Decreased interleukin 1 activity in culture supernatant of lipopolysaccharide stimulated monocytes from patients with liver cirrhosis and hepatocellular carcinoma.

Immunoregulatory function of peripheral blood monocytes was studied in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), by assaying interleukin 1 (IL-1) and prostaglandin E2 (PGE2) in the culture supernatant of lipopolysaccharide-stimulated monocytes. IL-1 activity of the monocyte culture supernatant without indomethacin was decreased in patients with HCC and LC, compared with that of controls. The activity was lower in patients with HCC than that in those with LC. The PGE2 content of the culture supernatant of monocytes from patients with LC and HCC was increased, compared to normal controls. To avoid the effect of PGE2 on the IL-1 assay, we cultured the monocytes with addition of indomethacin and assayed IL-1 activity in the culture supernatant. As a result, monocyte IL-1 production was increased in patients with HCC and LC, compared with normal controls. The decrease in IL-1 activity of the supernatant without indomethacin of patients with LC and HCC was considered to be due to increased secretion of PGE2 by the monocytes. Therefore, monocytes from patients with HCC and LC had an increased capacity of secreting both IL-1 and PGE2 over normal controls, but the effect of the suppressor function (PGE2 secretion) dominated in these patients.     

Increased peripheral blood Ia positive T cells and their effect on autologous mixed lymphocyte reaction in chronic active liver disease.

We measured Ia antigen bearing peripheral blood T cells, as an index of immunological stimulation, of patients with chronic active liver diseases (CALD) by the rosette assay method. We also examined the role of Ia antigen which represents the products of the genes of the major histocompatibility complex on the autologous mixed lymphocyte reaction (AMLR) since this reaction may reflect self regulation of immune responses. The percentages of Ia positive T cells of 29 patients with CALD (17.1 +/- 4.3%, P less than 0.001) and of 12 patients with other liver diseases (12.9 +/- 2.4%, P less than 0.05) were increased when compared with that of normal individuals (10.7 +/- 2.0%). However, levels of Ia positive T cells activated by phytohaemagglutinin-P in patients with CALD and other liver diseases did not differ from normal subjects. Ia positive cells in OKT8 positive cells were markedly elevated (P less than 0.001), whereas those in OKT4 positive cells were decreased (P less than 0.01) in CALD. The impaired values for the AMLR correlated inversely (P less than 0.01) with the increased percentages of Ia positive T cells in patients with CALD. Further analysis showed that there was no suppression of the proliferation of Ia and OKT4 positive cells by Ia and OKT8 positive cells although the culture of increasing numbers of Ia and OKT8 positive cells and decreasing numbers of Ia and OKT4 positive cells gave a lesser AMLR value. These data suggest that the increase in Ia positive T cells and the alteration of Ia positive cells in the T cell subsets reflect an activation of immune system and provide further evidence in favour of an abnormality of the immunoregulatory system in CALD.     

Soluble Fas and soluble Fas L levels in patients with acute pancreatitis

The FasL-Fas system is an apoptosis induction system and plays an important role in homeostasis and biophylaxis. The present study was conducted to investigate soluble Fas (sFas), soluble Fas ligand (sFasL), and tumor necrosis factor alpha (TNF-alpha) in patients with acute pancreatitis. As acute pancreatitis became severe, the levels of sFas in the serum increased significantly, while those of sFasL decreased significantly. A significant inverse correlation was observed between the serum levels of sFas and those of sFasL. Also, a significant positive correlation was observed between the levels of TNF-alpha and sFas. A greater increase in serum sFas and decrease in serum sFasL levels was observed in patients with complicating multiple organ dysfunction syndrome (MODS) than in those without it. The results of the study suggest that the pathological aggravation of acute pancreatitis could be related to changes in the Fas-FasL system.     

Effects of sodium, potassium and calcium ions on the slow wave in the circular muscle of the guinea-pig stomach

1. The contribution of Na, K and Ca ions to the generation of slow waves in the circular muscle of the guinea-pig stomach was studied.     

Frequent importation of enterovirus 71 from surrounding countries into the local community of Yamagata, Japan, between 1998 and 2003

Phylogenetic analysis of 45 enterovirus 71 (EV71) isolates for 6 years in Yamagata, Japan, clarified that the annual outbreak of hand-foot-and-mouth disease was due to four genetically distinct subgenogroups, including a novel "B5." Our results suggest that the importation of EV71 from surrounding countries has had a major epidemiological impact on the local community used in our study.     

Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.     

Open food challenge with milk, egg white and wheat

Background: A method for open food challenge test to determine food allergy has not been established in an evidence-based manner. Methods: We conducted an analysis of 438 open food challenges of raw milk (n=133, mean age 2.7+/-1.9 years), boiled egg white (n=216, 2.8+/-2.1 years) or udon noodles (n=89, 2.7+/-1.7 years) for the patients aged 1 year or more. Doses were increased (trace amounts, 1 g, 2 g, 5 g, 10 g, 20-30 g) every 20 minutes. Results: In total, 151 (38.5%) of food challenges were positive. The positive rates of milk, egg and wheat challenges were 35.8%, 42.4% and 33.3%, respectively. Of these, 76.2%, 32.5%, 27.8% and 0.7% had, respectively, skin, respiratory, gastrointestinal and cardiovascular symptoms. Although the prevalence of positive challenge increased with level of specific IgE, it did not correlate with the threshold amount of positive food challenge or the severity of symptoms. Among the challnege positive patients, 10.6% required injection of antihistamines, corticosteroids or adrenalines for the treatment of the symptoms. Conclusions: This challenge protocol seemed to be appropriate and safe.     

Studies on the osmophilic fungus Wallemia sebi as an allergen evaluated by skin prick test and radioallergosorbent test

Recently, Wallemia sebi, a species of osmophilic fungi, has been abundantly detected in house dust using low water activity media. In this study, allergenic activity of W. sebi was assessed by skin prick test and radioallergosorbent test (RAST) in 74 asthmatic patients ranging from 6 to 32 years of age. Aspergillus fumigatus and house dust were used for comparison. In skin prick test, W. sebi extract, A. fumigatus extract and house dust extract elicited positive reactions in 4 (5.4%), 4 (5.4%) and 51 (68.9%) patients, respectively. RAST showed positive results in 14 subjects (18.9%) for W. sebi extract, in 8 (10.8%) for A. fumigatus extract and in 59 (79.7%) for house dust extract. These results indicated that some asthmatic individuals showed immediate-type hypersensitivity to W. sebi, and which means this fungal species may be of importance to atopic diseases as a causative agent.     

Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer's disease

We studied promoter region polymorphisms in the interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, tumor necrosis factor, and transforming growth factor (TGF)-beta1 genes in Japanese patients with Alzheimer's disease (AD) (n = 172) and normal controls (n = 163). We also examined an association of a polymorphism located in the glutathione S-transferase omega 1 (GSTO-1) gene region with AD patients. None of these genotypes or allele frequencies showed a significant difference between AD patients and controls. We also failed to detect any difference in the disease onset between each genotype of the seven polymorphisms. Although AD patients carrying high producer alleles of TGF-beta1 and IL-1beta or TGF-beta1 and IL-6 showed a tendency for an early onset of the disease, neither of these combined effects reached a significant level after multiple comparisons. Our findings suggest that genetic polymorphisms in the cytokines and GSTO do not play a major role in Japanese AD patients.