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Biomedical subjects

S M Lemon

Publications and source records attributed to S M Lemon.

At least 127 records · Page 7Linked to original sources
PubMed1986

Acquired immunodeficiency syndrome: epidemiology and significance for the obstetrician and gynecologist.

A retrovirus, variously named human T-lymphotropic virus type III or lymphadenopathy-associated virus, is now recognized as the etiologic agent of the acquired immunodeficiency syndrome. As of January, 1986, more than 16,000 cases of acquired immunodeficiency syndrome have been reported, and it is estimated that greater than or equal to 1 million Americans are now infected with human T-cell lymphotropic virus/lymphadenopathy-associated virus. Most cases of overt acquired immunodeficiency syndrome still fall within well-defined "high-risk groups," that is, homosexual or bisexual men, intravenous drug users, recipients of transfused blood or blood components, and persons with hemophilia. Also at risk are heterosexual partners of persons who have overt acquired immunodeficiency syndrome or who are at risk for acquired immunodeficiency syndrome, as are children born to mothers who either have acquired immunodeficiency syndrome or are members of a "high-risk group." Transmission of the virus may occur via sexual contact, via parenteral exposure to contaminated blood products, or from an infected mother to her child. Of special concern to the practicing obstetrician are recent reports suggesting bidirectional heterosexual transmission, transmission via artificial insemination, and perinatal transmission. In addition, the isolation of human T-cell lymphotropic virus/lymphadenopathy-associated virus from human breast milk raises concerns regarding potential transmission by this route.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Clinical significance of low molecular weight (7-8S) immunoglobulin M antibody to hepatitis B core antigen in chronic hepatitis B virus infections.

Separation of 7-8S and 19S forms of serum immunoglobulin M (IgM) hepatitis B core antibody (anti-HBc) by rate-zonal centrifugation was carried out on serum from 80 American chronic carriers of hepatitis B surface antigen (HBsAg), all of whom were positive for IgM anti-HBc and had elevated levels of serum alanine aminotransferase (mean 164 IU/L). Seventy-three of the 80 sera showed a predominance of one or the other form of IgM anti-HBc. Fifty-four (68%) had predominantly 7-8S IgM anti-HBc, and 19 (24%) had predominantly 19S IgM anti-HBc. Sex, age, length of HBsAg-carrier state, mean alanine aminotransferase, mean total IgM anti-HBc level, presence of hepatitis B e antigen, and liver histology were similar in both groups. 19S IgM anti-HBc was detected in 11 (41%) of 27 male homosexuals compared with only 8 (17%) of 46 heterosexual patients (p = 0.03). Despite this apparent association, an explanation for the variable presence of 19S and 7-8S IgM anti-HBc predominance in chronic hepatitis B remains lacking.

Adolescent↗
PubMed1986

Preparation of a prototype inactivated hepatitis A virus vaccine from infected cell cultures.

Studies were conducted on the preparation, inactivation, safety, and immunogenicity of a prototype hepatitis A virus vaccine prepared from infected cell cultures. BS-C-1 cells maintained in medium 199 without serum were infected with the HM175 strain of hepatitis A virus and harvested after 21-28 days. The harvested virus preparation contained 6.8-7.4 (log 10) cell culture infectious doses/ml. After exposure to 1:4,000 formalin at 35 C, the infectivity titer decreased 10(6)-fold in 30 hr at an exponential rate, although virus was detected in 5.0-ml vaccine samples for up to three days. Three separate vaccine lots elicited antibody in all the guinea pigs given three doses. Owl monkeys given three doses of vaccine did not have any evidence of HAV infection but developed antibodies identifiable by radioimmunoassay and serum neutralization tests. After either oral or intravenous challenge with at least 10(6) monkey infectious doses of a virulent field strain of hepatitis A virus, none of the vaccinated monkeys shed virus in their feces or had elevated serum levels of alanine aminotransferase. The findings suggest that an effective inactivated whole virus hepatitis A vaccine can be prepared from cell culture.

Animals↗
PubMed1986

Occupational and geographic risk factors for hepatitis B among US Army enlisted personnel during 1980.

