Severe burn injury induces a characteristic activation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons.

We have studied scalding-type burn injury-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the spinal dorsal horn, which is a recognised marker for spinal nociceptive processing. At 5min after severe scalding injury to mouse hind-paw, a substantial number of phosphorylated ERK1/2 (pERK1/2) immunopositive neurons were found in the ipsilateral dorsal horn. At 1h post-injury, the number of pERK1/2-labelled neurons remained substantially the same. However, at 3h post-injury, a further increase in the number of labelled neurons was found on the ipsilateral side, while a remarkable increase in the number of labelled neurons on the contralateral side resulted in there being no significant difference between the extent of the labelling on both sides. By 6h post-injury, the number of labelled neurons was reduced on both sides without there being significant difference between the two sides. A similar pattern of severe scalding injury-induced activation of ERK1/2 in spinal dorsal horn neurons over the same time-course was found in mice which lacked the transient receptor potential type 1 receptor (TRPV1) except that the extent to which ERK1/2 was activated in the ipsilateral dorsal horn at 5 min post-injury was significantly greater in wild-type animals when compared to TRPV1 null animals. This difference in activation of ERK1/2 in spinal dorsal horn neurons was abolished within 1h after injury, demonstrating that TRPV1 is not essential for the maintenance of ongoing spinal nociceptive processing in inflammatory pain conditions in mouse resulting from at least certain types of severe burn injury.

Primary rhabdoid cancer of the ileum: a case report and review of the literature.

Since the first publication of a rhabdoid cancer, described as an infrequent variant of Wilms' tumor, several cases of extrarenal rhabdoid tumor have been reported in the literature. Here, we report on a primary rhabdoid cancer of the small intestine, and give a review of the data available in the literature. An 81-year-old male patient was admitted to the Department of Internal Medicine with subileus and bloody stools. While gastroscopy and colonoscopy failed to identify a neoplastic disease, abdominal US and CT raised the suspicion of a malignancy involving the descending colon. Ileus-mandated laparotomy disclosed an obstructive tumor of the ileum. This segment was resected, followed by several relapses, and the patient died after a 7-month-period of non-relenting deterioration. Histological work-up of the numerous biopsies disclosed a cellular, solid, necrotic, hemorrhagic, and invasive tumor. The cancer cells were round-to-polygonal, and scattered bizarre pleomorphic cells with prominent nucleoli were common. The overall appearance of the neoplasm was highly similar in every specimen. The immunohistochemical phenotype of the malignant cells indicated rhabdoid characteristics. A thorough search of the literature revealed additional 22 cases of primary rhabdoid GI cancers. This report aims to call the pathologist's attention to the differential diagnostic importance of this entity.

Tissue transglutaminase (TG2) acting as G protein protects hepatocytes against Fas-mediated cell death in mice.

Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis program. TG2 is also a G protein that mediates intracellular signaling by the alpha-1b-adrenergic receptor (AR) in liver cells. Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibodies to mice causes both disseminated endothelial cell apoptosis and fulminant hepatic failure. Here we report that an intraperitoneal dose of anti-Fas antibodies, which is sublethal for wild-type mice, kills all the TG2 knock-out mice within 20 hours. Although TG2-/- thymocytes exposed to anti-Fas antibodies die at the same rate as wild-type mice, TG2-/- hepatocytes show increased sensitivity toward anti-Fas treatment both in vivo and in vitro, with no change in their cell surface expression of Fas, levels of FLIP(L) (FLICE-inhibitory protein), or the rate of I-kappaBalpha degradation, but a decrease in the Bcl-xL expression. We provide evidence that this is the consequence of the impaired AR signaling that normally regulates the levels of Bcl-xL in the liver. In conclusion, our data suggest the involvement of adrenergic signaling pathways in the hepatic regeneration program, in which Fas ligand-induced hepatocyte proliferation with a simultaneous inhibition of the Fas-death pathway plays a determinant role.

Renal cell cancer associated with sarcoid-like reaction.

