Biomedical subjects

R Sciot

Publications and source records attributed to R Sciot.

At least 73 records · Page 4Linked to original sources

PubMed2000

Recurrent chromosome aberrations in fibrous dysplasia of the bone: a report of the CHAMP study group. CHromosomes And MorPhology.

The nosologic status of fibrous dysplasia (FD), a well-known and relatively common bone lesion, is controversial. Information collected by the CHromosomes And MorPhology (CHAMP) study group on published and unpublished cases of fibrous dysplasia shows the presence of clonal chromosome changes in at least a proportion of these lesions. The chromosome aberrations found in FD lesions have been quite variable and have included both structural and numerical changes. Two of the three cases investigated at the study group had trisomy 2 as the sole acquired anomaly. Combined with previously published data, +2 and rearrangements involving chromosome band 12p13 have each been detected in 3 of 8 cases with abnormal karyotype of 11 in which chromosomal analysis has been performed, suggesting that FD is a neoplastic lesion rather than a "dysplastic" process, as has been generally believed and as implied by its very name.

Adolescent↗

PubMed2000

Toxicological investigations of the effects carboxymethylcellulose on ciliary beat frequency of human nasal epithelial cells in primary suspension culture and in vivo on rabbit nasal mucosa.

The objective of this study was to investigate the safety of a mucoadhesive carboxymethylcellulose (CMC) formulation for intranasal administration of apomorphine. The effect of different concentrations of CMC on ciliary beat frequency (CBF) was studied using a human nasal epithelial suspension cell culture system. The CBF was determined by computerized microscope photometry. The in vivo rabbit nasal mucosal tolerance of the mucoadhesive polymer was investigated using light microscopy. Twice daily, six rabbits received CMC powder in one nostril and CMC/apomorphine powder in the alternate nostril for 4 weeks. Two control rabbits received air puffs in one nostril and nothing in the alternate nostril. The rabbits were subsequently sacrificed and the stained nasal sections examined microscopically. CMC showed both concentration- and time-dependent inhibitory effects on the CBF. Only mild-to-moderate cilio-inhibition was recorded with the different concentrations of the polymer. CMC (both with and without apomorphine) caused mild-to-moderate inflammation after 4 weeks. Necrosis, squamous metaplasia or ciliary degeneration was not observed. Based on: (1) the mild-to-moderate cilio-inhibition induced by different concentrations of CMC; and (2) the mild-to-moderate nasal mucosal inflammation caused by CMC with and without apomorphine, we conclude that this polymer can be considered as a safe carrier for short-term intranasal administration. However, further investigations are required for its use in the treatment of chronic diseases such as with apomorphine in Parkinson's disease.

Animals↗

PubMed2000

PLAG1 fusion oncogenes in lipoblastoma.

Lipoblastomas are pediatric neoplasms resulting from transformation of adipocytes. These benign tumors are typically composed of adipose cells in different stages of maturation within a variably myxoid matrix, and they contain clonal rearrangements of chromosome band 8q12. Because lipoblastomas resemble embryonic adipose tissue, characterization of their transforming mechanisms might reveal biological pathways in physiological adipogenesis. Herein, we demonstrate that lipoblastoma chromosome 8q12 rearrangements bring about promoter-swapping events in the PLAG1 oncqgene. We show that the hyaluronic acid synthase 2 (HAS2) or collagen 1 alpha 2 (COL1A2) gene promoter regions are fused to the entire PLAG1 coding sequence in each of four lipoblastomas. PLAG1 is a developmentally regulated zinc finger gene whose tumorigenic function has been shown previously only in epithelial salivary gland cells. Our findings reveal that PLAG1 activation, presumably resulting from transcriptional up-regulation, is a central oncogenic event in lipoblastoma.

Adipose Tissue↗

PubMed2000

Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group.

