A special type of scald caused by prolonged exposure to slowly heated water.

When skin is subjected to water temperatures gradually rising from moderate to critical ranges for a prolonged period of time, the resulting scalds will initially present as reddening, followed by blistering and at last by full-thickness burns. On changing from second- to third-degree burn, the blisters stop to become enlarged and solidify due to heat-induced coagulation necrosis. Such gradually intensifying tissue damage results in multiple firm skin blisters together with third-degree burn of the affected area. The initially serous blister fluid assumes a jelly-like consistency as the proteins undergo denaturation. Scalds of this special type may occur in persons taking a bath and becoming incapable to act so that the warm water tap remains turned on or a hairdryer continues to work after having been dropped into the bath water. On the basis of two relevant fatalities (suicidal electrocutions in bathtubs by means of hairdryers), the macroscopic and histological appearance of blisters which only secondarily turned into a full-thickness scald is compared with blisters in genuine second-degree scalds. The blister fluid of the latter ones was also investigated as to their protein composition and hemoglobin concentration.

Skin blister formation together with patterned intradermal hematoma: a special type of tire mark injury in victims run over by a wheel.

A traffic accident victim run over by a vehicle may show a patterned skin hematoma reflecting the grooves of the tire's profile. Apart from this well-known type of imprint mark, the affected skin can also be blistered provided that the wheel exerts high pressure on the body for a prolonged period of time. The macro- and micromorphological findings as well as the protein composition of the blister fluid were investigated on the basis of a relevant autopsy case. Analogous to blisters associated with hanging marks, the transudation of serous fluid with consecutive detachment of the epidermis is interpreted as a pressure-related effect which cannot be regarded as a sign of vitality.

A transgenic mouse line that develops early-onset invasive gastric carcinoma provides a model for carcinoembryonic antigen-targeted tumor therapy.

In an attempt to obtain suitable in vivo models for optimizing new tumor therapy strategies for intestinal adenocarcinomas, carcinoembryonic antigen (CEA) promoter/SV40 T antigen gene constructs have been used to generate transgenic mice. One transgenic line (L5496), which contains a 424-bp CEA promoter/SV40 T antigen transgene, exclusively developed multi-focal carcinomas in the pyloric region of the stomach in 100% of the offspring. Tumors were already observable in 37-day-old animals as dysplastic cell foci within the mucosal layer. In 50-day-old mice, the tumor mass was mainly restricted to the mucosa with invasive growth into the submucosal tissue. The animals became moribund at 100-130 days of age due to blockage of the pylorus. At this time, the tumor had penetrated into the duodenum and had invaded all tissue layers within the stomach. In contrast to most other stomach tumor models, this one perfectly matches the development of the most common stomach cancers found in humans. Furthermore, after crossing these mice with mice that are transgenic for the human CEA gene, the double transgenic offspring revealed expression of CEA in the resulting tumors. Thus, as well as being a model for studying gastric carcinoma development and prevention, this system should provide a useful preclinical model for CEA-targeted gastric tumor therapy.

Cyclosporin-A-induced effects on the free Ca2+ concentration in LLC-PK1-cells and their mechanisms.

Here we have examined the effects of Cyclosporin A (CyA) on the free intracellular Ca2+ concentration ([Ca2+]i) of LLC-PK1/PKE20 cells to evaluate mechanisms of CyA nephrotoxicity using Fura-2 microspectrofluorometry or digital fluorescence video imaging. The CyA-associated changes were compared to the effects of tacrolimus (Tac), a structurally unrelated immunosuppressant with similar cellular pathways which also causes nephrotoxicity. CyA (EC50(: 1 nmol/l, n=16) and Tac (EC50: 1 nmol/l, n=5) caused a concentration-dependent increase of [Ca2+]i which was substantially attenuated by reducing the external Ca2+ concentration (10(-6) mol/l). Similarly Cyclosporin H, a non-immunosuppressive analogue of CyA, stimulated a Ca2+ influx. Nicardipine (10(-6) mol/l) reduced the CyA- and the Tac-induced Ca2+ influx to 52+/-16% (n=10) and 13+/-10% (n=13) of control respectively. Diltiazem and verapamil (10(-6) mol/l) were also effective, but flufenamate (10(-4) mol/l), Gd3+ (10(-5) mol/l) and La3+ (10(-5) mol/l) were not. In the absence of extracellular Ca2+ CyA led to a small but significant [Ca2+]i increase, indicating additional release from internal stores. Depletion of inositol-1,4,5-trisphosphate-(InsP3-) sensitive Ca2+ stores by extracellular ATP (10(4) mol/l) in low-Ca2+ solution completely suppressed the CyA-induced [Ca2+]i rise. CyA had no effect on the cellular InsP3 concentration. Furthermore, inhibition of phospholipase-Cbeta (PLCbeta) by U73122 (2x10(-5) mol/l) did not alter the CyA-stimulated [Ca2+]i rise. A direct effect of CyA on InsP3-sensitive Ca2+ stores, the InsP3 receptor, the Ca2+ content of the stores or involvement of additional stores is assumed. Incubation with CyA for 1, 12 and 24 h enhanced the rise in [Ca2+]i peak induced by ATP, arginine vasopressin (AVP) and angiotensin II. In summary, CyA stimulated a [Ca2+]i increase in LLC-PK1 cells through Ca2+ release from InsP3-sensitive stores and Ca2+ influx via a nicardipine-sensitive pathway. The CyA-mediated [Ca2+]i increase is independent of PLCbeta activity and InsP3 metabolism. CyA caused long-term enhancement of the agonist-induced rise in [Ca2+]i. The effects of CyA on Ca2+ signaling appear to be independent of its immunosuppressive action.