Biomedical subjects

G Kontogeorgos

Publications and source records attributed to G Kontogeorgos.

At least 37 records · Page 2Linked to original sources

PubMed1998

Juvenile nasopharyngeal angiofibroma--a rare case of primary orbital development.

PURPOSE: To present a rare case of juvenile nasopharyngeal angiofibroma invading the ophthalmic orbit. METHODS: The CT scan examination and the ultrasound tomography revealed the existence of a homogeneous solid mass causing distention and erosion of the nasal wall as well as dislocation of the ocular bulbus. RESULT: The patient was operated, the mass was carefully liberated from its synechiae and it was totally excised with its capsule. CONCLUSION: A rare case of juvenile nasopharyngeal angiofibroma invading the orbit is presented. The tumor was totally excized and the patient is five years after the operation in good general health without recurrence of the tumor.

Adult↗

PubMed1998

Telomeres and telomerase in endocrine pathology.

Telomeres representing repetitive DNA sequences of chromosome ends are necessary for maintaining chromosomal integrity. The enzyme telomerase synthesizes de novo telomeric repeats and incorporates them onto the DNA 3'-ends of chromosomes. Stability of chromosome ends and activation of telomerase are elementary requirements for cell immortalization and tumor progression. The telomeric length and telomerase activity have been recently studied in several human neoplasms, including those of endocrine tissues. Assessment of telomerase activity may help to distinguish normal or hyperplastic from neoplastic tissues. Inhibition or inactivation of telomerase activity may provide novel strategies for cancer therapy.

Animals↗

PubMed1998

Transferrin and transferrin receptor in human hypophysis and pituitary adenomas.

Transferrin (Tf), a major transport protein for iron in the blood and an essential growth factor in some tissues, acts via specific transferrin receptor (TfR). We studied the cellular distribution of Tf and TfR gene expression in 50 human nontumorous autopsy pituitaries and 42 surgically removed pituitary adenomas. Tf and TfR mRNA accumulation was correlated with Ki-67 proliferation marker. In nontumorous pituitaries without iron deposits Tf immunoreactivity was localized in some growth hormone, prolactin, adrenocorticotropin, thyrotropin, and luteinizing hormone cells. Most adenohypophysial cells were immunopositive for TfR. In pituitaries with iron deposits, Tf and TfR were localized only in iron-free cells. Tf mRNA and protein were present in 27 and 32 adenomas, respectively; Ki-67 labeling index of tumors positive for Tf mRNA was significantly higher than in those without transcript (0.94% versus 0.51%; P < 0.025). A positive linear correlation between tumor growth fraction and Tf mRNA signal intensity was evident (r = 0.32; P = 0.04). TfR mRNA and encoded protein were demonstrated in 26 and 31 adenomas, respectively; Ki-67 immunoreactivities were not correlated with the presence of TfR transcripts and signal intensities. These data suggest that Tf may act as a growth-promoting factor for pituitary tumors.

Adenoma↗

PubMed1997

Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice.

To study the involvement of TNF in cerebral pathology in vivo and to define cellular interactions within the central nervous system (CNS) that promote TNF signaling, we have expressed this cytokine either as a wild-type or a mutant transmembrane form in astrocytes or neurons of transgenic mice. Mice expressing wild-type human TNF in either of these cell types spontaneously develop a neurologic disorder manifested by ataxia, seizures, and paralysis and bear histologic evidence of chronic CNS inflammation and degeneration. Moreover, astrocyte-specific expression of transmembrane TNF triggers a similar neurologic phenotype. Interestingly, transgenic mice producing a high level of transmembrane TNF in their neurons develop no apparent phenotypic abnormalities, suggesting that appropriate cellular interactions should form to allow for contact-dependent TNF signals to induce CNS pathology. These results demonstrate that target cells mediating the neuroinflammatory activities of TNF localize in the vicinity of astrocytes rather than neurons.

Animals↗

PubMed1997

Stress-response proteins in human pituitary adenomas. Expression of heat-shock protein 72 (HSP-72).