Hepatitis B hospitalization rates for US Army enlisted personnel were determined by occupation and geographic area for 1980. The only group in the US Army currently recommended to receive hepatitis B vaccine is medical personnel regularly exposed to blood. Other groups of Army personnel, specifically those working in areas of high hepatitis B endemicity, have been thought to be at higher risk. Therefore, this work was undertaken to document hospitalization rates for all personnel using occupational blood exposure criteria as well as geographic area of assignment as risk factors for hepatitis B. The hospitalization rates underestimate true rates of hepatitis B incidence by a wide margin, and therefore were not used to calculate specific costs and specific benefits for a new vaccination strategy. In spite of this limitation, these data were useful for calculating relative risk, attributable risk, and amount of vaccine preventable disease. The risk of hospitalization for blood-exposed employees was consistently higher than that for non-blood-exposed personnel. The magnitude of the relative risk for blood exposure may be as high as 3.8 times or as low as 1.2 times, depending on which occupational comparison group is used. The relative risk of hospitalization in South Korea vs. the United States was 3.1 (p less than 0.0001), that for Europe vs. the United States, 2.1 (p less than 0.0001). Of all occupational and geographic risk comparisons, assignment to South Korea carried the highest attributable risk: 225 per 100,000. The amount of vaccine preventable disease in personnel assigned to South Korea was similar to that in occupationally blood-exposed employees (5.5 vs. 5.2 hospitalized cases per 1,000 vaccinees) after prorating exposure to risk based on average number of days of exposure to risk over three years. These data support the argument that geographic factors are as important as occupational blood exposure in defining risk of hepatitis B hospitalization among the US Army enlisted personnel.

Blood↗
PubMed1985

Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine.

Factors associated with lack of antibody response to the hepatitis B virus plasma vaccine were retrospectively evaluated by means of a logistic regression in 194 previously seronegative staff members of a community hospital. All subjects had received three doses of vaccine by intramuscular buttock injection using a 1-in, 23-gauge needle. Overall, only 55.7% of subjects developed detectable antibody to hepatitis B surface antigen in serum after immunization. The weight-height index served as a surrogate measure of obesity. Predictors of poor immunogenic response to hepatitis B vaccine included higher weight-height index, older age, and vaccine batch. Sex, race, timing of vaccine doses, and timing of postimmunization determination of antibody to hepatitis B surface antigen were not predictors of vaccine efficacy.

Adult↗
PubMed1985

Neutralizing antibody to hepatitis A virus in immune serum globulin and in the sera of human recipients of immune serum globulin.

We determined the titer of neutralizing antibody to hepatitis A virus in five lots of immune serum globulin and in the sera of human recipients of immune globulin using a new and sensitive procedure, the radioimmunofocus inhibition assay. The neutralizing antibody titer of four immune globulin lots ranged from 1:170,000 to 1:406,000, and was approximately 100-fold the antibody titer determined by radioimmunoassay. The neutralizing antibody titer of a Bureau of Biologics reference immunoglobulin was 1:794,000. Sera collected from 18 healthy men who had undergone prophylaxis with immune globulin (0.02 ml/kg body wt) were negative when tested by radioimmunoassay. However, 2 of 18 sera collected before administration of immune globulin and sera from all 18 men collected 3 and 55 days later contained detectable neutralizing antibody. The measurement of neutralizing antibody should prove useful for standardizing passive immunoprophylaxis against hepatitis A as well as for evaluating the potential efficacy of new hepatitis A virus vaccines.

Antibodies, Viral↗
PubMed1985

A simple method for clonal selection of hepatitis A virus based on recovery of virus from radioimmunofocus overlays.

Hepatitis A virus (HAV), a non-cytopathic picornavirus, has been quantitated in cell culture by autoradiographic detection of foci of viral replication developing beneath an agarose overlay following fixation and 'staining' of the cell sheet with radiolabelled antibody (radioimmunofocus assay). Using a modification of this basic technique, a clonal variant of HM-175 strain HAV was isolated from agarose overlying individual radioimmunofoci. Virus recovered from the agarose was amplified in small volume cultures of BS-C-1 cells and identified in supernatant culture fluids by cDNA-RNA hybridization. No virus was recovered from agarose which did not overlie a focus of viral replication. This method offers a simple, yet relatively rapid and certain means of selecting clonal variants of non-plaquing viruses such as hepatitis A virus.

Animals↗
PubMed1985

Frequency of illness associated with epidemic hepatitis A virus infections in adults.

Hepatitis A virus infection is often described as mild or asymptomatic, particularly in children. The failure of most adults who are found to be immune to remember symptoms of an illness suggestive of hepatitis A virus supports this belief. In 1982, two large outbreaks occurred in well documented populations of military personnel. These outbreaks were each extensively studied epidemiologically and serologically. It was found that 28/29 (96.6%) hepatitis A infections recognized prior to immune serum globulin in Outbreak A and 35/46 (76.1%) infections in Outbreak A were symptomatic. Symptomatic cases failed to occur beyond eight days of immune serum globulin administration to these predominantly susceptible groups. Between 40 and 70% of patients were icteric. Apparent contrasts in symptoms associated with hepatitis A infection in adults and children suggest a basic age-dependent difference in immune response to such infection.

