Biomedical subjects
L J Anderson
Publications and source records attributed to L J Anderson.
Respiratory syncytial virus outbreak on American Samoa. Evaluation of risk factors.
Acute respiratory illness is one of the leading causes of childhood mortality in developing nations. We investigated an increase in hospitalizations of children less than 2 years old for severe lower respiratory tract illness (LRI) from October 1986 through December 1986 on the island of American Samoa. Hospitalization rates were highest in children less than 6 months of age (60 of 1000 compared with 22 of 1000 for those 6 to 11 months of age, and seven of 1000 for those 12 to 24 months of age). The outbreak was more severe than in previous years, with ten (19%) of 54 patients admitted to the intensive care unit (ICU) compared with three (7%) of 42 and one (3%) of 40 during the same months of 1985 and 1984. Two patients died. Most patients had clinical bronchiolitis; of 34 patients tested, serologic or nasal aspirate evidence of recent respiratory syncytial virus (RSV) infection was found in 18 (53%). A study of patients younger than 1 year of age demonstrated that patients hospitalized with LRI were more likely to have a household member who smoked cigarettes (18/20, 90%) than outpatient controls without recent respiratory illness (8/15, 53%). Maternal sera obtained between December 1985 and October 1986 showed no protective effect of either detectable IgG or neutralizing antibody to two major groups of RSV. Our study documents the involvement of RSV in an outbreak of severe LRI among infants in a tropical area and further suggests that exposure to cigarette smoke is a risk factor for LRI infants.
Infraspinatus muscle contracture in a working dog.
A five-year-old Border Collie bitch was presented to Massey University Small Animal Clinic, for examination of a right forelimb lameness of three months duration. The distal forelimb was deviated laterally, there was limited mobility of the shoulder joint, and the animal showed gait abnormalities. Marked atrophy of the infraspinatus, supraspinatus and deltoideus muscles were present. Contracture of the infraspinatus muscle caused the lameness, and tenotomy of the infraspinatus tendon resulted in restoration of a normal gait. Although the exact aetiology is unknown, several possibilities are discussed.
Antibody-mediated enhancement of respiratory syncytial virus infection in two monocyte/macrophage cell lines.
Monoclonal antibodies (MAbs) specific for two surface glycoproteins of respiratory syncytial virus (RSV) were found to enhance RSV infection in two macrophagelike cell lines (P388D1 and THP-1). MAbs to an irrelevant antigen (pneumococcal polysaccharide) and to the nucleocapsid of RSV did not enhance infection. Blocking either the Fc segment of the monoclonal antibody of the Fc receptor on the cells diminished the enhancement, suggesting that this phenomenon involves attachment of the monoclonal antibody to the virus followed by attachment of the Fc of this complex to the Fc receptor on the cells. These data indicate that antibody-mediated enhancement of RSV infection can occur in vitro in macrophages. This enhancement may contribute to the pathogenesis of RSV bronchiolitis and the more severe RSV disease seen in recipients of formalin-inactivated RSV vaccine.
A large outbreak of epidemic keratoconjunctivitis: problems in controlling nosocomial spread.
Between July 1985 and January 1986, 401 patients with adenovirus epidemic keratoconjunctivitis (EKC) were seen at the Illinois Eye and Ear Infirmary. Of the cases, 110 (27%) were nosocomial; the other 291 patients had community acquired infection. The highest attack rates of EKC occurred in patients attending specialty clinics; the overall attack rate among clinic patients was 4.7/1,000 clinic visits. All nosocomial cases were caused by adenovirus type 8; community acquired cases were a mixture of adenovirus types 8 and 37. Adenoviruses were isolated from conjunctival cultures up to 14 d after the onset of clinical illness. Initial efforts to prevent nosocomial transmission were unsuccessful. However, when a plan to triage all patients on entry to the infirmary and to sort patients and personnel caring for infected patients into cohorts was implemented, nosocomial transmission of EKC was promptly and effectively halted, despite the continuation of the community epidemic for another 4 mo. This outbreak clearly demonstrates the efficacy of rigorous infection control in preventing nosocomial transmission of adenovirus EKC.
