Role of human papillomavirus in the pathogenesis of genital tract warts and cancer.

During the last decade a large number of clinical, epidemiological, and experimental studies have elucidated the role of HPV in the pathogenesis of anogenital cancer. Although the clinical and epidemiological studies have been criticized for a variety of technical and design shortcomings, for the most part they have independently reached the same conclusion--there is a strong association between the presence of specific types of HPV and the development of anogenital cancer. Similarly, laboratory studies clearly indicate that specific types of HPV act in concert with other cellular changes to transform a variety of cell types in vitro, including human cervical epithelial cells.

Heparin inhibits c-fos and c-myc mRNA expression in vascular smooth muscle cells.

Heparin is a potent inhibitor of vascular smooth muscle cell (VSMC) growth. In this paper we show that heparin suppressed the induction of c-fos and c-myc mRNA in rat and calf VSMC. This effect of heparin is closely associated with its growth-inhibitory activity, as shown by isolating and characterizing a strain of rat VSMC that was resistant to heparin's antiproliferative effect; heparin did not suppress c-fos mRNA induction in these cells.

Heparin selectively inhibits a protein kinase C-dependent mechanism of cell cycle progression in calf aortic smooth muscle cells.

The proliferation of arterial smooth muscle cells (SMCs) plays a critical role in the pathogenesis of arteriosclerosis. Previous studies have indicated that the glycosaminoglycan heparin specifically inhibited the growth of vascular SMCs in vivo and in culture, although the precise mechanism(s) of action have not been elucidated. In this study, we have examined the ability of specific mitogens (PDGF, EGF, heparin-binding growth factors, phorbol esters, and insulin) to stimulate SMC proliferation.

Heparin suppresses the induction of c-fos and c-myc mRNA in murine fibroblasts by selective inhibition of a protein kinase C-dependent pathway.

Heparin is a complex glycosaminoglycan that inhibits the proliferation of several cell types in culture and in vivo. To begin to define the mechanism(s) by which heparin exerts its antiproliferative effects, we asked whether heparin interferes with the expression of the growth factor-inducible protooncogenes c-fos and c-myc. We show that heparin suppressed the induction of c-fos and c-myc mRNA by serum in murine (BALB/c) 3T3 fibroblasts.

Structural determinants of heparin's growth inhibitory activity. Interdependence of oligosaccharide size and charge.

The glycosaminoglycan heparin inhibits the growth of several cell types in vitro including smooth muscle cells and rat cervical epithelial cells. The commercially available heparin which has antiproliferative activity is a structurally heterogeneous polymer that undergoes extensive modifications during maturation. In this report we have performed structure-function studies on heparin's antiproliferative activity using three different cell types: both rat and calf vascular aortic smooth muscle cells and rat cervical epithelial cells.

Characterization of keratins from rat cervical epithelial cells in vivo and in vitro.

The keratins expressed in cultured rat cervical epithelial cells were analyzed by using two-dimensional gel electrophoresis and monoclonal antikeratin antibodies and were compared with those expressed in the rat cervix in vivo in the presence and absence of estrogen stimulation. The cervical epithelium in vivo responds to estrogen stimulation with alterations in keratin composition. In response to estrogen, the epithelium undergoes proliferation and stratification and begins expressing increased amounts of two basic Mr 57,000 and 58,000 keratins and two acidic Mr 51,000 and 52,000 keratins.

Metabolic effects of heparin on rat cervical epithelial cells.

The glycosaminoglycan heparin inhibits the growth of a number of different cell types in vitro including smooth muscle cells, mesangial cells, fibroblasts, and rat cervical epithelial cells (RCEC). Studies investigating the antiproliferative effects of heparin on smooth muscle cells have demonstrated the site of the cell cycle block and revealed several metabolic alterations that could be causally associated with growth inhibition. We have investigated these metabolic parameters in RCEC to determine whether they are also associated with the antiproliferative effects of heparin in epithelial cells.

Growth requirements and characterization of rat cervical epithelial cells in culture.

The extended culture of rat cervical epithelial cells can be achieved in the absence of a fibroblast feeder layer by utilizing collagen gels and a complex growth medium. The medium contains a 1:1 mixture of RPMI-1640 and Ham's F12 supplemented with 7.5% porcine serum and epidermal growth factor, cholera toxin, transferrin, insulin, and hydrocortisone.

Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF.

The effects of heparin on the in vitro growth of rat cervical epithelial cells were examined. Heparin was found to inhibit in a dose dependent fashion the log-phase growth of rat cervical epithelial cells (RCEC) grown in the absence of medium supplements. An inhibition of growth is observed at concentrations as low as 500 ng/ml and 50% inhibition of growth occurs at a concentration of 5 micrograms/ml.

