Manuel E. Velasco

Immunohistochemical localization of glial fibrillary acidic protein in human glial neoplasms

The presence and distribution of glial fibrillary acidic protein in fixed, paraffin embedded tissue were studied in 85 human intracranial neoplasms, using the peroxidase‐anti‐peroxidase method. In some cases, indirect immunofluorescence of frozen sections was used as well. In normal tissue, only the cell processes and perikarya of fibrous astrocytes were stained. Immunostaining was also observed in the following glial neoplasms: astrocytomas (all varieties), astroblastoma, subependymal giant cell astrocytoma, subependymoma, glioblastoma multiforme and ependymoma. The astrocytic elements of mixed gliomas and of medulloblastomas undergoing glial differentiation were likewise strongly stained. In contrast, oligodendrogliomas, meningiomas, pituitary adenomas, sarcomas, lymphomas and metastatic carcinomas were negative. Either a perikaryal or a diffuse fibrillary staining pattern was observed. Combination of the two patterns occasionally occurred. The perikaryal staining was prominent in gemistocytic astrocytomas and in astroblastomas. A distinct negative correlation existed between the degree of anaplasia and the intensity of immunostaining.

Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease

In cerebral amyloid angiopathy, the amyloid-beta (A beta) deposits lie primarily in the tunica media suggesting that smooth muscle cells play an important role in A beta deposition. To define this role, we conducted an immunocytochemical study of brain tissue from cases of Alzheimer disease with extensive cerebral amyloid angiopathy and cerebral hemorrhage. Antibodies specific to recombinant beta protein precursor (beta PP) and synthetic peptides homologous to various beta PP sequences from residue 18 to 689 of beta PP695 were used. Antibodies to actin, tropomyosin, alpha-actinin or desmin were used to label muscle cells. Antibodies to A beta sequences intensely recognized the extracellular amyloid deposit. Antibodies raised against beta PP sequences other than the A beta domain recognized smooth muscle cells. beta PP-immunoreactivity was reduced in regions of A beta deposits, since no muscle cells were recognized by cytoskeletal markers or observed ultrastructurally. In order to assess why A beta is deposited in the tunica media, we used biotin-labelled beta PP to determine if beta PP can be locally retained. We found beta PP bound to the tunica media of vessels but not other brain elements. These findings suggest A beta in blood vessels derives from degenerating beta PP-containing smooth muscle cells.

Glial fibrillary acidic protein (GFAP) in ependymal cells during development. An immunocytochemical study

Human ependymal cells show positive immunostaining for glial fibrillary acidic protein (GFAP) at one stage of the fetal development. The reaction seems to coincide with maturation of the epithelial layer and development of cilia. Two types of reactive cells are present: epithelial and tanycytes. The GFAP-positive reaction in both these cells is transient, appearing at different times and with different patterns in the various regions of the ventricular system. In order to explain the presence of detectable GFAP in developing ependymal cells and its absence in mature cells, it is proposed that either the synthesis of detectable amounts of GFAP occurs only at a stage of ependymal cell maturation, or that the intermediate filaments assembled in developing ependymal cell are antigenically distinct form those of the mature cells. The present findings indicate that tanycytes are not an immature from of ependymal cells but that they develop parallel to the epithelial cells. The role of the tanycytes remains obscure, but it is suggested that they are not related to radial glia.

The Presence of Glial Fibrillary Acidic Protein in the Human Pituitary Gland

The presence of glial fibrillary acidic protein (GFAP) was studied in human pituitary glands with the peroxidase-antiperoxidase (PAP) method. Positive reaction was observed in cells and processes of the neurohypophysis, in occasional cells lining the Rathkes cysts of the pars intermedia, and in scattered star-shaped cells and small follicles of the pars distalis. GFAP immunoreactivity was sparse and variable in amount from case to case. An increase in GFAP-immunoreactivity was observed as a reaction to injury. GFAP-positive cells were seen within and around pituitary adenomas regardless of their secretory cell type. Evidence is presented to indicate that these cells do not contain conventional pituitary hormones. It is postulated that the GFAP-positive cells of the pars distalis are nonsecretory elements, identical to the folliculostellate cells. They may become visible by immunostaining following increased synthesis of GFAP. The latter may be a response to cell injury or metabolic changes in adjacent secretory elements. A similar reaction in pituicytes may explain the appearance of immunoreactive GFAP in the neural lobe. The presence of GFAP in the adenohypophysis suggests that some of their cells are neuroectodermal in origin

Neuronal and astrocytic differentiation in human neuroepithelial neoplasms: An immunohistochemical study

Neuroepithelial neoplasms of childhood were examined immunohistochemically using antibodies against a neurofilament polypcptide and glial fibrillary acidic protein. Ninety-one cases, including 11 controls, were examined. Positively reacting cells, indicating neuronal and glial differentiation, were found in 59 of the 80 tumors. The study supports a neuroepithelial origin for medulloblastomas, central neuroblastomas, and primitive neuroectoder-mal tumors of childhood. The results also indicate that only a small number of the tumor cells differentiate along either neuronal or glial cell lines.

