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M Kujas

Publications and source records attributed to M Kujas.

At least 73 records · Page 4Linked to original sources

Evaluation of 29 monoclonal and polyclonal antibodies used in the diagnosis of pituitary adenomas. A collaborative study from pathologists of the Club Français de l'Hypophyse.

Fifteen polyclonal antibodies (pAbs) and 14 monoclonal antibodies (mAbs) directed against hGH, hPRL, beta hFSH, beta hLH, beta hTSH and alpha-subunit were assessed by five different laboratories on normal and adenomatous pituitary tissues. This study aims at providing pathologists with a selected panel of antisera suitable for diagnosis, and appreciating the interest of the recently introduced mAbs. All the anti-hGH Abs proved to be specific (3 pAbs and 4 mAbs); three mAb out of four gave a few false-negative reactions. Three out of six polyclonal anti-hPRL showed cross-reactivity with hGH; anti-hPRL mAbs gave a strong staining with no false-negativity detected so far. MAbs proved to be more efficient for detecting glycoprotein hormones and alpha subunit than pAbs, which, in several cases, gave widespread cross-reactivity. This lack of specificity could explain the noticeable discrepancies reported so far in the appraisal of gonadotropic and somatoprolactinic adenomas.

Adenoma↗

Apparently silent somatotroph adenomas.

We describe here 9 patients with somatotroph adenomas associated with mild features of acromegaly and basal plasma GH levels in the normal range. In 5 women and 4 men, 26 to 61 yrs old, the diagnosis of prolactinoma or non-secreting pituitary adenoma had been previously made on the basis of amenorrhea-galactorrhea or tumoral symptoms. However, they had discrete signs of coarsening of the facial features and moderate but evolutive changes of hand and foot sizes. Basal GH levels were in the normal range (0.4 to 4.5 micrograms/l, N less than 5 micrograms/l) but unaffected by oral glucose and insulin tolerance tests while IGF-I concentrations were elevated in all the cases (range 1.7 to 5.8 U/ml, N: 0.37-1.41 U/ml). Plasma PRL concentrations were elevated in 5 patients (range 16 to 80 micrograms/l, N less than 13 micrograms/l in men and N less than 19 micrograms/l in women). The 9 patients had a macroadenoma with an extrasellar extension in 8 of them and all were operated on by the transsphenoidal route. Immunocytochemical studies demonstrated IRGH-cells in all the adenomas and IRPRL-cells in 5 of them. Electron microscopic analysis of 3 tumors showed that the secretory granules were sparse and the Golgi apparatus poorly developed. Molecular biology of 7 tumors showed the presence of small amounts of GH mRNA. This result was in agreement with the morphological aspect, suggesting a low rate of GH synthesis. Thanks to these different approaches the diagnosis of silent somatotroph adenoma should sometimes be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Pituitary enlargement with suprasellar extension in functional hyperprolactinemia due to lactotroph hyperplasia: a pseudotumoral disease.

Beside the well characterized PRL-secreting adenomas, a wide spectrum of functional hyperprolactinemic states exists. We describe here five women, 21-38 yr old, all suspected of having a PRL-secreting adenoma because of a pseudotumoral appearance of the pituitary on computerized tomographic (CT) scan or magnetic resonance imaging (MRI). Four had oligomenorrhea with or without galactorrhea, one had amenorrhea with galactorrhea, and two complained of infertility. In the same patient, basal plasma PRL levels were variable on different days, sometimes normal (mean +/- SEM, 11.3 +/- 1.5 micrograms/L), sometimes elevated (49 +/- 7 micrograms/L), but in all cases, a PRL response of large amplitude to TRH (6- to 8-fold increase in the basal value) was observed. Basal plasma levels of estradiol were within luteal phase normal values (0.41 +/- 0.13 pmol/L), while progesterone levels were low (1.92 +/- 0.47 nmol/L). CT scan or MRI showed an intrasellar mass with suprasellar extension, suggesting a tumoral process. However, the signal intensity was homogeneous, and on coronal views, the suprasellar extension was pyramidal and symmetrical, and the pituitary stalk was always in the midline. The five patients were operated on by the transsphenoidal route, but no adenoma was found. Surgical biopsies were taken in four cases, and lactotroph hyperplasia, i.e. enlarged cell cords consisting mainly of PRL cells, was found in three of them. One case displayed a continuum between areas of lactotroph hyperplasia and adenomatous PRL cells. We conclude that functional hyperprolactinemia may mimic on CT scan or MRI a PRL-secreting adenoma.

Adult↗

A human TSH-secreting adenoma: endocrine, biochemical and morphological studies. Evidence of somatostatin receptors by using quantitative autoradiography. Clinical and biological improvement by SMS 201-995 treatment.

