Reduced bone mineral density in men and women with allogeneic bone marrow transplantation.
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Adolescent↗
Biomedical subjects
R L Ward
Publications and source records attributed to R L Ward.
Induction and persistence of local rotavirus antibodies in relation to serum antibodies.
The induction and persistence of local rotavirus antibodies, including stool IgA, jejunal IgA, and jejunal neutralizing antibody, were evaluated in 14 adult volunteers infected with the CJN strain of human rotavirus. In addition, the relationships between local rotavirus IgA and serum rotavirus IgA, IgG, and neutralizing antibody were determined. Both stool and serum rotavirus IgA appeared to have similar kinetics. Both antibodies peaked by days 14-17 after inoculation in all subjects, then decreased rapidly. By days 26-28, titers had fallen to 13% and 30% of their respective peaks. Serum rotavirus IgG peaked somewhat later, occurring in five subjects on days 26-28. Serum neutralizing antibody peaked on days 26-28 in all but three subjects. Both serum IgG and neutralizing antibodies also declined more slowly than rotavirus IgA. Although all antibody concentrations had decreased to only a fraction of their peak responses by days 270-365 after rotavirus inoculation they remained higher than baseline levels. For example, stool rotavirus IgA concentrations were 13.5-fold higher than baseline, while jejunal rotavirus IgA and neutralizing antibody were 8.9- and 4.3-fold above baseline, respectively. Similarly, serum antibodies remained 3.7- to 11.2-fold higher than baseline at 270-365 days after rotavirus inoculation. These studies imply that serum rotavirus IgA is a good indicator of local antibody responses. Furthermore, although both serum and local antibody titers peaked within 2-4 weeks after infection, these antibodies persisted at above baseline concentrations for at least 9-12 months after infection.
Adolescent↗
Local and systemic antibody response to rotavirus WC3 vaccine in adult volunteers.
An evaluation of the safety and immunogenicity of WC3 rotavirus vaccine was evaluated in adult volunteers. Pre- and post-vaccination titers of neutralizing antibody to WC3 and to the four human rotavirus serotypes as well as serum and stool rotavirus IgA levels were measured. Vaccination was safe and did not induce elevation of liver enzymes. None of the 12 volunteers receiving WC3 vaccine shed detectable amounts of virus although antibody rises were detected in 11 of 12 vaccines. Nine developed and increase in WC3 neutralizing antibody, one additional subject had a rise in Wa (human serotype 1) neutralizing antibody while another subject only developed a rise in stool rotavirus IgA. All of the vaccine recipients with a rise in WC3 neutralizing antibody also developed a rise in neutralizing antibody against at least one of the four most common human rotavirus serotypes. A stool IgA rotavirus antibody response was detected in 6 of 9 WC3 recipients with measurable stool antibody. None of the control subjects developed significant rises in any of the antibody titers measured. WC3 rotavirus vaccine appears to be safe and induces systemic and local immune responses in adults suggesting that further evaluation of WC3 should be considered in infants.
Adult↗
Effects of antibody to rotavirus on protection of adults challenged with a human rotavirus.
Effects of preinoculation rotavirus antibody titers on the probability of infection and illness were evaluated in adults challenged orally with different doses of a virulent human rotavirus (CJN strain). Preinoculation titers considered were serum neutralizing antibody, serum rotavirus IgA, serum rotavirus IgG, jejunal neutralizing antibody, jejunal rotavirus IgA, and stool rotavirus IgA. Doses of virus of either 9 x 10(1) or 9 x 10(3) focus-forming units were administered to 19 subjects each. Twenty-six were infected; 15 experienced illness. The probability of either outcome was unrelated to dose. Stool rotavirus IgA titers could not be correlated to either infection or illness, but the mean titers of the other five antibodies were significantly or nearly significantly lower in subjects infected or ill, when compared with those negative for either outcome. When analyzed by stepwise logistic regression, only serum rotavirus IgG remained significantly (P = .005) related to the probability of infection, and only jejunal neutralizing antibody remained significantly (P = .01) related to the probability of illness.
Adult↗
Genotypic selection following coinfection of cultured cells with subgroup 1 and subgroup 2 human rotaviruses.
