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Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 19 recordsLinked to original sources

Acute hemorrhagic conjunctivitis due to enterovirus 70 in American Samoa: serum-neutralizing antibodies and sex-specific protection.

Acute hemorrhagic conjunctivitis due to enterovirus 70 has caused extensive outbreaks in tropical areas since 1969. Between December 1, 1990, and March 4, 1991, an outbreak of acute hemorrhagic conjunctivitis due to enterovirus 70 occurred in American Samoa, where an outbreak due to the same agent had occurred in 1981. A survey of 5% of the households (134 households, 1,095 individuals) was conducted throughout the island of Tutuila. The outbreak affected 58% of the population, with age-specific attack rates greater than 50% for all age groups except children younger than 2 years. Attack rates were significantly higher for children 2-10 years old (65%) than in the remainder of the population. Women aged 21-40 years had higher rates than did men the same age (66 vs. 49%), possibly because of the close association of women and young children. At higher preepidemic titers, there was evidence of protection from clinical disease among males but not among females. Enterovirus 70 can cause large outbreaks even in a population already exposed in a previous large outbreak; protection due to previous infection is only partial.

Antibodies, Bacterial

Chronic parvovirus infection in a presumably immunologically healthy woman.

Infection due to parvovirus B19 is common and usually resolves over several weeks. Prolonged infection has been reported primarily in immunodeficient hosts. The present report describes a chronic infection in an apparently immunologically healthy woman. The illness was characterized by recurrent episodes of paresthesia without anemia. Laboratory studies demonstrated persistence of parvovirus-specific DNA for nearly 4 years.

Antibodies, Viral

Prenatal diagnosis of intrauterine infection with parvovirus B19 by the polymerase chain reaction technique.

Human parvovirus B19 is a recently recognized cause of fetal hydrops and death. Efforts to characterize the natural history of fetal infection with this virus have been hampered by the lack of sensitive and specific tests for diagnosis in utero. Using the highly sensitive polymerase chain reaction (PCR) assay, we determined the fetal infection status in 56 pregnancies by testing amniotic fluid, fetal serum, and maternal serum for B19 DNA and antibodies. Factors associated with a high risk of B19 infection were fetal disease, exposure to persons with erythema infectiosum, or signs or symptoms of acute B19 infection. Fifteen women (27%) were B19 IgM-positive, a status suggesting recent infection; the positivity of all of the corresponding fetal specimens for B19 DNA in the PCR was indicative of fetal infection. In four of these cases, serial ultrasonographic examinations documented spontaneous resolution of fetal hydrops. Twenty-four women (43%) were IgG-positive and IgM-negative; this pattern suggested prior infection. The PCR gave positive results, consistent with recent maternal infection, in four of these cases. Seventeen women (30%) were IgG-negative and IgM-negative, a pattern suggesting no prior infection; the PCR results in four cases were indicative of a possible early maternal infection or a possible atypical immune response. The PCR is a sensitive and rapid method for the diagnosis of intrauterine infection with human parvovirus B19 and promises to facilitate studies of the natural history and treatment of this infection.

Adolescent

Major trends in nosocomial viral infections.

Viruses have recently become appreciated as nosocomial pathogens. There is insufficient data to characterize trends in rates of viral nosocomial infections, but there have been major trends in methodologies and concepts. New groups of patients, such as infants and the elderly, are becoming appreciated as being at risk for serious nosocomial viral infections, whereas other groups, such as immunodeficient patients are expanding because of the epidemic of human immunodeficiency virus (HIV) infection and expanded use of immunosuppressive treatment. The continued addition of new viruses, such as HIV, human parvovirus B19, and rabies virus, to the list of potential nosocomial pathogens suggest that most human viruses can probably be serious nosocomial pathogens under the right circumstances. Advances in medical treatments and procedures, such as cadaveric dura mater grafts and laser treatment of warts, have provided new avenues for nosocomial transmission of viruses. Improved and wider availability of diagnostics promises to be a major force in improving our understanding and ability to prevent viral nosocomial infections. With these advances, viral diagnostic laboratories should become an important member of the infection control team. In parallel with trends in methodologies and concepts, there have been major advances in our understanding of ways to prevent some nosocomial viral infections. Application of these prevention measures is an important challenge to the infection control practitioner.

Cross Infection

Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions.

B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine.

Amino Acid Sequence

Human parvovirus B19 specific IgG, IgA, and IgM antibodies and DNA in serum specimens from persons with erythema infectiosum.