Adolescent↗
PubMed1985

Incomplete neutralization of hepatitis A virus in vitro due to lipid-associated virions.

Hepatitis A virus (HAV) released from infected BS-C-1 cells was incompletely neutralized when incubated with a variety of convalescent sera (non-neutralizable fraction of 17 to 32%). Chloroform extraction of virus resulted in a substantial reduction of the non-neutralizable fraction (to less than 1%), suggesting that non-neutralizable virions might be associated with lipids. Non-neutralizable HAV recovered from untreated cell culture supernatant fluids sedimented heterogeneously and less rapidly than normal virus in rate-zonal sucrose gradients and also banded at a lower density in CsCl (1.14 to 1.18 g/ml) than normal, neutralizable virus (1.32 g/ml). This bimodal distribution of HAV in CsCl gradients was confirmed by cDNA-RNA hybridization. Together, these observations suggest that a substantial proportion of HAV particles released from infected cells are lipid-associated and imply an important role for cell membranes in the assembly and release of HAV in vitro.

Animals↗
PubMed1985

Combined immunoaffinity cDNA-RNA hybridization assay for detection of hepatitis A virus in clinical specimens.

To apply cDNA-RNA hybridization methods to the detection of hepatitis A virus (HAV) in clinical materials, we developed a two-step method in which a microtiter-based, solid-phase immunoadsorption procedure incorporating a monoclonal anti-HAV capture antibody was followed by direct blotting of virus eluates to nitrocellulose and hybridization with 32P-labeled recombinant HAV cDNA. This immunoaffinity hybridization method is simple and involves few sample manipulations, yet it retains high sensitivity (10- to 30-fold more than radioimmunoassay) and is capable of detecting approximately 1 X 10(5) to 2 X 10(5) genome copies of virus. The inclusion of the immunoaffinity step removes most contaminating proteins and thus facilitates subsequent immobilization of the virus for hybridization. It also permits positive hybridization signals to be related to specific antigens and adds a level of specificity to the hybridization procedure. When the method was applied to 23 fecal specimens collected from individuals during week 1 of symptoms due to hepatitis A, 13 specimens were found to be reproducibly positive for HAV RNA by immunoaffinity hybridization, whereas only 11 contained viral antigen detectable by radioimmunoassay.

Animals↗
PubMed1985

Infectious hepatitis A virus particles produced in cell culture consist of three distinct types with different buoyant densities in CsCl.

Although hepatitis A virus (HAV) released by infected BS-C-1 cells banded predominantly at 1.325 g/cm3 (major component) in CsCl, smaller proportions of infectious virions banded at 1.42 g/cm3 (dense HAV particles) and at 1.27 g/cm3 (previously unrecognized light HAV particles). cDNA-RNA hybridization confirmed the banding of viral RNA at each density, and immune electron microscopy demonstrated apparently complete viral particles in each peak fraction. The ratio of the infectivity (radioimmunofocus assay) titer to the antigen (radioimmunoassay) titer of the major component was approximately 15-fold greater than that of dense HAV particles and 4-fold that of light HAV particles. After extraction with chloroform, the buoyant density of light and major component HAV particles remained unchanged, indicating that the lower density of the light particles was not due to association with lipids. Light particles also banded at a lower density (1.21 g/cm3) in metrizamide than did the major component (1.31 g/cm3). Dense HAV particles, detected by subsequent centrifugation in CsCl, were indistinguishable from the major component when first banded in metrizamide (1.31 g/cm3). However, dense HAV particles recovered from CsCl subsequently banded at 1.37 g/cm3 in metrizamide. Electrophoresis of virion RNA under denaturing conditions demonstrated that dense, major-component, and light HAV particles all contained RNA of similar length. Thus, infectious HAV particles released by BS-C-1 cells in vitro consist of three distinct types which band at substantially different densities in CsC1, suggesting different capsid structures with varied permeability to cesium or different degrees of hydration.

Animals↗
PubMed1984

Failure to achieve predicted antibody responses with intradermal and intramuscular human diploid cell rabies vaccine.

In a study to compare the immunogenicity of human diploid cell rabies vaccine (HDCV) given by intramuscular or automatic intradermal jet injection, neither method of administration resulted in antibody levels predicted by previous studies. 49 days after starting a series of three 0.1 ml doses of HDCV given intradermally, 85 volunteers had a geometric mean titre (GMT) of neutralising antibody to rabies of 1:170. 9 concurrent control subjects who received 1.0 ml doses of vaccine intramuscularly had a GMT of only 1:269. Although standard potency testing did not demonstrate that the vaccine used was subpotent , these results strongly suggest that the immunogenicity of HDCV is substantially less than previously reported.

