Biomedical subjects

C A Maurage

Publications and source records attributed to C A Maurage.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Choroidal heat shock overexpression in transpupillary thermotherapy: preliminary results].

PURPOSE: To assess retinochoroidal overexpression of heat shock proteins (HSP-70) induced by a transpupillary laser irradiation below the photocoagulation threshold. METHODS: Four pigmented rabbits were anesthetized and TTT was performed on the right eye using a 810nm diode laser (Iridis, Quantel-Medical, France) adapted on slit lamp (spot size: 1.3 mm, duration: 60 seconds; power 92-150 mW). Series of laser impacts were aimed at the posterior pole of the retina. Left eyes were used as control. Twenty-four hours after laser irradiation, a histological study was done on chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect HSP-70 immunoreactivity (mouse IgGl, SPA-810, Stress Gen, Canada), followed by a biotinylated goat antimouse antibody (Dako, Denmark), revealed by the avidin-biotin complex (Vectastain kit, Vector, USA) and the AEC chromogen. Retinal structures were further identified by HES coloration. RESULTS: The photocoagulation threshold was obtained for laser power at 150 mW. Under this threshold, HSP-70 immunostaining was the strongest for power 127 mW with a staining of some choroidal cells, including capillary endothelial cells. No HSP-70 immunoreactivity was observed on the retina. For the laser power 107 mW, HSP-70 reactivity was observed only in occasional choroidal cells. For the laser power 92 mW, as for nonirradiated eyes, no HSP-70 immunoreactivity was detected. CONCLUSIONS: Transpupillary 810 nm laser irradiation under the photocoagulation threshold induces choroidal HSP overexpression. This study concludes that choroidal HSP overexpression can be induced during TTT.

Animals↗

PubMed2000

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy.

BACKGROUND: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. OBJECTIVE: To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. METHODS: In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. RESULTS: Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. CONCLUSIONS: Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Acidosis, Lactic↗

PubMed2000

Skin biopsy value and leukoaraiosis.

In the field of leukoaraiosis, the identification of CADASIL and its link to Notch 3 mutation has shed light on the pathogenesis of white matter (WM) abnormalities related to small-vessel disease. Since 1993, its systemic vascular involvement allows skin biopsy diagnosis and research on tissues before postmortem examination. We received 160 skin biopsies from patients presenting subcortical dementia, recurrent strokes, behavioral disturbances or migraines, and suspected CADASIL. Almost all the patients lacked the well-known vascular risk factors. The ultrastructural study was systematically carried out looking at the vessel walls and the other components found in skin. In a third, we found endothelial changes, destruction of vascular smooth muscle cells (VSMCs), and characteristic granular osmiophilic material (GOM). In these cases, the genetic analysis confirmed the Notch 3 mutation. Curiously, the skin biopsies from the other two thirds presented marked alterations within the vessel walls. Such changes included destruction of VSMCs, lack of GOM, and replacement of these cells by an extracellular matrix. Frequently, we noticed endothelial pathological changes as well as other tissue impairments. By now, we are able to describe eight different groups of lesions according to either the prevalence of a lesion or the association of different lesions. The skin biopsy ultrastructural study seems to be highly informative given that we can observe vessel lesions and association of impairments in various tissues that might, in part, explain the brain vessel involvement and then the leukoaraiosis and probably some clinical symptoms. Moreover, these vessel lesions often belonged to young people (30-50 years old), and many of them seemed to run in families. These new data associated with early onset of clinical symptoms and leukoaraiosis would be extremely valuable in clarifying the wide field of leucoencephalopathy and might provide genetic research with new issues.

Adult↗

PubMed2000

Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions.

An 18 year old girl presented with acute visual loss. T2 weighted brain MRI showed areas of hyperintensities in the thalamic nuclei, internal capsule, lentiform nuclei, the subarachnoidal spaces, and a retrobulbar infiltration. Analysis of CSF showed numerous foamy histiocytes without malignant cells, raised protein, and depressed glucose concentration. Biopsy of the right thalamus demonstrated aggregates of histiocytes with immunohistological and ultrastructural characteristics of non-Langerhans cell histiocytosis. The patient improved with chemotherapy and corticosteroids. After 3 months of treatment, CSF analysis showed no more histiocytes. Cytological examination of CSF can be helpful for the management of patients with extensive histiocytic infiltration.

Adolescent↗

PubMed2000

Cyclin-dependent kinase inhibitory protein expression in human choroidal melanoma tumors.