An invasive TSH-secreting adenoma inducing mild hyperthyroidism was diagnosed in a 16-year-old male. Initial surgical treatment led to a temporary clinical and biological improvement. Recurrence of the thyrotoxicosis was treated with the somatostatin analogue, SMS 201-995 (octreotide) with normalization of the serum thyroid hormone levels with a dose of 200 micrograms per day. With immunoelectron microscopy, the tumour cells appeared poorly granulated with small secretory granules located at the periphery of the cells; only part of those were immunoreactive with an anti-TSH beta monoclonal antibody. No specific TRH binding site was found in a tumour membrane preparation. By quantitative autoradiography, somatostatin specific binding sites were as numerous in the TSH-secreting tumour as in control GH-secreting tumours. Binding kinetics and guanosine triphosphate dependency of the binding were equivalent in the TSH and GH tumours tested. Although all of the tumour cells displayed the same ultrastructural features, some were non-immunoreactive, suggesting that they could secrete an altered form of TSH. The absence of TRH receptors in the tumour cells is in accordance with previous reports on this type of tumour. We confirm the efficiency of octreotide treatment in this case of neoplastic TSH inappropriate secretion. The therapeutic effect of octreotide goes along with the presence of a high density of guanine nucleotide-dependent somatostatin binding sites in the tumour cells.

Adenoma↗

Pituitary granuloma and pyoderma gangrenosum.

Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.

Adult↗

Assessment of chromosome 22 anomalies in neurinomas by combined karyotype and RFLP analyses.

We report the cytogenetic study of 28 neurinomas; sixteen of them were also analysed using 11 polymorphic DNA markers for the loss of alleles of chromosome 22. Partial or total loss of chromosome 22 was found in nine cases. The results of the two approaches appear homogeneous, however, three tumors that yielded only cells with normal karyotypes demonstrated loss of constitutional heterozygosities. One of the tumors, which displayed an isodicentric or isopseudodicentric 22, was obtained in a patient with von Recklinghausen neurofibromatosis. It appears that loss of chromosome 22 is a characteristic of neurinomas whatever their context of occurrence.

Alleles↗

Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation.

Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level less than 4 micrograms/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 +/- 16.1 micrograms/l, mean +/- SEM). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1 +/- 0.37 vs 51.5 +/- 34.1 micrograms x (10(-6) cells) x min-1, p less than 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Immunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome.

Four tumors consisting of pituitary adenomatous cells (AD) intricated with ganglion cells (GC) were studied. Each case was associated with a different clinical syndrome: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome with no hormonal hypersecretion. (a) In the case with acromegaly, immunoreactive growth hormone (IR-GH) was present in 80% of AD. IR-vasoactive intestinal peptide (VIP) was found in 5%-10% of AD and in few GC. Rare GC and processes showed IR-GH-releasing hormone (GRH), -somatostatin (SRIH), -gonadotropin-releasing hormone and -adrenocorticotropin-releasing hormone. (b) In the case with amenorrhea-galactorrhea, IR-prolactin (PRL) was seen in 90% of AD. IR-PRL and -VIP were present in rare GC. (c) In the case with Cushing's disease, 60% of AD and very few GC contained IR-adrenocorticotropin (ACTH) and beta-lipotropin. Rare GC processes contained IR-SRIH. (d) In the case without pituitary hormone hypersecretion, PRL was localized in rare AD and GC. Pituitary hormone and neuropeptides were never colocalized in the same cells. No case displayed IR-neurophysins or -thyroliberin. Pituitary hormones were localized by ultrastructural immunogold labeling. These findings show that: (i) in three cases, pituitary hormones (PRL and ACTH), and, in one case, VIP could be localized in both adenomatous and ganglion cells; (ii) the pituitary hormone-containing cells in the tumors could be related to the hypersecretory syndromes; (iii) intratumoral IR-VIP and -GRH might be involved in GH and PRL hypersecretion in the cases with acromegaly and amenorrhea-galactorrhea.

Acromegaly↗

[Immunohistochemistry of epidermal growth factor receptors in human meningioma].

EGF receptors were assayed by immunohistochemistry using a monoclonal antibody against EGF-R in 32 surgical samples of meningioma. EGF-R were found in all samples (32/32). Only tumor cells were stained and staining was homogenous in tumor tissue. EGF-R was simultaneously assayed by 125I-EGF binding on membrane preparation and immunohistochemistry on frozen sections in 10 meningiomas. Results were qualitatively equivalent in 9 cases. Staining intensity was not correlated with the histological type, the proliferative status of the tumor or the age and hormonal status of the patients. The immunohistochemical data are in agreement with previous biochemical assays on tissue homogenates.

ErbB Receptors↗

Pathological findings in three non-Japanese patients with the POEMS syndrome.

