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Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 109 records · Page 6Linked to original sources

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↗

Management and outcomes of pregnancies complicated by human B19 parvovirus infection: a prospective study.

During a large statewide outbreak of fifth disease in Connecticut in 1988, 39 pregnant women were identified who had serologic evidence of recent human B19 parvovirus infection. The patients were followed up prospectively with targeted fetal ultrasonographic examinations to detect signs of fetal hydrops. Of these 39 pregnant women, 37 had healthy infants and two patients had miscarriages. None of the fetuses developed hydrops. We propose that pregnant women exposed to B19 parvovirus be tested for evidence of IgG and IgM B19-specific antibodies and that targeted fetal ultrasonography be considered when IgM antibodies are found. Percutaneous umbilical blood sampling and intrauterine transfusion can be considered in cases of B19 parvovirus-associated hydrops and anemia. The overall fetal loss rate in this prospective follow-up group was 5%.

Abortion, Spontaneous↗

Use of mixture models in determining laboratory criterion for identification of seropositive individuals: application to parvovirus B19 serology.

Selecting the cut-off value to identify infected individuals requires a trade-off between sensitivity and specificity. The standard technique for selecting a cut-off uses results of a population either known or assumed uninfected. Using mixture models, however, it is not necessary to identify an uninfected population. This technique also provides methods to estimate the probability that an individual will be accurately classified. We illustrate this technique in determining cut-off values for the serological diagnosis of human parvovirus B19 infection.

Antibodies, Viral↗

Human parvoviruses.

Human parvovirus B19 is a common infection that causes a number of clinical illnesses, most of which are benign. However, in patients with a need for increased red cell production, a deficient immune system, or both (such as occurs in the fetus), it can be a life-threatening infection. Intravenous immunoglobulin should be considered in the treatment of chronic B19 infection in immunodeficient patients and possibly in the management of other serious B19 infections. Recent advances in the laboratory, especially the increased sensitivity of polymerase chain reaction assay for detecting B19 DNA and the development of a cell line that produces B19 proteins in the form of empty capsids, should lead to significant advances in our understanding, treatment, and management of B19 disease in the near future.

Humans↗

Association between respiratory syncytial virus outbreaks and lower respiratory tract deaths of infants and young children.

The temporal patterns of respiratory virus isolations from 10 laboratories in the USA were compared with that of deaths of children less than 5 years old from July 1975 through June 1984. Isolations of respiratory syncytial virus (RSV) occurred as yearly winter outbreaks; parainfluenza virus 1 and 2 isolations occurred as well-defined outbreaks every other year in the autumn; parainfluenza virus 3 isolations occurred throughout the year with periodic, increased isolations suggestive of outbreaks; and influenza virus isolations (A, B, or A plus B) occurred as yearly winter outbreaks. After data were controlled for seasonal patterns, RSV isolations were strongly correlated with the winter peaks in lower respiratory tract illness (LRI) deaths of infants 1-11 months old; influenza virus isolations were correlated with the winter peak in LRI deaths of children 24-59 months old. The parainfluenza viruses were not correlated with respiratory deaths. This study supports the idea that RSV is a major contributor to winter peaks in LRI deaths of children 1-11 months old.

Child, Preschool↗

Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children.

Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics. Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%-100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%-85%) in 2 years, separated by a decade. The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were greater than or equal to 40% of the isolates. Subgroups A1 and A2 predominated, while B2, 3, and 4 occurred almost equally. A greater clinical severity for Group A strains was suggested by children with group A infections requiring intensive care significantly more often (15.4 vs. 8.3%, P = .008). Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs. 5.5%, P less than .01). Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and A1 in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated.

Age Factors↗

Monoclonal antibody-based capture enzyme immunoassays for specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to respiratory syncytial virus.

