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Biomedical subjects

A D Steele

Publications and source records attributed to A D Steele.

At least 37 records · Page 2Linked to original sources
PubMed2001

Atypical rotavirus identified from young children with diarrhoea in South Africa.

The study was undertaken for antigenic characterization of rotavirus strains isolated from South African children. During July 1996-July 1997, an epidemiological surveillance of rotavirus-associated gastroenteritis was carried out in Pretoria and Gauteng provinces. In total, 1,229 diarrhoeal faecal samples were collected from a pathology laboratory. Of 389 (32%) rotavirus strains detected, most (97%) were group A rotaviruses by serological assay. However, 12 rotavirus strains identified did not apparently carry the common group A-specific antigen as determined by both commercial and monoclonal antibody-based ELISAs. Electrophoretic analysis of the viral RNA genome revealed that these strains shared a common electropherotype and that this resembled the group A rotavirus constellation of RNA segments. Furthermore, the conserved terminal sequences of the group A VP6 and VP7 genes could not be targeted by standard reverse transcriptase-polymerase chain reaction with a routine set of primers to the VP6 or VP7 genes. These strains present an interesting phenotypic variation of the recognized rotaviruses and warrant further characterization.

Adult↗
PubMed2000

Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells.

Strong evidence for the direct modulation of the immune system by opioids is well documented. Mu-opioids have been shown to alter the release of cytokines important for both host defense and the inflammatory response. Proinflammatory chemokines monocyte chemoattractant protein-1 (MCP-1), RANTES, and IFN-gamma-inducible protein-10 (IP-10) play crucial roles in cell-mediated immune responses, proinflammatory reactions, and viral infections. In this report, we show that [D-Ala(2),N:-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO), a mu-opioid-selective agonist, augments the expression in human PBMCs of MCP-1, RANTES, and IP-10 at both the mRNA and protein levels. Because of the proposed relationship between opioid abuse and HIV-1 infection, we also examined the impact of DAMGO on chemokine expression in HIV-infected cells. Our results show that DAMGO administration induces a significant increase in RANTES and IP-10 expression, while MCP-1 protein levels remain unaffected in PBMCs infected with the HIV-1 strain. In contrast, we show a dichotomous effect of DAMGO treatment on IP-10 protein levels expressed by T- and M-tropic HIV-infected PBMCs. The differential modulation of chemokine expression in T- and M-tropic HIV-1-infected PBMCs by opioids supports a detrimental role for opioids during HIV-1 infection. Modulation of chemokine expression may enhance trafficking of potential noninfected target cells to the site of active infection, thus directly contributing to HIV-1 replication and disease progression to AIDS.

Cells, Cultured↗
PubMed2000

Characterisation of rotaviruses from children treated at a London hospital during 1996: emergence of strains G9P2A[6] and G3P2A[6].

Rotavirus strains from 171 patients treated in 1996 at a children's hospital in London were characterised. Use of a panel of typing monoclonal antibodies for serotypes G1-4 identified 105 (61%) of the strains. The majority, 90 strains (86%), were serotype G1. Characterisation of G (VP7) and P (VP4) types using reverse transcription-polymerase chain reaction was more efficient, and 167 of 171 (98%) of the strains were identified this way. The predominant strains were G1P1A[8] (55%) and G4P1A[8] (17%), which are prevalent throughout the world; however, a significant number of cases were associated with genotypes not recorded previously in the United Kingdom. There were 21 (13%) cases associated with G9P2A[6] and 11 (6%) cases associated with G3P2A[6]. The majority (seven of 10) cases of infection in children older than 3 years of age were caused by these two genotypes. A majority (15/21) of G9P2A[6] strains were recovered from children admitted to the hospital, and five children were sufficiently dehydrated to necessitate intravenous rehydration.

Antibodies, Monoclonal↗
PubMed2000

South African G4P[6] asymptomatic and symptomatic neonatal rotavirus strains differ in their NSP4, VP8*, and VP7 genes.

