Cloning of serum RNA associated with hepatitis C infection suggesting heterogeneity of the agent(s) responsible for the infection

Fifty-six lambda gt11-random-primed-cDNA recombinants of which translation products react with antibodies in the serum drawn from patients with hepatitis C (blood-borne non-A, non-B hepatitis) were cloned from serum pooled from donors presumably infected with hepatitis C. The specificity of these clones for hepaitits C infection was determined using 3 test panels. Of these 29 clones were determined to be specific for Japanese hepatitis C infection. However one of the 29 clones was positive for 1 out of 5 normals in an American test panel while 12 clones were positive for the American panel as well. The remaining 28 clones reacted well with serum from transfusion associated chronic hepatitis C comparing to the sporadic cases in the Japanese panel. When they were tested with normal donors, another clone reacted with a distinct donor group with which the other clones did not react. These results may suggest the presence of heterogeneity in Japanese hepatitis C.     

A cDNA clone encoding a peptide highly specific for hepatitis C infection

A random primed lambda gtll-cDNA library was constructed from donors plasma presumably infected by blood-borne non-A, non-B hepatitis (hepatitis C:HC) agent and immunoscreened with serum pooled from patients with acute or chronic HC. Twelve lambda gtll-cDNA clones encoding antigens associated with HC infection in Japan as well as in the USA were isolated. Of these one clone consisting of 114 nucleotides and showing a discrete band on an immunoblot analysis, was extensively studied. The clone is not derived from the host DNA encoding one polypeptide specific and highly sensitive for serum from patients with HC and has no homology to the nucleotide sequences of known human viruses including hepatitis A, B and D viruses, Ebstein-Barr virus, coxsackievirus, immunodeficiency virus type 1 or Japanese encephalitis virus. These results suggest that this clone is derived from the genome of HC agent.     

Studies on Duodenal Cyclic AMP Content in Pancreatic Disease after Administration of Pancreozymin and Secretin

Cyclic AMP (cAMP) output in the duodenal contents of 11 normal subjects, 18 patients with chronic pancreatitis, six convalescing from acute pancreatitis and five with pancreatic carcinoma was measured after a single dose of pancreozymin and secretin. The technic was indirect, utilizing recovery of duodenal contents by the Dreiling tube rather than direct measurements of fluid that was not contaminated by bile. In all patients groups, cAMP output reached a peak after this stimulation with a concomitant increase of bicarbonate and amylase outputs. A significantly decreased cAMP output was observed in all pancreatic disease groups compared to the normal group. Patients with chronic pancreatitis showed a slightly decreased cAMP output, considerably decreased bicarbonate output and normal amylase output. In acute pancreatitis cAMP output was reduced with normal bicarbonate and amylase outputs. In pancreatic carcinoma cAMP decreased significantly, bicarbonate output was moderately reduced and amylase output was normal. cAMP output in all groups studied did not correlate with either bicarbonate output or amylase output.     

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4–74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7–43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6–13.3% (mean 8.0%). In contrast to patients wtih acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the β7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced β7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and that HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.     

Augmentation of the activity of an immunotoxin,anti-Tac(Fv)-PE40KDEL,in T cell lines infected with human T cell leukemia virus type-I

Therapy with an immunotoxin, anti-Tac(Fv)-PE38, which is a conjugate of the variable domains of an anti-Tac monoclonal antibody and Pseudomonas exotoxin, was reported to be useful for adult T cell leukemia (ATL) patients but a considerable amount of the immunotoxin is needed for the therapy and some side effects were also observed. We have previously demonstrated that an immunotoxin, anti-Tac(Fv)-PE40KDEL, showed strong cytotoxic effects on malignant cells from ATL patients. Therefore, we searched for agents that enhance the effects of the immunotoxin. PAK-200, FK-506, quinidine, cepharanthine and cyclosporine A (CsA) augmented the ability of the immunotoxin to inhibit protein synthesis in two human T cell leukemia virus type-I infected T cell lines, KUT-1 and KUT-2. CsA was the most potent agent in both the cell lines. Augmentation of the cytotoxic effect of the immunotoxin by these agents, especially CsA, may be useful in the immunotoxin therapy of ATL.     

Malignant Mesenchymoma of the Liver with Hypercalcemia Report of a Case

A case of malignant mesenchymoma of the liver is reported. Thediagnosis was confirmed on the surgical specimen. The patientshowed marked hypercalcemia. Parathyroid hormone assay was negative.