The presence of heat-shock protein 72 (HSP-72) was investigated by immunohistochemistry (IHC) in a series of 28 surgically removed pituitary adenomas including six somatotroph, two mammosomatotroph, five lactotroph, six corticotroph, four null cell adenomas, and three oncocytomas. Overall, 25 tumors (90%) were positive for HSP-72. One somatotroph, one lactotroph, and one null cell adenomas each contained only sparse, small HSP-72 immunoreactive granules and were regarded as negative. The expression of HSP-72 was commonly uneven differing in degree from cell to cell and among various tumors. In most adenomas, the immunoreactivity was seen as fine granules of moderate density, distributed throughout the cytoplasm. In some cells, the immunoreactivity was strong and diffuse. In one somatotroph, two corticotroph, one null cell, and one oncocytic adenomas, nearly all tumor cells were strongly positive. Adenoma cells, located adjacent to capillaries and small vessels, commonly showed a selective and strong immunoreactivity for HSP-72. The fragments of nontumorous adenohypophysial parenchyma also contained fine immunoreactive cytoplasmic granules accumulating in scattered hormone-producing cells in stellate cells. These results show that HSP-72 is expressed in most pituitary adenomas with a mostly focal and less frequently diffuse pattern of overexpression.

Adenoma↗

PubMed1997

Effect of fixation on interphase cytogenetic analysis by direct fluorescence in situ hybridization on cell imprints.

The direct fluorescent in situ hybridization (FISH) technique using a centromerespecific DNA probe for chromosome 11 was applied on fresh tissue imprints from melanomas and pituitary adenomas. The cell imprints were fixed in acetone and formalin, and the influence of fixation was evaluated. Acetone fixed imprints gave a sharp and intense fluorescent signal in a large number of cells from both tumors without any pretreatment. In contrast, formalin fixed imprints disclosed a weak hybridization signal in a few cells even after careful enzymatic digestion. Direct FISH on acetone fixed cell imprints represents a simple and time saving technique applicable to any laboratory for the study of numerical chromosomal abnormalities.

Acetone↗

PubMed1997

Postadhesive technique for archival paraffin sections.

We present a postadhesive protocol for adhering paraffin sections of archival material to microscope slides. Appropriately posttreated sections, subsequently processed for immunohistochemistry, remained attached to the slides and were well preserved with no signs of artifacts, such as scratching and shrinkage. The immunohistochemical staining was intense and antigen-specific without nonspecific background. Specific staining intensity was equal to that produced in untreated control sections; however, the latter became partially or fully detached from the slides. The postadhesion protocol may be used with modern techniques and is recommended for reclaiming use of otherwise unsuitable paraffin sections of archival material.

Antigens↗

PubMed1997

Apoptosis in human pituitary adenomas: a morphologic and in situ end-labeling study.

Apoptosis seems to be an important process in normal tissues and in neoplastic lesions. Although electron microscopic features of apoptosis are characteristic, it is difficult to detect apoptotic cells with accuracy by light microscopy. Labeling of intranucleosomal DNA fragmentation can provide information on the apoptotic status of tumors. We studied apoptosis by the in situ end-labeling technique in 85 pituitary adenomas (63 functioning, 22 nonfunctioning). The functioning tumors included 19 somatotroph, 17 lactotroph, 9 mixed growth hormone/prolactin-producing, 2 thyrotroph, and 16 corticotroph adenomas. A few scattered cells displaying characteristic apoptotic changes were observed by histologic examination and electron microscopy. We estimated the apoptotic labeling index (ALI) of the adenomas by quantitating the percentages of positive nuclei. Overall, functioning adenomas showed a significantly higher ALI (5.64%) than did nonfunctioning tumors (1.84%). The ALI was higher in thyrotroph adenomas (10.26%) and lower in corticotroph (5.94%), somatotroph (5.51%), lactotroph (5.25%), and mixed growth hormone/prolactin-producing adenomas (5.11%). In conclusion, in situ end-labeling showed that apoptosis mostly occurs in functioning pituitary adenomas. These data suggest that assessment of apoptosis can be used to evaluate drug effects and to define which adenoma subtypes are more susceptible to drug therapy.

Adenoma↗

PubMed1996

Intravitreal application of ganciclovir in rabbits: ERG and electron-microscopic findings.