Over the past decade, a G4P[6] strain has been found to be circulating in different neonatal wards in the Pretoria area. This endemic strain was associated with both asymptomatic and symptomatic infection, providing the opportunity to undertake a molecular study of some of the putative "virulence" genes. The genes encoding NSP4, VP8*, and VP7 of two asymptomatic and two Symptomatic strains were sequenced and compared with ST3. Within each of these genes, amino acid substitutions unique to South African strains were recorded. Four conserved amino acid differences between asymptomatic and symptomatic strains at aa 82 (serine to leucine), aa 114 (aspartic acid to glutamic acid), aa 138 (proline to threonine), and aa 169 (leucine to serine) were identified within the NSP4 gene. The hypervariable region of VP8* exhibited 10 specific amino acid differences (at aa 73, 78, 98, 111, 116, 142, 145, 167, 169, and 188) between asymptomatic and symptomatic strains, while three amino acid substitutions within VP7 were noted. These changes to VP7 occurred within the glycosylation site at aa 70 (leucine to serine), at antigenic region A (aa 96, asparagine to threonine), and at aa 318 (aspartic acid to glycine). It may be speculated that these changes are specific to G4P[6] strains. Furthermore, the observed substitutions may also be particular to South African strains. NSP4, VP8*, and VP7 have been associated with virulence and the amino acid substitutions within these genes correlate with both asymptomatic and symptomatic infection observed in neonates.

Amino Acid Sequence↗
PubMed2000

VP6 subgroup and VP7 serotype of human rotavirus in Zaria, northern Nigeria.

A survey of rotavirus infection in infants and young children with acute diarrhoea was undertaken in Zaria, northern Nigeria during 1997 and 1998. In total, 375 faecal specimens were collected from children aged between 1 and 60 months and 122 specimens from age-matched control children without diarrhoea. Fourteen specimens were collected from neonates in the University Teaching Hospital. Rotavirus antigen was detected in 61 diarrhoeal and four control specimens; four neonates were shedding rotavirus. Polyacrylamide gel electrophoresis of the viral genome showed the presence of five strains of rotavirus with long RNA electropherotypes and one short pattern. The rotavirus VP6 subgroup was determined by monoclonal antibodies specific ELISA and showed that subgroup II strains predominated (72 vs. 9.8 per cent), while eight strains could not be subgrouped and three did not react at all. Examination of the VP7 serotype showed G1 and G3 strains circulating at similar levels (29 and 25 per cent), but no serotype G2 nor G4 strains were identified. G1/G3 'mosaic' virus strains circulated commonly (10 per cent).

Antibodies, Monoclonal↗
PubMed2000

Bidirectional heterologous desensitization of opioid and chemokine receptors.

Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed-type hypersensitivity. Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL-1, IL-6 and TNF-alpha, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established. Earlier studies have shown that both mu- and delta-opioid agonists induce a chemotactic response in monocytes and neutrophils. In addition, mu- and delta-opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization. We report here that mu-, delta-, and kappa-opioid agonists also induce a chemotactic response in T lymphocytes. Using the human T-cell line Jurkat, we have confirmed previous observations that pre-incubation with met-enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES. On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF-1 alpha. Moreover, we found that pre-treatment with RANTES prevented a subsequent response of monocytes to the mu-opioid agonist DAMGO. These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities.

Chemokines↗
PubMed2000

Relevance of commercial diagnostic tests to detection of enteric adenovirus infections in South Africa.

The prevalence of enteric adenoviruses detected by an in-house enzyme-linked immunosorbent assay (the RIVM-ELISA) ranged from 13 to 38%, and subgroup F adenoviruses comprised 86%. All subgroup F adenoviruses reacted with both RIVM anti-adenovirus type 40 (Ad40) and anti-adenovirus type 41 (Ad41) monoclonal antibodies but were not detected by Adenoclone Type 40/41 enzyme immunoassay (EIA). The correlation between the Biotrin EIA and RIVM-ELISA results was low (26%). Immunospecific tests suggest that a significant proportion of enteric adenoviruses, possibly comprising previously unidentified or emerging types, are not detected by commercial diagnostic tests in South Africa.

Adenovirus Infections, Human↗
PubMed1999

Seroepidemiological study of genogroup I and II calicivirus infections in South and southern Africa.

Diarrhoea is associated with the daily death of between 180 and 200 children under the age of 5 years in South Africa. Until recently, many cases and outbreaks of diarrhoea were not associated with a known aetiologic agent. Previous studies using baculovirus-expressed Norwalk virus (NV) and Mexico virus (MxV) capsid antigens have shown that human calicivirus infection is common in South Africa. In this study, our surveillance was extended to different populations, as well as to four other southern African countries: Namibia, Angola, Zimbabwe, and Mozambique. More than 1,700 specimens, some involved in previous cohort studies of infectious diseases, were enrolled in the surveillance. The overall seroprevalence of antibody against NV was >90% for all cohorts except for Mozambican refugees that had 83. 8% sero-positivity. The MxV antibody prevalence was higher than NV, with >95% positivity for all cohorts, except for one in Namibia that had 81% exposure. This study is one of only a few reporting on the concurrent incidence of NV and MxV infections in a cohort study, and has determined that small round structured viruses are prevalent in the local populations of South and Southern Africa. These agents may account for a number of previously unknown or unidentified causes of diarrhoeal illness, in both adults and children, in southern Africa.

