Interferon-beta reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects

Type I interferons (IFNs), IFN-alpha and IFN-beta, are widely used for treating chronic hepatitis C. Although retrospective studies have suggested that type I IFNs have direct antifibrotic effects, little is known about these mechanisms. The present study was designed to clarify the preventive mechanisms of type I IFNs in the progression of fibrosis for the establishment of a more effective therapy. A murine fibrosis model comprising immunological reactions was induced by the administration of concanavalin A (0.3 mg/body) into mice once a week for 4 weeks. Liver injury and the degree of fibrosis were determined by measuring the serum alanine aminotransferase activities and liver hydroxyproline contents with or without IFN-beta pretreatment. IFN-beta suppressed the hepatocellular injury and increased the hydroxyproline content induced by repeated concanavalin A injections, but had no effect on established fibrosis. Furthermore, IFN-beta reduced the expressions of transforming growth factor-beta, basic fibroblast growth factor, collagen type I A2 and tissue inhibitor of metalloproteinase 1 messenger RNAs, which are related to the progression of liver fibrosis. The IFN-beta reduced the liver injury and fibrosis induced by immunological reactions. These data suggest that type I IFNs suppress the progression of cirrhosis through inhibition of repeated hepatocellular injury and/or factors that promote the liver fibrosis induced by hepatitis virus infection.     

The feasibility of a bed net impregnation program to enhance control of Malayan filariasis along a swamp forest in southern Thailand

The purpose of this study is to document the potential feasibility of using a bed net impregnation program to enhance the control of Malayan filariasis in southern Thailand. A survey was conducted in one Muslim and one Buddhist village along the swamp forest in Narathiwat Province. Face-to-face interview was employed to collect data on practice of bed net use, knowledge and attitudes on filarial control and acceptance if a bed net impregnation program were to be introduced. Bed nets were used by 98.5% of the study households. Both Muslims and Buddhists were all in bed by 23.00 hrs. By 03.00 hrs, more than 20% of Buddhists were out of bed for rubber tapping, whereas more than 90% of the Muslim were still in bed until 04.30 hrs. Combining our data with biting rate from a previous study, approximately one-third of Mansonia bites were protected by the current bed net practice. The impregnation program was potentially welcome by both groups of villagers. From this study, we conclude that a bed net impregnation program in this area is feasible.     

Detection of auto-antibodies against L-myc oncogene products in sera from lung cancer patients

Auto-antibodies against L-myc oncogene products (L-Myc) in sera from lung cancer patients were examined using bacterially synthesized glutathione S-transferase (GST) L-Myc fusion proteins and Western blot analysis. The detection rate of anti-L-Myc antibodies in sera from lung cancer patients was 10%, while that in sera obtained from normal volunteers was 0%. Five patients with non-small-cell lung cancers (2 adenocarcinomas, 2 squamous-cell carcinomas and 2 large-cell carcinoma) were included in the group with anti-L-Myc antibodies. These auto-antibodies belonged to the IgG class and recognized the carboxy terminus of L-Myc. Circulating L-Myc was not detected in sera from patients with anti-L-Myc antibodies. Differences in age, sex, performance status, histology, stage, smoking history and prior treatment were not significantly different between anti-L-Myc antibody-positive and antibody-negative patients. Anti-nuclear antibodies were detected in 40% of lung cancer patients and 57% of those with anti-L-Myc antibodies. Our data suggest that detection of anti-L-Myc antibodies may be helpful in the diagnosis and evaluation of the host-immune response to L-Myc in a subset of lung cancer patients. © 1996 Wiley-Liss, Inc.     

Specific Detection of Pathological Three‐repeat Tau after Pretreatment with Potassium Permanganate and Oxalic Acid in PSP/CBD Brains

Immunohistochemisty with RD3, a monoclonal antibody specific for three‐repeat (3R) tau, is sometimes hampered by diffuse neuronal staining on formalin‐fixed, paraffin‐embedded sections pretreated with formic acid and heating. Additional pretreatment with potassium permanganate followed by oxalic acid completely eliminated this diffuse RD3‐immunoreactivity (IR) in neurons. Furthermore, this additional pretreatment uniformly enhanced RD3‐IR, as well as RD4‐IR, a monoclonal antibody specific for four‐repeat (4R) tau, on pathological deposits with tau IR. This enhanced sensitivity and specificity may allow more reliable identification of 3R and 4R tau in pathological deposits, which may be variable dependent on disease and regions. Cerebral cortex and midbrain from 8 patients [5 progressive supranuclear palsy (PSP) and 3 corticobasal degeneration (CBD)] were screened for RD3‐ and RD4‐IR with this improved procedure. In addition to RD4‐positive structures found both in cerebral cortex and brainstem, RD3‐positive neurofibrillary tangles (NFTs) were also found in midbrain in 7 of these 8 cases but not in the cortex. Multi‐labeling study demonstrated that most of RD3‐negative neurons were positive for RD4. This reliable demonstration of pathological 3R tau deposits in the brainstem of PSP/CBD, so far presumably characterized by deposition of 4R tau, is useful to map tau‐positive lesions according to their biochemical composition.