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Biomedical subjects

S M Lemon

Publications and source records attributed to S M Lemon.

At least 145 records · Page 8Linked to original sources

Experimental infection of the New World owl monkey (Aotus trivirgatus) with hepatitis A virus.

Epidemiological studies have demonstrated the susceptibility of the owl monkey (Aotus trivirgatus) to hepatitis A virus, but have not shown an association between infection and histopathological or chemical evidence of liver disease. Therefore, 12 seronegative, colony-bred monkeys were inoculated intravenously with a fecal suspension containing either PA33 strain hepatitis A virus (a strain recovered from a naturally infected Aotus sp.) or HM-175 virus (recovered from a human). Viral antigen was detected by radioimmunoassay in the feces of six monkeys 6 to 17 days after inoculation with PA33 virus, and by 9 to 21 days serum aminotransferase activities were significantly elevated in each. Antibody to the virus developed in each monkey by 28 days after inoculation. Similar findings were noted in five of six monkeys inoculated with HM-175 virus, although the incubation period preceding aminotransferase elevations was somewhat longer (25 to 39 days). Liver biopsies obtained from the 11 infected monkeys demonstrated mild to moderate portal inflammation, as well as random areas of focal necrosis and inflammation extending outward from the portal region. These data confirm the susceptibility of Aotus sp. to hepatitis A virus and indicate that the infection of this primate provides a useful animal model of human hepatitis A.

Animals↗

Antigenic relatedness of two strains of hepatitis A virus determined by cross-neutralization.

Cell culture-adapted HM-175 (Australia) and PA-21 (Panama) strains of hepatitis A virus were compared in a cross-neutralization radioimmunofocus inhibition assay. The ratio of antibody titers achieved with two sera against the two viruses differed by less than twofold, indicating a high degree of antigenic relatedness between epidemiologically disparate strains of virus.

Antibodies, Viral↗

Radioimmunofocus assay for quantitation of hepatitis A virus in cell cultures.

A new method is described for the quantitation of hepatitis A virus in cell cultures, based on the immune autoradiographic detection of foci of infected cells (radioimmunofoci) developing beneath an agarose overlay 14 days after the inoculation of petri dish cultures of continuous African green monkey kidney cells (BS-C-1). The number of foci developing in each culture was linearly related to the dose of hepatitis A virus (either HM-175 or PA-21 strain) inoculated. Focus development was prevented by prior incubation of virus with specific antisera, and the specificity of the radiolabeled antibody reaction was confirmed in competitive blocking experiments. This new assay method retains many of the advantages of conventional plaque assays for virus. Compared with existing end-dilution methods for the quantitation of hepatitis A virus, the radioimmunofocus assay offers greatly improved accuracy and comparable sensitivity, yet is relatively rapid and highly conservative of reagents.

Animals↗

Transmission of hepatitis A virus among recently captured Panamanian owl monkeys.

The presence of antibody to hepatitis A virus (anti-HAV) in 60% of procured owl monkeys (Aotus trivirgatus) held within the United States prompted a study of recently captured A trivirgatus in Panama. Only 2 of 145 newly captured monkeys, but all of 35 A trivirgatus held within a colony for over 100 days, were found to have anti-HAV. Of 41 sero-negative, newly captured monkeys followed prospectively, 25 became infected with hepatitis A virus (HAV) as evidenced by seroconversion or demonstration of virus in the liver at death. Only one monkey that survived over 60 days within the colony was not infected. HAV was identified in the feces of most infected monkeys prior to the development of antibody and was antigenically indistinguishable from human HAV in cross-blocking radioimmunoassays. This colony-centered epizootic provides strong evidence that A trivirgatus is susceptible to HAV and should be investigated further as a potential model of human hepatitis A.

Animals↗

Etiology of viral hepatitis in American soldiers.