Adolescent↗
PubMed1999

Comparative studies of human rotavirus serotype G8 strains recovered in South Africa and the United Kingdom.

Epidemiological studies on the VP7 serotype prevalence of human rotaviruses in South Africa and the United Kingdom identified several strains which could not be serotyped as G1-G4 by monoclonal antibodies. Further analysis of these strains with a G8-specific monoclonal antibody and with probes for human rotaviruses confirmed them as G8 rotaviruses. These G8 strains exhibited a high degree of sequence identity when compared with each other and with other rotavirus G8 strains. Five South African strains were further characterized as VP6 subgroup I, but with a long RNA electropherotype, which is similar to the G8 strains previously isolated in Finland. In the UK strains, one was VP6 subgroup II with a long RNA electropherotype (similar to the Italian G8 strain). The other two were subgroup I with a short RNA electropherotype. None of these strains exhibited the super-short RNA electropherotype described in the prototype G8 strains recovered from Indonesia (69M).

Amino Acid Sequence↗
PubMed1999

Seroepidemiology of human group C rotavirus in South Africa.

Sera from three separate healthy population cohorts were used to determine the incidence of group C rotavirus infections in 1,356 South Africans. Using an enzyme-linked immunosorbent assay based on a recombinant group C rotavirus VP6 protein, the total percent positivity was found to be 34.4% (range, 33 to 38%), with almost half of the population infected after the age of 20 years.

Adolescent↗
PubMed1998

Retreatment for significant regression after excimer laser photorefractive keratectomy. A prospective, randomized, masked trial.

PURPOSE: Regression, a gradual partial or complete return to the myopic state, remains a common complication of excimer laser photorefractive keratectomy (PRK) and limits the predictability of refractive outcome, especially in high myopia. An estimated 10% to 20% of patients, therefore, request a repeat PRK procedure. This study was designed to provide patient selection criteria and guidelines for successful retreatment. METHODS: One hundred six patients who had regressed were randomized to 1 of 4 retreatment groups comprising (1) those with minimal haze after their first PRK who received an exact retreatment; (2) those with minimal haze treated with a 50% deliberate overcorrection; (3) those with significant haze (> or = 2+ haze) given an exact retreatment; and (4) those with significant haze who received a 50% overcorrection. A Visx 20/20 laser was used in each case. Mean follow-up after retreatment was 12 months (range, 6-18 months). RESULTS: Deliberate overcorrection (groups 2 and 4) resulted in a statistically significantly better refractive outcome (P = 0.026 at 6 months). Analysis of variance showed that significant haze after the first PRK was the most important predictor of a poor outcome after retreatment, other factors being high original myopia, marked regression, and loss of best-corrected visual acuity. CONCLUSIONS: A retreatment PRK procedure for significant regression will reduce residual myopia significantly in the majority of patients, and a deliberate overcorrection (50%) reduces the chance of further regression. However, patients with high myopia who have regressed beyond approximately -3.50 diopters originally and who show significant anterior stromal haze (> 2+) should be retreated only with great caution, because of the risk of further regression, haze, and loss of visual acuity.

Adult↗
PubMed1998

Characterization of VP6 subgroup, VP7 and VP4 genotype of rotavirus strains in Lusaka, Zambia.

In a previous study, rotavirus infection was determined in young children at the University Teaching Hospital in Lusaka. In this study, selected rotavirus strains were characterized by monoclonal antibody assay to the VP6 subgroup antigen present and by hybridization analysis of the VP7 and VP4 genes carried by the virus. The majority of the strains were characterized as a VP6 subgroup II, VP7 serotype G1 strain with a long electropherotype and bearing the VP4 P8 genotype. A further four minor rotavirus strains with a long RNA electropherotype and subgroup II antigen were also observed to be circulating bearing G1 or G4 VP7 genes and the VP4 P8 genotype. Two electrophoretic strains with differing short RNA electropherotypes and subgroup I antigenicity were also present. These strains hybridized to the VP7 type G2 and VP4 P4 genotype probes.

Child, Preschool↗
PubMed1998

Astrovirus infection in South Africa: a pilot study.

