Search PubMed⌕ Search

Biomedical subjects

D Figarella-Branger

Publications and source records attributed to D Figarella-Branger.

At least 91 records · Page 5Linked to original sources
PubMed1999

Adult onset reducing body myopathy.

We report the case of a 28 year-old woman with left scapuloperoneal syndrome since the age of 24. The course was slowly progressive and diffuse weakness was observed 4 years later. Serum creatine kinase levels were moderately elevated (x3 normal value) and EMG showed mixed neurogenic and myogenic patterns. Muscle biopsy showed type I predominance and numerous reducing bodies in muscle fibers. Reducing bodies were strongly immunoreactive with antibodies to dystrophin, alpha-sarcoglycan, vimentin and ubiquitin. Desmin immunoreactivity was increased at the periphery of some reducing bodies but alphaB crystallin, alpha actinin, titin and nebulin were negative. Western blot analysis showed an increase in dystrophin, vimentin and desmin expression. Ultrastructurally, reducing bodies were composed of tubulofilamentous material, 17 nm in diameter, and immunoreactive with anti-Dys 2 antibody. Granulofilamentous material, immunoreactive with anti-desmin antibody was observed at the periphery of some reducing bodies. This report further highlights the proteinic composition of reducing bodies and shows that late onset reducing body myopathy may occur.

Adult↗
PubMed1999

Primary meningeal fibrosarcoma: a particular neuroradiological presentation.

Primary meningeal fibrosarcoma is a rare malignant tumor of the central nervous system. About seventeen cases have been reported in the literature since 1980. We present the case of a patient whose initial neuroradiological manifestation of primary meningeal fibrosarcoma was an en plaque meningioma. Fifteen months later, he developed a dramatic clinical deterioration and coma. CT scan revealed a large frontal lesion. The mass was completely removed and histological examination was characteristic of meningeal fibrosarcoma.

Adult↗
PubMed1999

Expression of PECAM-1/CD31 isoforms in human brain gliomas.

Microvascular proliferation is a histopathological hallmark of glioblastomas and anaplastic oligodendrogliomas. Platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31) is involved in angiogenesis. PECAM-1 mediates homophilic and heterophilic interactions (with glycosaminoglycans and alphaVbeta3), but deletion of exon 14 results in a loss of heterophilic adhesion. Expression of various PECAM-1 isoforms was searched for in brain gliomas, showing microvascular proliferation (glioblastomas and anaplastic oligodendrogliomas) or not (oligodendrogliomas). In addition, expression of alphaVbeta3 in some tumors was studied by immunohistochemistry. Various tissues and the HUVEC primary cell line were used as controls. Immunohistochemistry showed that PECAM-1 was expressed by all endothelial cells in all tissues and by some tumor cells in glioblastomas and anaplastic oligodendrogliomas. Microvascular proliferation always expressed alphaVbeta3. In addition, some tumor cells in anaplastic oligodendroglioma and glioblastomas expressed it. In all samples examined, PECAM-1 exists under at least two transcriptional isoforms: the whole length molecule and an isoform made by the splicing of exon 14. Western blot analysis revealed in all cases 130 and 110 kDa bands corresponding to the mature form and its precursor respectively. These results suggest that splicing of exon 14 occurs in vivo in various normal and tumoral tissues and may modulate PECAM-1 adhesion according to the presence or not of other PECAM-1 ligands such as alphaVbeta3. Expression of PECAM-1 by tumor cells in glioblastomas and anaplastic oligodendrogliomas may favour angiogenesis by specific PECAM-1 interactions between glial and endothelial cells.

Antigens, Neoplasm↗
PubMed1999

Expression of functional growth hormone secretagogue receptors in human pituitary adenomas: polymerase chain reaction, triple in-situ hybridization and cell culture studies.

