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M Kujas

Publications and source records attributed to M Kujas.

At least 55 records · Page 3Linked to original sources

[Histopathology of brain tumors. Histoprognosis and its limitations].

Although the current radiological imaging is really performing, histologic examination remains essential in as much regarding the diagnosis as the pronostical assessment of cerebral tumors pronostic. The difficulties of histological diagnosis are not the same according to the various processes such as cerebral biopsy, extemporaneous examination or routine examination. Grading of gliomatous tumors is one among all the components that might enable pronostical assessment. Predictivity of meningiomas and pituitary adenomas recurrences remain unreliable despite numerous histological techniques that can be used (proliferative markers, bromodeoxyuridine incorporation, nucleolar organizers, flow cytometry).

Adult↗

[Flow cytometry in the study of meningiomas. Preliminary results and attempt at clinical correlation].

Meningiomas are meningeal primitive tumors. These benign neoplasms can recur but the rate of recurrence is unknown as there is no reliable factor of predictibility. The aim of this study was to test Flow Cytometry based on clinical data and follow up in a series of meningiomas operated on in a neurosurgical department. This method allows the study of DNA content matched with the study of the cellular cycle. S cellular phase was chosen to be tested related to immunostaining with 2 proliferating markers, Ki67 and PCNA. This prospective study was carried out on neurosurgical samples, immediately frozen. On the one hand, results confirm well known discrepancies between Ki67 and PCNA immunostainings. On the other hand, two recurrent meningiomas belong to the diploid group. This is unexpected as aneuploid tumors are known to be biologically more agressive than diploid tumors.

Adult↗

[Granular cell tumors. Rare tumors of the neurohypophysis].

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17% of unselected adult autopsy cases. There are few reports of parasellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotroph microadenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyperprolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intrasellar and suprasellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted images. Transsphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that they may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow-growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of postoperative radiation therapy on postoperative recurrences.

Adult↗

Neurofibromatosis 1 (NF1) mRNAs expressed in the central nervous system are differentially spliced in the 5' part of the gene.

The neurofibromatosis 1 gene seems to play essential roles at several different stages of life. During embryogenesis, it is involved in cardiac development while in the adult, neurofibromin (the corresponding protein) is mainly expressed in the nervous system, and therein, essentially in neurons, non-myelinating Schwann cells and oligodendrocytes. In addition, the NF1 gene is considered a tumor suppressor gene, since mutations have been associated with the occurrence of benign and malignant tumors in neuralcrest-derived tissues. Using reverse transcription-polymerase chain reaction (RT-PCR) analyses with primers located in exons 7 and 13, we have identified evidence of alternative splicing in this region of the NF1 gene. Cloning and sequencing of cDNA allowed the characterization of an isoform bearing an extra 30 bp sequence between exons 9 and 10a, leading to the insertion of 10 amino acids between residues 420 and 421 of neurofibromin. The insertion is conserved in the mouse. Examination of the pattern of expression of this isoform demonstrated a high level of expression in the central nervous system and an absence of expression in all the other normal tissues tested including peripheral nervous tissues derived from the neural crest. Analysis of brain tumors indicated a reduced expression of the alternative exon in medulloblastomas and oligodendrogliomas. The results presented here are consistent with tissue-specific expression of this alternative exon which we propose to call exon 9br.

Amino Acid Sequence↗

Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas. An immunohistochemical study.

We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland.

Adenoma↗

Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas.

In order to see whether, in thyrotropic adenomas with thyrotoxicosis, plasma thyroid hormones regulate the thyrotropin-releasing hormone (TRH) binding sites and the thyrotropin (TSH) response to TRH, we investigated: the presence of TRH binding sites in two cases of thyrotropic adenomas associated with hyperthyroidism and in one case of thyrotropic adenoma secondary to thyroid failure: and the in vitro effect, in a perifusion system, of triiodothyronine (T3) on the response of TSH to TRH in three cases of TSH-secreting adenomas associated with hyperthyroidism. The TRH binding sites were absent in the adenomas associated with high levels of circulating thyroid hormones, whereas they were present in the adenoma secondary to primary thyroid failure (Kd = 47 nmol/l, Bmax = 40 nmol/kg membrane proteins). In vitro, the three adenomas spontaneously released TSH in the perifusion medium (1.49 +/- 0.06 (mean +/- SEM), 7.25 +/- 0.12 and 16.73 +/- 0.36 mIU.l-1 x 10(6) cells-1 x 2 min-1) and exhibited an ample TSH response to 10(-7) mol/l TRH pulses. In two cases, tumoral secretion of fragments was compared with those of fragments maintained since the time of surgical removal in the presence of 10(-8) mol/lT3. The TSH responses to TRH were abolished in the presence of T3 in these two cases. We conclude that thyrotropic adenomas associated with hyperthyroidism are still controlled in vivo by T3. In particular, T3 regulates the TSH response to TRH, probably via a down-regulation of the TRH binding sites.

