PubMed Health⌕ Search

Biomedical subjects

R Sciot

Publications and source records attributed to R Sciot.

At least 19 recordsLinked to original sources
PubMed2006

Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium.

From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion protein gene and brain neuropathology was collected. From 1-1-1998 to 31-12-2004, 188 patients were referred to the surveillance system. In 85 patients a 'definite' diagnosis of sporadic CJD (sCJD) could be made, whereas 26 patients remained 'probable'. We further identified two unrelated patients with an E200K mutation, and two patients with a seven octapeptide repeat insertion in one family. In one patient a familial history was noted but genetic analysis was not performed. In 72 patients different final diagnoses were made, Alzheimer's disease being the most frequent (N = 20). The demographic parameters of the Belgian population were similar to those observed in the rest of Europe. We did notice a significantly increased age-specific incidence (> 6/10(6)/year) of sCJD patients between 70 and 90 years old in the period 2002-2004 compared to 1998-2001 and retrospectively obtained data (1990-1997, p < 0.01). We undertook a detailed clinical and biochemical analysis to investigate this increase but could not identify any reason other than an increased vigilance for the diagnosis. In conclusion, our study identified that in the past sCJD may have been underestimated in patients over age 70 although these patients are both clinically and neurobiochemically similar to the general sCJD phenotype.

Age Distribution↗
PubMed2006

An extrarenal rhabdoid tumor of the cervical spine with bony involvement.

A case of a histologically proven rhabdoid tumor of the cervical spine in a 19-year-old Caucasian male is presented. Primary extrarenal rhabdoid tumors are very rare. When the central nervous system is involved, the tumor usually is located in the brain. Only three cases of primary spinal rhabdoid tumor have been reported. This case is the first reported extradural rhabdoid tumor of the spinal canal and the first case of a rhabdoid tumor located in the spinal canal with bony involvement.

Adult↗
PubMed2006

The normal phenotype of Pmm1-deficient mice suggests that Pmm1 is not essential for normal mouse development.

Phosphomannomutases (PMMs) are crucial for the glycosylation of glycoproteins. In humans, two highly conserved PMMs exist: PMM1 and PMM2. In vitro both enzymes are able to convert mannose-6-phosphate (mannose-6-P) into mannose-1-P, the key starting compound for glycan biosynthesis. However, only mutations causing a deficiency in PMM2 cause hypoglycosylation, leading to the most frequent type of the congenital disorders of glycosylation (CDG): CDG-Ia. PMM1 is as yet not associated with any disease, and its physiological role has remained unclear. We generated a mouse deficient in Pmm1 activity and documented the expression pattern of murine Pmm1 to unravel its biological role. The expression pattern suggested an involvement of Pmm1 in (neural) development and endocrine regulation. Surprisingly, Pmm1 knockout mice were viable, developed normally, and did not reveal any obvious phenotypic alteration up to adulthood. The macroscopic and microscopic anatomy of all major organs, as well as animal behavior, appeared to be normal. Likewise, lectin histochemistry did not demonstrate an altered glycosylation pattern in tissues. It is especially striking that Pmm1, despite an almost complete overlap of its expression with Pmm2, e.g., in the developing brain, is apparently unable to compensate for deficient Pmm2 activity in CDG-Ia patients. Together, these data point to a (developmental) function independent of mannose-1-P synthesis, whereby the normal knockout phenotype, despite the stringent conservation in phylogeny, could be explained by a critical function under as-yet-unidentified challenge conditions.

Animals↗
PubMed2005

Myosin storage myopathy: slow skeletal myosin (MYH7) mutation in two isolated cases.

Myosin storage myopathy is a congenital myopathy characterized by subsarcolemmal hyaline bodies in type 1 muscle fibers, which are ATPase positive and thus contain myosin. Mutations recently were identified in the type 1 muscle fiber myosin gene (MYH7) in Swedish and Saudi families with myosin storage myopathy. The authors have identified the arginine 1845 tryptophan mutation found in the Swedish families in two isolated Belgian cases, indicating a critical role for myosin residue arginine 1845.

