobacilli were identified as L. plantarum 299v. All other bacterial counts, enzyme activities, short-chain fatty acid concentrations, endotoxin concentration and pH remained unchanged. CONCLUSIONS: L. plantarum 299v significantly increased the number of lactobacilli in the faecal flora within 1 week, and this effect disappeared within 1 week after cessation of intake. No other changes in bacterial counts and metabolic products were observed.

Adult↗
PubMed2003

A novel CpG-associated brain-expressed candidate gene for chromosome 18q-linked bipolar disorder.

We previously identified 18q21-q22 as a candidate region for bipolar (BP) disorder and constructed a yeast artificial chromosome (YAC) contig map. Here we identified three potential CpG islands using CCG/CGG YAC fragmentation. Analysis of available genomic sequences using bioinformatic tools identified an exon of 3639 bp downstream of a CpG island of 1.2 kb containing a putative transcription initiation site. The exon contained an open reading frame coding for 1212 amino acids with significant homology to the SART-2 protein; weaker homology was found with a series of sulphotransferases. Alignment of cDNA sequences of corresponding ESTs and RT-PCR sequencing predicted a transcript of 9.5 kb which was confirmed by Northern blot analysis. The transcript was expressed in different brain areas as well as in multiple other peripheral tissues. We performed an extensive mutation analysis in 113 BP patients. A total of nine single nucleotide polymorphisms (SNPs) were identified. Five SNPs predicted an amino acid change, of which two were present in BP patients but not in 163 control individuals.

Amino Acid Substitution↗
PubMed2003

Probiotics in gastroenterology: indications and future perspectives.

Nowadays. there is a growing interest in probiotics as a safe way of changing the intestinal bacterial flora. Probiotics may have potential in several gastroenterological conditions, especially when the intestinal flora has been disturbed. Most scientific evidence is available for diarrhoea patients treated with Lactobacillus GG, Lactobacillus reuteri or Saccharomyces boulardii. Meta-analyses have shown an overall reduction in the risk of antibiotic-associated diarrhoea during treatment with probiotics, and benefits have also been demonstrated for patients with rota-virus-associated diarrhoea. Patients with inflammatory bowel disease, an inflammatory disorder characterized by a change in the intestinal flora, are another important target group for which probiotics may be beneficial. It has been claimed that in ulcerative colitis and Crohn disease patients, lactobacilli, S. boulardii and Escherichia coli reduce relapses. but most studies were not placebo-controlled. A reduction in relapses has also been demonstrated in pouchitis patients treated with a multispecies probiotic. Irritable bowel syndrome might be another clinical indication for probiotic therapy, but results of clinical trials performed in these patients are inconsistent. Additionally, probiotics may improve lactose absorption. Helicobacter pylori eradication and constipation. Finally, in animal models of colorectal cancer, treatment with probiotics reduces the prevalence of this disease, and in humans the amount of genotoxic substances in faeces has been reduced. In conclusion, the results of studies on the effects of probiotics in gastrointestinal conditions are encouraging. but well-designed placebo-controlled studies are warranted before recommendations for therapeutic or preventive use can be given. Many issues still have to be resolved, including optimal dose and duration of treatment, selection of and differences between the several available probiotic strains, and, importantly, their mechanisms of actions have to be elucidated.

Colorectal Neoplasms↗
PubMed2000

A soluble recombinant multimeric anti-Rh(D) single-chain Fv/CR1 molecule restores the immune complex binding ability of CR1-deficient erythrocytes.

CR1 (CD35, the C3b/C4b receptor) is a widely distributed membrane glycoprotein with a unique cluster conformation on the surface of erythrocytes (E). CR1 on E is responsible for the transport of immune complexes (IC) to liver and spleen. As a cofactor of the C3b cleavage by factor I, CR1 is also a potent inhibitor of C activation and inflammation. In some diseases (systemic lupus erythematosus, hemolytic anemia, AIDS, etc.) an acquired low level of CR1 on E has been observed, leading to an impaired clearance of IC. The aim of this study was to design a heterofunctional molecule that will bind to E and restore a normal or a supranormal CR1 density on E that could mimic the unique distribution pattern of CR1 on normal E. For that purpose a new multimerizing system based on the properties of the C-terminal part of the alpha-chain of the C4 binding protein (C4bp) was used. We first produced a multimeric soluble CR1 that proved to be a better inhibitor of in vitro C activation than the monomeric form of CR1, then a heteromultimeric molecule made of CR1 and single-chain Fv anti-Rh(D) valences able to attach E and providing E with as much as a 10-fold increase in CR1 density with the same CR1 distribution pattern as native E. CR1/single-chain Fv anti-Rh(D)-treated E were able in vitro to attach as many opsonized IC as native E. These data open the way for future use of multimeric and heteromultimeric forms of soluble recombinant CR1 as therapy of IC diseases.