We examined the expression of functional growth hormone secretagogue receptors (GHS-R) in a series of 30 human pituitary adenomas-six secreting GH, three GH-PRL, six prolactin (PRL), five adrenocorticotrophic hormone (ACTH), one thyroid stimulating hormone (TSH), four gonadotroph and five non-secreting adenomas. By reverse transcriptase polymerase chain reaction (RT-PCR), the coexpression of the two GHS-R isoforms (Ia and Ib) was found in all the GH-, GH-PRL- and PRL-secreting adenomas, and only in two out of three corticotroph, two out of four gonadotroph and one out of five non-secreting tumours. They were absent in the TSH-secreting adenoma. The PCR products of GHS-R Ia and Ib were identical in size to those from two normal pituitaries. PCR cloning and sequencing of isoforms performed in two somatotroph adenomas revealed only two single, silent base mutations. Triple in-situ hybridization showed colocalization of GHS-R mRNA with messengers of GH and PRL, conjointly or separately, in individual cells of somatotroph, mammosomatotroph, and lactotroph adenomas. The presence of GHS-R mRNA in cells expressing PRL mRNA is emphasized. In cultured cells from six somatotroph and two mammosomatotroph adenomas, the powerful GHS MK-0677 stimulated GH release in a dose-dependent manner, with maximal effect at 6 h. Contrarily, when GHRH was applied, only three somatotrophs and two mamosomatotrophs were stimulated. In the two mammosomatotrophs, the PRL response to MK-0677 and to GHRH was similar to the GH response. An homologous desensitization of the GHS-R and the GHRH receptor was observed 24 h after a first stimulation by a single dose of the corresponding agonist. Heterologous desensitization was not observed. Interestingly, MK-0677 also stimulated, in a dose-dependent way, the hormone release of cells from all tested lactotroph and corticotroph adenomas. The existence of a functional expression of GHS-R in somatotroph, mammosomatotroph, lactotroph and corticotroph adenomas rises the question of the role played by GHS-R in pituitary adenomas, particularly those not engaged in GH secretion.

Adenoma↗
PubMed1999

p16INK4a and p19INK4d mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index.

The INK4a-ARF locus encodes two unrelated proteins that both function in tumour suppression: p16INK4a and p19INK4d. Although p19INK4d expression has not been studied in central nervous system (CNS) tumours, it has been reported that p16INK4a inactivation is involved in the growth of glioblastomas. This observation has not been reported in relation to other CNS tumours. To understand further the role of p16INK4a and p19INK4d in neuroglial tumour growth, expression of both p16INK4a and p19INK4d mRNAs was studied by reverse transcription polymerase chain reaction RT-PCR in 59 neuroglial tumours, in which Ki67 labelling indices (LI) were also determined. P16INK4a mRNA was found in all pilocytic astrocytomas (7/7), in all grade II and III astrocytomas (7/7 and 4/4, respectively), in 4/12 glioblastomas, 8/8 oligodendrogliomas, 10/11 anaplastic oligodendrogliomas, 4/7 ependymomas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p19INK4d mRNA was detected in all tumours and control tissues. p16INK4a expression was associated with a low Ki67 LI in glioblastomas but not in other tumours. P16INK4a expression was not related to anaplasia in oligodendrogliomas and ependymomas. In tumours expressing p16INK4a, in situ hybridization showed a widespread expression of p16INK4a mRNA in tumour cells and in foci of microvascular proliferation. These results strongly support the concept that p16INK4a is involved in the regulation of proliferation in glioblastomas. Other cell cycle regulators which are yet unknown may also play a role in the control of oligodendrogliomas or ependymomas outgrowth. Further studies are required to evaluate the role of p19INK4d in neuroglial tumours.

Adolescent↗
PubMed1999

Cerebellar papillary meningioma in a 3-year-old boy: the usefulness of electron microscopy for diagnosis.

We report one case of papillary meningioma located in the posterior fossa in a 3-year-old boy. Despite a gross total resection, a major recurrence occurred 6 months later that was operated on. Eight months later, another recurrence was observed with intracranial metastases and dissemination throughout the cerebrospinal fluid. The tumor had a papillary architecture more obvious in the recurrence. Areas of necrosis were numerous. Tumor cells had large clear atypical nuclei. Many mitotic figures were seen and Ki-67 labeling index was high. The tumor cells were immunoreactive for vimentin and polysialylated neural cell adhesion molecule only, ruling out a diagnosis of ependymoma or medulloblastoma. Diagnosis of meningioma was done by electron microscopy, which showed interdigitating cytoplasmic processes and cell junctions. Cytogenetic study revealed unusual karyotypic abnormalities.

Cerebellar Neoplasms↗
PubMed1999

Expression of the members of the Ptx family of transcription factors in human pituitary adenomas.

