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E Horvath

Publications and source records attributed to E Horvath.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

Double-labeling immunogold electron-microscopic study of hormonal colocalization in nontumorous and adenomatous rat pituitaries.

According to the one cell, one hormone theory, the pituitary gland is composed of 5 cell types which secrete 6 hormones. Recent investigations indicate that this theory must be modified, as there are some bihormonal cells containing 2 hormones, i.e., mammosomatotrophs prolactin-growth hormone (PRL-GH). This study was undertaken in order to elucidate whether other adenohypophysial cells are capable of producing 2 hormones and to demonstrate the presence of cells coexpressing PRL-GH, PRL-thyrotropin (TSH), or TSH-GH. Sixteen nontumorous and 16 adenomatous male and female Sprague-Dawley and Long Evans rat pituitaries were removed immediately after the animals were killed and processed for transmission electron microscopy and the immunogold double-labeling technique. Coexpression of PRL-GH, PRL-TSH, and TSH-GH was found in both nontumorous and adenomatous pituitaries. Double labeling was present not only in the same cell cytoplasm but also in the same secretory granules. The question of whether these double-labeled cells represent different cell populations, transitional cell types, or precursor cells requires further investigation.

Animals↗
PubMedDate not supplied

Nimodipine effects on cerebral microvessels and sciatic nerve in aging rats.

At the ultrastructural level different anomalies of the cerebral microvasculature were encountered in the brains of aged rats. These aberrations can either be attributed to degeneration processes or to the perivascular deposition of, e.g., collagen fibrils and other, unidentified, proteinous debris. We previously reported that chronic treatment with the calcium antagonist nimodipine from 24-30 months especially reduced the incidence of aging-related microvascular deposits in the frontoparietal motor cortex of rats. The same drug treatment did not interfere with the degeneration of pericytes. The reduction of the microvascular depositions was, however, not consistent throughout different cortical layers. We now demonstrate that an earlier onset (16-30 months) of the drug application yields a prominent and consistent reduction of microvascular deposits for all cortical layers studied. The earlier onset of the drug treatment again did not influence the quantity of pericyte degeneration. The effect of long-term nimodipine treatment (16-30 months) was also examined in the sciatic nerve. Compared to young animals the sciatic nerve of aged control rats (30 months) showed a variety of alterations of myelinated fiber (MF) morphometry. Nimodipine treatment from 16-30 months did not significantly change these morphometric aging-related changes. Approximately 6% of the MF in aged rats display morphological myelin irregularities. After nimodipine application the frequency of these alterations was reduced, which was, however, only significant for partial demyelination known as myelin ballooning. These results indicate a consistent influence of nimodipine on cerebral microvessels, while there is only a moderate effect on the morphology of sciatic myelinated fibers during the aging process.

Animals↗
PubMedDate not supplied

Cholinergic fiber aberrations in nucleus basalis lesioned rat and Alzheimer's disease.

Innervation density and morphological aberrations of cholinergic fibers were studied with choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry in 30-35 month-old aged rats and rats with long-term bilateral lesions of the magnocellular basal nucleus (MBN). In addition, AChE histochemistry was performed on human cortical sections derived from autopsy brains of normal aged and Alzheimer's disease (AD) patients. A limited but variable number of morphological alterations were observed in ChAT-immunoreactive fibers in the cortex and the hippocampus of the aged control rats. The aged MBN-lesioned rats displayed a severely reduced number of cholinergic fibers in the denervated areas of the neocortex, whereas the surviving fibers showed a strongly increased number of aberrations. Fiber anomalies were also observed in the cortex of the aged human subjects and Alzheimer patients, the latter showing a higher incidence of such aberrations. Only a part of these distended profiles were seen in close association with senile plaques as detected in the AChE-stained material. These findings suggest that experimental MBN lesions combined with aging share with AD the induction of large quantities of fiber malformations. Implications of possible mechanisms in both conditions are discussed.

Acetylcholinesterase↗
PubMedDate not supplied

Leptin and leptin receptor in anterior pituitary function.

