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A case is presented of a 30-year-old woman with a malignant ependymoma with extracranial metastases involving the cervical lymph nodes. The positive reaction to antibody against glial fibrillary acidic protein confirmed the ependymoma origin of the lymph node metastases.

We reviewed the cases of 16 patients with primary intracranial lymphomas. The clinical and radiological data proved to be helpful in suggesting the diagnosis, but only tumoral biopsy provided unequivocal diagnosis. In our cases radiotherapy proved to be the most effective treatment.

The first case in the literature of a metastasizing meningeal melanocytoma is described. The tumor, which arose at the D9-D11 spinal cord level of a 46-year-old woman, metastasized 7 years later to the latero-suprasellar region.

A case of sublingual rhabdomyoma (adult type) in a 40-year-old man is reported. A review of the world literature revealed 28 acceptable previous cases.

A rare case of histiocytosis-X of the spine is presented. The clinical and histological features of histiocytosis-X are reviewed. Complete neurological recovery was exhibited by the patient after surgical treatment and radiotherapy. The literature dealing with the eight cases previously reported is reviewed.

To assess the value of transbronchial lung biopsy in the evaluation of disease activity in pulmonary sarcoidosis, lung biopsy specimens obtained from 37 patients with this disease and their cellular patterns of bronchoalveolar lavage were studied. Morphologic analysis has showed peculiar lesions: predominant interstitial alveolitis consisting of mononuclear cells and scattered neutrophils, and eosinophils, diffuse in 13 cases and focal in 11 cases, interstitial nodular clusterings of mononuclear cells (five cases), diffuse intraalveolar infiltration of macrophages (one case), granulomas (27 cases), hyaline membranes (one case), intraalveolar (two cases) and interstitial (six cases) fibrosis, and finally cuboidal metaplasia of alveolar lining cells (eight cases). Hyaline membranes were always combined to a diffuse alveolitis consisting of some neutrophils. Only diffuse alveolitis was significantly associated with a high lymphocytosis in BAL (p less than 0.05).

The receptors for polypeptide growth factors and proteins coded by oncogenes of the src family are endowed with protein kinase activity and share the uncommon property of autophosphorylating at tyrosine residues. It is unclear whether the tyrosine kinase activity is also directed towards other targets of physiological significance. In this work, phosphotyrosine antibodies were used to detect, by Western blots and immunoprecipitation, proteins phosphorylated at tyrosine in fibroblasts either stimulated by growth factors (PDGF and EGF) or transformed by oncogene-coded tyrosine kinases. In stimulated cells the antibodies detected the autophosphorylated receptors, but only trace amounts of other proteins phosphorylated at tyrosine. In fibroblasts transformed by retroviral oncogenes (v-src, v-abl, v-fps or v-fes) proteins other than the corresponding oncogene-coded kinase, were found. A p70 was found to be heavily phosphorylated in fibroblasts transformed by v-src, v-fes and v-fps. A p130 and a p36 were found in cells transformed by v-src and v-abl. A unique p70 was phosphorylated in v-abl-transformed fibroblasts. These proteins were also phosphorylated in vitro in an immunocomplex kinase reaction. This reaction was blocked by the specific kinase inhibitors. These data strongly suggest that tyrosine kinases phosphorylate protein targets other than themselves. These targets are barely detectable in normal cells stimulated by growth factors, where the kinase activity is triggered rapidly and transiently. By contrast, a number of intracellular proteins phosphorylated at tyrosine accumulate in cells transformed by v-onc-coded kinases, endowed with constitutive and non-regulated enzymatic activity.

Infiltrative diffuse lung diseases represent a heterogenous group of lesions with overlapping clinical and roentgenological features. Their diagnosis frequently needs a pathologic approach. We report our experience (671 patients with lung infiltrates) with transbronchial lung biopsy (TBB) procedure. The results of morphologic investigation were subdivided into three groups: 1) A specific morphologic diagnosis was made in 192 cases (29%) 2) Histopathologic changes well consistent with the clinical pattern were present in 258 patients (38%) 3) Non-specific lesions were found in 221 cases (33%). The diagnosis yield of the method was of 67%. UIP, DIP, Pulmonary Angiitis and Granulomatosis, Bronchiolitis Obliterans-Organizing Pneumonia and other rarer lung diseases may not be diagnosed on the basis of lesions present in TBB specimens.

A protein with an Mr of 145,000 (p145) was detected by antibodies to phosphotyrosine by Western blot (immunoblot) analysis. This protein was phosphorylated on tyrosine in a gastric carcinoma cell line. In cells that were metabolically labeled with 32Pi, this protein was phosphorylated on tyrosine and serine. p145 is a cysteine-rich transmembrane glycoprotein. The extracellular domain could be labeled by 125I under nonpermeating conditions and was cleaved by mild trypsin treatment of intact cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions revealed a shift of p145 mobility to an apparent Mr of 190,000. After immunoprecipitation with phosphotyrosine antibodies, p145 displayed a strong associated protein kinase activity in vitro, becoming phosphorylated on tyrosine. There was no immunological cross-reaction between p145 and known tyrosine kinases. Both in vivo and in vitro tyrosine phosphorylations were unaffected by the addition of known growth factors. However, p145 was rapidly dephosphorylated in vivo when cells were exposed to low pH, a condition that is known to dissociate ligands from their receptors. These data suggest that p145 is associated with a protein tyrosine kinase activity which, in the tumor cell line studied, is activated by an as yet unidentified factor.