The retinal toxic effect after intravitreal use of ganciclovir has been the subject of our experimental investigation on 20 New Zealand rabbits. Different doses of ganciclovir ranging from 200 to 600 micrograms/0.1 ml were injected intravitreously, and ERG changes were recorded at different time points after drug administration. Finally the animals were killed and the retinal lesions were studied by electron microscopy. According to our experiments, ganciclovir doses of 300-600 micrograms/0.1 ml have a clearly toxic effect on the retina as shown by ERG changes. One month after the injection, the electroretinogram is either extinguished or clearly affected. Noteworthy is the fact that in a dose of 200 micrograms/0.1 ml, the ERG b-wave shows a 20% reduction of its normal amplitude 4 months after ganciclovir delivery. Electron microscopy of the retina revealed in the inner segment of the receptor cells the existence of dilatation and vesiculation of the endoplasmic reticulum in the surrounding nuclear cytoplasm and swelling of the mitochondria with fragmentation of the cristae in several of them. In the outer segment of the photoreceptor cells, degeneration and destruction of the lamellae accompanied by disintegration of the adjacent protoplasm in parts of certain rods and cones appeared. Finally large vacuoles of irregular shape in the synapses and degenerative mitochondria and empty vacuoles in the optic nerve fibers were shown.

Animals↗

PubMed1996

DNA measurement in pituitary adenomas assessed on imprints by image analysis.

OBJECTIVE: To determine the DNA content and S-phase fraction (SPF) of pituitary adenomas by image analysis and to correlate them with clinical and morphologic parameters. STUDY DESIGN: The study group consisted of 26 prospectively collected cases of operated pituitary adenomas (3 microadenomas and 23 macroadenomas). The tumors were classified by histology, immunocytochemistry and electron microscopy. DNA measurement was performed on imprints from fresh pituitary tissue. Samples of nontumorous adenohypophysial parenchyma served as normal controls. RESULTS: Overall, 31% of adenomas, all but one functioning one, were aneuploid. The remaining nonfunctioning aneuploid tumor was a null cell adenoma with glycoprotein differentiation. All aneuploid tumors were macroadenomas, mostly at advanced stages, III and IV. Dural invasion, although frequent in macroadenomas (78%), was not correlated with DNA ploidy and SPF. An increased number of hyperpentaploid aneuploid cells was noted primarily in aneuploid tumors. The mean SPF was < 2.50%, with a statistically significant difference between aneuploid and diploid adenomas (3.60% vs. 1.70%). CONCLUSION: The results suggest that quantitative assessment of DNA content may provide important information, particularly in functioning adenomas. In addition, fresh tissue imprints represent excellent material for optimum cytometric measurements by image analysis systems, even for microadenomas.

Adenoma↗

PubMed1995

Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha.

Cytokines are now recognized to play important roles in the physiology of the central nervous system (CNS) during health and disease. Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of several human CNS disorders including multiple sclerosis, AIDS dementia, and cerebral malaria. We have generated transgenic mice that constitutively express a murine TNF-alpha transgene, under the control of its own promoter, specifically in their CNS and that spontaneously develop a chronic inflammatory demyelinating disease with 100% penetrance from around 3-8 weeks of age. High-level expression of the transgene was seen in neurons distributed throughout the brain. Disease is manifested by ataxia, seizures, and paresis and leads to early death. Histopathological analysis revealed infiltration of the meninges and CNS parenchyma by CD4+ and CD8+ T lymphocytes, widespread reactive astrocytosis and microgliosis, and focal demyelination. The direct action of TNF-alpha in the pathogenesis of this disease was confirmed by peripheral administration of a neutralizing anti-murine TNF-alpha antibody. This treatment completely prevented the development of neurological symptoms, T-cell infiltration into the CNS parenchyma, astrocytosis, and demyelination, and greatly reduced the severity of reactive microgliosis. These results demonstrate that overexpression of TNF-alpha in the CNS can cause abnormalities in nervous system structure and function. The disease induced in TNF-alpha transgenic mice shows clinical and histopathological features characteristic of inflammatory demyelinating CNS disorders in humans, and these mice represent a relevant in vivo model for their further study.

Animals↗

PubMed1995

The type I interleukin-1 receptor acts in series with tumor necrosis factor (TNF) to induce arthritis in TNF-transgenic mice.

The pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to be primary mediators in the pathogenesis of chronic inflammatory joint diseases. However, the relative contributions of these molecules to the development and progression of disease is not known. In the present study, we have investigated the involvement of the type I IL-1 receptor in the development and progression of chronic arthritis in a previously described TNF-transgenic mouse model of this disease. A neutralizing monoclonal antibody to the murine type I IL-1 receptor was injected intraperitoneally three times a week from birth to 9 weeks of age. In the positive control group of untreated transgenic mice the incidence of arthritis was 100% after 9 weeks of age. The injection of normal hamster IgG did not influence the incidence or development of arthritis. In contrast, the injection of antibody to the type I IL-1 receptor completely prevented the development of arthritis. Clinical evaluation of disease was confirmed histologically, anti-receptor antibody-treated mice showed no sign of arthritic change. Moreover, the analysis of sera taken at the end of the study period showed that the neutralization of arthritis by IL-1 receptor antibody treatment was accompanied by significantly lower levels of circulating human TNF compared to the control groups and to untreated transgenic mice prior to disease onset. Taken together, these results show that IL-1 signaling blockade exerts a direct negative feedback effect on TNF production. Our results show that in TNF-transgenic mice the IL-1 receptor accepts the whole pathogenic load of TNF, thereby acting as a potent downstream mediator in the pathogenesis of chronic arthritis.

Animals↗

PubMed1995

Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings.

This report describes the clinicopathological features of 16 patients with lymphocytic hypophysitis and compares the results with the published literature. There were 2 males and 14 females in this series. In 10 of the 14 females (71%), the presentation was associated with pregnancy. Nine patients (56%) presented with symptoms of an expanding pituitary sellar mass, 10 (63%) had anterior pituitary hypofunction, 3 had diabetes insipidus (19%). Progressive undiagnosed hypopituitarism led to the demise of 3 patients (19%). Hyperprolactinemia was encountered in 6 patients (38%), and elevated growth hormone levels (GH) resulted in IGF-1 excess in one patient. Computed tomography (CT) and magnetic resonance (MR) imaging revealed features of a pituitary mass mimicking an adenoma in 10 cases (83%). Four patients (25%) had associated autoimmune thyroiditis. Morphologic examination of the pituitary and immunohistochemistry showed a polyclonal lymphoplasmacytic infiltrate as well as occasional neutrophils, eosinophils, and macrophages; the chronic inflammatory process resulted in focal or diffuse adenohypophysial destruction of variable severity with associated fibrosis. The inflammatory infiltrate involved the neurohypophysis in 2 cases and one of these patients had diabetes insipidus; the posterior lobe of two other patients with diabetes insipidus was not examined morphologically. We conclude that lymphocytic hypophysitis should be considered in the differential diagnosis of females with pituitary enlargement presenting in the peripartum period as well as those patients in whom pituitary hormone deficiency and/or excess is noted in association with a co-existing autoimmune disorder. This clinical suspicion should probably also be extended to include patients presenting with rapidly growing pituitary masses associated with compressive symptoms with or without pituitary hormone dysfunction. Because of the transient endocrine and compressive features of this condition in many instances, conservative treatment on the basis of clinical suspicion alone may obviate the need for aggressive pituitary surgery.

Adult↗

PubMed1995

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide.

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.

Acromegaly↗

PubMed1995

Asynchronous pituitary adenomas with differing morphology.

Recurrent pituitary tumors can sometimes pose a diagnostic and therapeutic challenge. We report a case of a 43-year-old man who presented twice, 13 years apart, with pituitary adenoma marked by headaches, visual impairment, and no signs of endocrinologic abnormality. At initial presentation computed tomographic scan documented a pituitary mass eroding the sellar floor, with suprasellar and parasellar extension. The patient underwent transsphenoidal surgery and the tumor was classified as a silent corticotroph adenoma, subtype 2. Thirteen years later, clinical symptoms of a destructive pituitary mass reappeared. This time, the adenoma revealed typical ultrastructural features of an oncocytoma; it had a different immunocytochemical profile from the first tumor. Given these striking morphologic differences, we consider the two adenomas to represent asynchronous, de novo formations. We conclude that the recurrence of a resected pituitary tumor may also represent a metachronous development of two distinct pituitary adenomas.