Leptin is a 16 kDa protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the leptin receptor in the brain and in many other tissues. Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland. Many studies have implicated leptin in anterior pituitary function including the observation that homozygous mutations of the leptin receptor gene led to morbid obesity, lack of pubertal development and decreased GH and TSH secretion. In addition, leptin functions as a neuroendocrine hormone and regulates many metabolic activities. Leptin also interacts with and regulates the hypothalamic-pituitary-adrenal, the hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-gonadal axes. All of the anterior pituitary cell types express the leptin receptor. However, leptin has been localized in specific subtypes of anterior pituitary cells indicating cell type-specific production of leptin in the anterior pituitary. Subcellular localization of leptin indicates co-storage with secretory granules and implicates hypothalamic releasing hormones in leptin secretion from anterior pituitary hormone cells. Leptin signal transduction in the anterior pituitary has been shown to involve the janus protein-tyrosine kinase (JAK)/signal transducer and activation of transcription (STAT) as well as suppressor of cytokine signalling (SOCS). These proteins are activated by tyrosine-phosphorylation in anterior pituitary cells. The various steps in pituitary leptin signal transduction remain to be elucidated.

Aging↗
PubMedDate not supplied

Pituitary carcinoma: an ultrastructural study of eleven cases.

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.

Adenoma↗
PubMedDate not supplied

Ultrastructural features of apoptosis in human pituitary adenomas.

Although several recent studies deal with various molecular aspects of apoptosis, or programmed cell death, very little information is available on the ultrastructural changes associated with apoptosis in the adenohypophysis and its role in the regulation of pituitary adenoma growth and progression. This paper describes the distinct ultrastructural sequences that develop during the various phases of the apoptotic process. The study is based on the ultrastructural investigation of more than 8,000 surgically removed pituitary biopsies, which were examined by histology and immunocytochemistry for diagnostic purposes. No apoptosis was found in normal adenohypophysis and it is also a rare event in pituitary adenomas. When present, adenomatous adenohypophysial cells exhibit common and characteristic apoptotic changes. The ultrastructural alterations of membraneous organelles associated with apoptosis are similar to those previously reported in other tissues. It is noteworthy that apoptosis is clearly distinguishable from the ubiquitous dark cells denoting the common way of cell death. The findings suggest that apoptosis in pituitary adenomas is not a random event. Practically every specimen containing multiple apoptotic cells represents corticotroph adenoma. Occasional examples occur in lactotroph or gonadotroph adenomas. Although electron microscopic specimens are admittedly small, the large number of investigated cases gives credence to the observations.

Adenoma↗
PubMedDate not supplied

Pituitary adenoma in Carney complex: an immunohistochemical, ultrastructural, and immunoelectron microscopic study.

First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicatesthat pituitary tumors in patients with Carney complex may not exhibit the same phenotype.

Abnormalities, Multiple↗
PubMedDate not supplied

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

Adenoma↗
PubMedDate not supplied

Ultrastructural and immunoelectron microscopic study of three unusual plurihormonal pituitary adenomas.

Monomorphous pituitary adenomas expressing several hormones by immunocytochemistry are common, whereas adenomas displaying multiple immunoreactivities and consisting of more than one morphologic cell types are rare. Three such unusual pituitary adenomas, surgically removed from two patients with acromegaly and one patient with hyperprolactinemia, were investigated by histology, immunocytochemistry, transmission electron microscopy, as well as immunoelectron microscopy using double immunogold labeling. Immunocytochemistry revealed variable degrees of immunoreactivities for growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (beta-TSH), and alpha-subunit of glycoprotein hormones in all three tumors. The three adenomas consisted of phenotypically diverse cell populations as documented by transmission electron microscopy. In addition to monohormonal GH cells, immunoelectron microscopy demonstrated numerous cells colocalizing GH and PRL or GH and beta-TSH, and rarely PRL and beta-TSH in tumors of acromegalics. The adenoma causing hyperprolactinemia consisted chiefly of mammosomatotrophs colocalizing PRL and GH, whereas beta-TSH labeling was scant. The three tumors in the study were selected from a cluster of five plurimorphous plurihormonal adenomas received from the same locale where they accounted for an unprecedented 21% of adenomas producing GH and/or PRL. The enhanced susceptibility to develop plurimorphous adenomas of the acidophil cell line may have a genetic basis in the stable population the patients came from.