Leiomyosarcomas (LMS) of soft tissues frequently show complex karyotypic changes, and no specific aberration has been identified. The aim of this study was to search for recurrent chromosome aberrations in soft tissue LMSs and to correlate these, if present, with morphological and clinical parameters. From a series of soft tissue sarcomas thoroughly reexamined cytogenetically and histopathologically, 45 LMSs were retrieved; 35 were classified microscopically as spindle cell, 3 as epithelioid, and 7 as pleomorphic. Clonal chromosome changes were present in 14, 3, and 3 cases, respectively. This series was combined with 11 previously published, karyotypically abnormal pleomorphic LMSs for cytogenetic-clinico-histopathological correlations. The breakpoints were widely scattered, with no predilection of any of the recurrent breakpoints and losses to any of the morphologic subtypes. Combining numerical and unbalanced structural changes, the most frequently lost segments were 3p21-p23 (11 cases), 8p21-pter, 13q12-q13, 13q32-qter (10 cases each), 1q42-qter, 2p15-pter, 18p11 (9 cases each), 1p36, 11q23-qter (8 cases each), and 10q23-qter (7 cases). The most frequent gain was 1q12-q31 (6 cases). There was a greater frequency of losses in 1p and 8p and a lower frequency of losses in 10q and 13q in tumors that had metastasized than in localized tumors. We conclude that LMSs with clonal abnormalities display highly complex karyotypic changes and extensive heterogeneity. No significant correlation exists between these changes and age and sex of the patients, or with depth of tumor, topography, microscopic subtype, or tumor grade. Losses in 1p36 and 8p21-pter may be associated with increased risk of metastases. Comparison of our findings in soft tissue LMS with those previously reported in LMS in other locations suggest that the karyotypic profile is more dependent on site of origin than on microscopic features.

Adult↗

PubMed2000

Cytogenetic characterization of peripheral nerve sheath tumours: a report of the CHAMP study group.

The findings of characteristic, sometimes pathognomonic, chromosome aberrations in several types of soft tissue tumours have not only added to our understanding of the mechanisms behind the genesis of these tumours, but have also revealed the importance of cytogenetic analysis as a diagnostic tool. For many soft tissue tumours, including peripheral nerve sheath tumours, the number of analysed cases is, however, still very low, precluding evaluations of the clinical or biological significance of different chromosomal patterns. As part of an ongoing project aiming at identifying clinical-histopathological-cytogenetic correlations among soft tissue tumours, a series of 46 benign, the vast majority of which were located in the extremities, and 20 malignant peripheral nerve sheath tumours (BPNSTs and MPNSTs, respectively) that had been successfully analysed by chromosome banding techniques were evaluated with regard to clinical, morphological, and cytogenetic features. Clonal chromosome aberrations were found in 20 BPNSTs, with abnormal karyotypes being significantly more frequent among Schwannomas than among neurofibromas. Recurrent aberrations, all of which were confined to the Schwannoma subtypes, included loss of 22q material, loss of a sex chromosome, and trisomy 7. The results show that the cytogenetic features of Schwannomas are not dependent on the site of origin. The MPNSTs, all of which had clonal chromosome aberrations, displayed complex karyotypes with numerous structural and numerical changes, except in two cases showing +7 and -22, respectively, as the sole changes. None of the recurrent imbalances was restricted to either NF1-associated or sporadic MPNST, nor was any of the imbalances significantly associated with clinical outcome. The presence of a triploid or tetraploid clone was, however, associated with grade 3 tumours and a poor prognosis. The cytogenetic findings in peripheral nerve sheath tumours show that the karyotype is a good discriminator between BPNSTs and MPNSTs, and that the pattern of aberrations among the latter may add prognostic information.

Adolescent↗

PubMed2000

Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours.