Animals↗
PubMed2000

No evidence for the involvement of CAG/CTG repeats from within 18q21.33-q23 in bipolar disorder.

We previously identified 18q21.33-q23 as a candidate region in one BP family and constructed a yeast artificial chromosome (YAC) contig map. Here, we mapped eight known CAG/CTG repeats relative to 18q21.33-q23. We also isolated four CAG/CTG repeats from within the region using CAG/CTG YAC fragmentation, one of which is located in the 5' untranslated region of the CAP2 gene coding for a brain-expressed serine proteinase inhibitor. The triplet repeats located in the 18q21.33-q23 BP candidate region showed no expanded alleles in the linked BP family nor in a BP case-control sample. Moreover, only the CAP2 triplet repeat was polymorphic but no genetic association with BP disorder was observed.

Bipolar Disorder↗
PubMed1999

YAC fragmentation with repetitive and single-copy sequences: detailed physical mapping of the presenilin 1 gene on chromosome 14.

We constructed new LYS2 fragmentation vectors that allow direct acentric and centric fragmentation of yeast artificial chromosomes (YACs) and selection of fragmented YACs in yeast strain AB1380. The fragmentation vectors were used efficiently with repetitive (e.g., Alu), low-copy (e.g., CA-repeats) and single-copy (e.g., exons) sequences. High recombination efficiencies were obtained in fragmenting two different CEPH YACs with the Alu consensus sequence as target sequences for homologous recombination. Analysis of the acentric Alu fragmentation panel of 788H12, containing the presenilin 1 (PSEN1) gene for familial Alzheimer's disease (AD), indicated that high-resolution YAC fragmentation panels covering the entire parent YAC are obtained. Also, marker content analysis of the fragmentation panel indicated that fragmented YACs were propagated stably without rearrangements. The same fragmentation vectors were used efficiently for fragmentation of 788H12 with unique sequences, i.e., exons 3 and 12 of PSEN1 and D14S77, a polymorphic CA repeat, as target sequences. Together, our YAC fragmentation data of 788H12 provided a size estimate for the coding region of PSEN1 of 60kb and a more precise localization of D14S77 at 25kb upstream of PSEN1.

Alu Elements↗
PubMed1999

Characterization of a mouse liminin receptor gene homologous to the human blood group Lutheran gene.

The human Lutheran (Lu) blood group antigens are carried by two glycoproteins (gps) that belong to the immunoglobulin (Ig) superfamily. These gps represent adhesion molecules that function as the unique erythroid receptors for laminin. We report here the cloning and functional expression of the orthologous mouse Lu mRNA as well as the genomic organization of the mouse Lu gene. The deduced human and mouse Lu gps share 72.5% identity and similar organization of the Ig-like domains. As in the human, the mouse Lu gene is organized in 15 exons. The proximal promoter showed consensus CACC-binding sites whereas the distal promoter exhibits a GATA-1-binding site and multiple E boxes. Like the human gene, the mouse Lu gene is also widely expressed among tissues but is transcribed as a unique 2.4-kb mRNA species. Expression of the mouse Lu mRNA is upregulated upon dimethyl sulfoxide-induced erythroid differentiation of murine erythroleukemia cells (MEL). During mouse embryonic development, the Lu transcript is detected as early as day 7 of gestation. Analysis of transfected human erythroleukemia K562 cells indicated that the adhesive properties of the Lu gps to laminin are conserved between human and mouse.

Amino Acid Sequence↗
PubMed1999

Isolation of CAG/CTG repeats from within the chromosome 2p21-p24 locus for autosomal dominant spastic paraplegia (SPG4) by YAC fragmentation.