Adenoma↗

PubMed1993

Production of alpha-subunit of glycoprotein hormones by pituitary somatotroph adenomas in vitro.

Somatotroph adenomas of the pituitary secrete growth hormone in excess and are associated with acromegaly. Morphologically, they can be separated into two entities, densely and sparsely granulated variants. It has been shown that a number of somatotroph adenomas produce alpha-subunit of glycoprotein hormones; however, it is not clear whether alpha-subunit production correlates with tumor cell morphology. We studied 32 surgically removed pituitary somatotroph adenomas in tissue culture to determine structure-function correlations of growth hormone and alpha-subunit production. All tumors were classified on the basis of detailed histological, immunocytochemical and electron-microscopic studies. Fifteen tumors were densely granulated and 17 were sparsely granulated. In addition to growth hormone, all 15 densely granulated tumors released alpha-subunit in vitro, whereas of the 17 sparsely granulated tumors only 4 released alpha-subunit; moreover, the mean baseline levels of alpha-subunit were significantly higher in densely granulated adenomas than in sparsely granulated adenomas. Parallel response of release of both hormones was found during stimulation with growth hormone-releasing hormone or thyrotropin-releasing hormone and during suppression with somatostatin or bromocriptine in densely granulated tumors. alpha-subunit response to stimulation or suppression could not be determined with significance in sparsely granulated tumors because of low basal levels. The results indicate that alpha-subunit production and release is characteristic of densely granulated somatotroph adenomas and that alpha-subunit is coregulated with growth hormone by adenohypophysiotropic substances; in contrast, alpha-subunit production, by sparsely granulated somatotroph adenomas is rare and, when present, much lower in quantity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1992

Interleukin-6, a growth promoting cytokine, is present in human pituitary adenomas: an immunocytochemical study.

OBJECTIVE: The aim of this study was to investigate the presence of interleukin-6 (IL-6) in human pituitary adenomas. DESIGN: Immunocytochemistry was performed in 15 cases of pituitary adenomas obtained at transsphenoidal surgery. PATIENTS: Fifteen cases of pituitary adenomas were examined; these included five GH-secreting adenomas, four prolactinomas, four ACTH-secreting adenomas and two null-cell ('functionless') adenomas. MEASUREMENTS: Each tumour was stained for the presence of IL-6 by means of the avidin-biotin-peroxidase complex (ABC) technique, and was also stained for GH, prolactin, ACTH and alpha-subunit by conventional immunocytochemistry. RESULTS: Fourteen of the 15 tumours examined, excepting one GH-secreting tumour, demonstrated clusters of IL-6 positively stained cells; the specificity of the staining was established by a significant decrease in staining in parallel sections of all tumours studied when the anti IL-6 antibody was preabsorbed with recombinant human IL-6. CONCLUSIONS: It is concluded that IL-6 immunoreactivity is present in human pituitary tumours, and is independent of the specific secretory cell product. The role of this cytokine in the pathogenesis of such tumours requires further investigation.

Adenoma↗

PubMed1992

Double adenomas of the pituitary: a clinicopathological study of 11 tumors.

Of more than 3000 cases of surgically removed pituitary adenomas, 11 were defined as "double adenomas," i.e., 2 morphologically or immunocytologically distinct tumors. In 8 cases, the lesions exhibited differing histological features and immunophenotypes; in 2 specimens, distinct ultrastructural features were noted as well. In another instance, despite histological and immunocytological uniformity, the two neoplastic components demonstrated distinct ultrastructure. In yet another case, the two adenomas were consecutively removed; despite similar histological features, they differed in immunocytological and ultrastructural characteristics. Last, in one case, the adenoma was histologically uniform, but a portion of the mass exhibited immunoreactivity by ultrastructural features distinct from those of the remainder of the lesion. Hormonal excess attributed to both tumors could be correlated with endocrine manifestations in two cases. Double adenomas of the pituitary occur infrequently. In routine histological sections of surgical material, they are often difficult if not impossible to identify. Presented herein are clinical and endocrinological data on 10 cases of double pituitary adenomas correlated with morphological and immunocytochemical results. The literature regarding multiple adenomas is reviewed as are the diagnostic and therapeutic difficulties associated with these rare lesions.

Acromegaly↗