Atypical lipomatous tumours (ALTs) represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic differentiation. Most ALTs are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes derived from the chromosomal region 12q13-15. The 12q13-15 chromosome region contains several genes which may play an important role in human tumorigenesis. A series of ALTs was analysed by investigating the MDM2, CDK4, and HMGI-C genes and their proteins. The study was extended to a series of ordinary lipomas, to determine whether the immunohistochemical investigation of these gene products might play any diagnostic role. Cytogenetic analysis revealed the presence of various cytogenetic aberrations involving the 12q13-15 region in 11/18 (61%) lipomas and of ring chromosomes in all ALTs. Overexpression of mdm2 protein was observed in 6/12 (50%) atypical lipomatous tumours. All lipomas were mdm2-negative. cdk4 overexpression was present in 100% of ALTs. Weak cdk4 immunopositivity was detected in 2/18 (11%) ordinary lipomas in a minority of cells. HMGI-C immunopositivity was observed in 10/12 (83%) ALTs. Positive immunoreactivity was also observed in 8/18 (44%) lipomas. Southern blot analysis revealed amplification of the CDK4 and MDM2 genes in 3/5 ALTs analysed. HMGI-C was amplified in 3/5 cases and was deleted in one case. Mutation analysis of the CDK4 gene did not demonstrate any mutation. These data support the hypothesis that ordinary lipomas may form a molecular genetic and morphological continuum with ALT. At one end of the spectrum are lipomas characterized by 12q13-15 rearrangements and HMGI-C activation and at the other end are ALTs with ring chromosomes, 12q13-15 amplification with overrepresentation of the HMGI-C, CDK4 or MDM2 genes, and aberrant cdk4, mdm2, and HMGI-C protein expression. These findings not only provide insights into the molecular pathogenesis of lipomatous tumours, but also indicate that the immunohistochemical analysis of mdm2 and cdk4 may help to increase diagnostic accuracy.

Adult↗

PubMed2000

Myofibroblastoma of the breast: genetic link with spindle cell lipoma.

Mammary myofibroblastoma is a rare tumour, mainly occurring in male patients. This paper describes two cases of mammary myofibroblastoma, with typical histological features, including the presence of fat cells and mast cells. Immunohistochemically, the spindle cells stained positively for desmin and CD34. Cytogenetically, both tumours showed partial monosomy 13q and in case 1, there was, in addition, partial monosomy 16q. Rearrangements affecting 13q and 16q occur typically in spindle cell lipomas. In addition to histological similarities, the hitherto unreported chromosomal changes in mammary myofibroblastoma, which are similar to the chromosomal aberrations in spindle cell lipoma, strongly suggest a link between these two tumours and are not in favour of myofibroblastoma being a primary solitary fibrous tumour of the breast.

Aged↗

PubMed2000

Retrospective study of Creutzfeldt-Jakob disease in Belgium: neuropathological findings.

Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that affects about 1 in 10(6) inhabitants in most countries. Recently, a new variant of CJD has been linked to the epidemic of bovine spongiform encephalopathy. Therefore, vigilance concerning the disease's incidence has been increased. We conducted a comprehensive, nation-wide and retrospective study. In 79 Belgian autopsies, we found the characteristic triad of spongiosis, neuronal loss and reactive gliosis. The occipital cortex was most affected, while the cerebellum was mostly spared. Immunohistochemistry was performed using hydrated autoclave pretreatment and several monoclonal antibodies directed against the prion protein. We identified prion-immunoreactive patterns and locations reflecting the important heterogeneity, independently of the antibody that was used. Granular prion immunoreactivity was observed in astrocytes. We studied the regional intensity of the prion immunostaining and determined that the frontal cortex with 95% positive immunoreactivity was best suited for a biopsy. We studied the disease duration in sporadic CJD patients who showed neuropathological lesions of other neurodegenerative disorders (such as Alzheimer's disease). The study shapes the framework in which a prospective neuropathological registry will be able to function.

Amyloid beta-Peptides↗

PubMed2000

Familial Creutzfeldt-Jakob disease in a patient carrying both a presenilin 1 missense substitution and a prion protein gene insertion.

We describe a patient who was clinically diagnosed with familial early-onset Alzheimer disease (AD) carrying both the E318G substitution in presenilin 1 (PSEN1) and an insertion of 7 octapeptide coding repeats in the prion protein gene (PRNP). Neuropathological examination revealed elongated cerebellar prion protein deposits in the absence of AD pathology. Further analysis of other family members showed that the Creutzfeldt-Jakob disease phenotype in this family was caused solely by the PRNP insertion. This observation is consistent with our previous finding that PSEN1 E318G is not causally related to AD.