Astroviruses have been shown to be important aetiological agents associated with gastroenteritis in children, as have rotaviruses and the enteric adenoviruses. However, no inclusive studies have been conducted in South Africa to allow a comparison of the relative roles of these different viral agents. In this study, stool specimens were obtained between 1991 and 1993 from 225 young children with acute gastro-enteritis. These were examined for the presence of astroviruses using a monoclonal antibody-based ELISA, and for rotaviruses and enteric adenoviruses using commercially available kits. A control group of 56 infants and young children without symptoms of diarrhoeal illness was included in the study. Astroviruses were detected in 7% of the stools compared with 20% infected with rotaviruses and only 3% infected with enteric adenoviruses. In the control group, one specimen each had astrovirus or adenovirus and two shed rotaviruses. The astrovirus prevalence observed in this study is similar to that reported in other developing communities. Rotavirus and astrovirus infections were more prevalent in the autumn and early winter than in other seasons. Astrovirus and rotavirus infections predominated in children between 3 and 22 months of age.

Adenoviridae↗
PubMed1998

Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization.

Rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus diarrhoea in developing countries and the possible impact of these vaccines in reducing diarrhoeal morbidity and mortality among infants and young children. We examined the epidemiology and disease burden of rotavirus diarrhoea among hospitalized and clinic patients in African countries through a review of 43 published studies of the etiology of diarrhoea. The studies were carried out from 1975 through 1992, and only those in which a sample of more than 100 patients with diarrhoea were specifically screened for rotavirus by using an established diagnostic test were included. Rotavirus was detected in a median of 24% of children hospitalized for diarrhoea and in 23% who were treated as outpatients; 38% of the hospitalized patients with rotavirus were < 6 months and 81% were < 1 year of age. Rotavirus was detected year-round in nearly every country and generally exhibited distinct seasonal peaks during the dry months. In 5 countries where rotavirus strains had been G-typed, 74% of strains were of one of the four common serotypes (G1 to G4), G1 was the predominant serotype, and 26% were non-typeable. This cumulative experience from 15 African countries suggests that rotavirus is the most important cause of severe diarrhoea in African children and that most strains in circulation today belong to common G types that are included in reassortant vaccines. Wherever large numbers of cases of rotavirus diarrhoea occur early in infancy, immunization at birth may protect the children before their first symptomatic infection.

Africa↗
PubMed1998

Characterisation of gastro-enteritis-associated adenoviruses in South Africa.

OBJECTIVE: To analyse adenovirus (Ad) numbers and types associated with paediatric gastro-enteritis in South Africa. SETTING: Gauteng, 1994-1996. METHODS: A total of 234 paediatric diarrhoeal stool samples were screened for Ad using commercial enzyme-linked immunosorbent assays (ELISAs). Adenoviral isolates were typed, where possible, using restriction enzyme analysis. RESULTS: Ad was detected in 23 (9.8%) specimens, of which 8 (34.8%) were found by subgroup F-specific ELISA to contain Ad40 or 41. Six of these isolates were typed and 2 could not be typed. Of the remaining 15 specimens, 2 isolates had restriction profiles that did not correspond with known Ads, while 2 were identified as Ad31 and 1 as a subgroup C Ad. The remaining 10 specimens negative for Ad40/41 were non-cultivable and could not be typed. CONCLUSIONS: The high percentage of non-cultivable Ads other than Ad40/41 is unusual, and may possibly indicate the prevalence of hexon variants of Ad40/41 or of emerging Ad types in South Africa.

Adenovirus Infections, Human↗
PubMed1997

Study of Norwalk virus and Mexico virus infections at Ga-Rankuwa Hospital, Ga-Rankuwa, South Africa.

Small round-structured viruses (SRSVs) or Norwalk-like viruses have been implicated as an important causative agent of gastroenteritis outbreaks. We used the relatively newly developed recombinant enzyme immunoassays (EIAs) to determine the seroprevalence of Norwalk virus (NV) and Mexico virus (MxV) in a family-based cohort and an antenatal clinic cohort at Ga-Rankuwa Hospital, Ga-Rankuwa, South Africa. High prevalences (96 to 99%) of anti-NV and anti-MxV antibodies were detected in both cohorts. We also investigated the pattern of antibody acquisition in a cohort of infants and young children without gastroenteritis and found that by 48 months of age all children had acquired adult antibody levels to both these viruses. Lastly, we tested 276 stool specimens collected from infants and young children with gastroenteritis for the presence of NV or MxV antigen by recombinant EIAs to each virus, by electron microscopy (EM), and by reverse transcription (RT)-PCR. NV and MxV antigens were present in 1.8 and 4.3% of the stool specimens, respectively, by the recombinant EIAs; 9.2% were positive for SRSVs by EM, and 25% of these SRSVs gave a positive result by RT-PCR for primer pair 35-36 directed to a region of the RNA-dependent RNA polymerase gene. The seroprevalence studies indicate a high level of exposure to these viruses in both children and adults. Although the viral antigens are not highly prevalent in diarrheal stools, it was determined by the two assays for NV and MxV that children are, nevertheless, infected early in life.

Adolescent↗