Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma

Tumor cell invasion and metastasis is a complex, multistep process that is postulated to require degradation of extracellular matrix at several steps. Urokinase-type plasminogen activator (uPA) is expressed on the cell surface of B16 murine melanoma cells and is thought to contribute to the pericellular proteolysis necessary for tumor cell migration. In vitro modification of B16 melanoma cell surface uPA activity has been shown to alter the invasive and metastatic potential of these murine melanoma cells in vivo. Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of both uPA and tissue-type plasminogen activator (tPA) is the major physiologic regulator of plasminogen activator activity. To test the role of host PAI-1 in the invasive and metastatic capacity of B16 melanoma cells we analyzed local tumor growth and pulmonary metastasis in transgenic mice engineered to overexpress murine PAI-1 in multiple tissues including lung, and in mice completely deficient in PAI-1. No significant difference in the number of pulmonary metastases was observed after intravenous inoculation of tumor cells into PAI-1- overexpressing and PAI-1-deficient mice when compared with wild-type controls. Similarly, in a spontaneous metastasis model, PAI-1- overexpressing and PAI-1-deficient mice demonstrated no difference in primary tumor size or overall survival. These data demonstrate that wide variations of host PAI-1 expression, from complete absence to marked overexpression, does not significantly influence the metastatic potential of B16 melanoma cells in a murine model.     

Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease

Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.     

Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs

To delineate further the underlying mechanism by which amphiphilic drugs can modulate vesicle release from human RBCs, we studied the effect of chlorpromazine on erythrocyte vesiculation induced by ATP depletion. This was correlated with turnover of the phosphoinositides as well as RBC deformability during the process since phosphoinositide metabolism may be involved in shape regulation of RBCs. Echinocytic shape transformation and subsequent vesiculation of RBCs, which commonly occur during ATP depletion, were inhibited by chlorpromazine. Furthermore, with a newly developed two-dimensional thin-layer chromatography separation of RBC membrane phospholipids, we showed that chlorpromazine significantly decreased the dephosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) in both ATP-depleted RBCs as well as in cells with partly maintained ATP levels. Concomitantly, there was a smaller increase in the relative amount of phosphatidylinositol. In addition, chlorpromazine also inhibited the decreased in RBC deformability as well as the shift of osmotic fragility that occurs during ATP depletion of erythrocytes.     

Immunohistochemical studies on colloid bodies (Civatte bodies) in oral lesions of discoid lupus erythematosus

Abstract – By electron microscopy colloid bodies have been shown to be derived from epithelial cells. It has been suggested, however, that connective tissue cells or components from the basement membrane zone contributed to the formation of colloid bodies. In order to examine these possibilities we stained oral lesions of discoid lupus erythematosus (DLE) with antibodies against intermediate filaments (keratin, vimentin), basement membrane components (laminin, collagen type IV) and fibronectin. IgM was used as a marker for colloid bodies. Colloid bodies were stained positive for keratin, whereas vimentin was never found in colloid bodies. Laminin and collagen type IV were occasionally seen in their periphery probably owing to adherence of basement membrane fragments during apoptosis. Fibronectin was frequently seen at the entire periphery of colloid bodies which may facilitate their elimination by macrophages. In conclusion, connective tissue cells or basement membrane components do not seem to contribute to the formation of colloid bodies in oral DLE.     

Complete transection of the pelvi-ureteric junction in an adult

We present a unique case report of a 41-year-old man involved in a hit-and-run accident. The patient suffered a complete disruption of the pelvi-ureteric junction along with a fracture of the L3 transverse process. Occasionally seen in children, we believe this to be the first reported adult case. The report details the presentation and symptoms, with subsequent radiology. This case also demonstrates how using an effective multidisciplinary team approach and the ATLS principles, uncommon injuries can be identified and managed successfully. We revisit the classification of ureteric trauma and the accepted best surgical management.