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Biomedical subjects

S O'Shea

Publications and source records attributed to S O'Shea.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.

Adult↗
PubMed1998

Maternal viral load, CD4 cell count and vertical transmission of HIV-1.

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy.

CD4 Lymphocyte Count↗
PubMed1998

An altered intron inhibits synthesis of the acetylcholine receptor alpha-subunit in the paralyzed zebrafish mutant nic1.

The acetylcholine receptor (AChR), an oligomeric protein composed of five subunits, is a component of the postsynaptic membrane at the vertebrate neuromuscular junction that plays a central role in synaptic transmission. The zebrafish mutation nic1 blocks the expression of functional and clustered nicotinic muscle AChRs. To understand the mechanisms underlying this lack of AChRs, we characterized the molecular defect in nic1 mutants. Our results suggest that the mutation affects the gene coding for the alpha-subunit of the AChR. Southern blot hybridization and DNA sequence analyses showed that the nic1 AChR alpha-subunit gene lacks part of intron 6 where the splicing branchpoint normally forms. Several lines of evidence suggest that this deletion blocks normal splicing; most nic1 alpha-subunit mRNAs retain intron 6 and are larger and less abundant than wild-type, some nic1 alpha-subunit mRNAs are internally deleted, and wild-type alpha-subunit mRNA rescues nic1 mutant cells. The nic1 mutation reduces the size of an intron, which prevents efficient splicing of the pre-mRNA, thus blocking synthesis of the alpha-subunit and assembly of AChRs. By this route, the nic1 mutation leads to paralysis.

Amino Acid Sequence↗
PubMed1998

Rubella virus and chronic joint disease: is there an association?

Synovial fluid samples and/or biopsies from 79 patients with various chronic inflammatory joint diseases or traumatic joint injury were tested for rubella virus (RV) in order to confirm or refute results from other studies that suggested RV as a cause of chronic inflammatory joint disease. Sixty-eight of the 72 patients tested had RV antibodies. RV RNA was detected by reverse transcription-PCR in the synovial fluid cells from two patients. RV was also isolated by cell culture from the synovial fluid of one of these two patients. This patient was a 42-year-old female with common variable immune deficiency and Mycoplasma hominis arthritis, while the other was a 68-year-old female with rheumatoid arthritis. While these results fail to confirm that RV is associated with chronic inflammatory joint disease, they suggest that RV may persist within a joint and be reactivated when cell-mediated immunity is suppressed.

Adolescent↗
PubMed1996

Significance of placental damage in vertical transmission of human immunodeficiency virus.

The significance of physical breaches of the trophoblastic layer of the placenta in transmission of HIV from mother to infant was evaluated in 17 HIV-infected pregnant women. Samples of peripheral blood were obtained from the women during pregnancy and at delivery, at which time a small piece of placental tissue was obtained from a random site and immediately placed into fixative. Blood samples were obtained from infants at or shortly after birth and thereafter at approximately 3-month intervals, until the age of 18 months, in order to determine their HIV infection status. HIV RNA and p24 antigen were quantified in maternal plasma and CD4 cells enumerated. Paediatric diagnosis was conducted using polymerase chain reaction, virus isolation, detection of p24 antigen, and measurement of class-specific antibodies. Placental damage was quantified and evaluated using transmission electron microscopy. Maternal viral load was low, with a mean RNA copy number of 8,237 per millilitre of plasma (range 230-37,233 copies/ml). Only two women were p24-antigenaemic, and CD4 numbers ranged from 0.09 to 2.8 x 10(9)/l. There was evidence of breaks in the trophoblastic surface to the depth of the basement membrane in all 17 placentas, and perivillous fibrinoid deposits were also observed to a varying degree in all samples. However, none of the 13 infants available for follow-up had evidence of infection with HIV. Superficial damage to the trophoblastic surface of the placenta, with exposure of the basement membrane and potential exposure of CD4-expressing cells, does not appear to be a significant factor in the transmission of HIV from mother to infant during pregnancy.