Acromegaly↗
PubMedDate not supplied

Leydig cell hyperplasia due to a testicular embryonal carcinoma producing human chorionic gonadotropin.

Report of the case of a 21-year-old man who presented with gynecomastia and was found to have a testicular embryonal carcinoma producing human chorionic gonadotropin (HCG), associated with massive hyperplasia of Leydig cells. While the morphologic features of Leydig cell hyperplasia have been documented with excess endogenous luteinizing hormone (LH), as in Klinefelter's syndrome, and following administration of exogenous HCG, to our knowledge, this is the first description of the histologic and ultrastructural changes in Leydig cells associated with increased secretion of endogenous HCG. The Leydig cell stimulation which results from excess endogenous HCG is unusual in that it causes an elevation of estrogens which may be greater than the rise in androgens. It is concluded that embryonal cell carcinoma of the testis, producing HCG, may lead to Leydig cell hyperplasia with morphologic features similar to those seen in other conditions with such hyperplasia, and that there is no correlation between those morphologic features and testosterone production.

Adult↗
PubMedDate not supplied

Pituitary adenomas producing growth hormone, prolactin, and one or more glycoprotein hormones: a histologic, immunohistochemical, and ultrastructural study of four surgically removed tumors.

The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones--usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation.

Adenoma, Acidophil↗
PubMedDate not supplied

Sex-linked ultrastructural dichotomy of gonadotroph adenomas of the human pituitary: an electron microscopic analysis of 145 tumors.

The ultrastructure of 145 pituitary gonadotroph adenomas was investigated with special regard to the fine structural appearance of the Golgi apparatus. Eight-five of the tumors were removed from men, 60 from women. Except for a few males, gonadotropin oversecretion was not established clinically and the diagnosis had been made solely on morphologic grounds. Owing to sex-related dimorphism, the diagnostic criteria were different for tumors of men and women. In men, approximately 50% of adenomas were structurally well-differentiated, whereas the rest of the tumors consisted of areas showing varying degrees of differentiation. The Golgi complex exhibited no signs of vacuolar transformation in any of the tumors in men. In women, more than 70% of tumors were uniformly well-differentiated, displaying vesicular transformation of Golgi complex (honeycomb Golgi complex), a characteristic diagnostic marker. In two adenomas, instead of the honeycomb Golgi complex, another unique alteration of the Golgi apparatus was encountered, comprising transformation of Golgi complex into a tripartite cloverleaflike structure with a pair of centrioles at its base. As suggested by formation of vacuoles in the center of the loops, this unusual change may be the fore-runner of honeycomb Golgi complex. Differences of the Golgi complex are viewed as morphologic expression of the fact that gonadotroph regulation and function in the two sexes are not the same.

Adenoma↗
PubMedDate not supplied

Ultrastructural markers in the pathologic diagnosis of pituitary adenomas.

The functional-morphologic classification of pituitary adenomas increased the number of distinguishable morphologic entities from 3 (acidophilic, basophilic, chromophobic) to 15. Identification of tumor types requires histology as well as immunohistochemistry and electron microscopy. Electron microscopy has a pivotal role in the recognition and separation of entities with overlapping immunohistochemical profiles. Electron microscopic diagnosis is facilitated considerably by structural markers present in the majority of adenoma types. Two groups of ultrastructural markers are discussed. Organelle markers are represented by specific morphology/arrangement of ubiquitous cytoplasmic constituents (rough endoplasmic reticulum, Golgi apparatus, mitochondria). Special markers are usually restricted to a particular pituitary cell type, its tumors, or both (filamentous aggregates, particular morphology of secretory granules, etc). Evaluation of general ultrastructural features and identification of structural markers permit conclusive diagnosis in the majority of pituitary adenomas. Cell derivation remains uncertain in many so-called clinically nonfunctioning adenomas with no or insufficient markers and poorly developed cytoplasmic organization associated with low endocrine activity.

Adenoma↗
PubMedDate not supplied

Pituitary adenoma with neuronal choristoma (PANCH): composite lesion or lineage infidelity?

