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Biomedical subjects

G Kontogeorgos

Publications and source records attributed to G Kontogeorgos.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications.

In a review of autopsy material from two centers, 20 pituitary glands were found containing multiple adenomas. In total, 44 adenomas were identified histologically; 16 glands contained double tumors and in four glands triple adenomas were found. Size was measured in 30 tumors, all of which were microadenomas. Thirty-four adenomas were located in the lateral wings and 10 lay in the median wedge. Forty-one tumors were chromophobic and three were basophilic. Immunocytochemical analysis of the 44 tumors demonstrated the presence of prolactin in 11, adrenocorticotropic hormone in three, growth hormone in one, and alpha-subunit as well as follicle-stimulating hormone and luteinizing hormone in one. Of the 20 patients studied, there were 11 men and nine women, with an average age of 69 years. All patients died from various nonendocrine causes. With the exception of one patient who appeared mildly acromegalic, no correlation was observed between pituitary morphology and clinical data. This study found a 10.4% frequency of adenomas in pituitaries studied randomly at autopsy. Multiple tumors were encountered in 0.9% of cases. Despite its low frequency, adenoma multiplicity may underlie surgical failure in cases in which one adenoma is removed and the other is left behind.

Adenoma↗
PubMed1991

Alpha-subunit immunoreactivity in plurihormonal pituitary adenomas of patients with acromegaly.

Twelve plurihormonal pituitary adenomas, removed surgically from 11 of 20 patients with acromegaly, were investigated. The mean age of the 11 patients was 45 yr. Seven patients with eight tumors were men. The tumors were immunostained for all known adenohypophysial hormones by the avidin-biotin-peroxidase complex (ABC) technique. All 12 adenomas were immunoreactive for growth hormone (GH) and alpha-subunit; prolactin (PRL) was detected in five tumors. Stains for the beta-subunits of glycoprotein hormones [thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)] revealed immunopositivity for specific beta-subunits in ten adenomas. The close association between GH and alpha-subunit in pituitary tumors of acromegalic patients remains to be explained.

Acromegaly↗
PubMed1991

Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation.

The case of a 35-year-old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented. Histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level. Focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron-microscopic studies. It is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone-producing cell types. The factors accounting for differentiating to various cell populations have yet to be elucidated.

Adenoma↗
PubMed1990

ERG and electron microscopic findings after intravitreal use of aminoglycosides.

The electroretinographic (ERG) changes and the retinal lesions shown by electron microscopy were studied in rabbits after intravitreal use of amikacin and tobramycin. We studied 40 eyes of 20 rabbits in which different doses ranging from 250 micrograms to 1000 micrograms of aminoglycosides were injected into the vitreous cavity. Tobramycin, and to some extent amikacin, were toxic to the retina even in doses of 500 micrograms as shown by ERG changes. The pathologic retinal lesions shown by electron microscopy were characterized by membranous inclusions in the retinal pigment epithelium, tumefaction of the photoreceptors, and partial disorganization of the inner layers. In doses of 250 micrograms or less, these two antibiotics seem to be nontoxic after a follow-up of three months.

Amikacin↗
PubMed1988

S-100 protein and neuron specific enolase (NSE) expression by chordomas in relation to the composition of their stromal mucosubstances.

The immunoreactivity of S-100 protein and neuron specific enolase (NSE.) was correlated with the composition of stromal glycosaminoglycans in chordomas and human notochords, in a combined histochemical and immunohistochemical study. We found that S-100 protein is negative in notochordal and chordoma cells in the absence of stromal mucosubstances or in the presence of small quantities of hyaluronic acid. The positivity of S-100 immunoreaction was found to be related to the presence of stromal glycosaminoglycans of the chondroitine sulfate A and C type. NSE. was found positive in cells presenting features of high metabolic activity. Consequently S-100 protein and NSE. immunoreactivity cannot have any cytogenetic implications, but they could be considered as markers indicating specific cell-stromal functional interactions.

Chordoma↗
PubMed1986

Tubal conjoined twin pregnancy.

A unique case of tubal conjoined twin pregnancy is reported. The embryos presented a lateral type of conjunction, which also is extremely rare, and were classified as symmetrical iliothroacopagus conjoined twins.

Adult↗