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Biomedical subjects

W Saeger

Publications and source records attributed to W Saeger.

At least 109 records · Page 6Linked to original sources
PubMed1992

Immunohistology of islet amyloid polypeptide in diabetes mellitus: semi-quantitative studies in a post-mortem series.

Immunoreactivity for islet amyloid polypeptide (IAPP) in the islets of Langerhans of non-insulin-dependent diabetic patients and non-diabetic patients of a non-selected post-mortem series was studied with a new polyclonal IAPP antibody. Out of 133 patients examined, 124 exhibited immunoreactivity for IAPP. Immunoreactivity was localized intra- and extracellularly and was limited to the islets of Langerhans. No extracellular immunoreactivity was observed in amyloid-negative cases. Co-localization of insulin and IAPP in the same islet-cells was verified by double staining with monoclonal insulin and polyclonal IAPP antibodies. Of 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and islet amyloid, 98 exhibited IAPP-positive deposits and 71 exhibited intracellular immunoreactivity. Evaluation of intracellular immunoreactivity and degree of islet amyloid deposition in cases of overt NIDDM revealed an inverse relationship, in that intracellular IAPP immunoreactivity were reduced in patients with developing islet amyloid deposition. Our data are consistent with the hypothesis of primary beta-cell dysfunction leading to amyloid formation, with subsequent disturbance of beta-cell homeostasis.

Aged↗
PubMed1992

Autoradiographic demonstration of in vivo 125I-growth hormone-releasing hormone (GHRH) binding by human GH-secreting pituitary adenomas transplanted on athymic nude mice.

This study was designed for the purpose of investigating a method for in vivo tumor labelling of human GH (hGH) secreting pituitary adenomas. Pituitary adenoma tissue removed from four acromegalic patients was transplanted into 62 athymic nude mice. After positive GHRH stimulation tests 125I-GHRH(1-44) NH2 was injected intravenously (i.v.) in ten nude mice. 10 min after 125I-GHRH injection, the nude mice were sacrificed, the transplants excised and prepared for light microscopical autoradiography. The mouse pituitary and skeletal muscle specimens served as controls. After the i.v. injection of 125I-GHRH we observed a marked accumulation of silver grains within the adenoma tissue indicating tumor labelling. This study is a first step in investigating a new method for labelling small residues of hGH secreting pituitary adenomas intraoperatively.

Adenoma↗
PubMed1992

Ultrastructural-morphometric effects of radiotherapy on pituitary adenomas in acromegaly.

Within a series of 22 irradiated GH-producing adenomas we studied by light microscopical and morphometrical means the grading of nuclear pleomorphism, the proportion of densely granulated cells, the number of mitoses, multinuclear cells, necrotic or necrobiotic cells, and the degree of fibrosis in comparison to non-irradiated tumours. By electronmicroscopical morphometry we investigated the changes in area, circumference, area percentage, and number of intracellular structures. The rate of necrobiotic cells and the grade of nuclear pleomorphism were significantly higher in the irradiated tumours. The fibrotic areas were larger. No differences were observed in the degree of granulation and the rate of multinuclear cells. Mitoses were found in only one tumour. Within the group of the well-differentiated adenomas the areas and circumferences of the nuclei, nucleoli, mitochondria, immature secretory granules, and secretory granules increased significantly. The area percentages of the nuclei, mitochondria, immature secretory granules, and secretory granules increased as well. The mitochondria, Golgi-fields, and the rough endoplasmatic reticulum decreased in number. The undifferentiated adenomas changed almost in the same significant way. To us most of these changes are a sign of irradiation damage. The enlargement of intracellular structures could be a sign of an increased rate of secretory activity.

Acromegaly↗
PubMed1992

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.

Adrenal Gland Neoplasms↗
PubMed1991

Electron microscopical morphometry of well-differentiated and undifferentiated ACTH secreting adenomas in Cushing's disease and Nelson's syndrome.

