Pulmonary alveolar proteinosis mimicking idiopathic pulmonary fibrosis.

Pulmonary alveolar proteinosis (PAP) is a rare disorder of unknown etiology. While most biopsies from patients with PAP disclose a prominent positive periodic acid-Schiff, diastase-resistant intra-alveolar exudate, and minimal interstitial thickening, interstitial fibrosis and honeycombing can be the predominant histologic findings. We recently identified two patients with PAP who initially were thought to have idiopathic pulmonary fibrosis, but whose biopsies ultimately disclosed PAP with considerable interstitial fibrosis.

Tuberous sclerosis-associated lesions of the kidney, brain, and skin are angiogenic neoplasms.

Background: Tuberous sclerosis is an autosomal dominant condition characterized by the development of benign neoplasms of the brain, kidney, and skin. Progressive growth and malignant transformation of brain and kidney lesions constitute the major cause of morbidity and mortality in adults with tuberous sclerosis. In addition, growth of skin lesions may be disfiguring to patients.

Neuroendocrine lung tumors: grade correlates with proliferation but not angiogenesis.

Angiogenesis has been implicated in the progression of human neoplasia from benign precursor to invasive and metastatic phenotypes. The acquisition of dominant oncogenes in preneoplastic cells in vitro and in vivo has been associated with the increased ability of tumor cells to secrete angiogenic mediators and recruit blood vessels. However, in a subset of benign lesions, high levels of angiogenesis have been found before the conversion to invasive and metastatic phenotypes.

Consultative (expert) second opinions in soft tissue pathology. Analysis of problem-prone diagnostic situations.

We reviewed 500 consecutive soft tissue lesions referred for expert consultation to determine types of lesions and/or situations in which major discrepancies occur. Of 266 cases (53.2%) accompanied by a diagnosis, essential agreement with the second opinion was noted in 68%, minor discrepancy in 7%, and major discrepancy in 25%.

The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms.

Angiomyolipomas are benign tumors of the kidney derived from putative perivascular epithelioid cells, that may undergo differentiation into cells with features of melanocytes, smooth muscle, and fat. To gain further insight into angiomyolipomas, we have generated the first human angiomyolipoma cell line by sequential introduction of SV40 large T antigen and human telomerase into human angiomyolipoma cells. These cells show phenotypic characteristics of angiomyolipomas, namely differentiation markers of smooth muscle (smooth muscle actin), adipose tissue (peroxisome proliferator-activator receptor gamma, PPARgamma), and melanocytes (microophthalmia, MITF), thus demonstrating that a single cell type can exhibit all of these phenotypes.

Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy.

Background: Tumors of endothelium range from benign hemangiomas of infancy to highly malignant angiosarcomas of the elderly. Hemangiomas are the most common tumors in infants and may affect up to 10% of all children. The biologic behavior of these lesions ranges from self-resolving, in the case of hemangiomas and pyogenic granulomas, to lethal metastatic neoplasms in the case of angiosarcoma.

Vasopressin messenger ribonucleic acid regulation via the protein kinase A pathway.

Activation of vasopressin (VP) gene expression in vivo by osmotic stimuli results in an increase in both messenger RNA (mRNA) content and polyadenylate [poly(A)] tail length. VP gene transcription in vitro is stimulated by protein kinase A (PKA) activation. To examine the role of PKA in the regulation of VP mRNA poly(A) metabolism, constructs of the rat VP gene were permanently transfected into the mouse anterior pituitary cell line, AtT-20.

Regulation of the ectopically expressed human glycoprotein alpha-subunit gene in the human hepatoma cell line NPLC.

The human glycoprotein alpha-subunit is the common subunit of the heterodimeric hormones CG (hCG), TSH, LH, and FSH. Human glycoprotein alpha-subunit is produced eutopically in placenta, pituitary, and choriocarcinoma and ectopically in a large variety of human tumors. We report ectopic glycoprotein alpha-subunit messenger RNA (mRNA) and peptide production in the human hepatoma cell line, NPLC.

Effects of hydroxyurea and cyclic adenosine monophosphate/protein kinase A inhibitors on the expression of the human chorionic gonadotropin alpha subunit and c-myc genes in choriocarcinoma.

We have previously shown that treatment of choriocarcinoma cells with methotrexate or hydroxyurea leads to both cessation of cell growth, accompanied by repression of c-myc oncogene expression, and induction of genes associated with the placental phenotype, including both subunits of human chorionic gonadotropin (hCG) and placental alkaline phosphatase. Since the genes induced by these antimetabolites are also cyclic AMP inducible, we hypothesized that these antimetabolites may cause activation of the cyclic AMP/protein kinase A pathway, suppressing genes associated with cellular proliferation and inducing placental gene expression. Three inhibitors of the cyclic AMP/protein kinase A pathway were assayed for their ability to inhibit the induction of the human chorionic gonadotropin alpha gene by hydroxyurea, and none of these inhibitors eliminated this induction.

Differential regulation of choriocarcinoma gene expression by DNA synthesis inhibitors.

We have previously shown that methotrexate (MTX) and hydroxyurea (HU) stimulate expression of the human chorionic gonadotropin alpha and placental alkaline phosphatase genes and repress the expression of the c-myc oncogene in BeWo choriocarcinoma cells. In order to determine whether c-myc downregulation played a role in the induction of these placental genes, we treated BeWo choriocarcinoma cells with aphidicolin (APH), and 6-diazo-5-oxo-L-norleucine (DON), and compared the effects of these drugs with that of MTX. All of these drugs downregulate c-myc gene expression.

SCPB-and FMRFamide-like immunoreactivities in lobster neurons: colocalization of distinct peptides or colabeling of the same peptide(s)?

Virtually all of the SCPB-like immunoreactive neurons (ca. 60 cells) in the lobster Homarus americanus also contain FMRFamide-like immunoreactivity. Control experiments reveal that SCPB-and FMRFamide-like immunoreactivities are successfully preadsorbed with their specific antigens, while the normal staining pattern is retained following preadsorption of each antibody with the alternate peptide.

Regulation of gene expression in choriocarcinoma by methotrexate and hydroxyurea.

Choriocarcinoma, a highly malignant neoplasm of trophoblastic origin, is remarkable for its marked degree of sensitivity to chemotherapeutic agents. We treated two cell lines derived from choriocarcinoma patients with two antineoplastic agents, methotrexate and hydroxyurea (HU), both of which cause nucleotide depletion and have been previously shown to be effective against choriocarcinoma, and found pleiotropic regulation of several genes. Three genes, hCG alpha-subunit, beta-subunit, and placental alkaline phosphatase, were all strongly induced by methotrexate and HU.