Adult↗

PubMed2000

Multifocal epithelioid angiosarcoma of the small intestine.

A 67-year-old man presented with weight loss, intermittent severe abdominal pain and melaena. Initial radiology (including abdominal ultrasonography), gastroscopy and colonoscopy did not demonstrate any lesions that could explain the complaints. Three weeks later, upper gastrointestinal and small-bowel barium studies revealed two areas in the small intestine with an abnormal mucosal pattern. Explorative laparotomy revealed three tumoral lesions. Three partial enterectomies were performed. Gross examination showed centrally depressed dark reddish tumoral lesions extending from the mucosa throughout the full thickness of the bowel wall (diameter varying between 1.6 cm and 2.2 cm). The tumours, composed of large, plump, polygonal cells showing little architectural differentiation, were mainly situated in submucosa and muscularis propria. The growth pattern appeared rather solid. The epithelioid cells showed pronounced nuclear pleomorphism and atypia with central large nucleoli. There were several small blood vessels with occasional anaplastic endothelial cells. Immunohistochemical staining demonstrated an intense expression of CD 31, CD 34, factor VIII related antigen and keratin. This supported the diagnosis of an epithelioid angiosarcoma. The patient died 3 months after diagnosis. Tumours of the small intestine are very rare, and angiosarcomas of the small intestine are even more rare. Epithelioid variants have only been described in two patients and only one of these had a multifocal presentation. The prognosis is very poor. Because of the epithelioid growth pattern and the cytokeratin expression, these tumours may erroneously be diagnosed as a carcinoma.

Abdominal Pain↗

PubMed2000

Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the london mutant of human APP in neurons.

Deposition of amyloid beta-peptide (Abeta) in cerebral vessel walls (cerebral amyloid angiopathy, CAA) is very frequent in Alzheimer's disease and occurs also as a sporadic disorder. Here, we describe significant CAA in addition to amyloid plaques, in aging APP/Ld transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP) exclusively in neurons. The number of amyloid-bearing vessels increased with age, from approximately 10 to >50 per coronal brain section in APP/Ld transgenic mice, aged 13 to 24 months. Vascular amyloid was preferentially deposited in arterioles and ranged from small focal to large circumferential depositions. Ultrastructural analysis allowed us to identify specific features contributing to weakening of the vessel wall and aneurysm formation, ie, disruption of the external elastic lamina, thinning of the internal elastic lamina, interruption of the smooth muscle layer, and loss of smooth muscle cells. Biochemically, the much lower Abeta42:Abeta40 ratio evident in vascular relative to plaque amyloid, demonstrated that in blood vessel walls Abeta40 was the more abundant amyloid peptide. The exclusive neuronal origin of transgenic APP, the high levels of Abeta in cerebrospinal fluid compared to plasma, and the specific neuroanatomical localization of vascular amyloid strongly suggest specific drainage pathways, rather than local production or blood uptake of Abeta as the primary mechanism underlying CAA. The demonstration in APP/Ld mice of rare vascular amyloid deposits that immunostained only for Abeta42, suggests that, similar to senile plaque formation, Abeta42 may be the first amyloid to be deposited in the vessel walls and that it entraps the more soluble Abeta40. Its ability to diffuse for larger distances along perivascular drainage pathways would also explain the abundance of Abeta40 in vascular amyloid. Consistent with this hypothesis, incorporation of mutant presenilin-1 in APP/Ld mice, which resulted in selectively higher levels of Abeta42, caused an increase in CAA and senile plaques. This mouse model will be useful in further elucidating the pathogenesis of CAA and Alzheimer's disease, and will allow testing of diagnostic and therapeutic strategies.

Aging↗

PubMed2000

Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord.