An epidemic of acute hemorrhagic conjunctivitis in American Samoa caused by coxsackievirus A24 variant.
Between May 25 and July 5, 1986, an epidemic of acute hemorrhagic conjunctivitis affected an estimated 47% of the population on American Samoa. Coxsackievirus A24 variant was isolated from 18 of 22 patients. This is the first documented outbreak of acute hemorrhagic conjunctivitis due to coxsackievirus A24 variant outside of Southeast Asia and the Indian subcontinent. When this outbreak was compared with an outbreak on the island in 1981-1982 caused by enterovirus 70, conjunctival hemorrhage or injection and the severity of hemorrhage were less prevalent among cases in 1986, while upper respiratory and systemic symptoms were more common. Residents of traditional housing had significantly higher attack rates (48%) than residents of government housing (23%). Serum specimens collected from the residents of Samoa in 1985, before the outbreak, unexpectedly revealed the presence of neutralizing antibodies against coxsackievirus A24 variant. The presence of these antibodies correlated with protection against coxsackievirus A24 variant infection in this outbreak.
Serum immunoglobulin G antibody subclass response to respiratory syncytial virus F and G glycoproteins after first, second, and third infections.
Serum samples from 31 children who experienced two or three infections with respiratory syncytial virus (RSV) in the first four years of life were tested in an enzyme-linked immunosorbent assay to examine the immunoglobulin G (IgG) subclass responses to the RSV F and G surface glycoproteins associated with primary infection and reinfection. We sought to determine whether the greater degree of glycosylation of the G glycoprotein was reflected in an IgG subclass immune response more like that to a polysaccharide antigen than to a protein antigen. We found that the IgG1/IgG2 ratio of postinfection antibody titers to F was fourfold higher than that to the G glycoprotein after RSV infections 1, 2, and 3. The IgG2 response to the heavily glycosylated G glycoprotein differed from that to a polysaccharide antigen in that the IgG1/IgG2 ratio remained constant with age, whereas the response to a polysaccharide antigen decreased as the IgG2 response increased with age. We also noted that antibody responses to both surface glycoproteins in the IgG1 and IgG2 subclasses reached their maximum levels after RSV infection 2.
Comparison of monoclonal antibody time-resolved fluoroimmunoassay with monoclonal antibody capture-biotinylated detector enzyme immunoassay for respiratory syncytial virus and parainfluenza virus antigen detection.
An all-monoclonal antibody, time-resolved fluoroimmunoassay was compared with several enzyme immunoassays for the detection of respiratory syncytial virus and parainfluenza virus type 1, 2, and 3 antigens in clinical specimens. The most sensitive enzyme immunoassay for parainfluenza virus type 1 was an all-monoclonal antibody assay with biotin-labeled detector antibody and streptavidin-peroxidase conjugate, but for respiratory syncytial virus and parainfluenza virus types 2 and 3 the most sensitive assay was a polyclonal antibody assay with horse capture antibodies and bovine or rabbit detector antibodies with anti-species peroxidase. All tests were evaluated with nasopharyngeal aspirate specimens from respiratory illnesses and with cell culture harvests of multiple strains of each virus isolated over many years. The time-resolved fluoroimmunoassay detected respiratory syncytial virus antigen in 92% of the specimens positive by culture, which was a decidedly higher sensitivity than either the monoclonal or polyclonal antibody enzyme immunoassay format (62 and 76%, respectively). For the parainfluenza viruses the time-resolved fluoroimmunoassay detected type-specific antigen in 94 to 100% of culture-positive specimens and again was more sensitive than the all-monoclonal antibody enzyme immunoassays (75 to 89%) or all-polyclonal antibody enzyme immunoassays (66 to 95%). Combined with results from a previously reported adenovirus time-resolved fluoroimmunoassay, these tests identified respiratory antigens in large numbers of clinical specimens.
Serum immunoglobulin A response to Norwalk virus infection.