PURPOSE: Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CKIs) have been shown to play a critical role in the regulation of cell cycle progression. Alteration of CKI levels and/or functions could be implicated in cell transformation. The three CKIs-p16, p21, and p27-were investigated in human uveal melanoma tumors, and an attempt was made to correlate their levels with clinicopathologic parameters, as well as to p53 and Ki-67 (Mib-1) protein levels. METHODS: Immunochemistry was performed on 32 formalin-fixed, paraffin-embedded specimens of malignant choroidal melanoma. Immunoblot was performed to confirm the immunochemistry study. Prognostic histologic markers such as cell typing, pigmentation, larger tumor dimension, mitotic figures, nucleolar size, scleral invasion, and optic nerve head invasion were reported. RESULTS: Nuclear positivity for p16 was observed in 11 tumors (34%) without any association with clinicopathologic parameters. Tumor cells positive for p21 were detected in 12 choroidal melanomas (37%). Unexpectedly, a positive relationship was seen between p21 and scleral invasion (P: = 0.008). Nuclear positivity for p27 was observed in nine tumors (28%). An inverse correlation was observed between the number of mitotic figures and p27 immunoreactivity (P: = 0.03), as well as between Mib-1 positivity and p27 expression (P: = 0.02). Western blot assays of tumor extracts confirmed overexpression of p21 and p27. CONCLUSIONS: The results suggest that p21 and p27 may be involved in tumorigenesis in choroidal melanoma.

Adult↗

PubMed1999

Chester-Erdheim disease: a neoplastic disorder.

Chester-Erdheim disease is a rare non-langerhans cell histiocytosis characterized by a xanthomatous infiltration of foamy macrophages. The cause and pathogenesis remain unclear. The aim of the present study was to determine whether Chester-Erdheim disease is a polyclonal reactive disease or a clonal neoplastic disorder. The clonal status of samples obtained from five patients with Chester-Erdheim disease was studied. DNA was extracted from fixed and paraffin-embedded sections after microdissection and clonal status was studied using the Xchromosome inactivation pattern of the human androgen receptor gene (HUMARA assay). One patient was homozygous for the HUMARA gene and noninformative. Three other cases were monoclonal. One was polyclonal, and this case showed a dense reactive infiltrate in association with spumous macrophages. This study suggests strongly that Chester-Erdheim disease is a monoclonal lesion consistent with neoplastic disorder. Thus, Chester-Erdheim disease may be considered as the "macrophage" counterpart of Langerhan's cell histiocytosis in the histiocytosis spectrum. Further studies are needed to establish the origin of this clonal proliferation.

Adult↗

PubMed1999

Morphological changes induced by extensive endobronchial electrocautery.

Due to recent improvements of safety conditions for therapeutic devices, electrocautery is being considered with renewed interest in the field of therapeutic bronchoscopy. The efficiency of this technique for destructing intraluminal tumours is well documented and makes it an attractive alternative to Yttrium aluminium garnet (YAG) laser photo-coagulation. Little is known, however, about the morphologic changes induced by electrocautery within the bronchial wall structures. This information is, however, important since electrocautery has been proposed as an alternative to other techniques to treat superficial tumours of the bronchial wall. Soft coagulation, with autostop, using two different power setting (40 and 120 W), produced by a new generation of high frequency voltage regulated generators was applied circumferentially to the trachea or left main bronchus, in a series of 52 piglets. Early (48 h) and late effects (6 weeks) were assessed through gross examination (bronchoscopy and autopsy) and light microscopy. Early effects of electrocautery included coagulation necrosis of the mucosa only and intense acute inflammation extending deep into the bronchial structure. The inflammatory phase progressively resolved while extensive transmural fibrosis and deterioration of the cartilage plates developed. The nature and extent of these lesions did not depend upon the energy delivered (40 W versus 120 W). Retractile scar formation and loss of cartilaginous support then produced iatrogenic secondary stenoses. These results do not question the use of electrocautery to palliate endoluminal tumours but should make operators careful when treating extensive infiltration of the bronchial wall.

Animals↗

PubMed1999

X-linked immunodeficiency affects the outcome of Schistosoma mansoni infection in the murine model.

The incidence of the X-linked immunodeficiency (Xid) on the outcome of Schistosoma mansoni infection has been evaluated through a comparative analysis of parasitological and immune parameters in two different mouse strains: control BALB/c and BALB. Xid mice which carry the Xid mutation and lack B1 (CD5+ B) cells. This study clearly demonstrates that infected B1 cell-deficient animals display a higher susceptibility to S. mansoni infection as revealed by an increase in the tissue egg loads and a significantly elevated mortality, as well as an increase in the granuloma densities. The analysis of the humoral and the cellular responses, conducted in the same experimental conditions, indicates differences in terms of cytokine production after specific antigenic stimulation of splenocytes. Larger amounts of IFN-gamma and IL-4 are observed in BALB. Xid mice while IL-10 production is reduced. In parallel, the study of the specific antibody isotype profiles shows higher amounts of specific IgE and IgG1 antibodies and lower amounts of IgM and IgA in BALB. Xid mice. Taken together, these observations support the idea that B cells are playing a role in the ability of mice to tolerate infection with Schistosoma mansoni.

