Clinical significance of serum autoantibodies against Ras-like GTPases,RalA, in patients with esophageal squamous cell carcinoma

Background

The Ras-like GTPases, RalA and RalB are members of the Ras superfamily of small GTPases. Aberrant activation of Ral is a major cause of human tumorigenesis induced by oncogenic Ras. Serum anti-RalA antibodies are induced in esophageal carcinoma patients. However, detailed comparisons of their pathological characteristics are unavailable, and conventional serum markers have not been well evaluated.

Methods

Serum samples of 171 patients with esophageal squamous cell carcinoma and 73 healthy individuals were analyzed using specifically developed ELISA system for serum anti-RalA antibodies. A cut-off optical density value was fixed at 0.255 (the control mean + 2 SD). Clinicopathological characteristics and positive rates of conventional tumor markers were evaluated for seropositive patients.

Results

Overall positive rate for serum anti-RalA antibodies was 18 %, which gradually increased with the tumor stages. Although the positive rate for serum anti-RalA antibodies was comparable with that of carcinoembryonic antigen (24 %) and CYFRA21-1 (21 %), it was lower than the rate for serum p53 antibodies (31 %) and squamous cell carcinoma antigen (37 %). Although serum anti-RalA antibodies were not associated with other serum markers, it was inversely associated with serum p53 antibodies. No clear association was observed between serum anti-RalA antibodies and RalA immunoreactivity.

Conclusions

Presence of serum anti-RalA antibodies is associated with tumor stages, but not with conventional tumor markers. Serum anti-RalA antibodies may be candidate serum markers in combination with other serum markers for esophageal squamous cell carcinoma.

     

Ala601-Thr type dysplasminogenaemia genetically diagnosed in patients with retinochoroidal vascular disorders

Dysplasminogenaemia has been reported in patients with retinochoroidal vascular disorders. The precise genetic defects of these cases, however, remain unclear because of the limitations of conventional diagnostic techniques. In this study, three patients with these diseases were investigated at the DNA level for the first time to define the molecular bases of these disorders. Polymerase chain reaction–restriction fragment length polymorphism analysis revealed that all three cases carried the same Ala601-Thr mutation. This defect may also play a role in the pathogenesis of circulation disorders in small local vessels because of reduced fibrinolytic activity due to decreased functional plasminogen levels.     

Argyrophilic proteins of the nucleolar organizer region in acute leukemias and its relation to the S-phase fraction of leukemic cells.

Nucleolar organizer regions (NORs) are loops of DNA which transcribes to ribosomal RNA. The NOR-related protein becomes visible in nucleus by a silver-staining technique under a light microscope, and it has been named argyrophilic protein of NOR (Ag-NOR). In various malignancies, the correlation between the proliferation potential of tumor cells or histological grade and the number of Ag-NORs has been reported. In this study, we investigated the Ag-NOR of acute leukemic cells and its relation to the in vivo proportion of bone marrow leukemic cells in DNA synthetic phase. The number of Ag-NORs in bone marrow leukemic cells was more than that in peripheral blood (means values 2.78 and 2.48, respectively, p less than 0.01). This result shows that the number of Ag-NORs reflects the vigorous proliferative potential of bone marrow leukemic cells. However, no significant correlation was obtained between the number of Ag-NORs and the bromodeoxyuridine-labeling indices (r = 0.2064). These results suggest that Ag-NOR might be one of the markers for cellular proliferation in leukemia, while DNA synthesis of leukemic cells do not seem to be directly related to Ag-NOR. In order to clarify the role of Ag-NOR in leukemia, further studies are needed.     

Refractory Crow-Fukase Syndrome (POEMS Syndrome) Successfully Treated with High-Dose Melphalan followed by Autologous Peripheral Blood Stem Cell Transplantation

Crow-Fukase syndrome (CFS) is a multisystemic disorder. Because it is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, sclerotic bone lesions, and skin changes it is also known as POEMS syndrome. Extravascular volume overload is also one of the main symptoms. Uncontrollable extravascular volume overload is one of the major causes of death and one of the negative prognostic factors. Control of the extravascular volume overload is an important therapeutic strategy for this syndrome. We report here a case of CFS with extravascular volume overload resulting in pleural effusion and massive edema in the lower extremities, which was refractory to oral administration of melphalan and prednisolone. The patient's condition correlated with the serum level of vascular endothelial growth factor and markedly improved after administration of high-dose melphalan (200 mg/m²) followed by autologous peripheral blood stem cell transplantation. This approach should be considered in patients with CFS who fail to respond to conventional chemotherapy and have uncontrollable extravascular volume overload.     

