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Hepatocyte nuclear factor 4α (HNF4α) isoforms in the human stomach have not been fully investigated. The purpose of the present study was to evaluate the expression of P1 and P2 promoter-driven HNF4α (P1 and P2-HNF4α) in differentiated-type early gastric carcinomas (DEGC). P1- and P2-HNF4α expression was examined immunohistochemically both in non-neoplastic mucosa and carcinoma from surgical specimens. In all samples of non-neoplastic mucosa, foveolar, cardiac, fundic and pyloric gland epithelium was negative for P1-HNF4α, but was positive for P2-HNF4α. Intestinal metaplasia was positive for P1 and P2-HNF4α in all cases. Gastric carcinomas were classified into four mucin phenotypes based on the pattern of mucin expression: gastric, intestinal, mixed and null type. DEGC showed striking differences in the staining pattern for P1-HNF4α according to the mucin phenotype. Gastric carcinomas of intestinal, mixed and null type showed high positivity for P1-HNF4α, but the gastric type was negative for P1-HNF4α in all but one tumor. In contrast, P2-HNF4α was expressed in all tumors regardless of the mucin phenotype. Negative expression of P1-HNF4α was indicated as one of the useful immunohistochemical markers in the classification of mucin phenotype of both non-neoplastic mucosa and cancers of gastric phenotype. [ABSTRACT FROM AUTHOR]

Abstract: The fibroblast growth factor receptor substrate (FRS)-2 protein family comprises FRS2α, a well-known central mediator for fibroblast growth factor signaling, and FRS2β, whose endogenous expression pattern and function are not yet defined. Immunohistochemical analysis revealed that expression of FRS2β was restricted to neural tissues and it colocalized with Tuj1, a neuronal marker. There are two distinct patterns of FRS2β expression in neural cells: punctate and cup/ring-shaped; moreover, some particles colocalized with lysosomes. Stimulation with brain-derived neurotrophic factor (BDNF) enhanced FRS2β phosphorylation and the cup/ring-shaped pattern. These results suggest a probable role of FRS2β in the intracellular degradation systems of neural cells, which involves lysosomes. [Copyright &y& Elsevier]

Nuclear receptors (NR) are transcriptional regulators expressed in a variety of tissues and they play important roles in embryonic development, organogenesis and metabolic homeostasis. In order to investigate the tissue-specific expression pattern of NR, mouse anti-human monoclonal antibodies newly generated against various NR. Specificities of the antibodies were confirmed on immunoblotting using overexpressed proteins. Most of the antibodies recognized intrinsic protein. Among 60 monoclonal antibodies generated, 32 were applicable for immunohistochemistry. The expression pattern of NR in human liver and pancreas was confirmed on immunohistochemical staining using these antibodies. The P2 promoter-driven hepatocyte nuclear factor 4α (HNF4α) isoform and progesterone receptor were expressed in pancreatic α-cells, but not β-cells in the human pancreas, suggesting an unknown role of these NR in diabetes mellitus. These antibodies were also useful for immunohistochemistry of the murine liver and pancreas. Immunoblotting using these antibodies produced similar corresponding bands both in human and mouse tissues. These monoclonal antibodies may serve as powerful tools to detect tissue-specific localization of NR and provide a platform for future studies of NR in human and murine tissues. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor 4α (HNF4α) is a member of the nuclear receptor superfamily and is expressed in several endodermal tissues. The aim of the present study was to examine the expression of HNF4α on ovarian epithelial tumors with immunocytochemistry and immunohistochemistry using mAbs recognizing P1 and P2 promoter-driven HNF4α. Ovarian mucinous adenoma, mucinous tumors of borderline malignancy, and mucinous adenocarcinoma had positive nuclear staining for HNF4α (41/45, 91%). One-third (34%) of mucinous tumors had P1-positive staining and most had P1/P2-positive staining (93%). MUC2- and MUC5AC-positive staining was observed in 34% and 95% of mucinous tumors, respectively. The histological subtype of these mucinous tumors was not correlated with HNF4α expression. On cytology it was found that cancer cells in the ascites from ovarian mucinous adenocarcinomas were HNF4α positive, but tumor cells in ascites from other types of ovarian carcinomas were negative for HNF4α. Thus, HNF4α is demonstrated to be a useful marker for histological and cytological diagnosis of ovarian mucinous tumors. [ABSTRACT FROM AUTHOR]

Abstract: DJ-1, the causative gene of a familial form of Parkinson''s disease (PD), has been reported undergo oxidation preferentially at the 106th cysteine residue (Cys-106) under oxidative stress. Recently, it has been found that the levels of oxidized DJ-1 in erythrocytes of unmedicated PD patients are markedly higher than those in medicated PD patients and healthy subjects. In the present study, we examined the changes in oxidized DJ-1 levels in the brain and erythrocytes of PD animal models using specific antibodies against Cys-106-oxidized DJ-1. Treatment with PD model compounds such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine significantly elevated the levels of oxidized DJ-1 in erythrocytes. Immunohistochemical analysis also revealed that the number of oxidized DJ-1 antibody-positive cells in the substantia nigra of MPTP-treated mouse increased in a dose-dependent manner. These results suggest that the oxidative modification of DJ-1 in the brain and erythrocytes is involved in the pathogenesis of PD in animal models. [Copyright &y& Elsevier]