Adenoma↗

[Intracerebral extension of cervical paraganglioma].

A large paraganglioma invaded the neck and skull, with extension into the right supratentorial cerebral hemisphere through the calvarium. Immunohistological markers were found useful for the diagnosis. The patient died rapidly. Despite no evidence of metastasis, the usually benign paraganglioma can have a malignant course.

Brain Neoplasms↗

[Primary meningeal gliomatosis].

A 44 year old woman presented with chronic meningitis. Magnetic resonance imagery showed a diffuse contrast enhancement of the leptomeninges. Cerebrospinal fluid studies showed a high hyperproteinorachia and light pleiocytosis. A left temporal tumor appeared four months later. Histological studies revealed an anaplastic oligosatrocytoma leading to the diagnosis of primary leptomeningeal gliomatosis.

Adult↗

Meningioma.

Meningiomas more often behave as benign tumors although their very rate of recurrence is unknown. These neoplasms have been exhaustively studied but neither their subtypes nor their histologic features were ever considered as reliable data of their biologic behavior. Different types of assays have been achieved in order to assess the aggressiveness of these neoplasms. The first one concerned the mitosis index and different markers of proliferation. Other ways have been explored as the dual expression of the differentiation and the steroid receptors of the neoplasms, with no evidence of a clear cut prognostic value. Aneuploidy is thought to be associated with a rather poor behavior, and chromosome 22 is the most frequent abnormality. Recent studies on growth factors related with some of the factors previously mentioned and expression of oncogenes complete the overview of the methods involved in the search for prognostic data.

Biomarkers, Tumor↗

Immunocytochemical study of progesterone receptor in human meningioma.

Progesterone (PR) and oestrogen (ER) receptors were examined in meningiomas from 36 patients, using immunocytochemistry. The present experiments were performed to evaluate: (a) the presence and intracellular localization of these receptors, (b) whether PR immunostaining can be correlated (or not) with proliferation potential, as evaluated by histopathological features or the clinical evolution of this neuropathological tumour. Twenty six tumours (72%) tested were positive for PR but none for ER. The presence of PR immunostaining was more frequently observed in females (79% versus 58% in males) and premenopausal status (84% versus 3/5 in postmenopausal). Correlations of PR immunostaining with the histologic type showed 89% of meningothelial, 4/6 cases of transitional, 1/3 case of fibroblastic and 1/4 cases of anaplastic meningiomas to be immunostained for PR. Staining was confined to tumours arachnoidal cells. A heterogeneous distribution was observed in most PR-positive meningiomas. The preferential immunostaining in meningothelial histological types correlates with the presence of PR in normal arachnoidal cells. The proliferating potential of these meningiomas was evaluated by the immunostaining of an antigen only present in proliferating cells (Ki antigen). There was no significant correlation between PR status and the Ki labelling rate, or rapid clinical evolution. These data were compared with those previously reported. They confirm that the cellular biosynthesis of PR in meningiomas is not oestrogen regulated as it is in other sex steroid tissues, such as the breast and the endometrium.

Adult↗

Somatostatin cells in human somatotropic adenomas.