Female↗
PubMed1995

bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival. However, mice lacking functional bcl-2 exhibited normal development and maintenance of the central nervous system (CNS). Since bcl-2 appears dispensable for neuronal survival, we have examined the expression and function of bcl-x, another member of the bcl-2 family of death regulatory genes. Bcl-2 is expressed in neuronal tissues during embryonic development but is down-regulated in the adult CNS. In contrast, Bcl-xL expression is retained in neurons of the adult CNS. Two different forms of bcl-x mRNA and their corresponding products, Bcl-xL and Bcl-x beta, were expressed in embryonic and adult neurons of the CNS. Microinjection of bcl-xL and bcl-x beta cDNAs into primary sympathetic neurons inhibited their death induced by nerve growth factor withdrawal. Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS.

Aging↗
PubMed1995

Use of PCR for prenatal and postnatal diagnosis of congenital rubella.

A reverse transcription-nested PCR assay (RT-PCR) was evaluated for diagnosis of congenitally acquired rubella in utero and during infancy. RT-PCR was compared with virus isolation for retrospective detection of rubella virus in placental and fetal tissues obtained after termination of pregnancy following primary rubella or rubella virus reinfection. Concordant results were obtained for 85% of samples; rubella virus RNA was detected by RT-PCR alone in four samples, and rubella virus was detected by isolation alone in two samples. Samples were also obtained for prenatal diagnosis of congenital infection; rubella virus RNA was detected in three of seven chorionic villus samples and one of three amniotic fluid samples by RT-PCR, while rubella virus was isolated in only one chorionic villus sample. To demonstrate that the RNA extracted from chorionic villus samples contained amplifiable RNA, a nested RT-PCR was used to detect keratin mRNA. Rubella virus was detected in placenta in two cases in which the fetus was uninfected, and there was no evidence of rubella virus in the placenta from one case in which the fetus was infected. Thus, detection of rubella virus in chorionic villus samples by RT-PCR may not always correctly predict fetal rubella virus infection. RT-PCR was successfully used for the diagnosis of congenitally acquired rubella in infancy. Rubella virus RNA was detected in cyropreserved or formalin-fixed lens aspirates obtained from infants in India with serologically confirmed congenital rubella but not in samples from controls with inherited cataract.

Amniotic Fluid↗
PubMed1995

PCR for detection of rubella virus RNA in clinical samples.

A reverse transcription nested PCR (RT-PCR) assay for the detection of rubella virus RNA using primers from the E1 open reading frame was established. This assay was found to be sensitive (detecting approximately two synthetic RNA copies and RNA extracted from 0.1 50% tissue culture infective dose of rubella virus) and specific; five wild-type rubella strains and four vaccine strains were detected, and no nonspecific amplification of 16 other RNA viruses or RNAs from seven cell types occurred. Rubella virus RNA was detected in 12 pharyngeal swabs from patients with serologically confirmed rubella; these RT-PCR results were in complete agreement with virus isolation. Analysis of products of conception obtained after confirmed primary maternal rubella infection by RT-PCR gave 92% agreement (12 of 13 samples) with virus isolation. No false-positive results were obtained. The potential use of this assay for prenatal diagnosis of congenital rubella infection and for investigating aspects of the pathogenesis of chronic disease is discussed.

Base Sequence↗
PubMed1994

Rubella reinfection; role of neutralising antibodies and cell-mediated immunity.