Phosphotyrosine antibodies were employed to immunodecorate and immunoprecipitate proteins phosphorylated at tyrosine residues in cells transformed by Abelson murine leukemia virus (A-MuLV). In pre-B and pre-T lymphoma cells transformed by A-MuLV, the major phosphotyrosine-containing protein has an MW of 160 kDa and shares immunologically detectable sequences with the v-abl oncogene product. Moreover, two different proteins of approximately 100 and 68 kDa, heavily phosphorylated at tyrosine, were identified. Lack of immunological cross-reactivity with viral products and phosphopeptide mapping showed that the 100 and 68 kDa proteins are coded by cellular genes. Phosphoproteins were undetectable in control resting lymphocytes. The 68 and the 100 kDa proteins were phosphorylated to different extents in proliferating lymphocytes, either stimulated by the growth factor IL-2, or transformed by M-MuLV (lacking the oncogene coded kinase). In fibroblasts transformed by A-MuLV, phosphotyrosine antibodies identified 2 proteins of 120 and 70 kDa. By immunological cross-reaction and by phosphopeptide mapping, the first was identified as a 120 kDa form of the v-abl coded kinase. The 70 kDa protein is coded by a cellular gene, is not structurally related to the 120 kDa v-abl kinase, and is different from any phosphotyrosine-containing protein detected in A-MuLV-transformed lymphocytes. These data show that, upon v-abl-induced transformation, phosphorylation at tyrosine takes place also on proteins other than the 160 or 120-kDa oncogene products. In lymphocytes and fibroblasts these proteins are different, suggesting that the cascade of events triggered by the v-abl gene in different cell types involves tyrosine phosphorylation of different specific proteins.

We investigated 801 patients with lung infiltrates who underwent transbronchial lung biopsy (TBB) and performed cytologic studies of lavage fluid of 491 patients who also underwent bronchoalveolar lavage (BAL). A specific histopathological diagnosis was made in 232 cases (29%). Histopathological changes consistent with the clinical pattern were present in 296 cases (37%). The diagnostic yield of TBB was 66%. Routine evaluation of BAL fluid allowed us to make a specific diagnosis in 49 cases. The role of the pulmonary pathologist in the interpretation of TBB and BAL specimens is discussed.

Fusion of P3/X63-Ag8 mouse myeloma cells with splenocytes obtained from mice hyperimmunized with a BHK hamster fibroblast line transformed by an env-strain of Rous sarcoma virus (RSV) resulted in the production of antibody-secreting hybridomas. Seven hybrid clones secreted antibodies binding to RSV-transformed BHK fibroblasts but not to the parental control non-transformed line. The antibodies produced by three of these clones did identify antigenic determinants expressed also on BHK cells transformed by SV 40. The antibodies produced by four other clones reacted specifically with cells transformed by RSV but not with cells productively infected by the transformation-defective Rous-associated virus-1; one of these reacted with RSV-transformed hamster cells only, three others identified antigenic determinants common to RSV-transformed cells of different animal species. These data give further support to the idea that RSV-transformed cells express a cell-surface antigen, specific for transformation, the expression of which is controlled by the transforming src gene, and that the specificities carried on it follow a complex pattern, arising from the interaction between antigenic determinants of cellular and viral origin.

A patient with a dural cavernous angioma of the middle cranial fossa eroding the tegmen tympani and causing an isolated palsy of the facial nerve is presented. The rarity of this lesion is stressed, as are the peculiar clinical findings and the magnetic resonance imaging.

The Triton X-100-insoluble skeleton of baby hamster kidney BHK cells consists of the nucleus, intermediate-size filaments, and actin fibers. By transmission electron microscopy, membrane fragments were found to be associated with these insoluble structures. When radioiodinated or [3H]glucosamine-labeled cells were extracted with 0.5% Triton, most plasma membrane glycoproteins were solubilized except for a glycoprotein with a molecular weight of 85,000 (gp85) that remained associated with the insoluble skeletons. Immunoprecipitation with a specific antiserum indicated that the gp85 is not a proteolytic degradation product of fibronectin, an extracellular matrix glycoprotein insoluble in detergent. A monoclonal antibody of BHK cells specific for gp85 was produced. Immunofluorescence analysis with this monoclonal antibody indicated that gp85 is not associated with the extracellular matrix, but is confined to the cell membrane. Both in fixed and unfixed intact cells, fluorescence was concentrated in dots preferentially aligned in streaks on the cell surface. Gp85 was found to behave as an integral membrane protein interacting with the hydrophobic core of the lipid bilayer since it was extracted from membrane preparations by ionic detergents such as SDS, but not by 0.1 N NaOH (pH 12) in the absence of detergents, a condition known to release peripheral molecules. Association of gp85 with the cell skeleton was unaffected by increasing the Triton concentration up to 5%, but it was affected when actin filaments were dissociated or when a protein-denaturing agent (6 M urea) was used in the presence of Triton, suggesting that protein-protein interactions are involved in the association of gp85 with the cell skeleton. We conclude that gp85 is an integral plasma membrane glycoprotein that might have a role in cell surface-cytoskeleton interaction.

A cerebral neoplasm containing a well differentiated epidermoid cyst surrounded by islands of infiltrating squamous cell carcinoma and a pleomorphic spindle cell stroma was described. By immunoperoxidase staining all these components contained keratin. The lesion was therefore similar to malignant squamous cell lesions with sarcoma-like stroma occurring in other body sites.