Changes in liver carbohydrate metabolism in mouse viral hepatitis.
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Serial intraperitoneal passage in mice of a saline extract of the pooled livers, spleens, and kidneys of such animals has led to the demonstration after three or more passages of a transmissible agent causing hepatitis. The mice developed an illness after 3 to 4 weeks characterized by hepatosplenomegaly, and serous ascites. Spontaneous diuresis and recovery usually occurred during the subsequent 2 to 4 weeks. Histological studies of the livers showed diffuse mononuclear infiltrations, focal accumulations of mononuclear cells, perivascular mononuclear cuffing, dilated sinusoids, and occasionally focal areas of necrosis. Mice which have recovered from the disease showed no noteworthy resistance to it, and their sera failed to protect against the infectious agent. Attempts to infect rabbits, guinea pigs, monkeys, and embryonated hens' eggs yielded negative results, but young hamsters developed the disease in mild form.
A transmissible agent (AHA) causing ascites and hepatitis in mice has been described. No known pathogenic bacteria, fungi, protozoa, leptospira, rickettsia, or viruses have been demonstrated in the infected mice. AHA does not pass through a Seitz filter and differs in most respects from the agents previously described which produce hepatitis in mice.
Experimental infectious mouse hepatitis is associated with an increase in glutamic-oxaloacetic transaminase activity of the serum (SGO-T). A relationship appears to exist between the rise in SGO-T activity and (a) the size of the virus inoculum, (b) the blood virus titer, and (c) the degree of liver necrosis. Trauma to the liver following partial hepatectomy results in a rise in SGO-T activity in mice. Although mouse hepatitis differs from human hepatitis in the incubation period, histological changes, and natural course, both infections bring about comparable changes in SGO-T activity.
At the onset of an epidemic in a closed institution about one-fourth of the inmates were skin-tested. During the year following the skin test, 5 cases of hepatitis with jaundice were recorded among 320 skin-tested individuals with unknown histories, one in the 144 skin test-positive, and 4 in the 176 skin test-negative subjects. In contrast 112 cases occurred among the 825 non-skin-tested individuals. Thus, the incidence of jaundice in the skin-tested group was 1.6 per cent as against 13.6 per cent in the non-skin-tested individuals. Possible explanations for this observation have been discussed.
A study of experimental infectious canine hepatitis in dogs by means of specific fluorescent antibody indicates that the intranuclear inclusions of this disease contain high concentrations of viral antigen. The increase in virus in the nuclei, as indicated by the accumulation of specific antigenic material, begins on the nuclear membrane and spreads from there to the interior of the nucleus, with the gradual formation of larger granules. Subsequently there appear the homogeneous inclusion bodies characteristic of this infection.
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