Immunochemical Characterization of Antisera to Rat Neurofilament Subunits

Abstract: Antisera raised to the 68,000, 145,000 and 200,000 molecular weight subunits of rat neurofilaments were used for immunochemical staining of polypeptides separated by one‐ and two‐dimensional gel electrophoresis. It was found that each antiserum reacts intensely with its corresponding neurofilament subunit and weakly with the other two subunits. All the antisera also react with a polypeptide of molecular weight 57,000 present in neurofilament‐rich preparations from both rat spinal cord and peripheral nerve. This polypeptide is different from either tubulin or vimentin and may represent a neurofilament breakdown product, since it varied in amount from preparation to preparation. The three antisera also reacted with the polypeptide subunits of chicken and goldfish neurofilament despite the considerable difference in molecular weight between these subunits and those of mammalian neurofilament. Key Words: Neurofilaments–Antibodies–Immunochemical. Autilio‐Gambetti L. et al. Immunochemical characterization of antisera to rat neurofilament subunits. J. Neurochem. 37, 1260‐1265(1981).

Oncogenic Osteomalacia and Inappropriate Antidiuretic Hormone Secretion Due to Oat-Cell Carcinoma

The syndrome of tumor-induced osteomalacia has been previously thought to occur only in association with mesenchymal tumors, although one report has linked prostatic carcinoma with the syndrome. We report the case of a patient who presented first with the clinical and biochemical features of the syndrome of inappropriate antidiuretic hormone secretion, and then oncogenic osteomalacia. The first syndrome was characterized by headaches, nausea, and vomiting; serum sodium determinations ranged between 107 and 118 meq/L with simultaneous urine spot sodium concentrations of 100 to 116 meq/L. The circulating antidiuretic hormone level was markedly elevated to 261.5 microU/mL. The osteomalacia was discovered incidentally when depressed serum phosphorus levels of 1.2 to 1.7 mg/dL were noted in association with 24-hour urine phosphorus excretion exceeding 1000 mg/24 h. Undecalcified tetracycline-labeled bone biopsy samples confirmed oncogenic osteomalacia. Only afterward was a small-cell carcinoma of the lung identified as the likely source of both of these syndromes.

GALACTORRHEA ASSOCIATED WITH LYMPHOCYTIC ADENOHYPOPHYSITIS CASE REPORT

A young woman, 14 months post partum, committed suicide when she noticed milk discharging from her nipples and thought she was pregnant. At autopsy the uterus was found to be non‐gravid and the pituitary gland enlarged. Histological examination revealed lymphocytic adenohypophysitis, a rarely identified condition usually associated with hypopituitarism. Immunoperoxidase studies of the pituitary demonstrated prolactin cell hyperplasia. None of the other known causes of galactorrhea was present suggesting that this may be a new addition to the differential diagnosis of galactorrhea. To this date lymphocytic adenohypophysitis has been reported only in women, the majority within 14 months postpartum, and is usually identified only at autopsy.

Striation is the characteristic neuritic abnormality in Alzheimer disease

In this study, we found that neuropil threads of Alzheimer disease, rather than being continuous filaments along cell processes, show multiple interruptions. They are segmental in nature and therefore appear as striations rather than continuous filaments along the length of the neurite. Neuritic striation is not an artifact of section thickness since the majority of abnormal filament accumulations are extremely short. The dominance of short striations demonstrates that argyrophilic grains, rather than being distinct structures, simply represent a short variant of striation and that longer striations are arbitrarily considered neuropil threads. Ultrastructural examination showed that the intervals between striations lack a cytoskeleton. We suggest that neuritic striations may interrupt the microtubule system functionally blocking fast neuritic transport as well as playing a role in loss of neuronal connectivity.

RECOVERY OF PITUITARY FUNCTION FOLLOWING SURGICAL REMOVAL OF LARGE NONFUNCTIONING PITUITARY ADENOMAS

Pituitary function was evaluated in eleven patients with large nonfunctioning pituitary adenomas before and 3 months after surgical adenomectomy. The longest anteroposterior dimension from the anterior wall to the dorsum of the sella on a lateral skull x‐ray ranged between 22 and 45 mm. All adenomas were confirmed histologically and had negative immunostaining for GH, PRL, ACTH and HCG.