The purpose of this study was to determine why identifiable reassortants between subgroup 1 and subgroup 2 rotaviruses have been so rarely isolated from human specimens. Cultured cells were coinfected with pairs of subgroup 1 and 2 human rotaviruses and passaged multiple times to simulate natural reassortant formation and selection in vivo. After coinfection of MA-104 cells with subgroup 1 (DS-1) and subgroup 2 (either Wa or P) strains, approximately 14% of the plaque-picked progeny were shown to be reassortants. During multiple passages of these coinfected cultures, however, complete (Wa virus coinfection) or nearly complete (P virus coinfection) loss of detectable DS-1 segments from progeny was observed. Thus, when all segments of the subgroup 2 viruses were present in coinfected cultures, these segments dominated in the selected progeny. Coinfection with subgroup 1-subgroup 2 rotavirus reassortants and the DS-1 strain followed by multiple passages, however, resulted in complete loss of some segments from the subgroup 2 strains originally present in the reassortants. Therefore, segments from the parental subgroup 2 viruses appeared to be selected in toto during multiple passages because they were dominant as a group, not because individual segments of these viruses were consistently favoured over their subgroup 1 virus counterparts.
Cell Line↗
Reassortant formation and selection following coinfection of cultured cells with subgroup 2 human rotaviruses.
Reassortant formation following coinfection has been suggested as a mechanism of evolution of rotaviruses. This study was designed to examine the selection of reassortants following coinfection of cultured cells with pairs of subgroup 2 human rotaviruses. The three pairs studied (Wa x P, CJN x 31, 62 x 69) were chosen to maximize the number of RNA segments that could be electrophoretically distinguished. After coinfection and multiple passages, reproducible selection of reassortants was observed with each pair. Although more segments were selected from the virus of a pair that grew to higher titre, certain segments were selected independently of the relative growth properties or multiplicities of infection of the coinfecting viruses; selection of other segments was dependent on both. In determining the time and cause of selection it was found that no selection of genomic RNA segments was detectable prior to or during viral particle assembly in coinfected cells. However, selection was evident within the infectious progeny population after a single cycle of replication. Therefore, selection of specific reassortants following coinfection was apparently due to differences in the infectivities of progency viruses and not in their assembly. This implies that these infectivities were a function of the parental origin of specific genomic segments.
Cells, Cultured↗
Phenotypic mixing during coinfection of cells with two strains of human rotavirus.
Coinfection of MA-104 cells with serotype 1 (Wa strain) and serotype 3 (P strain) human rotaviruses resulted in progeny viruses that were phenotypically mixed in their major outer-shell structural-protein VP7 and in the genome segment that encodes this protein (segment 9). Segments from the Wa virus predominated in these progeny whether they were of parental or reassortant genotype. Neutralization with monoclonal antibodies specific for VP7 proteins of the coinfecting viruses caused an alteration in genomic distribution favoring the strain heterologous to the neutralizing monoclonal antibody. Because the percentage of change in distribution of segment 9 was similar to that of the other combined segments, there appeared to be no greater association between VP7 and segment 9 than with other segments of the homologous virus during encapsulation. From these results, it was calculated that the progeny of coinfection with P segment 9 were 77.4% mosaic structures and 14.8% pseudotypes; progeny of coinfection with Wa segment 9 were 40.2% mosaic structures and 1.3% pseudotypes. Similar determinations were made for the reassortant progeny alone.
Antibodies, Monoclonal↗
Relative concentrations of serum neutralizing antibody to VP3 and VP7 proteins in adults infected with a human rotavirus.
Two outer capsid rotavirus proteins, VP3 and VP7, have been found to elicit neutralizing-antibody production, but the immunogenicity of these proteins during human rotavirus infection has not been determined. The relative amounts of serum neutralizing antibody against the VP3 and VP7 proteins of the CJN strain of human rotavirus were, therefore, determined in adult subjects before and after infection with this virus. Reassortant strains of rotavirus that contained the CJN gene segment for only one of these two neutralization proteins were isolated and used for this study. The geometric mean titer of serum neutralizing antibody to a reassortant virus (CJN-M) that contained VP7 of CJN and VP3 of another human rotavirus was 12.7 times less than that of antibody to CJN before infection and 20.3 times less after infection. This indicated that most neutralizing antibody was against the VP3 rather than the VP7 protein of CJN. This result was confirmed with other reassortants between CJN and animal rotavirus strains (EDIM and rhesus rotavirus). These findings suggest that VP3 is the primary immunogen that stimulates neutralizing antibody during at least some rotavirus infections of humans.
Animals↗
Comparison of seven kits for detection of rotavirus in fecal specimens with a sensitive, specific enzyme immunoassay.