Thyroid hemiagenesis with postpartum silent thyroiditis

A 28-year-old woman with thyroid hemiagenesis, who had been diagnosed as having Graves' disease, became pregnant during the course of methimazole treatment. The treatment was terminated in the second trimester. She delivered a normal infant at full term. She became thyrotoxic 3 months after the delivery, hypothyroid 6 months after the delivery, and finally euthyroid 11 months after the delivery without undergoing any treatment. This clinical course indicates that she developed silent thyroiditis after the delivery. A diagnosis of thyroid hemiagenesis was made on the basis of ultrasonography of the thyroid and 99mTc-pertechnetate thyroid scintiscan.     

EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt

The cadherin-catenin complex is the major machinery for cell-cell adhesion in many animal species. This complex in general associates with actin fibers at its cytoplasmic side, organizing the adherens junction (AJ). In epithelial cells, the AJ encircles the cells near their apical surface and forms the "zonula adherens" or "adhesion belt." The mechanism as to how the cadherin-catenin complex and F-actin cooperate to generate these junctional structures, however, remains unknown. Here, we show that EPLIN (epithelial protein lost in neoplasm; also known as Lima-1), an actin-binding protein, couples with alpha-catenin and, in turn, links the cadherin-catenin complex to F-actin. Without EPLIN, this linkage was unable to form. When EPLIN had been depleted in epithelial cells, the adhesion belt was disorganized and converted into zipper-like junctions in which actin fibers were radially arranged. However, nonjunctional actin fibers were not particularly affected by EPLIN depletion. As EPLIN is known to have the ability to suppress actin depolymerization, our results suggest that EPLIN functions to link the cadherin-catenin complex to F-actin and simultaneously stabilizes this population of actin fibers, resulting in the establishment of the adhesion belt.     

Scintigraphic comparison of neorectal emptying between colonic J-pouch anastomosis and straight anastomosis after stapled low anterior resection

BACKGROUND AND AIMS. Colonic J-pouch anastomosis after low anterior resection of the rectum has been reported to be associated with an increased risk of evacuation difficulty. Using scintigraphy we compared neorectal emptying after stapled low anterior resection between colonic J-pouch anastomosis and straight anastomosis. PATIENTS AND METHODS. We studied 19 patients after colonic J-pouch anastomosis and 22 after straight anastomosis. After the introduction of an artificial stool containing (99m)Tc-DTPA into the neorectum sequential lateral gamma images were obtained. From the time activity curve of radioactivity in the whole pelvis the time taken to evacuate one-half of the introduced artificial stool ( t(1/2)) and the percentage of artificial stool evacuated in 1 min (Evac(1)) were calculated. Fourteen volunteers were also studied as the reference group. RESULTS. The t(1/2) was significantly longer and Evac(1) significantly lower in patients after low anterior resection than in the reference group. t(1/2) was significantly longer in the pouch group than in the straight group. Anastomotic height was significantly correlated with both t(1/2) and Evac(1). Neither t(1/2) nor Evac(1) was correlated with the severity of impaired defecatory function. CONCLUSION. Although neither of the two parameters of neorectal emptying was correlated with the severity of impaired defecatory function, less effective neorectal emptying in patients after colonic J-pouch anastomosis than in those after straight anastomosis may be a factor causing evacuation difficulty after colonic J-pouch anastomosis.     

Focal nodular hyperplasia-like lesion with venous washout in alcoholic liver cirrhosis

A case of 22 mm hypervascular nodule in segment two of the liver but without hepatitis B or C virus infection in a 32-year-old Japanese woman with a history of alcohol abuse is presented. Imaging studies such as contrast-enhanced ultrasound, computed tomography and magnetic resonance imaging showed hypervascularity in the early phase and venous washout in the late phase. Histologically, stellate scar-like fibrous septa, pericellular fibrosis, fatty change, neutrophilic infiltration, slight increase of cell density, and diffuse capillarization of the sinusoids together with small unpaired arteries were observed. The nodule was diagnosed as focal nodular hyperplasia-like lesion in alcoholic liver cirrhosis.