Data from our group have shown that the human adenomatous and normal anterior pituitary may be the source of somatostatin (SRIH). SRIH-producing cells were identified in two somatotropic adenomas. Immunoreactive SRIH cells were present in both cases. In case 2, material was available for RNA studies, in situ hybridization and electron microscopy. The size of the transcript identified by Northern blot analysis was identical to that of hypothalamic SRIH mRNA. In situ hybridization showed that the SRIH gene was expressed in a cell subset superimposable to that identified by immunocytochemistry. Co-localization studies revealed that SRIH and growth hormone (GH) immunoreactivities were not present in the same cells. Ultrastructural immunogold labelling showed that SRIH cells had features distinct from those of the somatotropes. The results confirm that the somatotropic adenomas have the ability to synthesize SRIH, indicate that SRIH expression is restricted to a subset of adenoma cells different from GH-producing cells, and imply that SRIH cells are involved in paracrine regulation of neighbouring somatotropes.

Adenoma↗

Specific alterations of the basement membrane and stroma antigens in human pituitary tumours in comparison with the normal anterior pituitary. An immunocytochemical study.

Our report is the first immunocytochemical study of the principal elements of the basement membrane (BM) and connective tissue in normal and adenomatous human anterior pituitaries. In normal tissues, both the parenchymatous BM limiting the endocrine cell cords and the endothelial BM around the capillaries were continuous and were stained with anti-laminin (LM), anti-type IV collagen (CIV) and anti-fibronectin (FN) antisera. Antiserum to type I collagen (CI) stained the connective tissue only. The same antigens were investigated in 23 human pituitary adenomas, 6 of them having been diagnosed as locally invasive by the radiologist and the neurosurgeon. In all cases a lack of cordal structure was observed and the parenchymatous BM was completely absent (9 cases) or fragmented (14 cases). No correlation could be established between the extent of parenchymatous BM alterations and the invasive behaviour of the tumour. In contrast, a continuous endothelial BM was observed around the blood vessels in all cases and its presence was confirmed in double immunofluorescence experiments using anti-von Willebrand factor and anti-LM or anti-CIV antisera. Anti-FN and CI also stained the wall of the vessels. The tumours showed arterial development, in addition to the capillaries found in normal tissue. The present results favour the hypothesis of a decreased synthesis of parenchymatous BM by human adenomatous pituitary cells in comparison with normal cells and show that these tumours are the site of an active arterial neovascularization.

Adenoma↗

[Primary non-Hodgkin's malignant lymphoma of the central nervous system].

The incidence of primary central nervous system lymphoma (PCNSL) is increasing, not only in immunodeficiency states, but also in apparently normal individuals. The most common presentation of PCNSL is that of an intracranial mass lesion. Ocular involvement is associated in 20% of patients. CT/MR scan typically shows one or several periventricular tumors with indistinct margins that diffusely and densely enhance following contrast infusion. The diagnosis relies on lumbar puncture, vitreous biopsy, or stereotactic biopsy of a brain lesion demonstrating lymphomatous cells. If possible, corticosteroids should be used only after definite diagnosis. Corticosteroids have a cytotoxic effect responsible for transient remission in 40% of patients. Whole brain radiation therapy induces a complete or partial response in 80% of patients but recurrence always occurs and the median survival does not exceed 14-18 months. The addition of systemic and intrathecal chemotherapy seems to substantially improve the prognosis with median survival exceeding 3 years in some studies. PCNSL associated with AIDS generally occurs at a late stage of the disease and is the fourth cause of death in AIDS patients. Radiation therapy is useful but the median survival does not exceed 5.5 months because patients most often die of opportunistic infections.

Acquired Immunodeficiency Syndrome↗

[Contribution of nucleolar organizers staining to the prognostic evaluation of meningioma].

Meningioma is often regarded as a benign tumour. It is easy to diagnose, but its prognosis is difficult to determine. Recurrences are numerous and occur at different periods of time. Various predictability factors have been studied, including Nucleolar Organizers Regions (NORs) staining. This technique is easy to perform and enables retrospective studies to be carried out. Comparisons of staining indices with the histoprognostic grades established by Zülch, and correlations between these indices, as well as with the time elapsed before a recurrence occurred, showed that NORs staining can be useful to determine the prognosis. In this retrospective study 69 cases were reviewed. The meningiomas had been removed surgically between January 1979 and December 1991. The clinical follow-up, which lasted from 11 months (for the most recent cases) to 132 months (for the earlier cases), shows that the staining index reaches a critical value beyond which an early recurrence might be expected.

Humans↗