An unusual granulomatous reaction within a conventional clear cell renal cancer in a 62 year-old woman is reported. Using immunohistochemical evaluation, cells of the granuloma were CD68 (Kp1), carboxypeptidase M and CD3 positive. No signs of sarcoidosis were found in other organs. According to the few publications that mention cancer associated sarcoid-like reaction, such lesions do not influence the prognosis. Our patient is still well for a 15 months follow-up.

[Immunohistochemical study of P-cadherin in breast cancer]. / P-cadherin immunhisztokémiai vizsgálata emlórákokban.

INTRODUCTION: Cell adhesion molecules play a significant role in the cellular connection of normal cells. The cadherins are believed to act as tumour suppressors, and their altered expression and function have been associated with tumour development. AIM AND METHODS: The authors examined the expression of a Ca++ dependent intercellular adhesion molecule, P-cadherin using an immunohistochemical method in 69 surgically resected breast carcinomas. RESULTS: P-cadherin was detected in 30 cases (43.5%, cytoplasmic and/or membrane staining). The expression of P-cadherin was independent of tumour size and lymph node status, but correlated with a high tumour grade (grade III). In contrast, expression of E-cadherin correlated with lower tumour grade (grade I-II). P-cadherin expression was not detected in invasive lobular carcinomas. CONCLUSION: In general, P-cadherin was expressed at a lower frequency compared to E-cadherin, alpha-, and beta-catenin. These results suggest that an inverse relationship may exist between E- and P-cadherin in relation to grade, and that the expression of P-cadherin may be a marker of aggressiveness.

Comparison of the morphology of renal cysts and cystic renal tumors.

Renal tumors appear uncommonly with cystic changes. They may develop due to necrosis though well-formed real cysts are also known. Such lesions may present problems in distinguishing them from benign renal cysts. Conditions leading to cyst formation are not known, however cell proliferation, altered extracellular matrix production and oncoprotein expression have been reported in cystic renal disorders. In the present study, we analysed the morphological features of 23 cystic renal tumors in comparison with 16 benign cysts using immunohistochemical and lectin binding methods. By our knowledge there has not been any piblication on such studies. The cystic renal tumors were represented predominantly in males and the size of the cysts was slightly larger than that of benign cysts. Tumorous cysts shared similar morphological appearance to solitary and multilocular cysts. They all showed strong epithelial membrane antigen reactivity on the luminal surface of the cells indicating distal tubular origin. Cell proliferation and p53 expression proved to be low excluding their role in the formation of the cysts. The amount of extracellular matrix and basement membrane was increased with an elevated type IV collagen and reduced fibronectin content. Polycystic kidney disease is different from tumorous cysts as cell proliferation, p53 oncoprotein expression and the composiition of extracellular matrix proved to be the opposite. As renal cell tumors arise from proximal tubules, neoplastic or metaplastic differentiation toward distal tubular direction seems to be the key even in cyst formation. Altered cell-matrix or cell-cell contact can modulate this transformation providing a basis for further results.

Accumulation of Hg(II) Ions in Mouse Adrenal Gland.

Female BALBc mice were administered HgCl2 at a single dose of 4 mg/kg i.p. The acute intoxication with Hg(II) salts (2 hr) caused accumulation of Hg(II) ions in the adrenal gland in general, and in the medulla, in particular. Based on data obtained with atomic absorption spectroscopy and quantitative cytochemistry, we determined the amount of mercury (II) in the adrenal glands and found it to be 14.2 ng Hg(II) (3.5 mg/kg wet weight of the adrenals). An uneven distribution of Hg(II) was found within the adrenal gland, not only between the medulla and cortex, but also within the cortex. The applied autometallographic method revealed that the cortex was negative except the zona glomerulosa, whereas the medulla showed a strong reaction localised to the chromaffin granules of the secretory cells. Both adrenaline and noradrenaline producing cells reacted. The comparison of the density of silver grains by scanning densitometry in the medulla and cortex revealed a significantly higher Hg(II) concentration in the medulla compared to the cortex (10 mg/kg vs 2 mg/kg, respectively). The results presented here suggest that there may be a connection between the symptoms of acute Hg(II) intoxication and its adrenal accumulation.