Growth hormone receptor expression in the nucleus and cytoplasm of normal and neoplastic cells.

Growth hormone (GH) exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific receptors which trigger a phosphorylation cascade, resulting in the modulation of numerous signalling pathways dictating gene expression. A panel of five monoclonal antibodies was used in mapping the presence and somatic distribution of the GH receptor by immunohistochemistry in normal and neoplastic tissues and cultured cells of human, rat and rabbit origin. A wide distribution of the receptor was observed in many cell types. Not all cells expressing cytoplasmic GH receptors displayed nuclear immunoreactivity. In general, the relative proportion of positive cells and intensity of staining was higher in neoplastic cells than in normal tissue cells. Immunoreactivity showed subcellular localisation of the GH receptor in cell membranes and was predominantly cytoplasmic, but strong nuclear immunoreaction was also apparent in many instances. Intense immunoreactivity was also observed in the cellular Golgi area of established cell lines and cultured tissue-derived cells in exponential growth phase, indicating cells are capable of GH receptor synthesis. The presence of intracellular GH receptor, previously documented in normal tissues of mostly animal origin, is the result of endoplasmic reticulum and Golgi localisation. Heterogeneity of immunoreactivity was found in normal and neoplastic tissue with a variable range of positive cells. The nuclear localisation of immunoreactivity is the result of nuclear GH receptor/binding protein, identically to the cytosolic and plasma GH-binding protein, using a panel of five monoclonal antibodies against the GH receptor extracellular region. The expression of GH receptors, not only on small proliferating tumour cells such as lymphocytes, but also on well differentiated cells including keratinocytes, suggests that GH is necessary not only for differentiation of progenitor cells, but also for their subsequent clonal expansion, differentiation and maintenance.

Computed tomography in the diagnosis of posterior fossa lesions.

A series of 3,500 cases examined by computed tomography (CT) of the head were reviewed to identify patients who had symptoms and signs suggestive of neurologic disease in the posterior fossa. Three hundred forty eight such cases (about 10%) were found, and the scans were reviewed to determine the character of lesions that could be detected and the accuracy of the neuroradiologic diagnosis. Overall, 16 errors were made (4.6%), of which 13 were false negatives and 3 were false positives. False negatives included nine tumors, two infarcts, and two arteriovenous malformations. Four of the tumors and the two arteriovenous malformations were small and caused no visible alterations in density even when analyzed retrospectively. In the remaining seven cases, specific findings either were overlooked or were obscured by artifacts, and, therefore, the diagnosis was not made. The three false positive diagnoses were made through a misinterpretation of density changes that were artifactual. No changes in the intracranial absorption coefficients were detected in 109 cases. Abnormal changes were evident in 226 cases in which structural lesions were subsequently found. Many of the lesions had a characteristic appearance, but in certain clinical situations, which include searches for metastatic disease, acoustic neuromas, meningiomas aneurysms of the basilar artery, and arteriovenous malformations, the injection of intravenous contrast medium was helpful, or even essential, for diagnostic success. The prominence of clinical signs and symptoms is not always an accurate index to the presence of structural alteration of the posterior fossa. We believe, therefore, that this portion of the cranium should be included in every CT study.