To determine the diagnostic use of different markers of acute parvovirus B19 infection, serum specimens obtained from 128 persons with erythema infectiosum were tested for specific immunoglobulin G (IgG), IgA, and IgM antibodies by capture enzyme immunoassay (EIA) using Chinese hamster ovary (CHO) cell-expressed B19 antigen, and tested for circulating B19 DNA by polymerase chain reaction (PCR). A significant rise in specific IgG and IgA antibodies was detected in 87% and 77%, respectively, of persons from whom acute- and convalescent-phase serum specimens were available. Specific IgA antibodies were detected in single serum specimens from 90% of cases and were present in 22 (18%) of 120 persons from a control group without a history of recent exposure to B19. Specific IgM antibodies were detected in 97% of cases and one person (1%) from the control group. B19 DNA was detected in 94% of cases and was absent in 20 persons from the control group positive for both IgG and IgA antibodies. Serum specimens obtained between 4 and 6 months after onset of illness from six additional persons were also tested. All had specific IgG antibodies, four (67%) had IgA, five (83%) had IgM, and none had detectable B19 DNA. Our data indicate that 1) specific IgA antibodies are too persistent to be a useful indicator of recent B19 infection; 2) specific IgM antibodies are the most sensitive indicator of acute B19 infection in immunologically normal persons but can persist up to 6 months; and 3) B19 DNA can often be detected up to 2 months after onset of illness even in immunologically normal hosts and might be a useful adjunct test for diagnosis of acute B19 infection.

Adolescent

Multicenter study of strains of respiratory syncytial virus.

Two major groups of respiratory syncytial virus (RSV) strains, A and B, have been identified and their patterns of isolation determined in different communities but not simultaneously in multiple communities. In this study, we tested 483 RSV isolates from 14 university laboratories in the United States and Canada for the 1984/1985 and 1985/1986 RSV seasons; 303 (63%) isolates were group A, 114 (24%) were group B, and 66 (14%) could not be grouped. Isolates were subdivided into six subgroups within group A and three within group B; up to six and often four or more different subgroups were isolated in the same laboratory during the same RSV season. The pattern of group and subgroup isolations varied among laboratories during the same year and between years for the same laboratory. These differences suggest that RSV outbreaks are community, possibly regional, but not national phenomena. The ability to identify group and subgroup differences in isolates is a powerful tool for epidemiologic studies of RSV.

Antigens, Viral

Antigenic and genomic diversity within group A respiratory syncytial virus.

Antigenic analysis using monoclonal antibodies and genomic analysis using ribonuclease protection was done on 47 isolates of group A respiratory syncytial virus (RSV) recovered from children in St. Louis during four RSV seasons. Antigenic analysis identified four subgroups; of the three that included more than one member, those designated A/2 and A/2V had characteristic ribonuclease protection patterns. A third subgroup, A/4, exhibited more extensive genomic heterogeneity, but all isolates were distinguishable from those in subgroups A/2 and A/2V. Individual RSV epidemic seasons included isolates representing multiple subgroups of group A and multiple intrasubgroup variants, in addition to isolates from group B. Isolates that were indistinguishable by either antigenic or genomic analysis were present in more than one epidemic season. The subgroups may represent parallel evolutionary lineages, whose relevance to RSV immunity and pathogenesis requires further study.

Antibodies, Monoclonal

Group-specific serum antibody responses in children with primary and recurrent respiratory syncytial virus infections.

Antigenic group-specific serum antibody responses to first and second respiratory syncytial virus (RSV) infections were studied in children who had been followed longitudinally from early infancy in a research day-care center. Plaque-reduction neutralizing (PRN) antibody assays and ELISAs for the fusion (F) and attachment (G) glycoproteins were done using antigens of prototype RSV strains from groups A and B. Responses to antigens of viruses homologous and heterologous to the antigenic group of the infecting viral strain were compared. Primary group A infection elicited antibodies cross-reactive with group B virus in the PRNB and the ELISAS for GB and FB. In contrast, primary group B infection induced significant increases in mean concentrations of antibody cross-reactive with group A virus only in the FA ELISA. Second RSV infections caused by group B viruses in children with histories of primary group A infection induced heterologous rises in the PRNA and GA assays, suggesting that prior group A infection had primed for a more extensive cross-reacting antibody response at the time of second RSV infections with group B viruses.

Antibodies, Viral

Nosocomial transmission of respiratory syncytial virus in immunocompromised adults.

