Efficacy of interferons in treating children with chronic hepatitis C

Twenty-two children with chronic hepatitis serologically positive for hepatitis C virus (HCV) were treated with interferon-alpha (IFN-alpha). Liver biopsy showed chronic active hepatitis in 13 and chronic persistent hepatitis in 9 patients. A sustained clearance of HCV was observed in 8/22 children 12 months after the administration of IFN-alpha for 26 weeks, associated with normalization of HCV core antibody. Of these eight patients six had HCV genotype III and two HCV genotype II or IV. Hepatitis relapsed in seven other patients after completion of IFN-alpha with an increase in HCV core antibody titre, five with HCV genotype II, and two with HCV genotype III or IV. A second course of IFN-alpha suppressed the reactivation of HCV in all seven patients. Three of seven responders who relapsed after the first course remained negative for HCV RNA 12 months after their second course of IFN-alpha. However, the remaining four patients with HCV genotype II again relapsed after completing their second course of IFN-alpha. Seven children with the HCV genotype II resistant to IFN, including 8 weeks of IFN-beta administration, and showed no significant reduction in HCV core antibody titre. CONCLUSION: The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-alpha therapy.     

ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb

OBJECTIVE: The purpose of this study was to evaluate ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb. CONCLUSION: Although rare, the diagnosis of ectopic drainage of the common bile duct into the duodenal bulb is important to prevent inadvertent damage during biliary tract or gastric surgery and to clarify the cause of chronic peptic ulcers.     

Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers

Loss of heterozygosity at chromosome 8p21-22 is common in human prostate cancer, suggesting the presence of one or more tumor suppressor genes at this locus. A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21. Fine structure in situ mapping showed that NKX3.1 is proximal to MSR32 (macrophage scavenger receptor type II) and LPL (human lipoprotein lipase) and very close to NEFL (human neurofilament light chain) on 8p21. Single-strand conformational polymorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumor-specific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21. NKX3.1 was found to have a polymorphism at nucleotide 154 in codon 52 that resulted in a CGC-->TGC sequence change and an Arg-->Cys amino acid alteration (R52C). This polymorphism was present in 20% of DNA samples. If NKX3.1 is a target of the 8p21 LOH, it is not via disruption of the coding region of the gene.     

Memory beyond the hippocampus

Cultured hepatocytes of silver eel actively secreted only chylomicron-like lipoprotein. The rate of secretion per mg cellular protein per 24 hr was 2.2 times higher compared with that by yellow eel hepatocytes. Silver eel hepatocytes secreted lipids 2.5 times higher through the lipoprotein than yellow eel hepatocytes. Main lipid was triacylglycerol in either secreted lipoprotein and composition of apolipoproteins of both secreted lipoproteins was the same. The incorporation of 3H-leucine into the lipoprotein secreted by silver eel hepatocytes was 2.4 times higher, but that of 14C-acetate was not significantly different. Protein and lipids composition of plasma lipoproteins of silver eel was significantly higher and lower compared with those of yellow eel, respectively. We suggest that the secreted lipoprotein of silver eel hepatocytes transport much more lipids to other tissues than that of yellow eel hepatocytes.     

Decreased levels of a soluble form of the human adhesion receptor CD58 (LFA-3) in sera and synovial fluids of patients with rheumatoid arthritis

The mode of interaction between muramyl dipeptide (MDP), a compound with immunopharmacological activities, and 5-hydroxtryptamine (5-HT, serotonin) was studied in isolated nerve-smooth muscle preparations of the carp stomach. Application of exogenous 5-HT evoked direct smooth muscle contractions; electric neurogenic stimulation evoked twitches due to release of 5-HT from nerve endings. Contractions evoked by a high concentration of 5-HT (3-30 microM) were resistant to atropine and potentiated in the presence of MDP. Isamoltan (5-HTID antagonist) decreased the amplitude of contractions, whereas ketanserin (5-HT2 antagonist) and MDL 72,222 (5-HT3 antagonist) had no effect. The addition of low concentrations (0.1-1.5 microM) of 5-HT did not contract the preparation but caused a decrease in the amplitude of neurogenic twitches, which might be due to the presynaptic inhibition of serotonin release. This effect of 5-HT was not changed by isamoltan or ketanserin, but it was largely reduced in the presence of 5-HT3 antagonists tropisetron and MDL 72,222. This inhibitory effect of 5-HT on twitch amplitude was potentiated by MDP. The interaction of MDP with the serotonergic system thus involved not only potentiation of the postsynaptic effect of higher 5-HT concentrations, which might have been mediated via the 5-HT1 subsystem, but also presynaptic inhibition. MDP enhancement of 5-HT's inhibitory effect, mediated via 5-HT3 receptors, might represent a new feature in mutual 5-HT-MDP interactions.     

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.