Interleukin-4 and Interferon-γ Inhibit Prostaglandin Production by Interleukin-1β-Stimulated Human Periodontal Ligament Fibroblasts

The purpose of the present study was to investigate the involvement of cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human periodontal ligament (PDL) fibroblasts stimulated with a proinflammatory cytokine, inerleukin-1 (IL-1), and to examine the effect of interleukin-4 (IL-4), a Th2 cytokine, and interferon- (IFN-), a Th1 cytokine, on PG production by the cells. IL-1-stimulated PDL fibroblasts produced prostaglandin E₂ (PGE₂) in a time-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor, completely inhibited PGE₂ production by IL-1-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detected in IL-1-stimulated PDL cells, although not detected in unstimulated cells, while expression of COX-1 mRNA was in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA expression, COX activity and PGE₂ production in IL-1-stimulated cells. IL-4 and IFN- suppressed PGE₂ production by IL-1-stimulated PDL fibroblasts, but COX activity enhanced by IL-1 treatment was significantly inhibited by IL-4, not by IFN-. Northern blot analysis showed that IL-4 depressed COX-2 mRNA expression with no effect on COX-1 mRNA expression. On the other hand, IFN- had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2 is primarily responsible for PGE₂ production by IL-1-stimulated human PDL fibroblasts and that IL-4 inhibited PGE₂ production by IL-1-stimulated PDL fibroblasts through down-regulation of COX-2 expression, while IFN- suppressed the PGE₂ production with no effect on COX-2 expression.     

The central inhibitory effect of interleukin-1 on gastric acid secretion

The effect of interleukin-1 (IL-1) on gastric secretory functions was examined in pylorus-ligated conscious rats. Intracisternal (i.c.) injection of IL-1 beta (1-100 ng) induced dose-related, long-lasting inhibition of gastric acid output, which was due to the reductions of both the amount and the acid concentration of the gastric juice. A much higher dose of IL-1 alpha was required to achieve identical effects on gastric acid secretion when it was given by intravenous routes. The i.c. injection of IL-1 alpha also had an inhibition of gastric secretion. This inhibitory effect of i.c. applied IL-1 beta on gastric acid secretion was completely abolished in indomethacin-pretreated animals but not in reserpine-pretreated ones. These results suggest that IL-1 may have an inhibitory action on the regulation of gastric secretory functions by its central action which is dependent on the eicosanoid metabolism.     

Non-A, non-B hepatitis related AN6520 Ag is a normal cellular protein mainly expressed in liver. II

Detection of AN6520 Ag/Ab in human sera had indicated a close association with non-A, non-B hepatitis (NANBH). In this study, we investigated the immunochemical nature of AN6520 Ag and measured the amounts in various human and chimpanzee organs in order to clarify the association with NANBH. AN6520 Ag was found to be composed of polypeptide(s) with an apparent molecular weight of 45,000 daltons (45 kD), which are noncovalently linked together. Human antibodies in convalescent sera from NANBH patients as well as monoclonal antibodies were found to recognize only the high-order structure of the antigen, whereas rabbit antibody recognized both the high-order structure and the reduced form of 45 kD polypeptide(s). AN6520 Ag could be detected in most of the livers tested including those without any liver damage and fetal livers; their amounts varied considerably from each other. The antigen could be detected also in organs other than liver, but in contrast to liver, the amounts were small and did not vary as much between individuals. From the data of immunoblotting using rabbit antibody, our observed variation of antigen content in liver was considered to be due to the difference in expression of 45 kD polypeptide(s). Although no specific relationship was found between the amount of the antigen in liver and NANBH, the antigen was found to increase several times in livers of chimpanzees after the inoculation of NANBH virus. These data suggest that AN6520 Ag is a normal cellular protein existing mainly in liver and that its quantity may vary under some conditions such as NANBH.     

Extraskeletal myxoid chondrosarcoma arising from the retroperitoneum

A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.     