Fifteen cases of the rare association of pituitary adenoma and neuronal choristoma (PANCH) were investigated by histology, immunohistochemistry, and electron microscopy. Acromegaly was apparent clinically in 11 patients and was equivocal in 1, and 3 lesions appeared to be nonfunctioning. Histology revealed various proportions of chromophobic PA and nervous tissue consisting of neuronlike cells and neuropil. Immunohistochemistry documented growth hormone (GH) in every PA, including those unassociated with clinical acromegaly. In contrast, the NCH component showed no consistent immunohistochemical profile. Most frequent reactivities were for the pituitary hormone alpha subunit, thyroid-stimulating hormone, and GH, whereas only a few cases displayed scattered positivity for GH-releasing hormone. Low-molecular weight keratin tested positive in PAs and in a few cells and processes of an NCH. A few fibrous bodies were immunoreactive for neurofilament protein. Electron microscopy revealed sparsely granulated GH cell adenoma, neurons, and neuropil. Cells intermediate between PA and neurons were numerous in 1 lesion. The present morphologic findings as well as lack of GH cell hyperplasia and the consistent association of NCH with but one type of PA do not support the causative role of NCH in the initiation of PA, as proposed previously. It appears that NCH is the result of neuronal differentiation within sparsely granulated GH cell adenomas.

Adenoma, Chromophobe↗
PubMedDate not supplied

Pituitary adenoma: a DNA flow cytometric study of 192 clinicopathologically characterized tumors.

A clinically, immunohistochemically and ultrastructurally characterized series of 192 pituitary adenomas was analyzed for DNA content by flow cytometry. Results were assessed not only relative to tumor immunotype, size, and invasiveness, but also with frequency of recurrence. Case selection was non-random; males predominated (1.8:1) and the ratio of macro-to-microadenomas was 4.2:1. Female patients were slightly younger and, in all adenoma categories, less often had invasive tumors: PRL (15%/30%), ACTH (17%/44%), LH/FSH (8%/27%) and null cell adenomas (0%/27%). With the exception of prolactin cell adenomas, similar proportions of macroadenomas and invasive tumors in all tumor subtypes were diploid and non-diploid. Prolactin adenomas differed in that tumors of males showed a high rate of non-diploidy (65%); such tumors were predominantly macroadenomas, but only 28% were invasive. Among GH-containing tumors 78% were macroadenomas, 40% were nondiploid, and the frequency of invasive macroadenomas was higher (49%) than in PRL tumors (21%). ACTH adenomas were mainly microadenomas (81%), their rate invasion (29%) and of non-diploidy being low (14%). Among "non-functioning" (LH/FSH, null cell adenomas), LH/FSH-producing tumors were all macroadenomas, but with low rates of invasion (23%) and non-diploidy (9%). Null cell adenomas, nearly all macroadenomas, had similar low invasion rate (21%), but were more often non-diploid (39%). In all adenoma subgroups S-phase fractions were higher in non-diploid adenomas by an overall ratio of 2.1:1. Prolactin adenomas showed the highest (15.2%) and LH/FSH adenomas the lowest (5.6%) mean S-phase fraction. When compared to long-term follow-up, neither this parameter nor ploidy correlated with tumor size or invasiveness. Lastly, long-term follow-up showed ploidy to be an unreliable predictor of tumor persistence or recurrence.

Adenoma↗
PubMedDate not supplied

Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome.

We report the case of a 42-year-old woman with Cushing's disease and Nelson's syndrome. When she was 17 years old, transsphenoidal surgery was performed. A detailed morphologic study demonstrated nodular hyperplasia of corticotroph cells but no adenoma. Following a long-lasting remission (14 years), Cushing's disease recurred. After an unsuccessful second transsphenoidal surgery, Cushing's disease persisted and both adrenals were removed (at the age of 34). Subsequently the patient developed Nelson's syndrome. The pituitary tumor proved to be a corticotroph adenoma; it was removed by the transsphenoidal approach (at the age of 42). Although in most patients Cushing's disease is due to an ACTH-secreting pituitary corticotroph adenoma which precedes the manifestation of Nelson's syndrome, our case indicates not only that corticotroph hyperplasia may cause Cushing's disease but that it may exist before the development of Nelson's syndrome after the removal of both adrenals. Our study supports the view that protracted stimulation of corticotrophs resulting from the elimination of the negative inhibitory feedback effect by corticosteroids plays a role in adenoma initiation.

ACTH-Secreting Pituitary Adenoma↗