The pathological features of three European patients with plasma cell dyscrasia, osteosclerosis and a multisystem disorder, most frequent in Japan, that includes polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS syndrome), are reported. The material was obtained from biopsies (peroneal nerve, lymph node) and general autopsy, including hypophysis, in one case. The most salient findings were: peripheral nerve lesions, including both segmental demyelination and axonal degeneration, with so-called uncompacted myelin lamellae (UML); angiofollicular lymph node hyperplasia (AFLNH); and non inflammatory vascular changes. Though not specific, it appears that UML and AFLNH may be contributive findings in atypical cases of POEMS syndrome (incomplete forms, lack of underlying malignant plasma cell dyscrasia or circulating monoclonal immunoglobulin). Among the various autopsy findings we emphasize the skin thickening which was secondary to a hyaline sclerosis of the papillary dermis, and the presence in adenohypophysis of numerous cells showing positive reactions with the anti-alpha MSH antibody. Though immunological, vascular and hormonal disturbances have been implicated at the origin of several manifestations of the disorder, the pathogenesis of the POEMS syndrome remains obscure.

Adult↗

Immunocytochemical study of S-100 protein in human pituitary adenomas.

The S-100 protein was localized by immunocytochemistry in 70 pituitary tumors including 30 prolactin, 16 growth hormone, two corticotropin and 22 non-functioning adenomas. Positive immunostaining was observed in only one case (prolactin adenoma). It is concluded that in functioning and non-functioning pituitary tumors there is no particular involvement of S-100 protein-containing cells, at least under the conditions of this study.

Adenoma↗

Absence of receptors for thyrotropin (TSH)-releasing hormone in human TSH-secreting pituitary adenomas associated with hyperthyroidism.

In patients with TSH-secreting pituitary adenomas associated with hyperthyroidism, TSH secretion usually does not respond to exogenous TRH stimulation. To determine the basis for this unresponsiveness, we studied TRH binding to the membranes of two such TSH-secreting pituitary adenomas. The patients, a 28-yr-old man and a 60-yr-old woman, had clinical and biochemical hyperthyroidism with increased serum TSH levels (15.7 and 14 mU/L, respectively; normal range, 1.1-7.2) and alpha-subunit to TSH molar ratios greater than 1 (2.4 and 1.7, respectively). Neither patients had an increase in serum TSH in response to TRH (200 micrograms, iv). Immunocytochemistry of the two adenomas, removed by transsphenoidal surgery showed a pure population of thyrotropic cells. Binding studies were performed by incubation of tumor cell membrane suspensions with increasing amounts of [3H]TRH. Two PRL-secreting adenomas and one normal human pituitary were used as controls. The characteristics of the TRH-binding sites from the control tissues were similar to those previously reported (Kd, 56, 30, and 49 nM; maximum binding, 187, 46, and 94 fmol/mg protein, respectively). In contrast, no specific TRH binding was found in the two TSH-secreting adenomas. We conclude that the unresponsiveness of TSH after TRH administration is related to the absence of specific TRH-binding sites in these thyrotropic tumors.

Adenoma↗

The immunocytochemical heterogeneity of silent pituitary adenomas.

An immunocytochemical study was performed by the indirect peroxidase method on the pituitary tumour of 37 patients with clinical and biological signs of silent adenoma. Antisera were used against human PRL, human GH, ACTH1-24, human ACTH17-39, alpha-melanocyte stimulating hormone (alpha-MSH), human beta-endorphin, alpha-subunit of hCG (hCG-alpha), and beta-subunits of human LH (LH-beta), human FSH (FSH-beta) and human TSH (TSH-beta). Immunostaining in at least 5% of the tumour cell population, with one or more antisera, was present in 13 cases; hCG-alpha immunostaining was the one most frequently observed. Combined immunostaining was found in 7 cases. Exclusive immunostaining was present in 6 cases: 4 with hCG-alpha, 1 with ACTH1-24 and 1 with TSH-beta. It is concluded that a significant number of silent pituitary adenomas show a certain secretory pattern of pituitary hormones or subunits of glycoprotein hormones as revealed by the immunocytochemistry.

Adenoma↗

[Chemodectoma of the orbit. Apropos of a case and review of the literature].

The clinical, follow up and diagnostic features of a case of chemodectoma (paraganglioma) of the orbit are reviewed. 30 cases are reported in the literature. Chemodectoma may arise in any area of the body where non chromaffin paraganglion structures are situated. These are localized in the orbit of the chimpanzee but not in the orbit of man. Malignant behavior of chemodectoma has been a controversial subject, with most authors considering them to be benign tumors. Some authors have diagnosed locally recurrent and infiltrative tumors as malignant. The authors report one case of chemodectoma of the orbit. A 5 year old child has had right exophthalmos. She was treated by tumorectomy. The follow-up is marked by recurrence of the tumor and infiltration of the right hemi-face.

Child, Preschool↗