The PPARgamma ligand, 15-Deoxy-Delta12,14-PGJ2, regulates apoptosis-related protein expression in cholangio cell carcinoma cells

PPARgamma is known to induce apoptosis in malignant tumor cells, but the mechanism of this induction is not well understood. We investigated induction of apoptosis with 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a PPARgamma ligand, in cholangio cell carcinoma (CCC) cells (RBE, ETK-1 or HuCCT-1). Apoptosis was induced in RBE and ETK-1 cells with 15d-PGJ2, but not in HuCCT-1 cells, although PPARgamma was expressed in all CCC cells. Apoptosis-related proteins were also expressed, including FLIP, bclx, Apaf-1 and XIAP, but expression levels differed among the three cell lines. RBE cells treated with 15d-PGJ2 showed caspase activation, and it appeared that PPARgamma-induced apoptosis was dependent on caspase activation. However, neither ETK-1 nor HuCCT-1 cells showed significant activation of caspase-8 or -3 with 15d-PGJ2 treatment, raising the possibility of a caspase-independent apoptosis induction pathway. XIAP was down-regulated by 15d-PGJ2 in all three CCC cell lines. Therefore, 15d-PGJ2 induces apoptosis in CCC cells via caspase-dependent or independent pathways. 15d-PGJ2 may also induce down-regulation of XIAP and may promote caspase cascade activation through TNF-family receptor signaling pathways.     

GLOMERULAR TISSUE INJURY IN IgA NEPHRITIS

The glomerular lesions In 129 cases of IgA nephritis were analyzed. The development of glomerular injury occurred in two ways, one being a chronic mesangial depositive and sclerosing lesion commonly found in most glomeruli, and the other an acute but local injury initiating from the local peripheral glomerular basement membrane abnormality, i.e., thinning and/or splitting, which was seen at least in one third of all cases. The activation of the local coagulatory process could add segmental glomerular changes including small crescents, adhesion, and local tuft necrosis to the mesangial lesion. ACTA PATHOL. JPN. 33; 367–380, 1983.     

Arthus-type nephritis. II. Glomerular clearing system against poorly soluble and insoluble immune complexes

The uptake and transport of immune complexes (IC) in glomeruli were studied in Arthus-type nephritis induced by ferritin anti-ferritin IC. This experimental nephritis was transient in nature, forming electron dense aggregates and deposits in glomeruli, and was considered to be suitable for the analysis of the glomerular defence against immune complex injury. The IC were taken up and removed from the glomerular circulation first by polymorphonuclear leukocytes and later by macrophages. The IC in the glomerular capillary walls and mesangium were seen to shift slowly from the peripheral part of the glomeruli to the more central and juxtaglomerular area. It is speculated that the glomerular integrity is maintained from the immune complex induced tissue injury through the handling and removal of phlogogenic IC by the blood derived phagocytic system and intrinsic glomerular clearing system.     

Histologic transformation in extranodal non-Hodgkin's lymphoma

Histologic transformation in the course of non-Hodgkin's lymphoma (NHL) has been reported to occur in 18 to 30% of the cases. Less favorable prognosis in cases with initial low grade malignancy followed by emergence of high grade malignancy has been previously described. In the previous literature, the histologic transformation has been examined mostly in nodal NHL. In the present study, histologic transformation in the course was investigated on 20 cases with early extranodal NHL. All these 20 cases were diffuse lymphomas, and were composed of 7 cases with low grade malignancy and 13 cases with high grade malignancy. Histologic transformation was not observed in any of these cases. These findings indicate that the frequency of histologic transformation is much lower in extranodal NHL than in nodal NHL. The prognostic significance of these findings is also discussed.     

Vitamin D receptor gene polymorphism is associated with serum total and ionized calcium concentration

Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/-0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/-0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/-0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects.     

Immunoreactivity and receptor expression of insulinlike growth factor I and insulin in human adrenal tumors. An immunohistochemical study of 94 cases.

Using immunoperoxidase methods, 94 human adrenal tumors were examined for evidence of immunoreactivity and receptor expression of insulinlike growth factor I (IGF-I) and insulin. The frequency of IGF-I in adrenocortical carcinomas was significantly higher than that in adenomas of the adrenal glands. The adrenocortical carcinomas showed strong intensity of staining for IGF-I, IGF-I receptors, and insulin receptors. A significant correlation between immunoreactivity and receptor expression of both IGF-I and insulin was found only in the adrenocortical carcinomas. The adrenocortical adenomas with Cushing's syndrome and pheochromocytomas, more than adrenocortical adenomas with Conn's syndrome, also stained strongly for insulin receptors. Thus the IGF-I and insulin probably play a role in the growth of adrenocortical carcinoma tissues, possibly through autocrine mechanisms. The expression of insulin receptors in adrenocortical adenomas in the presence of Cushing's syndrome and pheochromocytomas may be associated with functions.     

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma

Clinical and Experimental Nephrology - The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. Patients diagnosed with...