Adrenocorticotrophic hormone (ACTH)-secreting adenomas of patients with Cushing's disease (undifferentiated and well-differentiated ACTH-cell adenomas) were studied ultrastructurally and analysed morphometrically by a computer-supported quantitative image-analysing system. They were compared with identically prepared ACTH tumours (undifferentiated and well-differentiated ACTH-cell adenomas) of pituitaries from bilateral adrenalectomised patients with Nelson's syndrome. The aim of our study was to look for significant differences in ultrastructure and to evaluate these findings statistically regarding adenoma types and clinical syndromes. Clinical syndromes aside, more secretory granules and larger-sized prosecretory granules were measured in the well-differentiated ACTH-cell adenomas. The undifferentiated adenomas showed a greater content of nucleoli and prosecretory granules. Within the adenoma types, comparison of well-differentiated ACTH-cell adenomas showed that the clinical group of Cushing's disease contained larger areas of cytofilaments, whereas the clinical group of Nelson's syndrome had a larger tumour size and more lysosomes. Comparing the undifferentiated adenomas of both clinical groups the adenomas in Cushing's disease contained larger nuclei and more lysosomes, whereas the adenomas in Nelson's syndrome were larger in tumour size and contained larger prosecretory granules. Comparison of well-differentiated and undifferentiated adenomas in Cushing's disease showed more secretory granules and bigger prosecretory granules in well-differentiated adenomas whereas in undifferentiated adenomas the total area of the nuclei is larger, the nucleoli increase in number and size and the lysosomes are more frequent. Comparison of well-differentiated and undifferentiated adenomas in Nelson's syndrome demonstrated more lysosomes in well-differentiated adenomas and a larger total area of the nuclei in undifferentiated adenomas. The differences between the well-differentiated adenomas (mainly more secretory granules and larger prosecretory granules) and undifferentiated adenomas (mainly more and larger nuclei and nucleoli and more prosecretory granules) prove the clear separability between the adenoma types, not demonstrated in the literature up to now. The significant differences between adenomas in Cushing's disease (mainly more cytofilaments) and Nelson's syndrome (mainly more ribosomes and larger prosecretory granules) may be interpreted as different cell reactions due to the hypercortisolism present in Cushing's disease and lacking in Nelson's syndrome following adrenalectomy. Despite the fact that both clinical syndromes are based on the same adenoma types, indistinguishable by light microscopy, significant morphometrical findings in ultrastructure allow a clear discrimination of both clinical types.

Adenoma↗
PubMed1991

HGH, PRL and beta HCG/beta LH gene expression in clinically inactive pituitary adenomas detected by in situ hybridization.

Within our surgical collection clinically inactive pituitary adenomas represent 30.7% of all pituitary tumours. To characterize their endocrine activity we studied 40 clinically inactive pituitary adenomas with in situ hybridization (ISH) using cRNA probes labelled with 35S encoding growth hormone (GH), prolactin (PRL) and chorionic gonadotrophin (beta HCG). No tumour was associated with clinical evidence of elevated hormone secretion. A mild hyperprolactinaemia not correlated with hormone or the mRNA content of the cells was interpreted to be incidental in 11 patients. By histological analysis, immunohistochemistry (IH) and electron microscopy the adenomas were diagnosed as small cell chromophobic (n = 16) and large cell chromophobic (n = 8) adenomas, and oncocytomas (n = 16). Gene expression of one or more hormones was identified by ISH in 18 of 40 adenomas in few cells. GH and PRL gene expression was rare (GH mRNA in 3 of 40 tumours and PRL mRNA in 8 of 40 tumours) whereas in 14 of 40 adenomas beta HCG/beta LH gene expression was identified in scattered cells. Five of 40 adenomas lacking hybridization signals revealed hormones by IH. The detection of mRNA was accompanied by positive immunostaining for the respective hormones in 72%. The combination of ISH and IH reveals good evidence that the hormones are synthesized in the tumours and not taken up from the serum and stored in the cells. The two methods used together permit a more precise analysis of tumour biology than each alone.

Adenoma↗
PubMed1991

Detection of growth hormone, prolactin and human beta-chorionic gonadotropin messenger RNA in growth-hormone-secreting pituitary adenomas by in situ hybridization.