To define better which types of hepatitis are prevalent among American soldiers, the authors studied 413 separate episodes of acute viral hepatitis among 412 soldiers admitted to US Army hospitals during 1978-1979. Most soldiers (68.8%) had acute hepatitis B (estimated annual hospitalization rate: 5.41/1000 soldiers in West Germany, 2.51/1000 in South Korea, less than 1/1000 in the United States). Subtype ayw was predominant in Germany, whereas adr was predominant in South Korea. Hepatitis B was more often associated with contact history or parenteral use of drugs in West Germany than in South Korea (p less than 0.001). Non-A, non-B hepatitis accounted for 27% of cases in West Germany (2.16/1000), but only 3% in South Korea (0.11/1000); hepatitis A only 15% in South Korea (0.48/1000) and 1% in West Germany (0.08/1000). These findings indicate that hepatitis B is the most prevalent form of viral hepatitis among US soldiers worldwide but also suggest substantial differences in the epidemiology of this infection in South Korea and West Germany. Such data will be useful in developing hepatitis B immunization policy within the military.

Adult↗

IgM antibody to hepatitis B core antigen as a diagnostic parameter of acute infection with hepatitis B virus.

Because many patients with acute hepatitis B lack detectable hepatitis B surface antigen (HBsAg), a radioimmunoassay for IgM antibody to hepatitis B core antigen (anti-HBc) was developed and evaluated as a diagnostic test. IgM anti-HBc was detected in each of 47 patients with acute hepatitis and transient HBsAg (geometric mean titer, greater than or equal to 1:191,000), but also in five of 12 HBsAg carriers (geometric mean titer, 1:459) and one of 46 healthy individuals positive for anti-HBc. However, it was not present in one patient during the first six months of a persistent infection. Of 255 patients with acute hepatitis and HBsAg and/or anti-HBc, 210 were HBsAg-positive whereas 230 had IgM anti-HBc. The latter was the only specific marker in 12.3% of all cases of acute hepatitis B. Thus, IgM anti-HBc is a valuable marker for the diagnosis of acute infection with hepatitis B virus.

Acute Disease↗

A military community outbreak of hepatitis type A related to transmission in a child care facility.

An outbreak of hepatitis type A occurred among military personnel and dependents on a military post in Anchorage, Alaska, August 1976-April 1977. One hundred sixteen clinical cases of hepatitis were identified over a nine-month-period. Ninety-six per cent of those cases that were tested demonstrated IgM antibody to hepatitis A virus. A large child care facility was implicated as a major focus of hepatitis virus transmission. Sixty-four (55%) of the cases were directly or indirectly linked to the child care facility. The length of time that a child spent at the facility appeared to increase the child's risk of developing hepatitis and the risk of his transmitting the hepatitis A virus to other members of the immediate household.

Adolescent↗

Specific immunoglobulin M response to hepatitis A virus determined by solid-phase radioimmunoassay.

Immunoglobulin M antibody to hepatitis A virus (IgM anti-HAV) is found in most patients with acute type A hepatitis. To determine the duration of this IgM response as well as to confirm that IgM anti-HAV is a specific marker for acute infection, we developed a solid-phase radioimmunoassay for IgM anti-HAV. This new assay is 25-fold more sensitive than a conventional blocking radioimmunoassay for anti-HAV, and interference due to rheumatoid factor was eliminated by simultaneously testing sera against virus-free control antigen. Maximum IgM anti-HAV titers (1:6,400 to greater than or equal to 1:51,200) were detected during the first 30 days after the onset of illness. Although the IgM anti-HAV titer subsequently declined 64-fold over the ensuing 90 days, low-titer IgM anti-HAV (1:100 to 1:400) persisted in many sera for 90 to 150 days. Acute sera having an IgM anti-HAV titer of greater than or equal to 1:25,600 possessed a significantly higher mean IgM concentration (492 mg/dl) than acute sera with an IgM anti-HAV titer of less than or equal to 1:12,800 (344 mg/dl; P < 0.05). IgM anti-HAV titers did not correlate with other clinical or laboratory measures of disease severity. Detection of IgM anti-HAV proved to be both a highly specific (>99%) and a sensitive (>99%) method for the diagnosis of type A hepatitis.

Animals↗

Lack of specific effect of adenine arabinoside, human interferon, and ribavirin on in vitro production of hepatitis B surface antigen.

