No abstract

A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.

In epithelia, tight junctions (TJs) create a primary barrier to the diffusion of solutes through the paracellular pathway. Although TJ-related molecules are present in the epidermis, the precise mechanisms underlying TJ functions in this tissue remain unclear. In this study, we use an ultraviolet (UV) B-irradiated murine skin model, in which the epidermal barrier function has been perturbed, to demonstrate a correlation between the expression patterns of TJ-related molecules and the epidermal permeability of TJs. Occludin remained localized in the upper epidermis, regardless of UVB irradiation (0.15 J per cm(2)). ZO-1 was localized in the upper portion of normal epidermis, and within 3-4 days of UVB irradiation, it was expressed throughout the upper epidermis and their expression coincided with epidermal thickening. Protein expression of claudin-1 and occludin did not alter until 3 and 4 days after UVB irradiation, respectively and thereafter expression remained elevated above pre-irradiation levels. An in vivo epidermal permeability assay revealed that tight junction-barrier function was perturbed by UVB irradiation, whereby biotinylated markers clearly permeated the stratum granulosum 3-5 days after irradiation. These results suggest that TJ-related molecules play important roles in epidermal barrier function in murine skin and show that changes in their expression patterns are associated with epidermal barrier perturbation after UVB irradiation. Specifically, it appears that epidermal barrier recovery is accelerated by the increased production and dense localization of occludin in the cell-cell contact region of the stratum granulosum.

This article proposes an innovative concept of interventional radiology for hemodynamically unstable trauma patients. Damage control interventional radiology (DCIR) is an aggressive and time-conscious algorithm that prioritizes saving life of the hemorrhaging patient in extremis which conventional emergency interventional radiology (CEIR) cannot efficiently do. Briefly, DCIR aims to save life while CEIR aims to control bleeding with a constant concern to time-awareness. This article also presents the concept of "Prompt and Rapid Endovascular Strategies in Traumatic Occasions" (PRESTO) that entirely oversees and manages trauma patients from arrival to the trauma bay until initial completion of hemostasis with endovascular techniques. PRESTO's "Start soon and finish sooner" relies on the earlier activation of interventional radiology team but also emphasizes on a rapid completion of hemostasis in which DCIR has been specifically tailored. Both DCIR and PRESTO expand the role of IR and represent a paradigm shift in the realm of trauma care.

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.