A number of putative transcription factors described in the pituitary have been implicated as key elements in the processes that direct pituitary development. Three recently described proteins, Ptx1, Ptx2, and Ptx3, define a new family of transcription factors, the Ptx subfamily, within the paired-like class of homeodomain factors. In mice, Ptx1 and Ptx2 gene expression has been detected in the area of the pituitary primordium and is maintained throughout development in Rathke pouch and adult pituitary. In the present study, the expression of the Ptx1, Ptx2, and Ptx3 genes was characterized in the normal human pituitary and in the different types of human pituitary adenomas. Although no Ptx3 gene expression could be detected in these tissues, Ptx1 presented with a quite ubiquitous pattern of distribution, being expressed at quite constant levels in normal tissues and in all 60 pituitary tumors analyzed. The pattern of expression of the Ptx2 gene among the different subsets of pituitary adenomas was even more varied. No Ptx2 expression could be detected in corticotroph tumors. In contrast, high levels of Ptx2 messenger ribonucleic acid were measured in the gonadotroph tumors, although no specific correlation to other markers of the gonadotroph lineage differentiation, such as alphaGsu, LHbeta, or FSHbeta, could be evidenced. Finally, Ptx2 was also expressed in pure lactotroph adenomas and not in somatotroph adenomas. Ptx2 is, therefore, the first paired homeodomain pituitary transcription factor differentially expressed in these two lineages, which derive from a common precursor. These results support a role for Ptx2 in the terminal differentiation of somatotroph and lactotroph cell phenotypes.

Adenoma↗
PubMed1999

[Expression of adhesion molecules in idiopathic inflammatory myopathies. Immunohistochemical study of 17 cases].

We investigated the immunohistochemical expression of endothelial cell adhesion molecules in 17 cases of idiopathic inflammatory myopathies. The present study revealed: 1) a constitutive expression of ICAM-1, ICAM-2 and PECAM-1, but not VCAM-1, LFA-3 and E-selectin, on endothelial cells in normal muscles; 2) a modification of cell adhesion molecules expression in idiopathic inflammatory myopathies with an increased expression of the expressed molecules constitutively; an expression of LFA-3 and VCAM-1 on capillary endothelial cells in polymyositis/inclusion body myositis, these molecules being only observed on endothelial cells of some arterioles in dermatomyositis; 3) an expression of all these molecules on inflammatory cells in inflammatory myopathies. In dermatomyositis, the expression of ICAM-1 and VCAM-1, predominated on mononuclear cells located near vessels. In polymyositis/inclusion body myositis, a strong expression of ICAM-1, VCAM-1 and LFA-3 was present on inflammatory cells invading non necrotic muscle fibers; 4) absence of E-selectin on endothelial and inflammatory cells in all cases.

Cell Adhesion Molecules↗
PubMed1999

[Lumbar canal stenosis caused by amyloidosis of the yellow ligament].

Symptomatic lumbar canal stenosis without bony stenosis has previously been described. We describe the pathological modifications of ligamentum flavum among such operated patients. Ten patients were prospectively included in this study. Their mean age was 74, ranges: from 52-90. Clinical manifestation was a radicular claudication (sciatic or crural). Neuroradiology confirmed in all cases the ligamentum flavum thickness as the main cause of the symptomatology. This feature was also confirmed operatively and complete resection of the ligamentum flavum was performed. Resolution of the radicular pain was obtained in all cases at last follow-up. Pathological examination of the ligamentum flavum displayed characteristic features of degenerative modifications and elastic fibers fragmentation caused by numerous amorphous deposits. The deposits were studied using red Congo staining, polarized light and immunostaining methods. Such technique showed evidence of amyloid origin of the deposits. Immunodetection was positive for the P component in the amyloid deposits and for beta-2-microglobulin in one case (chronic renal failure and hemodialysis). The deposits did not express antitransthyretin antibodies. In parallel, control ligamentum flavum were obtained from 10 operated patients affected by bony lumbar stenosis. Moderate degenerative features were observed but small amounts of amyloid deposits were found in only 3 of those cases, without thickening of the ligamentous structure. This study correlates the presence of thickened ligamentum flavum caused by amyloid deposition, with symptomatic non-osseous lumbar canal stenosis. Association with degenerative modifications of the spine in the studied cases is suggestive of a microtraumatic origin.

Aged↗
PubMed1998

Macrophagic myofasciitis: an emerging entity. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l'Association Française contre les Myopathies (AFM).

BACKGROUND: An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases. METHODS: We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar. FINDINGS: Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two. INTERPRETATION: A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.