PLC/PRF/5 hepatoma cells continue to produce hepatitis B surface antigen (HBsAg) after greater than 80 passages in vitro, but they do not express other markers of heaptitis B virus (HBV) replication. In this respect, they resemble most liver cells that are persistently infected with HBV. PLC/PRF/5 cells were cultured in the presence of adenine arabinoside, human fibroblast interferon, and ribavirin to determine whether production of HBsAg was sensitive to these antiviral agents. HBsAg released into culture media was detected by radioimmunoassay, and cellular protein synthesis was assessed by [3H]amino acid incorporation studies. A dose-related inhibition of HBsAg occurred with each antiviral agent that was tested, but in each case, this inhibition was matched by a reduction of cellular protein synthesis to a similar degree. Thus, no specific effect on the production of HBsAg was found with any of the antiviral agents tested.

Amino Acids↗

Cytofluorometry of lymphocytes infected with Epstein-Barr virus: effect of phosphonoacetic acid on nucleic acid.

DNA synthesis in Epstein-Barr virus (EBV)-infected lymphocytes was inhibited by phosphonoacetic acid (PAA) as measured by [3H]thymidine incorporation. PAA, at a concentration of 200 microgram/ml, inhibited [3H]thymidine incorporation by human umbilical cord lymphocytes infected with EBV strain P94 but had little effect on DNA synthesis in mitogen-stimulated cells. Transformed cell lines did not develop from infected cord cell cultures treated with 100 microgram of PAA per ml. Cytofluorometric analysis showed marked increases in cellular nucleic acid content (RNA plus DNA) as early as 9 days after infection of cord cells in the absence of PAA and before significant enhancement of [3H]thymidine incorporation became apparent. Moreover, EBV led to increases in cellular nucleic acid even when 200 microgram of PAA per ml was added to cell cultures before infection. The apparent discrepancy between results obtained by [3H]thymidine incorporation and cytofluorometry is explained either by significant inhibition of cellular DNA polymerases by PAA or by a block at the G2 + M phase of the cell cycle. The data suggest that EBV initiates alterations in cellular nucleic acid synthesis or cell division without prior replication of viral DNA by virus-induced DNA polymerases.

Cell Transformation, Viral↗

Replication of Epstein-Barr virus DNA in epithelial cells in vivo.

Epstein-Barr virus (EBV)-specific complementary RNA (cRNA) was hybridized in situ to oropharyngeal epithelial cells taken from patients with infectious mononucleosis. Cells from patients shedding virus in the throat hybridized signifnicant quantities of cRNA, whereas cells from EBV-negative sources did not. The degree of hybridization indicated a large EBV genome number per infected epithelial cell and suggested that these cells were the source of virus found in the throat. This finding may explain the presence of the EBV genome in the malignant epithelial cells of nasopharyngeal carcinoma.

Autoradiography↗

IgM antibody to hepatitis B core antigen in Korean patients with hepatocellular carcinoma.

Primary hepatocellular carcinoma (PHC) has been linked etiologically to persistent hepatitis B virus (HBV) infections by epidemiologic, serologic and molecular lines of evidence. To evaluate the frequency of IgM antibody to the viral core antigen (IgM anti-HBc) detected by a highly sensitive radioimmunoassay, we compared 110 Korean patients with PHC to a group of 63 age- and sex-matched control patients with other tumors. Results were correlated with those of commercially available HBV assays. IgM anti-HBc was found in 74 of 110 PHC patients (67%), but only 1 of 63 (1.6%) control patients. Although HBsAg was found in a larger percentage of PHC patients (81%), it was also present in more control patients (14%). Thus, IgM anti-HBc was more specifically associated with PHC than was the presence of HBsAg. IgM anti-HBc was found in 91% of PHC patients with detectable HBeAg and 74% of PHC patients with positive anti-HBe tests (p less than 0.04). The frequency of IgM anti-HBc was similar among HBsAg-positive PHC patients with and without anti-HBs, or those with low or high levels of serum alpha-fetoprotein. In 18 patients with PHC, IgM anti-HBc was further characterized by rate-zonal centrifugation of sera, all were found to have 19S IgM anti-HBc although 6 also had greater or equal IgM anti-HBc reactivity in the low molecular weight region. The presence of IgM anti-HBc in adult Korean HBsAg carriers may indicate an especially high risk for the development of PHC, and this should be evaluated in prospective studies.

Adult↗