Respiratory syncytial virus (RSV) isolates obtained from nine infected immunocompromised adult patients hospitalized during two consecutive winters (January through April 1987 and 1988) were collected and analyzed against a panel of monoclonal antibodies by an enzyme immunoassay. The history of the patients' illness, onset of symptoms, and date of initial isolation of virus was correlated with the hospital ward and time of hospitalization. Three patients died of respiratory failure related to RSV infection acquired nosocomially. A cluster of RSV disease in four patients hospitalized simultaneously during the 1987 season was demonstrated to be caused by four antigenically distinct viruses; despite an epidemiologic link among the patients, each had been infected from a different source. The RSV disease in the five immunocompromised adults in 1988 was caused by two distinct strains; three patients were infected with RSV subgroup A/4, and two were infected with RSV subgroup B/2. Combining the epidemiologic and strain characterization studies, none of four patients in 1987 were infected from each other, and two of five patients in 1988 may have been infected, directly or indirectly, from one of the other five. The strain characterization studies demonstrated the potential complexity of RSV nosocomial transmission and the need to consider a number of sources for transmission in developing effective prevention strategies. The three deaths underscore the importance of nosocomial RSV disease and the importance of effective prevention strategies.

Adult

Antigenic characterization of respiratory syncytial virus group A and B isolates in Rio de Janeiro, Brazil.

The antigenic characteristics of 87 strains of respiratory syncytial virus isolated in Rio de Janeiro, Brazil, from 1982 to 1988 were determined with a panel of monoclonal antibodies (MAbs) in an enzyme immunoassay. Four of these MAbs immunoprecipitated the fusion protein, and five immunoprecipitated the large glycoprotein. On the basis of the patterns of reaction of these MAbs to respiratory syncytial virus isolates in an enzyme immunoassay, we were able to separate isolates into the two major groups, A and B, and also to identify four variants within group A and three within group B. Strains from groups A and B were isolated each year, and the prevalence of the two groups varied over the seven study years.

Antibodies, Monoclonal

Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus.

Monoclonal antibodies to the hemagglutinin protein, fusion protein, phosphoprotein, matrix protein, and nucleoprotein of measles virus were evaluated as detector antibodies in capture enzyme immunoassays (EIAs) for the detection of specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to measles virus. A pool of monoclonal antibodies to hemagglutinin protein and nucleoprotein proved optimal and was further evaluated. Specific IgM was detected in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of clinical measles cases and vaccinees, in 26% of healthy persons, and in 36% of infants 8 months postvaccination; consequently, IgA antibodies were not a useful indicator of recent measles infection. A significant increase in IgG antibodies between paired specimens was detected in 92% of clinical cases and all vaccinees. Only 59% of infant specimens had persistent IgG antibodies as detected by capture EIA at 8 months postvaccination, whereas all specimens had antibodies as detected by hemagglutination inhibition and plaque neutralization. An alternative indirect EIA, in which antigen was directly absorbed to the solid phase, was more sensitive than the capture design, detecting IgG antibodies in all infants postvaccination. When standardized with a microneutralization assay for the detection of persistent antibodies, the indirect IgG EIA gave predictive values for positive and negative tests exceeding 90%. Our capture IgM and indirect IgG EIAs provide a practical combination of serologic tests for the determination of acute measles virus infection and past exposure to measles virus or vaccine, respectively.

Antibodies, Monoclonal

Genetic diversity of the attachment protein of subgroup B respiratory syncytial viruses.

Respiratory syncytial (RS) virus causes repeated infections throughout life. Between the two main antigenic subgroups of RS virus, there is antigenic variation in the attachment protein G. The antigenic differences between the subgroups appear to play a role in allowing repeated infections to occur. Antigenic differences also occur within subgroups; however, neither the extent of these differences nor their contributions to repeat infections are known. We report a molecular analysis of the extent of diversity within the subgroup B RS virus attachment protein genes of viruses isolated from children over a 30-year period. Amino acid sequence differences as high as 12% were observed in the ectodomains of the G proteins among the isolates, whereas the cytoplasmic and transmembrane domains were highly conserved. The changes in the G-protein ectodomain were localized to two areas on either side of a highly conserved region surrounding four cysteine residues. Strikingly, single-amino-acid coding changes generated by substitution mutations were not the only means by which change occurred. Changes also occurred by (i) substitutions that changed the available termination codons, resulting in proteins of various lengths, and (ii) a mutation introduced by a single nucleotide deletion and subsequent nucleotide insertion, which caused a shift in the open reading frame of the protein in comparison to the other G genes analyzed. Fifty-one percent of the G-gene nucleotide changes observed among the isolates resulted in amino acid coding changes in the G protein, indicating a selective pressure for change. Maximum-parsimony analysis demonstrated that distinct evolutionary lineages existed. These data show that sequence diversity exists among the G proteins within the subgroup B RS viruses, and this diversity may be important in the immunobiology of the RS viruses.