Animals↗

PubMed1999

Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins.

The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.

Adolescent↗

PubMed1999

[Late onset of type I familial amyloid neuropathy: results of biopsy from accessory salivary glands].

Familial amyloidotic polyneuropathy (FAP) type I is usually characterized by onset in the third decade, autonomic nervous system failure, and heart block conduction occurring after the onset of neurological symptoms. A 74-year-old woman, with past medical history of a third degree heart block treated by a pace-maker, was hospitalized because of an axonal sensory-motor polyneuropathy, without autonomic dysfunction. There was no familial history. Because she complained of mouth dryness, biopsies of the labial salivary glands were performed, showing amyloid deposits. Immuno-histochemicals studies confirmed the presence of transthyretin. We analysed the transthyretin gene of the patient and her asymptomatic son, and found in both cases, the point mutation leading to the single amino acid substitution of a methionine for valine at position 30, which is typical of type I FAP. This case revealed the clinical variation of FAP type I and the interest of biopsies of the labial salivary glands in the diagnosis of polyneuropathies.

Age Factors↗

PubMed1999

[Cyclin-dependent kinase inhibitory proteins in normal and transformed choroidal melanocytes].

PURPOSE: Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin dependent kinase inhibitory proteins (Ckis) have been shown to be implicated in cancer progression. We investigated the levels of the different regulatory inhibitory proteins involved in the G1 progression and G1/S in choroidal melanomas. METHODS: Immunoblotting, immunoprecipitation and immunohistochemistry were performed on human choroidal cell lines and human choroïdal tumors. RESULTS: Our findings suggested a lack of expression of Cdk inhibitor p21 in two of three melanoma cell lines and a striking underexpression of p27 in the three transformed cell lines. The p16 level was found to be almost the same in both normal and transformed cells, a loss of p16-Cdk4 interaction was observed in two of the three melanoma cell lines. In immunohistochemistry, nuclear positivity for p16 was observed in six tumors. Nuclear positivity for p21 was observed in five tumors. All of theses tumors had scleral invasion (p = 0.003). Nuclear positivity for p27 was observed in only two tumors. CONCLUSION: Our results demonstrate that immunoreactivity for p16, p21 and p27 could be implicated in progression of melanoma tumors. More cases are required to further clarify this issue.

Cell Cycle↗

PubMed1999

[Angiogenesis and neuropathology].

Angiogenesis is crucial for both tissue development and tissue function and is an integral part of central nervous system embryogenesis and tumor growth. Angiogenesis is extremely active during development, then remains stable during adulthood and decreases gradually during aging. Physiological processes and inflammation can transiently stimulate angiogenesis in adults. Angiogenesis is modulated by a host signaling pathways, growth factors, growth factor receptors, and membrane proteins associated with these receptors or transcription factors. In disorders affecting the central nervous systems, as in those arising elsewhere in the body, angiogenesis can become inadequate, excessive, or qualitatively abnormal (dysplasia). These abnormalities can result in cerebral trophic disorders and in secondary remodeling. A few examples are given to illustrate various types of primary angiogenesis disorders responsible for cerebral lesions and of secondary angiogenesis disorders caused by an underlying cerebral disorder.

Adult↗

PubMed1999

[Sjögren's syndrome and necrotizing sarcoid-like granulomatosis].

We report the first description of a Sjögren's syndrome associated with nectrotizing sarcoid-like granulmatosis. A 62-year old woman was admitted for diagnostic exploration of fatigue, weight loss, and fever at 38 degrees C which had progressed for more than 3 months. Chest X-ray showed several pulmonary opacities. There was a history of tuberculosis and thyroiditis at the age of 20 years. Physical examination revealed a sicca syndrome. There was no objective evidence of respiratory disease. Her heart and chest were clear on auscultation. The patient had autoantibodies for SSa and SSb specific antigens. Minor salivary gland biopsy gave a score of 3 in the Chisholm classification. Chest X-ray and CT-scan showed diffuse infiltrative opacities which were dense and peripheral with no retraction. Bronchoalveolar lavage, and bronchial and transbronchial biopsies were non-specific. Surgical lung biopsy showed typical aspects of necrotizing sarcoid-like granulomatosis. After high-dose pulse corticosteroid therapy, the opacities disappeared with no recurrence under oral steroids at three years.

Adrenal Cortex Hormones↗

PubMed1998

In vivo diagnosis of Kufs' disease by extracerebral biopsies.

