Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P<0.01), in those with regional lymph node metastasis (P<0.05) and in those that had invaded beyond the submucosa (P<0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.     

Generation of a transgenic animal model of hyperthyroid Graves' disease

Graves' disease (GD) is an organ-specific autoimmune disease characterized by hyperthyroidism. Agonistic anti-thyrotropin receptor antibodies (thyroid-stimulating antibodies, TSAb), which mimic the thyrotropin (TSH) action, are thought to cause GD. The precise immunological mechanism of TSAb production, however, remains elusive. Previous immunization approaches using TSH receptor led to transient hyperthyroidism, but did not seem sufficient for comprehensive understanding of the development of autoimmune responses. To create GD-related autoimmunity in mice, we here generated TSAb-transgenic mice in which a patient-derived TSAb is expressed in B cells. Expression of the human TSAb in mice resulted in various manifestations of hyperthyroidism including increased free thyroxine levels with concomitantly decreased TSH levels, increased thyroid uptake of technetium pertechnetate, hyperthermia and thyroid hyperplasia. We found a correlation between the serum levels of human TSAb immunoglobulin and free thyroxine. In addition, conventional B cells expressing the TSAb were partially deleted in the periphery while B1 cells expressing the TSAb persisted and accumulated in the peritoneal cavity, a finding consistent with previous demonstrations that the maintenance of B1 cells plays an important role in the development of autoimmune diseases. Thus, our transgenic mouse may provide a novel and useful animal model for elucidating the pathogenesis and pathophysiology of GD.     

Possible involvement of apoptotic death of myocytes in left ventricular remodeling after myocardial infarction

Pathophysiological roles of apoptosis in post-infarction left ventricular (LV) remodeling have not been well characterized. This study showed that TUNEL- or cleaved caspase-3-positive myocytes were identified late after ligation of the left coronary artery in rats, suggesting that apoptotic myocyte death contributed to the morphological change associated with LV remodeling.     

Subsequent progression to membranous glomerulonephritis following exacerbation of urticarial rash in systemic lupus erythematosus: report of 2 cases

Two Japanese female adolescents with systemic lupus erythematosus (SLE), known cases of urinary tract involvements: one with biopsy-proven class II lupus nephritis and the other one with lupus cystitis without overt glomerulonephritis (silent lupus), who after more than 4 years' observation presented with subsequent progression to membranous glomerulonephritis (MGN) following exacerbation of urticarial rash. Although it is well known that lupus nephritis shows histological transformation with time, the late progression to MGN from another World Health Organization histologic pattern has been reported to be less common in pediatric-onset SLE. Although pathogenesis of their MGN remains speculative, these clinical observation might suggest that a possible association between exacerbation of urticarial rash and subsequent progression to MGN in the selected patients with SLE.     

Profound ionized hypomagnesemia induced by therapeutic plasma exchange in liver failure patients

BACKGROUND: Various adverse effects, including cardiac arrest, have been induced by plasma exchange (PE). Electrolyte derangement is frequently observed. The purpose of this study was to assess the effect of PE on the serum ionized magnesium (Mg2+) concentration in acute liver failure patients. STUDY DESIGN AND METHODS: Seven liver failure patients requiring PE were enrolled in this study. PE was performed 21 times in total. Blood samples were drawn before PE and serially after the start of the PE. Serum Mg2+ was measured by the ion- selective electrode method. RESULTS: After PE was started, Mg2+ concentrations began to fall significantly. The low Mg2+ blood concentration continued during PE. After PE, the Mg2+ level recovered to about 80 percent of the control value within 2 hours in six patients. However, in one patient, the Mg2+ concentration was still low even at 2 hours after PE. This patient complained of chest discomfort during PE and ECG analysis showed sporadic supraventricular premature contractions. CONCLUSION: Profound ionized hypomagnesemia was induced by PE in liver failure patients.     

Drug-induced arrhythmias

Drug-induced arrhythmias are commonly described as proarrhythmia, arrhythmogenesis or aggravation of arrhythmias. A variety of drugs including cardiotonic drugs (antiarrhythmics, digitalis, cathecholamines), psychiatric drugs(phenothiazines, antidepressants), and macrolide antibiotics would worsen or induce arrhythmias. Among them are bradyarrhythmias and tachyarrhythmias, especially torsade de pointes(TdP) resulting from QT prolongation. There exist some predisposing factors which could potentiate proarrhythmic effect of drugs. They include age, congestive heart failure, ischemic heart disease, renal or hepatic dysfunction, electrolyte disturbance and previous history of proarrhythmia. It should be, therefore, very cautious when drugs with potentially proarrhythmic effect are given to subjects with predisposing factors. Correction of these factors and prevention of bradycardia are important in the management of proarrhythmia and TdP can be treated by infusion of magnesium.