We describe the serum immunoglobulin A (IgA) antibody response to Norwalk virus infection in human volunteers and compare it with previously described IgM and total antibody responses. Whereas specific IgA and IgM peak within 2 weeks after onset of symptoms, titers of total blocking antibody continue to rise, implying mediation by IgG antibody.
A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve.
Recent work has demonstrated that apo E secretion and accumulation increase in the regenerating peripheral nerve. The fact that apoE, in conjunction with apoA-I and LDL receptors, participates in a well-established lipid transfer system raised the possibility that apoE is also involved in lipid transport in the injured nerve. In the present study of the crushed rat sciatic nerve, a combination of techniques was used to trace the cellular associations of apoE, apoA-I, and the LDL receptor during nerve repair and to determine the distribution of lipid at each stage. After a crush injury, as axons died and Schwann cells reabsorbed myelin, resident and monocyte-derived macrophages produced large quantities of apoE distal to the injury site. As axons regenerated in the first week, their tips contained a high concentration of LDL receptors. After axon regeneration, apoE and apoA-I began to accumulate distal to the injury site and macrophages became increasingly cholesterol-loaded. As remyelination began in the second and third weeks after injury, Schwann cells exhausted their cholesterol stores, then displayed increased LDL receptors. Depletion of macrophage cholesterol stores followed over the next several weeks. During this stage of regeneration, apoE and apoA-I were present in the extracellular matrix as components of cholesterol-rich lipoproteins. Our results demonstrate that the regenerating peripheral nerve possesses the components of a cholesterol transfer mechanism, and the sequence of events suggests that this mechanism supplies the cholesterol required for rapid membrane biogenesis during axon regeneration and remyelination.
A rapid method for staining large chylomicrons.
In this report, we present a rapid method for producing high-quality micrographs suitable for determining the size distributions of particles in concentrated samples of postprandial chylomicrons and chylomicron remnants. The procedure consists of mixing particles with osmium tetroxide in water to stabilize the lipids of the particles. These fixed and positively stained particles are then negatively stained with phosphotungstate in the presence of dilute sucrose. This dual staining procedure prevents the fusion and clustering of chylomicrons during processing for electron microscopy and is effective with particles of different lipid compositions. In addition, this procedure is simple and rapid, adding only one mixing step and 5 min to the preparation time required for conventional negative stains.
Diarrheal deaths in American children. Are they preventable?
We reviewed national mortality data for 1973 through 1983 to assess the importance of diarrheal diseases as a cause of preventable childhood death in the United States. An average of 500 children aged 1 month to 4 years died each year with diarrhea reported as the cause of death. These diarrheal deaths were most common among children who were younger than 1 year of age, black, and living in the South, and were most common during the winter. In Mississippi, review of fatal cases of diarrhea identified maternal factors--black race, young age, unmarried status, low level of education, and little prenatal care--to be most associated with diarrheal death in the child. Fifty percent of these deaths occurred after a child had reached a medical facility. Our findings suggest that diarrheal deaths may be preventable and that targeted interventions could contribute to improved child survival in the United States.
Analysis of antigenically intermediate strains of subgenus B and D adenoviruses from AIDS patients.
We carried out detailed antigenic and restriction enzyme (RE) analyses on the subgenus B and D adenovirus isolates from 48 AIDS patients. These isolates were unusual both in the diversity of serotypes and in the number of intermediate strains identified. All unusual isolates were strain-purified and tested by serum neutralization (SN) and hemagglutination-inhibition (HI) tests with reference horse and rabbit antisera to all the prototype human adenoviruses; conversely, rabbit antisera were prepared to 16 selected strains from this study and tested by SN and HI with all prototype viruses. Among subgenus B strains, 6 DNA variants of Ad 11 isolates were distinguished by endonucleases BamHI, BglII, BstEII, HindIII, and SmaI. The D 2 variant of Ad 11 was prominent with 5 isolates, and 7 other isolates differed from D 2 in only 1 or 2 enzymes. HindIII was the most discriminative endonuclease for Ad 11 and related strains. Within subgenus D, there were 16 isolates of intermediate strains, including 4 intermediate types related to new Ad types 43-47. The RE patterns of subgenus D strains showed fragment distributions typical of subgenus D, with various unique patterns. Particular care was taken to analyze multiple strains from the same patient, recovered as much as 8 months apart, for evidence of genetic changes. The possible long-term infections with these viruses may provide the opportunity for mutations and recombination to occur, with the resultant generation of a variety of new strains of adenoviruses.
Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.
Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.
Purity, antigenicity and immunogenicity of the hepatitis B surface antigen purified by five different methods.
Five published methods for the purification of HBsAg from plasma were compared for specific activity (SA), degree of purification, and yield. The SA value was determined by dividing the reciprocal of the end point dilution per milliliter as determined using a commercial radioimmunoassay (AUSRIA II; Abbott Laboratories, North Chicago, IL) by the protein concentration quantitated by the Lowry method. HBsAg purified by two consecutive isopycnic ultracentrifugation separations in KBr and one rate-zonal separation in sucrose using a zonal rotor (Ti-14, Beckman, Palo Alto, CA) yielded a preparation which gave the highest SA value, degree of purification and yield as compared to four other methods. Each purified preparation was adsorbed to alum adjuvant and injected into mice to determine the immunogenic dose at which 50% of the animals elicited an anti-HBs response (ID50). The zonal rotor method resulted in the lowest ID50 value (365 ng/ml) supporting the highest SA value. Furthermore, SDS polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis revealed that this preparation had the greatest number of HBsAg-specific polypeptides (N = 7) and the fewest contaminating polypeptides (N = 5). The contaminating proteins were identified as alpha-2-macroglobulin, heavy chains of IgG and IgM, immunoglobulin kappa chain, and albumin.
Risk of adverse outcomes of pregnancy after human parvovirus B19 infection.
Human parvovirus B19 (B19) infection during pregnancy has been associated with fetal deaths. We conducted several studies to develop data needed to make recommendations for preventing fetal death associated with infection. In the first study, after an outbreak of B19 infection, specimens of cord blood from 47 infants with congenital anomalies, 10 with suspected intrauterine infection, and gestational age-matched controls were tested for IgG and IgM antibodies to B19. None had evidence of recent infection. Next, 192 women with unknown exposure to B19 who had stillbirths or spontaneous abortions were studied. Two patients and two controls had evidence of recent B19 infection. In a second case-control study of women who had stillbirths after outbreaks of erythema infectiosum in area schools, none of the 20 patients or 26 controls were IgM positive at the time of delivery. The rate of infection, as demonstrated by IgM positivity, among 267 pregnant control subjects was approximately 1%. These studies suggest that among pregnant women unselected for exposure to B19, neither infection nor stillbirths are common.
Adenoviruses from patients with AIDS: a plethora of serotypes and a description of five new serotypes of subgenus D (types 43-47).
We analyzed 67 adenovirus isolates from 48 patients with AIDS. The isolates included 5 of subgenus A (all Ad31), 23 of subgenus B, 4 of subgenus C (all Ad5), and 35 of subgenus D. The subgenus A and C strains were from liver, lung, blood, urine, and stool and were unremarkable in their antigenic characteristics. The subgenus B strains were mostly from urine and were serotyped by neutralization (SN) and hemagglutination-inhibition (HAI) tests as Ad11 (12 isolates), Ad16 (1), Ad35 (3), and Ad21/H21 + 35 (1) plus new intermediate strains 34/H11 (3), 35/H11 (1), and 11 + 35/H11 (2). The subgenus D serotypes from 24 patients were mostly from stool specimens and consisted of 8 isolates of known serotypes, 16 of antigenically intermediate strains, and 11 of five new adenovirus types with distinct antigenic and restriction enzyme characteristics. The new serotypes were described as candidate types 43-47 in accordance with currently accepted taxonomic criteria. Ad45, 46, and 47 showed a major relation by HAI with Ad29, 24, and 20, respectively. Four intermediate types were related to the new serotypes. The plethora of serotypes from patients with AIDS suggests that no epidemiological significance can be attached to any one serotype.
Rotavirus as a cause of diarrheal morbidity and mortality in the United States.
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