Adult↗
PubMed1998

Local expression of cytokines in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are regarded as autoimmune diseases. They are characterized by chronic lymphocytic and macrophagic infiltration in muscle tissue. Of particular importance in understanding the immune response to IIM is the specific pattern of locally produced cytokines. Frozen muscle tissues from IIM (5 DM, 3 PM, and 1 IBM) were used to investigate the cytokine responses. The RT-PCR technique was instrumental to determine the pattern of expression of pro-inflammatory (IL-1 beta, IL-6, TNF-alpha), Th1 (IFN-gamma IL-2), and Th2 (IL-4) cytokines. Immunohistochemistry was also used to localize morphologically IFN-gamma and IL-4. Our results show that pro-inflammatory cytokines and Th1 cytokines are mainly expressed in IIM. The accumulation of mononuclear inflammatory cells and the inflammatory syndrome in IIM are probably related in part to the production of pro-inflammatory cytokines. Moreover, the pattern of local cytokine expression is consistent with a Th1 immune response related to autoimmune diseases.

Cytokines↗
PubMed1998

Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas.

Since glioblastomas in adults are uniformly fatal, evaluation of easily reproducible prognostic criteria which would attempt to define groups of patients is required. However, there is lack of a clear consensus regarding the expression of some markers in the literature. Therefore, an immunohistochemical study was performed to determine the prognostic significance of Ki67, p53, and epidermal growth factor receptor (EGFR) in a retrospective series of 63 glioblastomas. Image analysis was carried out in positive specimens to quantify the immunoprecipitates. p53 and EGFR expression were specifically addressed in the 36 primary glioblastomas reported in this series. In all cases, clinical data (age, Karnofsky performance scale index [KPS] before surgery, extent of surgery) and immunohistochemical features were analysed using univariate and multivariate analysis to ascertain whether any significant correlation exists between [1] EGFR expression [2], p53 accumulation [3], Ki67 labelling index and prognosis (survival time and disease-free survival time, DFST). The results showed that in this series of glioblastomas, none of these markers had any prognostic value. Among the clinical parameters, a high KPS before surgery was found to be indicative of a shorter DFST and survival time (P < 0.05), whereas a younger age at onset and total or subtotal surgical excision were associated with a longer survival (P < 0.001 and 0.05, respectively). EGFR protein accumulation was inversely correlated with p53 accumulation (P = 0.01). The percentage of the primary glioblastomas expressing EGFR was much lower in our study (33%) than in the literature suggesting that the molecular distinction between primary and secondary glioblastomas is not so clear-cut.

Aged↗
PubMed1998

Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice.

Charcot-Marie-Tooth disease type 1A is most commonly caused by a duplication of a 1.5 Mb region of chromosome 17 which includes the peripheral myelin protein 22 gene (PMP22). Over-expression of this gene leads to a hypomyelinating/demyelinating neuropathy and to severely reduced nerve conduction velocity. Previous mouse and rat models have had relatively high levels of expression of the mouse or human PMP22 gene leading to severe demyelination. Here we describe five lines of transgenic mice carrying increasing copies of the human PMP22 gene (one to seven) and expressing increasing levels of the transgene. From histological and electrophysiological observations there appears to be a threshold below which expression of PMP22 has virtually no effect; below a ratio of human/mouse mRNA expression of approximately 0.8, little effect is observed. Between a ratio of 0.8 and 1.5, histological and nerve conduction velocity abnormalities are observed, but there are no behavioural signs of neuropathy. An expression ratio >1.5 leads to a severe neuropathy. A second observation concerns the histology of the different lines; the level of expression does not affect the type of demyelination, but influences the severity of involvement.

Animals↗
PubMed1998

Endolymphatic sac tumors: report of three cases.

OBJECTIVE AND IMPORTANCE: We present three cases of endolymphatic sac tumors and review the previously published cases. Despite frequent extension to the cerebellopontine angle, these rare tumors have only recently been recognized by neurosurgeons. CLINICAL PRESENTATION: A 26-year-old man developed a progressive hearing loss, revealing an intrapetrous retrolabyrinthine tumor on the right side. A 28-year-old woman experienced a left cerebellopontine angle syndrome, with a lytic intrapetrous mass extending into the cerebellopontine angle. A 38-year-old woman presented with an intracranial hypertension syndrome caused by a tumor of the jugular foramen. INTERVENTION: For the first and second patients, the tumors originated from the operculum of the endolymphatic sac. Total removal was achieved, via a transpetrosal approach, in these two cases. No recurrence was detected after a 20-month follow-up period. For the third patient, the tumor originated from the distal part of the sac. Recurrence was observed 8 years after subtotal removal via a retrosigmoid route. Histological analysis revealed a papillary-cystic adenocarcinomatous pattern in all cases, without features of aggressiveness. CONCLUSION: Endolymphatic sac tumors are locally invasive neoplasms characterized by bipolar intrapetrous and posterior fossa involvement. The anatomic complexity of the endolymphatic sac may explain the distinct patterns of extension of these tumors. Early radical surgery is related to good outcomes.