Binding and internalization of heparin by vascular smooth muscle cells.

Previous work from our laboratory has demonstrated that heparin specifically inhibits the proliferation of vascular smooth muscle cells in vivo and in vitro. In this paper, we examine the binding and mode of internalization of heparin by smooth muscle cells. For these studies, radiolabeled and fluoresceinated (FITC) heparin probes were synthesized that retained their antiproliferative capacity.

Localization of calmodulin in differentiating pulmonary type II epithelial cells.

Pulmonary surfactant is synthesized by alveolar type II pneumonocytes and stored in inclusions called lamellar bodies. In the present study we have investigated the role of the calcium-binding protein, calmodulin, in regulating surfactant secretion in differentiating rat fetal type II pneumonocytes. Lamellar body secretion is stimulated in differentiating type II cells in vitro by the calcium ionophore, A23187.

Increased adhesiveness of Down syndrome fetal fibroblasts in vitro.

We compared the in vitro rate of divalent cation-independent aggregation of fibroblasts derived from abortuses with normal karyotypes and with trisomy 21 (Down syndrome). Fibroblasts from five lung and two of three cardiac cultures from subjects with Down syndrome aggregated more rapidly than matched fibroblasts from normal controls or lung fibroblasts from an abortus with trisomy 13. In contrast, skin fibroblasts derived from the trisomy 21 subjects had low rates of aggregation.

Effects of urea treatment on the divalent cation-independent cell aggregation of 3T3MIT fibroblasts.

Growth of nontransformed 3T3MIT fibroblasts in media containing 200 mM urea leads to the rapid acquisition of the transformed adhesive phenotype as evidenced by an increased rate of divalent cation-independent cell aggregation. The increased rate of divalent cation-independent cell aggregation of urea treated 3T3MIT cells shares many properties with the high rate of aggregation of transformed cells including a sensitivity to treatment with trypsin or hyaluronidase and a reduction in the presence of exogenously added hyaluronic acid. Reversal of the urea-induced increase in aggregation occurs within 24 hours in the absence of urea and can be blocked by 0.

Divalent cation-independent aggregation of rat-1 fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus.

Rat-1 fibroblasts infected with the temperature-sensitive transformation mutant LA 24 of Rous sarcoma virus have a high rate of divalent cation-independent homotypic cell aggregation when grown at the permissive temperature, 34 degrees. Cells grown at the nonpermissive temperature, 39 degrees, have a low rate of homotypic cell aggregation. Hyaluronic acid is involved in the homotypic aggregation of permissively grown cells since aggregation is blocked by either treatment of the cells with hyaluronidase or the presence of exogenously added hyaluronic acid.

A large functioning parathyroid lipoadenoma found in the posterior mediastinum.

A patient who was evaluated for a voice change was found to have a large posterior mediastinal mass on chest roentgenogram. Laboratory parameters suggested hyperparathyroidism. The 190-g resected tumor had the histologic features of a parathyroid lipoadenoma, that is, a diffuse mixture of parathyroid glandular elements and fat or myxoid stroma throughout.

Differentiation of recurrent pulmonary emboli from chronic obstructive lung disease as a cause of cor pulmonale.

A patient with chronic obstructive pulmonary disease had severe dyspnea and cor pulmonale that were suspected in life and proved at autopsy to be the result of multiple small pulmonary thromboemboli. Radionuclide lung scanning and pulmonary angiography failed to diagnose the extensive peripheral embolization in this setting. The sensitivity and specificity of these diagnostic techniques are discussed, as well as the pulmonary function and gas exchange characteristics that led to the clinical suspicion of recurrent small emboli in this patient.

The role of negative charge in spontaneous aggregation of transformed and untransformed cell lines.

No correlation between net negative surface charge as determined by electrophoretic light-scattering techniques and the rates of spontaneous aggregation of 3T3MIT and SVPy 3T3MIT cells has been found. Neuraminidase treatment of both 3T3MIT cells and SVPy 3T3MIT cells causes a significant decrease in electrophoretic mobility but only the 3T3MIT cells show an increase in spontaneous aggregation. An increase in spontaneous aggregation of 3T3MIT cells is seen after growth in 200 mM urea for 18 h but no change in net surface charge occurs.

Rates of aggregation, loss of anchorage dependence, and tumorigenicity of cultured cells.

The net rate of spontaneous aggregation of cells suspended with EDTA was measured for various cell types including spontaneous transformants and cells transformed with DNA and RNA viruses. The anchorage dependence as determined by growth in methyl cellulose and the tumorigenicity in vivo were also determined. All cells that had lost their anchorage dependency and were tumorigenic showed a high net rate of spontaneous adhesion.