In a series of 39 adenomas from patients with the clinical hyperfunction syndrome of acromegaly and in one from a case of prolactinoma we studied the mRNA expression of growth hormone (GH), prolactin (PRL) and beta-human chorionic gonadotropin (HCG) by using this technique of in situ hybridization (ISH). This technique allows the direct identification and localization of cells expressing mRNA and thus synthesizing the respective hormone. The aim of our study was to demonstrate the frequent co-expression of PRL mRNA and HCG mRNA in pituitary adenomas of acromegalic patients. Probes for ISH of the above-mentioned hormones were obtained by subcloning cDNA fragments into pGEM plasmids. Subsequent Sp6-polymerase catalysed in vitro transcription with 35S-CTP revealed radiolabelled single-stranded antisense RNA probes [the probe for beta HCG detects beta-luteinizing hormone (beta LH) simultaneously because of a sequence homology of 90%]. To localize the labelled hybrids, autoradiography was carried out. Light microscopical evaluation of the tissue sections demonstrated positive signals in all cases for GH, in 80% of cases for PRL and in 25% of cases for HCG [LH] mRNA. The comparison of mRNA content shown by ISH with immunocytochemical (ICC) hormone detection revealed that in all cases the detection of GH corresponded to GH mRNA content of the cells. For PRL and HCG [LH] positive mRNA detection (ISH) and negative hormone detection (ICC) occurred in some cases (PRL 17.5%; HCG [LH] 15%). In contrast, negative mRNA detection (ISH) and positive hormone content (ICC) was also demonstrated (PRL 5%; HCG [LH] 37.5%). The remaining adenomas showed both mRNA and the respective hormone, as well as negative ISH and ICC.

Acromegaly↗
PubMed1991

In situ hybridization for different mRNA in GH-secreting and in inactive pituitary adenomas.

In a series of 40 pituitary adenomas in acromegaly all tumors showed mRNA for GH by in situ hybridization (ISH). The signals were mostly very strong and found in more than 80% of adenoma cells by using frozen sections. In paraffin sections the number of positive cells and the intensity of signals are lower. Prolactin mRNA was found in 87% of adenomas. In 27% more than 80% of cells were marked. beta-HCGmRNA (with 90% hormology for LH-mRNA) was demonstrable in very sparse cells of 25% of adenomas. Comparing ISH with immunohistology (IH) we found a correlation between signals and hormone content in 100% of adenomas for GH, in 60% for Prolactin and in 10% for Gonadotropins. In 18% Prolactin mRNA but not the hormone was demonstrable and in 5% Prolactin was immunostained but no hybridization signals were detected. In a series of 40 clinically inactive adenomas sparse cells of three tumors expressed GHmRNA and two of these contained also the hormone, whereas in one adenoma GH but not GHmRNA was demonstrable. Prolactin mRNA was found in 8 adenomas. 7 of these also contained the hormone. In two cases Prolactin but not Prolactin mRNA was present. Beta-HCG(LH)mRNA and the respective hormones were shown in very sparse cells of 6 adenomas, whereas only beta-HCG(LH)-mRNA was found in 8 cases. The significance of the findings is discussed.

Acromegaly↗
PubMed1991

Surgical pathology of the pituitary in Cushing's disease.

The frequency and the significance of the 3 main features of pituitary in Cushing's disease (ACTH secreting adenomas, ACTH cell hyperplasia, and Crooke's cells) are reported and discussed. In our most recent surgical series (1989-1990) the rate of demonstration of adenoma increased up to 96%. The frequency of paraadenomatous ACTH cell hyperplasia depends on the amount of resected tumor-free tissue. The significance of such peritumorous hyperplasia seems to be low. Crooke's cells as suppressed and transformed ACTH cells were present in each case and are a reliable indicator of a hypercortisolism.

Adenoma↗
PubMed1991

Lectin-bindings in pituitary adenomas and normal pituitaries.