Adenocarcinoma, Papillary↗
PubMed1998

Expression of peptide-23/pancreatitis-associated protein and Reg genes in human pituitary and adenomas: comparison with other fetal and adult human tissues.

Peptide 23, the rat homolog of the human pancreatitis-associated protein (PAP)/hepatocarcinoma-intestine-pancreas (HIP) protein, has been identified in primary culture of rat pituitary cells. Its secretion was shown to be stimulated by GH-releasing factor and inhibited by somatostatin in a similar fashion to GH. This observation led the researchers to speculate that peptide 23 does have a physiological hormonal role. We tested this hypothesis by screening by RT-PCR reactions the expression of the PAP/HIP gene in several human pituitary adenomas, especially GH-producing adenomas. Our results show a weak expression of the PAP/HIP gene in the pituitary gland and in most of the tumors, but independent of their origin. The significant homology of the PAP/HIP gene to the Reg gene family prompted us to study in the same pituitary adenomas the presence of the related Reg genes. Reg expression was never observed in the adenomas tested or in the pituitary gland. In contrast, the RegL transcript was observed in pituitary gland and in some subtypes of adenomas. We then extended our work to normal adults and developing human tissues to compare the expression patterns of the PAP/Reg gene family. We observed the presence of the PAP/HIP transcript in each tissue tested. In contrast, the Reg gene was expressed only in fetal pancreas and in some adult tissues, whereas the RegL gene was expressed not only in fetal pancreas but also in fetal colon and brain as well as some adult tissues. In conclusion, our results show that all of the human fetal and adult tissues examined express at least one of the different transcripts of the PAP/Reg family, suggesting that the regulation of these homologous genes is coordinately controlled.

Acute-Phase Proteins↗
PubMed1998

Pronostic and therapeutic consequences of Gs alpha mutations in somatotroph adenomas.

Human pituitary somatotroph adenomas can be associated with mutations of the s alpha-subunit of G proteins. However, the impact of the gsp mutations on the tumoral phenotype is not well understood at present. This study aims to determine whether the detection of this mutation could impact on the management of acromegalic patients. We examined 30 acromegalic patients; 8 were gsp positive, and 22 were gsp negative. The gsp-positive adenomas appeared to secrete significantly more when the ratio of basal GH level/tumor size was considered. A better octreotide sensitivity of mutated adenomas was clearly shown under in vivo (short and long term) and in vitro conditions. During the acute octreotide test, the GH nadir was significantly lower in the gsp-positive adenomas (85% of maximal inhibition vs. 52%). Eighteen patients were treated with octreotide (300 micrograms/day) for at least 3 months before surgery: the percent inhibition of GH hypersecretion was higher in gsp-positive adenomas (76% vs. 47%). In cell culture, the octreotide-induced inhibition of GH release was significantly higher in gsp-positive adenomas (71% vs. 30%). Finally, during 2 yr of postoperative follow-up, GH hypersecretion was controlled in all patients with gsp mutation even in those in whom tumoral tissue remained after surgery. On the contrary, in the gsp-negative group, octreotide treatment was unable to control hypersecretion in 4 patients bearing tumoral remnants. The Gs alpha mutation could, therefore, be a new marker to foresee the susceptibility of the tumor to be controlled by somatostatin analogs, which improves prognosis.

Acromegaly↗
PubMed1998

[Neuromuscular diseases with eosinophilia].

Neuromuscular diseases with eosinophilia include a number of disorders associated with variable degrees of muscle, peripheral nerve, and connective tissue involvement. Eosinophilic infiltration in blood and/or tissue is a consistent finding. In addition to the neurologic manifestations of systemic vascularitis, in particular Churg and Strauss syndrome, there are three main forms of neuromuscular disease. Diffuse fasciitis or Shulman syndrome which can be limited to the fascia or associated with perimyositis is sensitive to corticosteroids. Eosinophilic myositis corresponds to focal muscle involvement and is also sensitive to corticosteroids. Eosinophilic polymyositis is a manifestation of essential hypereosinophilic syndrome and is life-threatening. Eosinophilia-myalgia syndrome and toxic oil syndrome are separate entities that occur in outbreaks and involve poisoning by ingestion of L-tryptophan and adulterated oil containing aniline respectively. The key to diagnosis of these neuromuscular diseases is muscle biopsy to detect the presence of polynuclear eosinophils.

Anti-Inflammatory Agents↗