Monoclonal antibodies (MAbs) to the fusion protein (F), attachment protein (G), and nucleoprotein (N) of respiratory syncytial (RS) virus were evaluated for use as detector antibodies in immunoglobulin G (IgG), IgA, and IgM capture enzyme immunoassays. MAb assays were tested against assays using polyclonal antibodies (PAbs) with serum specimens from patients with and without evidence of recent RS virus infection. Assays developed with N MAbs were comparable to or better than PAb assays for detecting specific IgG and IgM antibodies but were somewhat less sensitive for IgA. F MAb assays were less sensitive for IgG and IgM antibodies but identified specific IgA in some specimens negative by N MAb assay. G MAb assays were insensitive for IgG and IgM antibodies but did detect about 50% of the IgA antibodies identified by the PAb assay. The basis for the low sensitivity of the G MAb assays is unclear, since many of these specimens were positive for IgG antibodies to G by Western immunoblot. The sensitivity of MAb assays varied with patient age: N MAb assays detected specific antibody responses to RS virus in all immunoglobulin classes in both adults and infants less than 1 year of age, F MAb assays detected specific IgG responses in adults and IgA responses in both adults and infants, and G MAb assays only detected IgA responses in adults. A mixture of N and F MAbs was complementary overall, identifying 54 of 55 (IgG), 51 of 52 (IgA), and 16 of 17 (IgM) serum specimens positive by PAb assay. These MAb assays were also specific with specimens tested from persons without a history of recent RS virus infection. The availability of these MAb-based assays offers other laboratories the opportunity to have long-term, standardized reagents and tests for serological diagnosis of RS virus infection.

Adult↗

Differentiation of respiratory syncytial virus subgroups with cDNA probes in a nucleic acid hybridization assay.

A new approach to respiratory syncytial (RS) virus subgroup determination was developed by using a simple nucleic acid filter hybridization technique. By this method, virus-infected cells are bound and fixed in a single step, and the viral RNA in the fixed-cell preparation is characterized directly by its ability to hybridize to cDNA probes specific for either the A or B subgroups of RS virus. The subgroup-specific probes were constructed from cDNA clones that corresponded to a portion of the extracellular domain of the RS virus G protein of either a subgroup B RS virus (8/60) or a subgroup A RS virus (A2). The cDNA probes were labeled with 32P and used to analyze RS virus isolates collected over a period of three decades. Replicate templates of infected cell preparations were hybridized with either the subgroup A or B probe. The subgroup assignments of 40 viruses tested by nucleic acid hybridization were in agreement with the results of subgroup determinations based on their reactivities with monoclonal antibodies, which previously has been the only method available for determining the subgroup classification of RS virus isolates. The nucleic acid hybridization assay has the advantage of providing broad-based discrimination of the two subgroups on the basis of nucleic acid homology, irrespective of minor antigenic differences that are detected in assays in which monoclonal antibodies are used. The nucleic acid hybridization technique provides a reliable method for RS virus subgroup characterization.

Antibodies, Monoclonal↗

MR imaging of the knee with a 0.064-T permanent magnet.

Magnetic resonance (MR) imaging has proved beneficial in the evaluation of internal derangements of the knee. A limitation to general acceptance of MR imaging of the knee has been availability and cost. The recent introduction of low-field-strength MR imaging has shown promise in decreasing the cost and increasing the availability of this modality. High-resolution (pixel size, 0.7 mm2), three-dimensional Fourier transform (3DFT), thin-section (3.5 mm) imaging performed on a 0.064-T permanent magnet was used to evaluate 117 knees in 114 consecutive patients. The appearance of normal anatomy and internal derangements of the knee at low-field-strength imaging is described. Arthroscopic correlation was available for 28 knees. Findings from low-field-strength MR imaging and arthroscopy agreed in 79% of cases in the determination of meniscal tears. Partial-flip-angle techniques with 3DFT produced thin-section images of the knee of diagnostic quality. The authors conclude that in patients with internal derangements of the knee, low-field-strength (0.064-T) MR imaging may provide useful information.

Adolescent↗

Risk of infection following exposures to human parvovirus B19.

In response to concern about the effect of human parvovirus B19 infection of the fetus, we have developed estimates of the risk of adults becoming infected following B19 exposures at home, in schools or day-care centers, and in hospitals. These estimates can then be used with other data to estimate the risk to the fetus of a B19 exposure during pregnancy. The risk to the fetus equals the rate of maternal susceptibility to infection times the rate of maternal infection following the specific type of exposure times the rate of fetal death following maternal infection. Data from studies of outbreaks of B19 associated erythema infectiosum and aplastic crisis suggest that the risk of infection among susceptible adults following household exposure to a B19 infected person is approximately 50% and following school exposures during outbreaks of erythema infectiosum is 20% to 30%. All susceptible school staff members, not just teachers, appear to be at risk for infection during outbreaks. Additional study is needed to determine the risk of infection following exposure to B19 infected patients in the hospital. Based on these and other data we can estimate that pregnant women whose serologic status is unknown have less than 2.5% chance of suffering fetal loss after household exposure and less than 1.5% chance after school exposure.

Adolescent↗