A useful antibody panel for differential diagnosis between peritoneal mesothelioma and ovarian serous carcinoma in Japanese cases

Malignant mesothelioma is increasing in incidence worldwide, including in Japan. However, the accurate pathologic diagnosis of pleural or peritoneal mesothelioma (PM) is sometimes difficult if adequate histologic and immunohistochemical analyses are not undertaken. The aim of this study was to identify a useful antibody panel for distinguishing PM from ovarian serous papillary adenocarcinoma (SC). We obtained 29 PMs (23 epithelioid mesotheliomas and 6 biphasic mesotheliomas) and 20 SCs from our surgical pathology files. Immunohistochemical analysis was undertaken using 13 commercially available antibodies. No significant sex differences in antigen expression among the 29 PMs were observed. The results identified calretinin and thrombomodulin as positive markers and Ber-EP4, MOC-31, CA19-9, and estrogen receptor as negative markers with relatively high sensitivity and specificity for the differential diagnosis of PM and SC. The combination of these positive and negative markers may contribute to accurate diagnosis and adequate therapy for PM and ovarian SC.     

Critical role of activation-inducible lymphocyte immunomediatory molecule/inducible costimulator in the effector function of human T cells: a comparative in vitro study of effects of its blockade and CD28 blockade in human beings and monkeys

Activation-inducible lymphocyte immunomediatory molecule (AILIM; also referred to as inducible costimulator, ICOS) is the third homolog of the "professional" costimulatory molecule, CD28. To date, the characteristics and role of AILIM/ICOS, especially in effector function of T cells, have been determined through numerous studies in vitro and in vivo using mice. Considering potential differences among species, whether the AILIM/ICOS blockade acts as an efficacious immunomodulator for human diseases remains to be elucidated. In the present study, ability of AILIM/ICOS blockade to modulate immune responses of human and monkey cells was investigated using a fully human antibody (JTA-009), comparing the effect of CD28 blockade. JTA-009 blocked the response of human and monkey T cells co-stimulated with anti-CD3 and AILIM/ICOS ligand, B7h. AILIM/ICOS and CD28 blockade both inhibited human mixed lymphocyte reaction in different fashions, as well as cytokine production in T helper (Th) 1-/Th2-type recall responses. In monkeys however, CD28 blockade by CTLA4-Ig effectively prevented mixed lymphocyte reaction to a greater extent than AILIM/ICOS blockade. These results suggest that AILIM/ICOS blockade is valuable for suppressing both primary allogenic response and recall responses of T cell in human beings, and that there are differences between human and monkey use preferences for costimulatory molecules.     

Superoxide-induced potentiation in the hippocampus requires activation of ryanodine receptor type 3 and ERK

Reactive oxygen species (ROS) are required for the induction of long-term potentiation (LTP) and behave as signaling molecules via redox modifications of target proteins. In particular, superoxide is necessary for induction of LTP, and application of superoxide to hippocampal slices is sufficient to induce LTP in area CA1. Although a rise in postsynaptic intracellular calcium is necessary for LTP induction, superoxide-induced potentiation does not require calcium flux through N-methyl-d-aspartate (NMDA) receptors. Ryanodine receptors (RyRs) mediate calcium-induced calcium release from intracellular stores and have been shown to modulate LTP. In this study, we investigated the highly redox-sensitive RyRs and L-type calcium channels as calcium sources that might mediate superoxide-induced potentiation. In agreement with previous studies of skeletal and cardiac muscle, we found that superoxide enhances activation of RyRs in the mouse hippocampus. We identified a functional coupling between L-type voltage-gated calcium channels and RyRs and identified RyR3, a subtype enriched in area CA1, as the specific isoform required for superoxide-induced potentiation. Superoxide also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) in area CA1, and ERK was necessary for superoxide-induced potentiation. Thus superoxide-induced potentiation requires the redox targeting of RyR3 and the subsequent activation of ERK.     

Enhanced Expression of CXCL13 in Human <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-Associated Gastritis

Background and Aims

Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles where the CXCL13/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans.

Methods

Using endoscopic biopsies taken from the gastric antrum of 29 subjects infected with Helicobacter pylori and 22 uninfected subjects, mucosal CXCL13 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results

The CXCL13 expression levels were significantly more elevated in H. pylori-positive patients than uninfected ones. The CXCL13 expression levels correlated with the degree of chronic gastritis and bacterial colonization. Immunohistochemistry and in vitro infection assay showed that CXCL13 was not produced by the gastric epithelium, but the α-smooth muscle antigen expressing mesenchymal cells were the possible source of CXCL13 within H. pylori-infected gastric mucosa. CXCR5 immunostaining was seen in the CD20-positive lymphoid aggregates.

Conclusions

The enhanced induction of CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis.

     

A case of gastrointestinal stromal tumor of the duodenum with a huge abscess

A 36-year-old man admitted for upper abdominal pain and fever. Enhanced abdominal computed tomography showed a cystic tumor with an air fluid level, measuring 140mm in size, along the side of the first and second portions of the duodenum. The common bile duct, portal vein, and proper hepatic artery were displaced by the tumor. Upper gastrointestinal endoscopy showed duodenal ulcer, but fistula was not confirmed. Combining all imaging and clinical findings, it was clinically diagnosed as duodenal submucosal tumor with abscess, and elective surgery was performed. There was a huge mass in the Morrison pouch, with severe adhesion to the second portion of the duodenum, gall bladder, common bile duct, and transverse colon. Subtotal stomach-preserving pancreaticoduodenectomy with transverse colectomy was performed. A fistula from the second portion of the duodenum to the tumor was confirmed on the resected specimen. Histological examination showed gastrointestinal stromal tumor originating in the duodenum.