Amino Acid Sequence

Antibody enhancement of respiratory syncytial virus stimulation of leukotriene production by a macrophagelike cell line.

The clinical and epidemiologic features of respiratory syncytial virus (RSV) infections suggest that RSV-specific antibody may sometimes contribute to the disease process. Recently, it has been demonstrated that virus-specific antibody can enhance RSV infection of macrophagelike cells in vitro. We evaluated the possibility that antibody might also enhance RSV stimulation of the bronchoactive mediator of inflammation leukotriene C-4 (LTC4)in a macrophagelike cell line, U937. The addition of RSV led to little increase in LTC4 production, but addition of RSV plus anti-RSV antibody increased production to a level similar to that achieved with calcium ionophore, a known stimulator of LTC4 production. The antibody-enhanced increase in LTC4 production occurred rapidly (within 15 min), peaked at 60 min, and achieved levels 1.5- to 3.0-fold above that for cells or cells plus virus. RSV plus anti-RSV antibodies in the form of polyclonal serum, monoclonal antibodies, or F(ab')2 fragments and parainfluenza virus types 1 and 3 plus their respective antibodies all increased LTC4 levels over that for the virus alone. These results demonstrate that antibody plus the corresponding virus or protein can increase leukotriene production. This phenomenon could contribute to diseases, such as RSV bronchiolitis, that appear to be caused by an interaction between the virus (or antigen) and host immunity.

Antibodies, Viral

The AIDS crisis and the medical-legal implications of transfusion therapy.

An increased awareness of the potential to be harmed by blood transfusions has come with the AIDS crisis. Patients and health care providers alike are concerned with the complications of a transfusion, and various alternatives to traditional transfusion therapy have emerged. They include autologous transfusions, directed donations, and outright refusals of transfusion therapy. This article examines the medical-legal considerations that accompany a decision to transfuse. Various legal theories used in cases where persons injured by transfusions have sought legal redress and the outcomes of those cases will be examined. The question of whether directed donations are a reasonable alternative to traditional transfusion therapy will also be explored.

AIDS Serodiagnosis

Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve. Identification of apolipoprotein D, apolipoprotein A-IV, apolipoprotein E, and apolipoprotein A-I.

In this report, we have identified two apolipoproteins (apo), apoD and apoA-IV, that, together with the previously identified apoA-I and apoE, accumulate in the regenerating peripheral nerve. These four apolipoproteins were identified in regenerating rat sciatic nerves by their molecular weights, their isoelectric points, and their recognition by specific antibodies. Antibodies were also used to document the changing concentrations of these apolipoproteins in homogenates of regenerating sciatic nerves collected 1 day to 6 weeks after a denervating crush injury. By 3 weeks after injury, at their peak accumulation, apoA-IV and apoA-I had increased 14- and 26-fold, respectively, relative to their concentrations in the normal nerve. Apolipoproteins D and E, in contrast, increased over 500- and 250-fold, respectively, by 3 weeks. These same apolipoproteins also accumulated in the regenerating sciatic nerves of two other species, the rabbit and the marmoset monkey. Immunocytochemistry showed that apoD was produced by astrocytes and oligodendrocytes in the normal central nervous system, and by neurolemmal or fibroblastic cells in the normal peripheral nervous system. Metabolic labeling of both apoD and apoE by [35S]methionine during an in vitro incubation of regenerating rat sciatic nerve segments confirmed that these apolipoproteins are synthesized by the nerve. Neither apoA-IV nor apoA-I was metabolically labeled, however, suggesting that they enter the nerve from the plasma. The results from this study provide evidence that several different apolipoproteins from various sources may play a role in lipid transport within neural tissues.

Animals

Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum.

Human parvovirus B19, the cause of erythema infectiosum, has recently been associated with adverse fetal outcomes. During a large outbreak of erythema infectiosum in Connecticut, a survey was conducted on 571 (90%) of 634 school and day-care personnel to determine the risk of acquiring B19 infection. Serologic evidence of B19 infection was determined by using an enzyme-linked immunosorbent assay. Of the school and day-care personnel, 58% had evidence of previous B19 infection. The minimal rate of B19 infection in susceptible personnel during the outbreak was 19%. The risk was increased for teachers and day-care providers who had contact with younger children and with greater numbers of ill children. These results suggest that B19 infection is an occupational risk for school and day-care personnel.

Adult