A sensitive, specific enzyme immunoassay (SSEIA) was compared to four commercial, enzyme-linked immunosorbent assay (ELISA) kits and three latex agglutination assay (LAA) kits: (1) Rotavirus EIA, International Diagnostic Laboratories (IDL), (2) Pathfinder, Kallestadt (KAL), (3) Rotavirus Bio-EnzaBead, Litton (LIT), (4) Rotazyme II, Abbott (RTZII), (5) Slidex Rota-Kit, bioMerieux (SRK), (6) Meritec-Rotavirus, Meridian (MER), and (7) Rotalex, Medical Technology Corporation (RLX). The SSEIA was chosen as the reference method due to its greater sensitivity in comparison to immunoelectron microscopy and polyacrylamide gel electrophoreses of viral RNA segments. Upon evaluation of 136 specimens (of which 44 were positive by SSEIA), the ELISA kits (LIT, KAL, IDL, and RTZII) had sensitivities of 80%, 98%, 91% and 84%; specificities of 95%, 78%, 100%, and 88%; positive predictive values (PPV) of 88%, 68%, 100%, and 77%; and negative predictive values (NPV) of 91%, 99%, 96%, and 92%. When compared with SSEIA, the three LAA tests (SRK, MER, and RLX) had sensitivities of 73%, 75%, and 62%; specificities of 99%, 93%, and 95%; PPVs of 97%, 85%, and 84%; and NPVs of 88%, 89%, and 84%. LAA test results appeared to be reliable, if positive, but the sensitivities of these tests were less than those of the ELISA tests. The ELISA tests that employed specimen specific negative controls were superior in minimizing false positive reactions.
Evaluation Studies as Topic↗
Characterization of virucidal agents in activated sludge.
A comprehensive study was carried out to determine the properties of agents responsible for loss of virus infectivity in mixed-liquor suspended solids (MLSS) of activated sludge. Initial experiments revealed that model enteric viruses (poliovirus-1 and rotavirus SA-11) were irreversibly inactivated in MLSS and released their RNA genomes. Enteric viruses belonging to other genera (echovirus-12, coxsackievirus A13, reovirus-3) were also shown to lose infectivity in MLSS. Although the virucidal activity decreased at reduced temperatures, MLSS still retained significant activity at 4 degrees C. The virucidal agents in MLSS were stable for months at 4 degrees C, but their activity decreased approximately 50% during 4 days of aeration at 26 degrees C. Primary effluent, the nutrient source for activated sludge, also contained virucidal activity. After centrifugation of MLSS, almost all virucidal activity was found in the particulate fraction because of inhibitory substances retained in the supernatant fraction. Decreasing or increasing the solids concentration of the particulate fraction did not increase the virucidal activity of the fraction. The effects of heat and antibiotics on the virucidal activity of MLSS, coupled with the finding that the activity can be produced in autoclaved primary effluent seeded with MLSS, strongly support the conclusion that microorganisms are responsible for this activity. Attempts to characterize the virucidal microbial components of MLSS indicated that treatments that resulted in the inactivation or removal of microorganisms also caused a loss of virucidal activity. Thus, it appears that the virucidal components of microorganisms are either short-lived or active only while bound to the organisms themselves.
Antiviral Agents↗
Betaxolol vs timolol. A six-month double-blind comparison.
Betaxolol hydrochloride (0.5%) and timolol maleate (0.5%) were compared in a six-month randomized, double-blind study involving 29 patients with glaucoma. The two drugs were comparable with regard to efficacy in lowering intraocular pressure. Betaxolol effected an average reduction of 7.6 mm Hg (26%); timolol, 8.4 mm Hg (29%). No patient required adjunctive medications during this study. Ocular side effects were mild and similar for both treatments. Neither drug affected corneal sensitivity, visual acuity, basal tear production, or pupil size. Since betaxolol has been shown to have little effect on the cardiopulmonary system, it should be strongly considered for the treatment of glaucoma.
Adult↗
Rotavirus fecal IgA antibody response in adults challenged with human rotavirus.