Adult↗
PubMed2005

Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO.

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. MATERIALS AND METHODS: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). RESULTS: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. CONCLUSIONS: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.

Benzamides↗
PubMed2005

Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall.

AIMS: The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on morphological features and KIT (CD117) immunoreactivity. Most patients with advanced GISTs show a major clinical response after treatment with imatinib mesylate. The histopathological features of GISTs in patients on prolonged imatinib treatment have, thus far, not been addressed in detail. In this report, we present three patients with metastatic GISTs, who received more than 1 year of therapy with imatinib, and whose tumours changed their morphological and immunohistochemical characteristics during continued treatment with the drug. METHODS AND RESULTS: All three primary GISTs from these patients were classical spindle-type tumours, showing diffuse, strong CD117, CD34, and focal alpha-smooth muscle actin expression. During treatment, two clinically progressive and one clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary epithelioid growth pattern, characterized by rounded cells with eosinophilic cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably, two of these tumours also became CD34 immunonegative and in one case the progression was accompanied by desmin expression. KIT mutational analysis revealed the presence of distinct exon 11 mutant isoforms in all cases examined, while the same genotype was sustained in the base line and on-therapy tumour specimens, proving the common origin of analysed specimens. CONCLUSIONS: GISTs subject to imatinib treatment can undergo striking (immuno)phenotypic changes, which are not necessarily corroborated by new genotypic modifications. Because these may mimic other tumour types, this feature creates a differential diagnostic challenge, of which the pathologist should be aware.

Actins↗
PubMed2005

Tissue distribution of the murine phosphomannomutases Pmm1 and Pmm2 during brain development.

The most common type of the congenital disorders of glycosylation, CDG-Ia, is caused by mutations in the human PMM2 gene, reducing phosphomannomutase (PMM) activity. The PMM2 mutations mainly lead to neurological symptoms, while other tissues are only variably affected. Another phosphomannomutase, PMM1, is present at high levels in the brain. This raises the question why PMM1 does not compensate for the reduced PMM2 activity during CDG-Ia pathogenesis. We compared the expression profile of the murine Pmm1 and Pmm2 mRNA and protein in prenatal and postnatal mouse brain at the histological level. We observed a considerable expression of both Pmms in different regions of the embryonic and adult mouse brain. Surprisingly, the expression patterns were largely overlapping. This data indicates that expression differences on the cellular and tissue level are an unlikely explanation for the absence of functional compensation. These results suggest that Pmm1 in vivo does not exert the phosphomannomutase-like activity seen in biochemical assays, but either acts on as yet unidentified specific substrates or fulfils entirely different functions.

Animals↗
PubMed2005

Case report. Rectus abdominis endometriosis: a report of two cases.

Endometriosis is characterized by the presence of histological normal endometrial tissue outside the uterine cavity. Most frequently endometriosis occurs within the pelvis. Extrapelvic endometriosis is less common, but can involve nearly every organ. We present two patients in whom endometriosis was found in the rectus abdominis muscle and discuss the imaging findings and pathological correlation.

Adult↗
PubMed2005

Medullary thyroid carcinoma in a child with a new RET mutation and a RET polymorphism.

We report a 12 year old boy with an isolated medullary thyroid carcinoma (MTC). A mutation analysis of the RET-proto-oncogene in this boy showed an in frame insertion-deletion mutation (insTTCTdelG) at codon 666 of the RET proto-oncogene. This RET mutation has not been reported previously. The boy's mother and his 82-year-old maternal grandfather showed the same mutation. None of the two ever showed symptoms of MTC. The mother underwent a preventive total thyroidectomy and pathological examination showed C-cell hyperplasia and early MTC. Further genetic analysis showed that the boy inherited a well-known coding polymorphism in exon 11 (G691S) from his father. Therefore the boy is a compound heterozygote for the insertion-deletion mutation at codon 666 and the G691S polymorphism in the RET gene. We hypothesize that the insTTCTdelG mutation at codon 666 is associated with low penetrance for MTC and that the young age of MTC in the reported child results most likely from the additive effects of both mutations (insTTCTdelG and G691S).