BACKGROUND: Rubella virus may be transmitted to the fetus following rubella reinfection in early pregnancy. The mechanisms responsible for maternal-fetal transmission in women with pre-existing rubella antibodies are, however, unclear. OBJECTIVES: To evaluate the protective role of rubella specific neutralising antibodies and cell-mediated immunity in rubella reinfection. STUDY DESIGN: Rubella Nt antibodies were measured in sera obtained from: women who experienced rubella reinfection during pregnancy, volunteers experimentally challenged with rubella vaccine and women attending for routine rubella antibody screening. Cell-mediated immunity was assessed by measuring rubella specific LT responses among women who had experienced rubella reinfection during pregnancy. RESULTS: Some women experienced rubella reinfection during pregnancy despite the presence of Nt antibodies in sera obtained before contact. Only 2 of 13 (15.3%) volunteers with low levels (< 15 IU/ml) of rubella antibody had detectable Nt antibodies prior to experimental challenge. Despite this, they did not develop rubella viraemia following challenge and virus excretion was detected in only one case, although the majority (11/13, 84.6%) demonstrated a significant rise in antibody titre. Among pregnant women screened as having a low level of rubella antibody antenally, only 37% had detectable Nt antibodies. Among 23 women who experienced rubella reinfection during pregnancy 4 months to 6 years (mean 32 months) previously, 20 (86.9%) had a positive rubella-specific LT response. Only one of 4 cases where rubella virus was transmitted to the fetus failed to produce a a specific LT response. CONCLUSIONS: This study indicates that rubella reinfection is not associated with a lack of Nt antibodies or persistent impairment of rubella-specific LT responses.

Journal Article↗
PubMed1994

Stability of infectious HIV in clinical samples and isolation from small volumes of whole blood.

AIMS: To evaluate the stability of infectious HIV in clinical samples and the efficiency of isolating it from small volumes of whole blood. METHODS: Titres of infectious HIV were measured in peripheral blood mononuclear cells and plasma 2, 24, and 48 hours after peripheral blood had been collected from 10 HIV positive adult volunteers. Volumes of whole blood (1 ml to 5 microliters), collected from a further five volunteers, were used to determine the minimum volume from which HIV could be isolated. Infectious HIV was isolated by co-culture with phytohaemagglutinin stimulated umbilical cord mononuclear cells. RESULTS: Geometric mean titres of infectious HIV seemed to be more stable in peripheral blood mononuclear cells than in plasma. HIV was recovered from all 10 peripheral blood mononuclear cell samples during the 48 hours after sample collection, but from only four plasma samples. HIV could occasionally be isolated from 5 microliters of whole blood and reliably from 200 microliters. CONCLUSIONS: HIV can be isolated from peripheral blood mononuclear cells and plasma for up to 48 hours after sample collection. Isolation of HIV from small volumes of whole blood has applications for the diagnosis and management, of HIV positive children.

Adult↗
PubMed1993

Slow maturation of IgG1 avidity and persistence of specific IgM in congenital rubella: implications for diagnosis and immunopathology.

Without appropriately timed specimens, serological confirmation of congenital rubella infection may be a problem. We have compared the persistence of specific IgM and low avidity specific IgG1 in 141 sera from 120 cases of serologically confirmed congenital rubella infection with the known time scales for postnatal primary rubella. The results demonstrate that the maturation of the immune response to the rubella virus is abnormally slow in congenital rubella cases both in terms of the isotype switch and especially the development of high avidity specific IgG1. Thus avidity studies may permit serological confirmation of congenital rubella for longer than is possible with tests currently in use. The pathological implications of prolonged low avidity antibody production are discussed.

Aging↗
PubMed1992

A lymphocyte transformation assay for the diagnosis of congenital rubella.

A rubella-specific lymphocyte transformation assay, using cryopreserved mononuclear cells, has been developed and used to evaluate specific responses among 21 children with congenitally acquired rubella (CAR), 25 healthy control children and 10 children with sensorineural deafness of unknown aetiology. Although all 21 children with CAR were seropositive, 12 (57.1%) failed to respond to rubella antigen in the transformation assay. Negative in vitro lymphocyte transformation responses were detected significantly more frequently among congenitally infected children below 3 years of age. Thirteen of the 25 (52%) control children were seropositive; only one of these seropositive children (7.6%) gave a negative transformation response. A negative rubella-specific lymphocyte transformation response in a seropositive child, particularly when aged 3 years or younger, is therefore suggestive of CAR. Four of the 10 children with deafness of unknown aetiology were rubella seropositive but gave negative responses in the transformation assay, suggesting that these children had CAR. Our assay may provide a very useful test for retrospective diagnosis of CAR, particularly in children under the age of 3.

Adult↗