Adrenomedullin (AM) is a novel hypotensive and vasodilator peptide. We previously examined the localization of AM in human, rat, and porcine tissues using a polyclonal antibody against synthetic human AM[40-52]. We demonstrated that AM is widely distributed in the endocrine and neuroendocrine systems, but not in the heart, kidney, or blood vessels, although high levels of AM mRNA were detected in the latter tissues. In this study, we further investigated the distribution of AM by using two newly developed monoclonal antibodies against synthetic human AM peptides, [12-25] and [46-52]. AM immunoreactivity was observed in cardiac myocytes, vascular smooth muscle cells, endothelial cells, and renal distal and collecting tubules. In addition, AM-immunoreactive (IR) cells were found in mucosal and glandular epithelia of the digestive, respiratory, and reproductive systems, as well as the endocrine and neuroendocrine systems. These findings indicate that AM-IR cells are more widely distributed in human tissues and suggest that AM might play multiple biological roles in humans.
SummaryThrombus formation and neointimal growth are the critical events in restenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal development following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (first injury), and 4 weeks later the same vessels were subjected to the second injury with a Swan-Ganz 5F balloon catheter at 1.4 atm (mild-injury group) or 1.8 atm (severe-injury group), and immediately after that a retrograde bolus injection of rTFPI (100 μg/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the injured surfaces were covered with platelet-rich thrombi in the mild-injury group and with fibrin-rich thrombi in the severe-injury group. Damaged intimal smooth muscle cells, which were immunohistochemically positive for tissue factor (TF), were observed beneath the fibrin-rich thrombi. The neointima 4 weeks after the second injury was significantly thicker in the severe-injury group than in the mild-injury group. The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These results indicate that TF-dependent coagulation pathway is primarily responsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rabbit aortic neointima. Additionally the bolus administration of rTFPI to the injured vessels could prevent mural thrombus formation and neointimal growth after balloon angioplasty.
It is well known that up to 2% of chronic burn scar lesions can transform into malignant tumors. Most of them are squamous cell carcinoma (SCC) and, more occasionally, basal cell carcinoma (BCC). The incidence of malignant melanoma (MM) is extremely low. To the best of our knowledge, there are only 23 such cases reported in the literature. We report here three cases of MM arising on burn scars and analyze the 23 cases reported previously. Case 1: a 74-year-old Japanese man sustained a burn injury on about 54% of his whole body surface when he was accidentally bathed in boiling oil at the age of 37 years old. Some small tumors developed on the burn scar on his right lumbar region. A wide excision of the tumor was performed. Case 2: a 51-year-old Japanese woman was injured on her right forearm and face by deep burns from a flame when she was 7 months old. She presented with a rapidly growing, painless black nodule on the dark skin lesion on her right forearm. She was treated with a wide excision followed by a full-thickness skin graft. Intravenous administration of one unit of OK-432 every week has been continued. Case 3: a 73-year-old Japanese woman was burned on her left leg and hand from a flame when she was 6 years old. A nodular lesion appeared within the ulcer two months previously and it was growing rapidly. This lesion was ulcerated on the top of its central area and was slightly reddish without any pigmentation. The patient was treated with a wide excision and a split-thickness skin graft. The 5-year survival rate of MM in an old burn scar is 53.6%. It is suggested that the prognosis of burn scar carcinoma is not worse than that of non-burn scar carcinoma.
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