In almost all of the earlier reported cases of Kufs' disease, the adult form of ceroid lipofuscinosis, the diagnosis was ascertained by cerebral tissue examination, while peripheral biopsy examination revealed an apparent poor diffusion of specific lipofuscinic deposits, the finger print profiles (FPs). We report the ultrastructural data from skin, muscle and rectal biopsy specimens from two siblings, both still living, who present clinical features of Kufs' disease. We observed the presence of FPs in locations that differ from the previous classic reports. Our results emphasize the value of extracerebral biopsies for the diagnosis of Kufs' disease in vivo, and suggest some physiopathological assumptions based on vascular wall involvement.

Adult↗

PubMed1998

Endothelial changes in muscle and skin biopsies in patients with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is characterized by the deposition of granular osmiophilic material in association with vascular smooth muscle cells in many different organs. However, the cause of the subsequent destruction of smooth muscle cells that are surrounded by granular osmiophilic material is unclear. In the present study, the ultrastructural changes that occur in endothelial cells in CADASIL have been evaluated by examining blood vessels in six skin biopsies and seven muscle biopsies belonging to three different CADASIL pedigrees. The appearances have been compared with five skin biopsies and five muscle biopsies from age-matched controls without vascular disease. The most striking features observed in vessels in the skin of CADASIL patients were attenuation of endothelial cells and increased density of endothelial cytoplasm, accompanied by the presence of compact bundles of microfilaments within the cytoplasm of endothelial cells. Endothelial cells in muscle biopsies from CADASIL patients, on the other hand, were swollen until destruction of tight junctions were observed. These findings suggest that impaired permeability of vascular endothelium may play a role in the destruction of vascular smooth muscle cells in CADASIL. Furthermore, the results of this study suggest that further fine structural investigation of blood vessel endothelium and underlying smooth muscle may lead to a better understanding of the pathophysiology of CADASIL.

Adult↗

PubMed1998

Lipomatous differentiation in ependymomas: a report of three cases and comparison with similar changes reported in other central nervous system neoplasms of neuroectodermal origin.

Three cases of surgically removed ependymomas with lipomatous transformation of tumor cells are reported. Patients' ages were 13, 16, and 48 years at the time of operation. One patient's tumor was located in the third ventricle; the other two occupied paraventricular hemispheric white matter. Histologically all three cases fulfilled the criteria of ependymomas. In case 1, electron microscopy also confirmed this diagnosis, and preoperative radiologic studies (scans) suggested large amounts of lipids to be present in the tumor. Histologically, in all three cases many tumor cells contained fat droplets coalescing into a single large droplet, resulting in an appearance indistinguishable from adipocytes by conventional stains, but maintaining immunohistological positivity for glial fibrillary acidic protein and neuron-specific enolase in the cytoplasmic rims of the affected cells, attesting to their glial nature as opposed to being true adipocytes in a mixed glial/mesenchymal hamartoma. The alterations were also different from the "xanthomatous" changes seen in some gliomas. Lipomatous transformation of neuroectodermal tumor cells has been previously observed in neurocytomas, medulloblastomas, cerebellar and spinal cord astrocytomas, and primitive neuroectodermal tumors. Our three cases represent the first reported ependymomas with such changes. In medulloblastomas of adults, lipomatous changes have been found to signal relatively benign biologic behavior. So far, all three of our patients are doing well, but only more extended follow-up will show whether such benign behavior applies to lipomatous ependymomas as well.

Adolescent↗

PubMed1998

Creutzfeldt-Jakob disease: neurophysiologic visual impairments.

OBJECTIVE: The predictive value of electrophysiologic visual testing in Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic findings in three cases are reported. BACKGROUND: The fatal prognosis of CJD, its transmissibility, and the lack of treatment make early diagnosis essential in averting human-to-human transmission. Electroretinogram and visual evoked potentials have been studied in few cases of CJD. METHODS: A visual electrophysiologic examination was performed in 41 consecutive patients referred with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15 were confirmed neuropathologically and 9 by clinicolaboratory methods in accordance with diagnostic criteria). The remaining 17 patients were diagnosed with other neurologic disorders, and served as a control group. RESULTS: Flash electroretinogram revealed a significant decrease in the amplitude of the B1 wave (<60 microV) and the B/A ratio (<2) in the CJD group compared with those in the control group. Flash visual evoked potentials revealed no significant difference in latency, but amplitude was increased (>10 microV) in the CJD group, especially in patients with myoclonus. CONCLUSIONS: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.

Adult↗

PubMed1998

The first European family with tibial muscular dystrophy outside the Finnish population.

We report the first European tibial muscular dystrophy (TMD) family outside the Finnish population. Clinical examination showed late onset distal leg myopathy similar to the description of TMD. A molecular genetic study was made owing to the very recent TMD linkage findings on chromosome 2q31. All five clinically affected patients segregated a specific haplotype for the locus, whereas two unaffected patients had different haplotype. The results of this family without Finnish ancestors show that TMD exists outside the Finnish population.

Aged↗