Pure autosomal dominant spastic paraplegia (SPG) is a genetically heterogeneous neurodegenerative disorder of the central nervous system clinically characterized by progressive spasticity mainly affecting the lower limbs. Three distinct loci have been mapped to chromosomes 14q (SPG3), 2p (SPG4) and 15q (SPG6). In particular, SPG4 families show striking intrafamilial variability suggestive of anticipation and evidence has been provided that CAG/CTG repeat expansions may be involved. To isolate CAG/CTG repeat containing sequences from within the SPG4 candidate region, a novel approach was developed. Fragmentation vectors were assembled allowing direct fragmentation of yeast artificial chromosomes (YACs) with a short (> or = 21 bp) CAG/CTG sequence as the target site for homologous recombination. We used the CAG/CTG YAC fragmentation vectors to isolate CAG/CTG containing sequences from four YACs spanning the SPG4 candidate region between D2S400 and D2S367. A total of four CAG/CTG containing sequences were isolated of which three were novel. However, none of the four CAG/CTG repeats showed expanded alleles in two Belgian SPG4 families. In addition, we showed that the CAG/CTG alleles detected by the repeat expansion detection (RED) method could be fully explained by two polymorphic nonpathogenic CAG/CTG repeats on chromosomes 17 and 18, respectively. Also, the RED expansions in six SPG families could not be explained by amplification of the CAG/CTG repeats at the SPG4 locus. Together, our data do not support the hypothesis of a CAG/CTG repeat expansion as the molecular mechanism underlying SPG4 pathology.

Adenosine Triphosphatases↗
PubMed1998

Predictors of hospital mortality in type A aortic dissections: a retrospective analysis of 148 consecutive surgical patients.

Reports in the literature frequently concern miscellaneous types of dissections. This makes correct interpretation of data difficult. In order to assess the determinants of hospital mortality, the results of 148 consecutive patients over a 23-year period, all operated on for a type A dissection, were reviewed. Mean(s.d.) age was 56(13.1) years, 64% were male. An acute dissection (surgery within 14 days after onset of symptoms) was performed in 139 patients. Stigmata of the Marfan syndrome were present in 6.1% (n = 9). Peripheral vascular ischaemic complications were observed in 27.7%. Nowadays, diagnosis is primarily confirmed using transoesophageal echocardiography (75 correct diagnoses among 76 performed). Operation consisted of repair or replacement of the ascending aorta. Resuspension of the aortic valve was performed in 74 patients, and arch replacement in 25. In 74 patients, distal repair was done under deep hypothermic circulatory arrest. Hospital mortality rate was 23.6% (35 patients), though mortality rate calculated over the period 1990-1993 was 17.4% (P = n.s.). Univariate analysis revealed the following variables to be statistically significant predictors of hospital mortality (P < 0.05): preoperative ischaemic complications, preoperative resuscitation, haemopericardium, postoperative neurological complications, rethoracotomy, renal insufficiency and intestinal ischaemia. Multivariate stepwise logistic regression indicated preoperative resuscitation, postoperative haemodialysis and postoperative neurological complications as the only independent predictors of hospital death. Dissections arising from a primary intimal tear in the descending aorta had a more favourable outcome (P = 0.06, odds ratio 0.1). Although hospital mortality has declined over the past few years, no decline was seen in operative mortality since gelatine-resourcine-formol (GRF) glue is used as a routine. Transoesophageal echocardiography is the first choice in confirming diagnosis. Early operation is advocated, with careful haemostasis, before the development of cardiac tamponade or end-organ ischaemia, as the cornerstone of a successful treatment of a type A dissection. Reduction of neurological complications will further improve the results.

Aortic Dissection↗
PubMed1998

Molecular genetic analysis of autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was previously mapped by linkage analysis studies to chromosome 3p12-p21.1 (SCA7). Positional cloning efforts have recently identified a novel gene, SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig spanning the SCA7 candidate region. Using a combination of genomic sequencing and cosmid-based exon trapping, two expressed sequence tags were identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis identified the full-length SCA7 cDNA. Together, our sequence data defined the intron/exon boundaries of the first two coding exons of the SCA7 gene, with the first exon containing the expanded CAG repeat. Further, sequence comparison with the published SCA7 cDNA identified one additional putative exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at least 55 repeats with allele lengths being inversely correlated with onset age of ADCAII symptoms. The SCA7 repeats increased in length in successive generations. Normal alleles had from four to 18 repeats, with 10 repeats being the most common allele.

Alleles↗