Characterization of cortical potentials evoked by oesophageal balloon distention and acid perfusion in patients with functional heartburn.

Oesophageal visceral hypersensitivity is thought to be important in generating symptoms in functional heartburn (FH). However, the neurophysiological mechanisms involved are poorly understood. The aim of this study was to compare the characteristics of oesophageal cortical evoked potentials (CEPs) induced by balloon distension and acid perfusion in FH and controls. We studied 21 FH patients and 12 healthy volunteers. Oesophageal mechanical stimulation was performed using the specially constructed mechanical pump. CEPs were recorded using the 10-20 international system of electroencephalogram recording. Oesophageal distention elicited recognizable, reproducible and muti-peak CEPs. CEP latencies for N1, P1 and N2 components were significantly shorter (P = 0.016, P = 0.003 and P = 0.031, respectively) in FH than in controls before perfusion. Acid perfusion significantly decreased the latencies of N1, P1 and N2 (P = 0.022, P = 0.007 and P = 0.041, respectively) and significantly increased the amplitude of P1-N2 components (P = 0.020) in FH patients, but not in controls. In conclusion, cortical evoked potential responses evoked by oesophageal distention and acid perfusion were greater in FH than in controls, suggesting that dysfunction of visceral neural pathways and/or alterations in cortical processing may produce and mediate oesophageal hypersensitivity in FH. These findings provide the evidence that central sensitization contributes to the development and maintenance of oesophageal hypersensitivity.

Alpha-fetoprotein reaction to Pisum sativum agglutinin in differentiation of benign liver diseases from hepatocellular carcinoma.

Alpha-fetoprotein reactive to Pisum sativum agglutinin levels (AFP-R-PSA) was measured in sera from 124 patients with hepatocellular carcinoma (HCC) and 54 patients with benign liver diseases (BLD). The level of AFP-R-PSA in the HCC group (42% +/- 22%) was significantly higher than that in the BLD group (10% +/- 8%). When an AFP-R-PSA level above 25% was used as a value highly suggestive of HCC, the sensitivity of the test was 82%, the specificity was 96%, the accuracy was 86%, and the positive prediction value was 98%. The positive rates of AFP-R-PSA in HCC patients with a serum AFP level below 100 micrograms/L and with a serum AFP level below 400 micrograms/L were 78% and 84%, respectively. Corresponding value was 74% for 31 patients with a tumor size less than 5cm. If AFP was combined with AFP-R-PSA, the detection rate of small HCC in this study would be increased from 32% to 87%. These data indicate that measurement of AFP-R-PSA is useful for the differentiation of BLD and for the early diagnosis of HCC.

[Alpha-fetoprotein (AFP) variant in the diagnosis of small liver cancer].

From May 1983 to June 1986, 40 patients with primary liver cancer, less than 5 cm in diameter, were treated by operation. The smallest lesion was 1.4 x 0.9 x 0.4 cm in size. Fifteen patients came to the hospital for treatment due to the finding of AFP greater than or equal to 31 ng/ml by public survey and 8 with space occupying lesion (SOL) in the liver by ultrasonography (US). The serum AFP levels ranged from 0 to 6800 ng/ml in this group with AFP negative in 6 cases, 31-400 ng/ml in 19 and over 400 ng/ml in 15. The positive rate of AFP was 37.5%. US displayed SOL in 25 cases, suspicious SOL in 5 and negative in 10. The positive rate was 62.5% by US. The overall positive rate was 77.5% by AFP and US combined. In addition, AFP variant was determined by LCA affino-crossed-immunoelectrophoresis autoradiography. LCA-nonreactive-AFP varied from 0 to 100% with a mean value of 57.0 +/- 26.7%. Taking less than 75% as diagnostic criterion for liver cancer, the positive rate of LCA-nonreactive-AFP was 65.0%. 12 patients who were AFP variant positive but SOL suspicious or negative were regularly followed by US for 1-20 months. They all showed distinct SOL. Composite results of AFP, AFP variant and US gave a diagnostic rate of 97.5% for small liver cancer. The determination of AFP variant is helpful in early detection of small liver cancer.

Immunogenicity of human hepatitis B virus P-gene derived proteins.

The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). For antibody detection an immunoprecipitation gel assay was performed with radioactively labeled polypeptides produced by in vitro translation of RNA of different P-gene regions. Thus, five antigenic regions were identified. All anti-P antibody positive sera reacted with carboxy-terminal P-poly-peptides, a subset with polypeptides of the amino-terminal and middle region, and none reacted with P-protein derived from the most sequence variable region. Anti-P antibodies were detected at very high frequency in sera of acute (73%) and chronically infected patients without HCC (87%), but less often in HCC patients (27%). These data indirectly demonstrate the expression of most hepatitis B virus P-gene sequences and the immunogenicity of P-proteins in vivo. Moreover, they establish hepatitis B virus anti-P-antibodies as a frequent serologic marker of infection and identify the carboxy-terminal region of the P-protein(s) as immunodominant.

A t(3;8) chromosomal translocation associated with hepatitis B virus intergration involves the carboxypeptidase N locus.

Integrated hepatitis B virus (HBV) DNA is found in the great majority of human hepatocellular carcinomas, suggesting that these viral integrations may be implicated in liver oncogenesis. Besides the insertional mutagenesis characterized in a few selected cases and the contribution of viral transactivators to cell transformation to malignancy, HBV has been shown to generate gross chromosomal rearrangements potentially involved in carcinogenesis. Here, we report a t(3;8) chromosomal translocation present in a hepatocellular carcinoma developed in noncirrhotic liver tissue. One side of the translocation, in 8p23, is shown to be in the vicinity of the carboxypeptidase N gene, a locus that is heavily transcribed in liver tissue and frequently deleted in hepatocellular carcinomas and other epithelial tumors. The other side of the translocation, in 3q27-29, is widely implicated in several types of translocations occurring in different malignancies, such as large-cell lymphomas. The present data strongly support a model in which HBV-induced chromosomal rearrangements play a key role during multistep liver oncogenesis.

Mapping of B-cell epitopes of the human hepatitis B virus X protein.

The immune response to the X protein of human hepatitis B virus (HBV) was studied by epitope mapping by using a set of MS2-HBx fusion proteins and synthetic peptides. Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response. Each serum contained antibodies to a different set of epitopes, which taken together cover most of the HBx sequence. Some of the epitopes were detectable only by immunoblotting with fusion proteins; others were detectable only by an enzyme-linked immunosorbent assay (ELISA) with synthetic peptides. The carboxy-terminal half of the HBx protein was preferentially recognized by antibodies from patients with chronic hepatitis and contained a short immunodominant antigenic region with at least two major nonoverlapping epitopes. Anti-HBx antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers. The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral HBx immune response which can be monitored by HBx-specific peptide ELISAs. Such tests may become useful diagnostic tools.