Properties of hepatitis B virus genome recovered from Vietnamese patients with fulminant hepatitis in comparison with those of acute hepatitis

Among the many mutations found in the hepatitis B virus (HBV) genome, some have been associated with fulminant hepatitis, as exemplified by precore-defective mutations. The aim of this study was to determine whether such mutations also are found in Vietnamese cases of fulminant hepatitis B. The full-genome nucleotide sequence of HBV in three patients with fulminant hepatitis (F-2, F-3, and F-6) and one with acute hepatitis (A-3), who were admitted to Cho Ray Hospital, Ho Chi Minh City, Vietnam was ascertained. Additionally, two patients with fulminant hepatitis (F-1 and F-7) and three with acute hepatitis (A-1, A-2, and A-5) were examined only for the precore/core region of HBV. Remarkably, the nonsense mutation at precore codon 28 (Trp82Stop) was found in four of the five patients with fulminant hepatitis, while all the acute hepatitis patients harbored wild type (one had a mixture of wild and mutant types). The missense mutations within the core region, Ile97Leu and Pro130Ile/Thr/Ser, were also remarkable in fulminant hepatitis. Only F-2 was free from these precore/core mutations, but F-2 was unique in that it possessed a chimeric genotype: it could be classified into genotype C as a whole, but its X region was of genotype B, like the other four fulminant hepatitis isolates (F-1, F-3, F-6, and F-7). The codon 41 of the X protein was Pro in all three fulminant hepatitis cases examined for this region, while it was Ser in the wild-type isolates of genotype B. Of note as negative data, the mutations C1653T and T1753M of the enhancer II (Enh II) and A1762T and G1764A of the precore/core promoter regions, once reported to be relevant to severe or fulminant hepatitis, were not found in the present cases. The results with the Vietnamese cases of fulminant hepatitis corroborated results of previous studies with respect to the mutations Trp28Stop of precore and Ile97Leu and Pro130Ile/Thr/Ser of core, but not for the mutations within Enh II and precore/core promoter region. Whether the Ser41Pro mutation in the X region of genotype B HBV is Vietnam-specific or disease-specific deserves further investigation.     

Disseminated necrotizing encephalopathy induced by methotrexate therapy alone

This report describes the autopsy findings in a 62-year-old woman who died of pneumonia and disseminated necrotizing encephalopathy following intrathecal methotrexate (MTX) therapy for meningeal infiltration of lymphoma cells. Radiation therapy was not given. An interesting pathological finding was exudation of fibrin around the small vessels in the demyelinated foci, suggesting increased vascular permeability. This observation and analysis of previous reports of similar cases suggest that primary vascular injury, probably due to the direct effect of MTX, may be involved in the pathogenesis of MTX-related disseminated necrotizing encephalopathy.     

BRONCHIAL CARCINOID ACCOMPANIED BY THYROID ADENOMAS AND ADRENAL ADENOMAS

A large tumor massively occupying the left pleural cavity had the Andings of both typical carcinoid and oncocytoma which were thought to be of bronchogenic origin. The ultrastructural observation of the tumor revealed a mixture of rod-shaped granules in addition to usual round neurosecretory ones. In the nuclei of dark cells of the oncocytoma, a latticed or hatched structure was detected. Besides two adenomas and hyperplastic foci of large acidophilic cells in the thyroid, a black adenoma and cortical adenoma in the adrenal gland, were detected. Moreover, there was an ectopic adrenal gland in the retroperitoneum. Briefly it was suggested that the bronchial carcinoid presented may be related to multiple endocrine adenomatosis.     

Mechanism of the formation of megamitochondria by copper-chelating agents. IV. Role of fusion phenomenon in the cuprizone-induced megamitochondrial formation

Megamitochondria were induced within 36-40 hours in mouse hepatocytes by injecting cuprizone into the peritoneal cavity. Induction of megamitochondria was dependent upon the amount and the time intervals of the injection of cuprizone: 200 mg of cuprizone/kg of body weight-injected every 12 hours or 400 mg of cuprizone/kg of body weight-injected every 24 hours. When the latter amount of the noxious reagent was administered to the animal every 12 hours, fatty changes of the liver was observed. Involvement of the fusion phenomenon in the mechanism of megamitochondrial formation is discussed in the light of turnover rates for various components of the mitochondrion.