Our studies of rotavirus challenge in adult volunteers enabled us to evaluate the relationship of pre-existing antirotavirus fecal IgA antibody to infection and illness and to investigate the local response to this infection. No relationship could be found between the pre-existing levels of fecal antirotavirus IgA antibody and protection from infection or illness. A greater than six-fold increase in the level of antibody was seen in 16/19 infected volunteers with determinable increases but in 0/15 controls who received less than the minimal infectious dose of rotavirus. Antibody levels increased rapidly in infected volunteers and were consistent with an anamnestic response. Two of seven volunteers who received an infectious dose of rotavirus but were considered uninfected on the basis of other laboratory methods had greater than or equal to six-fold increases of fecal antibody and one of these experienced symptoms compatible with a rotavirus infection. This finding indicates that an increase in fecal antibody may be a reliable indicator of rotavirus infection even in the absence of detectable shedding or seroconversion.
Adolescent↗
Trends in old-age pensions for women: benefit levels in ten nations, 1960-1980.
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Aged↗
Human rotavirus studies in volunteers: determination of infectious dose and serological response to infection.
An unpassaged, safety-tested strain (CJN) of human rotavirus from a stool specimen of a hospitalized child was administered orally to 62 adult volunteers for determination of the dose required to produce infection with or without illness. Subjects ingested doses ranging from 9 X 10(-3) to 9 X 10(4) focus-forming units in buffered salt solution after consumption of 50 ml of 4% NaHCO3. The amount of virus in the inoculum required to cause infection (shedding of virus, seroconversion, or both) in study subjects was comparable to the minimum detectable in cultures of primary monkey kidney cells. Seventeen of 30 infected subjects became ill with doses equivalent to that required for infection. Although the preinoculation titers of serum neutralizing antibody to the challenge virus in study subjects ranged from less than 1:2 to 1:1,600, the concentration of serum antibody could not be correlated with protection from infection or illness in subjects given an infectious dose of virus.
Adult↗
Mechanism of inactivation of enteric viruses in fresh water.
Fresh water obtained from nine sources was shown to cause inactivation of poliovirus. Further testing with four of these water samples showed that enteric viruses from different genera were consistently inactivated in these freshwater samples. Studies on the cause of inactivation were conducted with echovirus type 12 as the model virus. The results revealed that the virucidal agents in the waters tested could not be separated from microorganisms. Any treatment that removed or inactivated microorganisms caused loss of virucidal activity. Microbial growth in a sterilized creek water seeded with a small amount of stream water resulted in concomitant production of virucidal activity. When individual bacterial isolates obtained from a stream were grown in this sterilized creek water, most (22 of 27) produced a large amount of virucidal activity, although the amount varied from one isolate to the next. Active and inactive isolates were represented by both gram-positive and gram-negative organisms. Examination of echoviruses inactivated in stream water revealed that loss of infectivity first correlated with a slight decrease in the sedimentation coefficient of virus particles. The cause appeared to be cleavage of viral proteins, most notably, VP-4 and, to a lesser extent, VP-1. Viral RNA associated with particles was also cleaved but the rate was slower than loss of infectivity. These results suggest that proteolytic bacterial enzymes inactivate echovirus particles in fresh water by cleavage of viral proteins, thus exposing the viral RNA to nuclease digestion.
Enterovirus B, Human↗
Discharging the long-term mentally handicapped.
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Adult↗
Effect of mutation in immunodominant neutralization epitopes on the antigenicity of rotavirus SA-11.
Exposure of rotavirus SA-11 to polyclonal neutralizing antibody from hyperimmunized guinea-pigs permitted selection of variants which were poorly neutralized by antisera against the parental virus. In one-way cross-neutralization experiments, at least 22 of 24 plaque-purified variants could be classified as belonging to a serotype different from that of the parent. Most antisera generated against the variants, however, readily neutralized the parental virus. This indicates that immunodominant neutralization epitopes in the parent differed from those in the variants. Changes in immunodominant epitopes caused the serotypic relationships between the variants and other strains of rotavirus to differ from those of the parental SA-11. The serotypic relatedness of human strain P (human serotype 3) was reduced while, in contrast to results found with the parental SA-11, several of the antisera against the variants recognized the bovine rotavirus NCDV as the same serotype. Causes for these changes are discussed.
Antigens, Viral↗
In vitro activities of bismuth salts against rotaviruses and other enteric viruses.
Bismuth salts inhibited plaque formation of all enteric viruses tested, which included four strains of rotavirus and one strain each of echovirus, reovirus, and poliovirus. The compounds had no direct virucidal effect at concentrations ranging from 0.025 to 2.5 mg/ml, and the inhibitory effects were observed only at concentrations slightly below those that caused extensive cytotoxicity. Plaque inhibition appeared to result from interference with host cell functions, with secondary inhibition of virus production.
Animals↗