The epsilon 4 allele of the human apolipoprotein E gene (ApoE4) constitutes an important genetic risk factor for Alzheimer's disease. Recent experimental evidence suggests that human ApoE is expressed in neurons, in addition to being synthesized in glial cells. Moreover, brain regions in which neurons express ApoE seem to be most vulnerable to neurofibrillary pathology. The hypothesis that the expression pattern of human ApoE might be important for the pathogenesis of Alzheimer's disease was tested by generating transgenic mice that express human ApoE4 in neurons or in astrocytes of the central nervous system. Transgenic mice expressing human ApoE4 in neurons developed axonal degeneration and gliosis in brain and in spinal cord, resulting in reduced sensorimotor capacities. In these mice, axonal dilatations with accumulation of synaptophysin, neurofilaments, mitochondria, and vesicles were documented, suggesting impairment of axonal transport. In contrast, transgenic mice expressing human ApoE4 in astrocytes remained normal throughout life. These results suggest that expression of human ApoE in neurons of the central nervous system could contribute to impaired axonal transport and axonal degeneration. The possible contribution of hyperphosphorylation of protein Tau to the resulting phenotype is discussed.

Animals↗

PubMed2000

Common chromosome aberrations in the proximal type of epithelioid sarcoma.

A new case of the proximal type of epithelioid sarcoma with a complex karyotype 70-98 <4N>,XX,-X,-X,+5,i(5)(q10),+7,del(7)(q31),i(8)(q10)x3 approximately 4,del(12)(p13),der(18)ins(18:?) (q11;?)del(18)(p11). ish der(18)ins(18;X)del(18)(p11)(wcp18+,wcpX+),+20,+20,dmin [cp9] is described. Both, dual-color FISH using probes specific for OATLI1/OATL2 genes and RT-PCR analysis excluded the presence of t(X;18), typical for synovial sarcoma. Our case together with the previously published ones suggest that the presence of i(8)(q10), losses of 12p and 18p together with the gain of chromosome 20 may represent a common cytogenetic aberrations in the proximal type of epithelioid sarcoma.

Adolescent↗

PubMed2000

Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa.

OBJECTIVE: The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. MATERIALS AND METHODS: The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). RESULTS: Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. CONCLUSIONS: Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.

Acrylates↗

PubMed2000

Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology.

Whether fibromatoses are neoplastic or reactive lesions has long been controversial and the relationship, if any, between the superficial and deep forms (desmoid tumors) are poorly understood. Clinical, pathologic, and cytogenetic data of 78 cases of fibromatosis were analyzed and correlated with each other. The results demonstrate that clonal chromosome aberrations are a common feature of this entity, being present in 46% of desmoid tumors, although less frequent in the superficial types (10%). In the deep-seated extra-abdominal fibromatoses, trisomies 8 and 20 and loss of 5q material were the only recurrent features. No correlation between +8 and local recurrence was found. Our findings provide additional evidence for the neoplastic nature of fibromatoses.

Adult↗

PubMed2000

Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.

Adolescent↗

PubMed2000

Malignant angiomyolipoma of the liver: a hitherto unreported variant.

AIMS: After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML. METHODS AND RESULTS: A 70-year-old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC-3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal-like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB-45, NKIC-3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease. CONCLUSIONS: This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.

Actins↗

PubMed2000

Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP study group.

AIMS: Cutaneous benign fibrohistiocytic tumours are among the most common soft tissue lesions. Their biological nature, in particular whether they are neoplastic or reactive, has long been disputed. Some morphological subtypes can be confused with sarcoma. Since available karyotypic data in these lesions are scarce, this study was undertaken to determine whether their cytogenetic analysis might demonstrate clonality and might help in differential diagnosis. METHODS AND RESULTS: Thirteen karyotyped benign cutaneous fibrous histiocytomas (BFH) were morphologically reassessed and classified as ordinary BFH (eight cases), cellular BFH (four cases), and one ankle-type lesion. Five cases (38%) showed clonal cytogenetic changes, although the aberrations varied and did not correlate with histological subtypes. Karyotypic aberrations were more common in cellular BFH (3/4) than in the ordinary BFH (2/8). CONCLUSIONS: The demonstration of clonal chromosome abnormalities, in at least some cases, supports the neoplastic nature of cutaneous BFH. The karyotypic changes identified are different from those in dermatofibrosarcoma, with which cellular BFH is often confused histologically.

Adolescent↗