The first study was undertaken for detecting hormone-receptors for estrogen and progesteron with immunohistochemical methods in frozen sections of 58 pituitary adenomas of different types. In all cases the result was negative. In the second study we tested the binding pattern for the lectins Peanut lectin (PNA), Ulex europaeus agglutinin (UEA-1) and the Concanavalin agglutinin (Con-A) in 144 pituitary adenomas of different types and in 20 post-mortem pituitaries using the two-layer indirect technique. All normal pituitaries reacted positive for all three lectins, elsewhere the binding feature for pituitary adenomas was different. Via statistical analysis, correlating lectin-bindings with clinical hyperfunction and immunohistochemical hormone content, we found an association of acromegaly and PNA and ConA and of Cushing's disease and PNA and UEA-1; furthermore of GH and UEA-1 and Con-A, of TSH and UEA-1 and of ACTH and PNA and UEA-1. Using serial sections (AB-method for demonstrating hormones and two layer indirect technique for lectin-binding) and the double-staining technique (labelled Streptavidin-Biotin-method for demonstration of hormones and the two-layer indirect technique for lectins) we found Con-A reacting with GH and PRL cells and with a part of FSH-cells, UEA-1 reacting with most of the ACTH-cells and PNA reacting with FSH-cells.

Adenoma↗
PubMed1991

Invasiveness of pituitary adenomas.

528 biopsies from 396 pituitary adenomas were re-examined by light microscopy and checked for invasion of neighbouring tissues. The overall invasion rate was 41.9%. Highly differentiated ACTH-cell adenomas were invasive in 24.1%, undifferentiated mucoid-cell adenomas in 66.7%. The histological type of invasion was influenced by the adenoma type and by the invaded tissue. There was no obvious correlation between the adenoma type and the invaded tissue.

Adenoma↗
PubMed1991

Use of athymic nude mice for in vivo studies of human growth-hormone-secreting pituitary adenomas.

Human growth hormone (hGH)-secreting pituitary adenoma tissue of 31 acromegalic patients was transplanted subcutaneously onto 291 athymic nude mice. 37% of the transplanted adenoma fragments could be maintained vital up to 46 days. Histological examinations of the transplants revealed neither alterations in their morphological characteristics nor signs of growth. A maintenance or linear decline of hGH secretion of the transplants related to their vitality was observed by hGH radioimmunoassay. Estimation of graft vitality was improved by GH-releasing hormone (GHRH) stimulation in regular intervals. The rate of pituitary adenomas responding to GHRH was as high as in a major collective of acromegalic patients. Our method of positive selection of vital xenotransplanted hGH-secreting pituitary adenomas via hGH detection at regular intervals in combination with GHRH stimulation gives the opportunity of reliable in vivo research with these tumors.

Acromegaly↗
PubMed1990

[Vascular tumors of the liver. Morphology, differential diagnosis, prognosis].

A group of 5 primary angiomas of the liver (4 angiosarcomas, 1 cavernous hemangioma) was studied. Classification, differential diagnosis and pathogenesis are discussed. Angiosarcomas may be caused by exposure to thorotrast (2 of our 4 tumors) or of polyvinylchloride. Highly cellular tumors with a herringbone-pattern must be differentiated from primarily extrahepatic fibrosarcomas or myosarcomas, and highly cellular solid or medullary tumors from metastasis from a carcinoma or lymphoma. Immunohistology--also in our tumors--permits the identification of angiomas by the demonstration of factor VIII and basement membrane protein, which are negative in other tumors. The binding of lectin Ulex europaeus can also be helpful. The common benign cavernous hemangioma is diagnosed very readily morphologically, but clinical and sonographic diagnosis can be difficult. Its biological significance is to be seen merely in possible rupture and hemorrhage.

Adult↗
PubMed1990

Amyloid in intervertebral discs of surgery and autopsy material. A new class of amyloid?

Intervertebral discs from 82 consecutive operations on herniation and 59 autopsies (one case with generalized amyloidosis) were studied. Amyloid deposits observed in surgical and autopsy specimens increased with age in both series. Degenerative changes were related to age and to amyloid deposits in autopsy, but not in surgical cases. Calcium pyrophosphate dihydrate deposits (often in proximity to amyloid deposits) were found in autopsy discs of six patients and in surgical specimens of three patients with previous operations on herniated discs. Antisera against amyloid fibril proteins of different types including AA-, A lambda-, A kappa, AF- and AB-types showed no reaction with disc amyloid. In one case with generalized A lambda-amyloidosis the disc amyloid was not of the A lambda-type. Based on our results, we suppose that disc amyloid is a form of localized senile amyloidosis - possibly representing a new class of amyloid limited to cartilage tissue.

Adult↗