Carcinoma, Medullary↗
PubMed2005

Pneumosinus dilatans and orbital meningioma in neurofibromatosis type 2.

We report on a 9-year-old boy with neurofibromatosis type 2 and a progressive proptosis of the left eye. Imaging studies revealed a pneumosinus dilatans of the left ethmoidal and frontal sinuses and an adjacent left orbital mass. Incision biopsy of the orbital mass showed a meningiothelial meningioma. Orbital and intracranial meningiomas are frequently associated with pneumosinus dilatans. This report illustrates the relationship of pneumosinus dilatans, intra-orbital meningioma and neurofibromatosis type 2.

Child↗
PubMed2004

Differential protein expression profile in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal through gain of function mutations of the oncogene KIT. Imatinib offers the first effective treatment for patients with GISTs, but the therapeutic outcome strongly depends on the type of KIT mutation. We used ProteinChip technology to investigate whether GISTs with different KIT mutations express different proteins. In total, 154 proteins were significantly differentially expressed in GISTs with exon 9 KIT mutation compared to GISTs with exon 11 KIT mutation.

Exons↗
PubMed2004

Invasion and MMP expression profile in desmoid tumours.

Desmoid tumours are locally invasive soft tissue tumours in which beta-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription-PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion.

Culture Media, Conditioned↗
PubMed2004

MRI findings in acute cerebellitis.

Acute cerebellitis is an inflammatory process involving the cerebellum. We report the clinical, CT and MRI features of four cases and a review of the literature. Bilateral diffuse hemispheric abnormalities represent the most common imaging presentations. Our observations demonstrate the various imaging appearances of acute cerebellitis. Simultaneous involvement of both hemispheres and the vermis has not been reported previously. The development of cerebellar atrophy following an initial normal MR imaging examination is also a new finding. In atypical clinical presentation, MR imaging can lead to the diagnosis. MR imaging findings have, however, no prognostic value.

Acute Disease↗
PubMed2004

Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group.

Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy. Mutations were screened by denaturing high-pressure liquid chromatography (DHPLC) and characterised by bi-directional DNA sequencing. Activating mutations of c-KIT or PDGFRA were found in 29 (78%) and 2 (6%) GISTs, respectively. Most c-KIT mutations involved exon 11 (n=24; 83%), all but one being an in-frame deletion; no isolated point mutations were found. The other c-KIT mutations included exon 9 AY 502-503 duplication (n=4; 14%) and exon 13 Lys-->Glu(642) missense mutation (n=1; 3%). Two tumours with no detectable c-KIT mutations demonstrated PDGFRA Asp-->Glu(842) amino acid substitutions. Patients with GISTs harbouring exon 11 mutations were more likely to achieve a partial response (PR) on imatinib therapy (83%) than all of the others (23%). The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3% and 46.9%, respectively. Based on a Kaplan-Meier analysis, patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients. These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy.

Adult↗
PubMed2003

A phase II trial with rosiglitazone in liposarcoma patients.

Agents of the thiazolidinedione drug family can terminally differentiate human liposarcoma cells in vitro by activating genes responsible for lipocyte differentiation. One study has shown clinical activity of troglitazone treatment in liposarcoma patients. We sought to find further evidence for this result. In all, 12 patients with a liposarcoma received rosiglitazone 4 mg b.d. They were followed clinically and with repeated biopsies for histological and biological studies. At the molecular level the mRNA translation of three genes that are induced by this treatment (peroxisome proliferator-activated receptor gamma (PPARgamma), adipsin and fatty acid binding protein) was determined. Nine patients were eligible for evaluation. One patient had to stop treatment due to hepatotoxicity. The mean time to progression was 6 months (2 - 16 months), with one patient still on treatment. We did not see any significant change in histologic appearance of the liposarcomas by the treatment. The level of gene expression changed significantly in two patients, but this did not result in a clinical response. Based on this study, rosiglitazone is not effective as an antitumoral drug in the treatment of liposarcomas. Increased PPARgamma activity does not correlate with the clinical evolution.

Adult↗