Specific cellular immune responses to pancreatic antigen in chronic pancreatitis and Sjögren's syndrome

The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögren's syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index >2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%;P<0.05), 6 of 7 patients with Sjögren's syndrome-associated chronic pancreatitis (86%;P<0.0005), and 6 of 11 patients with Sjögren's syndrome (55%;P<0.01), compared to normal controls whose stimulation index was 0.94±0.28 (mean ± SD;n=14; range, 0.56–1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%;n=12), stone-related chronic pancreatitis (0%;n=7), primary biliary cirrhosis-associated chronic pancreatitis (33%;n=3), primary biliary cirrhosis (0%;n=4), systemic lupus erythematosus (17%;n=6), and autoimmune thyroiditis (0%;n=6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4⁺ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögren's syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.     

Brain blood flow autoregulation and metabolism during halothane anesthesia in monkeys.

Past studies suggest that halothane causes cerebrovascular dilatation and increased cerebral blood flow (CBF); these properties may be relevant to its use for neurosurgical procedures. We studied CBF autoregulation in monkeys during anesthesia with 66% N2O/33% O2 and with 0.5%, 1.0%, and 2.0% inspired halothane at various cerebral perfusion pressures (CPP) achieved by infusion of trimethaphan camsylate or phenylephrine. CBF was measured by monitoring brain xenon-133 clearance after intra-arterial injection of the isotope in saline. CBF autoregulation was intact during N2O/O2 and during 0.5% halothane/N2O/O2 anesthesia at CPPs ranging from 50 to 100 mmHg, but began to fail at 1.0% halothane. Complete loss of autoregulation occurred during 2% halothane/N2O/O2 anesthesia. Estimated brain O2 consumption fell by 30%, 40%, and 50% during 0.5%, 1.0%, and 2.0% halothane anesthesia, respectively, compared to O2 consumption during N2O/O2 anesthesia (100%).     

Increased concentrations of soluble tumour necrosis factor receptor (sTNFR) I and II in peritoneal fluid from women with endometriosis

Tumour necrosis factor alpha (TNFalpha), a proapoptotic cytokine, is known to be present in peritoneal fluid from women with endometriosis. An emerging view is that soluble TNF receptors (sTNFR) can modulate the effects of TNFalpha by acting as TNFalpha antagonists. To assess the relevance of sTNFRs in the pathophysiology of endometriosis, concentrations of sTNFR I, sTNFR II and TNFalpha in peritoneal fluid from women with endometriosis (n = 53) and without endometriosis (n = 40) were measured. Concentrations of both sTNFR I and sTNFR II in peritoneal fluid from women with endometriosis were significantly higher than in peritoneal fluid from women without endometriosis, both in the follicular and the luteal phases. TNFalpha concentrations did not differ in patients with and without endometriosis in both phases. When stratified by the stage of the disease, women with both stages I/II and stages III/IV exhibited significantly higher concentrations of sTNFR I and sTNFR II in peritoneal fluid, compared with women without endometriosis, whereas no appreciable difference in the concentrations was detected between stages I/II and stages III/IV. A significant correlation was found between the concentrations of sTNFR I and sTNFR II; while the correlations between TNFalpha and sTNFR I or sTNFR II, were either not significant or were very weak. Furthermore, mRNA for the membrane-associated TNF receptor type 1 and TNF receptor type 2, both of which convey the effects of TNFalpha, were shown to be expressed in endometriotic tissues as well as eutopic endometrium. Together, these findings suggest a possible involvement of sTNFRs in the pathophysiology of endometriosis.     

Anti-myeloperoxidase and anti-lactoferrin antibodies in patients with IgA nephropathy and Henoch-Schönlein purpura

Antineutrophil cytoplasmic antibodies (ANCA) for two antigens, i.e. myeloperoxidase (MPO) and lactoferrin (LF) in sera from 19 IgA nephropathy (IgAN), 3 adult Henoch-Sch?nlein purpura (HSP) and 8 child HSP patients were examined by enzyme-linked immunoabsorbent assay (ELISA) for immunoglobulin isotypes. All of child HSP patients showed negative ANCA. On the other hand, one IgAN patient and two adult HSP patients showed weak positivity for IgA class anti-MPO antibody. There was no patients who showed positivity for IgG and IgM class anti-MPO antibody. In anti-LF antibody, one IgAN and one adult HSP showed positivity in IgG class; 2 IgAN and 2 HSP in IgA class and 2 IgAN and one HSP in IgM class. These results indicate that adult HSP patients have higher prevalence of IgA class anti-MPO antibody and anti-LF antibody than IgAN or child HSP.     