Antibodies, Viral↗
PubMed1984

Primary isolation and serial passage of hepatitis A virus strains in primate cell cultures.

Although several primate cell types have been reported to support replication of hepatitis A virus, optimal conditions for the isolation and production of quantities of virus have not been defined. We therefore examined seven different primate cell types for their ability to support replication of primate-passaged and wild-type virus as reflected by intracytoplasmic accumulation of viral antigen (direct immunofluorescence and radioimmunoassay) and propagation of cell culture-adapted virus. Of the cells tested, low-passage African green monkey kidney (AGMK) cells were most sensitive for initial isolation. Viral replication was documented after inoculation of AGMK cells with seven of nine hepatitis A virus antigen-positive fecal specimens (from seven epidemiologically distinct sources). With six inocula, virus was successfully passed in serial cultures. AGMK-adapted virus was readily propagated in continuous AGMK (BS-C-1) cells. The optimal temperature for the growth of virus in BS-C-1 cells was 35 degrees C. Viral release into supernatant fluids was documented in the absence of any cytopathic effect, and infectivity titers in supernatant fluids 21 days after inoculation (50% tissue culture infective does [TCID50], 10(6.0)/ml) equalled or exceeded those in the cell fraction (TCID50, 10(5.5)/ml). Cells maintained in serum-free media readily supported viral growth, with yields of virus (TCID50, 10(6.5)/ml) equal to or greater than those obtained with cells maintained in 2% fetal bovine serum.

Animals↗
PubMed1984

Pathology of hepatitis A infection in the owl monkey (Aotus trivirgatus).

Sequential liver biopsies of owl monkeys that had been experimentally infected with one of two strains of hepatitis A virus (HM-175 or PA-33) were examined for histopathologic alterations. Preinoculation biopsies were normal with only occasional minimal mononuclear cell infiltrates in portal tracts and hepatic lobular parenchyma. Histopathologic features that were present in biopsies taken during the period of elevated serum alanine aminotransferase activity (16-43 days after the intravenous inoculation of virus) included infiltration of predominantly mononuclear inflammatory cells into portal tracts and surrounding parenchyma, degeneration and necrosis of hepatocytes, and hypertrophy of Kupffer cells. Changes were similar in monkeys infected with either HM-175 or PA-33 virus strains. Convalescent biopsies (147-186 days after inoculation) showed resolving lesions with mild portal inflammation and occasional focal collections of inflammatory cells in the parenchyma. These histologic changes are similar to those associated with hepatitis A infection in man, chimpanzees, and several species of marmosets, and support the further use of the owl monkey as a model of human hepatitis A.

Acute Disease↗
PubMed1983

Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection.

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-microgram doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8 degrees C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3-10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.

Adult↗
PubMed1983

Low-molecular-weight IgM antibody to hepatitis B core antigen in chronic infections with hepatitis B virus.

IgM antibody to hepatitis B virus core antigen (IgM anti-HBc) develops during acute hepatitis B but frequently persists in chronic infections. To characterize persistent IgM anti-HBc better, 7-8S and 19S immunoglobulin fractions were prepared by rate-zonal centrifugation of sera from 17 patients with persistent hepatitis B (chronic active hepatitis) and were tested for IgM anti-HBc by a specific radioimmunoassay. In 16 sera peak activity was found in 7-8S fractions, although in 11 sera a minor peak was also present in 19S fractions. The low molecular weight of the predominant IgM anti-HBc was confirmed by gel filtration. In competition experiments, the binding of 7-8S antibody to an anti-IgM-coated solid phase was blocked more effectively by purified IgM than by purified IgG. These findings indicate that hepatitis B carriers with chronic active hepatitis have predominantly 7-8S IgM anti-HBc and represent a novel demonstration of naturally occurring 7-8S IgM with defined antiviral specificity.

Adult↗
PubMed1983

Serum neutralizing antibody response to hepatitis A virus.

Serum neutralizing antibody to hepatitis A virus (HAV) was measured in experimentally infected primates and naturally infected humans by means of an assay based on the autoradiographic detection of viral replication foci in vitro. Infection of primates with either PA-33 or HM-175 strains of HAV elicited antibody capable of neutralizing either strain. Sequential testing of two monkeys showed that neutralizing antibody correlated closely with antibody detected by immunoassay, developed before liver enzyme elevations, and was associated with a substantial reduction in fecal shedding of viral antigen. In tests performed on human subjects involved in an outbreak of hepatitis A, neutralizing antibody was present three to five days before the onset of symptoms and was found in both 19S and 7S immunoglobulin fractions. Immunity to HAV is probably due primarily to neutralizing antibody, and the ability to quantitate this antibody will be helpful in the evaluation of new HAV vaccines.

Animals↗