Cloning and characterization of the cDNA encoding the HA protein of a hemagglutination-defective measles virus strain

cDNA clones corresponding to the mRNA for the hemagglutinin of the hemagglutination-defective strain AK-1 of measles virus were isolated and characterized. Compared with the prototype Edmonstron strain, 60 nucleotide substitutions that resulted in 18 amino acid changes were detected. An additional potential N-linked glycosylation site was added by point mutation, which was supported by the observation that the hemagglutinin of the AK-1 strain was stained more heavily after NaDodSO₄PAGE and periodic acid-Schiff (PAS) staining than the Edmonston strain. Computer-assisted analysis revealed that three reverse turns in the secondary structure had disappeared in the hemagglutinin of the AK-1 strain. Moreover, one of these structural changes occurred in the closely glycosylated region at amino acid residues 168–240, which appeared to be a biologically important functional domain. The isoelectric point calculated from the predicted amino acid sequence became about 1 pH unit more basic in the AK-1 strain than the Edmonston strain. This present study is the first sequence analysis of the hemagglutinin gene in a hemagglutination-defective strain of the measles virus.     

An autopsy study of lung cancer in University of Tokyo for the last 27 years, from 1958 to 1984, with special reference to the characteristics of lung cancer in Japan

Four hundred and sixty-five male and 159 female consecutive autopsy cases of lung cancer, autopsied over the 27 years from 1958 to 1984, were analysed and were compared with other materials and mortality statistics, including statistics from other countries. Malignant tumor autopsy cases are gradually increasing and now comprise more than 60% of total autopsy cases. The percentage of lung cancer cases among all autopsy cases was 7% in males and 4% in females. The percentage of lung cancer in autopsies of patients with malignancies was about 13% for males and 9% for females. The most frequent fatal malignant tumors were gastric cancer, lung cancer, and leukemia. The relative incidence of gastric cancer was decreasing, while that of lung cancer was increasing. In the distribution of the histological types of lung cancer, adenocarcinomas were the most frequent types in both sexes. As has been noted in mortality statistics, we noticed a gradual shift in the peak age of lung cancer autopsy cases towards older patients. During the period under study, the peak shifted from patients in their sixties to patient in their seventies; this was true for most of the major histological types in both sexes. The male/female ratio of all lung cancer cases was 2.9, which was much lower than the ratio found in the United States and Europe, and very similar to the ratio of the mortality rates in Japan and other Asian countries. It was pointed out that the male/female ratios by age-group in each country is a very good reflection of the histological distribution.     

A statistical analysis of lung cancer registered in the Annual of Pathological Autopsy Cases in Japan between 1958 and 1987, with special reference to the characteristics of lung cancer in Japan

Autopsy cases of lung cancer, 41,988 in males and 13,818 in females, consecutively registered between 1958 and 1987, were analysed statistically and compared with other case materials and mortality statistics. Cases of malignant tumor showed a gradual increase, and now comprise 60% of the total male and 55% of the total female autopsy cases. The percentage of lung cancer cases among the total autopsy cases was 9% for males and 5% for females. The percentage of lung cancer cases among total cases of malignant tumor was about 17% for males and 9% for females. Among fatal malignant tumors, gastric cancer and lung cancer showed the highest frequency. The relative incidence of gastric cancer was seen to decrease, whereas that of lung cancer increased. Of the histological types of lung cancer in both sexes, adenocarcinoma was the most frequent, followed by squamous cell carcinoma. During the period studied the peak age of patients with lung cancer shifted from the seventh to eighth decade, and a significant elevation of mean age was demonstrated for all of the major histological types in both sexes. The male:female ratio for all lung cancer cases was 3.0, which was much lower than those for the United States and Europe, but very similar to the ratios of mortality statistics in Japan and other Asian countries. As a result of a previous autopsy study at the University of Tokyo, it was also confirmed that the male:female ratio relative to age in each country reflects very well the histological distribution.     

Infiltrating eosinophils and eotaxin: their association with idiopathic eosinophilic esophagitis.

BACKGROUND: Idiopathic eosinophilic esophagitis (IEE) is a very rare disease characterized by thickening and eosinophil infiltration of the esophagus. The most potent chemotactic factor for eosinophils is eotaxin, and its pathophysiologic significance in IEE needs to be elucidated. OBJECTIVE: To study the association between eotaxin and IEE. METHODS: We examined eotaxin expression in the esophagus of an IEE patient in comparison to controls by immunohistochemistry using a monoclonal antibody for human eotaxin. We also measured the free eotaxin level and the total (free and bound-form) eotaxin level in blood by enzyme-linked immunosorbent assay before and after the initiation of steroid therapy. RESULTS: Most of the infiltrating eosinophils in the affected esophageal tissue showed immunohistochemical staining with anti-eotaxin antibody. In blood samples, the free eotaxin level was slightly elevated before treatment, whereas the total eotaxin level was within the normal range. Unexpectedly, the total eotaxin level increased dramatically after the initiation of steroid therapy, whereas the increase of free eotaxin was modest. CONCLUSION: Infiltrating eosinophils that express eotaxin and the changes of blood eotaxin levels during steroid therapy suggest that eotaxin may be associated with IEE.     

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.