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Biomedical subjects

J Y Mok

Publications and source records attributed to J Y Mok.

At least 19 recordsLinked to original sources
PubMed1997

In vitro measurement of cytotoxic T cell activity does not predict clinical progression in paediatric HIV disease--two case studies.

Cytotoxic T cells are believed to be an important immune response in HIV infection, both in the initial response to viraemia, and in controlling HIV replication and maintaining clinical stability. We report here the detailed findings in two vertically infected children, from the Edinburgh perinatal cohort. Both were clinically stable for the first 7 years of life. One had vigorous HIV-specific cytotoxic T lymphocyte (CTL) responses, and non-lytic suppression, measured in vitro, while the second had no CTL activity against HIV. Despite her HIV-specific immunity, the first child had a declining CD4 count, and a high and fluctuating viral load, whereas the second child maintained a stable CD4 count, a low viral load and had a virus which could not be cultured in peripheral blood mononuclear cells (PBMC) in vitro. The first child subsequently progressed to AIDS and has now died, while the second remains clinically well. More detailed investigations showed the clinically stable child to be heterozygous for the CCR5 receptor, and to be HLA-B49--both of which markers have been associated with slow HIV disease progression. These findings question the role of CTL in maintaining stable HIV disease, and stress the need for immunological investigations to be considered in the light of the genetic make-up of the patient. They may also reflect a different immunopathogenesis of HIV disease in children compared with adults.

Adult↗
PubMed1996

Maternal HIV and drug use: effect on health and social morbidity.

A retrospective analysis of routine child health surveillance information was performed on health visitor records of 459 children, to examine the independent effects of maternal HIV infection and drug use during pregnancy on morbidity in the first 3 years of life. No significant differences were observed in the developmental progress of children born to HIV infected or drug using women when compared to community controls. The pattern of medical consultations in the first 18 months of life was significantly different, maternal drug use exerting a negative influence on outpatient visits (odds ratio 0.6, 95% confidence interval 0.4 to 1.0). At 6 weeks, the majority of children lived with their birth parent(s), and no differences were observed between the groups. By 10 months of age, only 81% of children born to HIV infected drug using women lived with their parent(s). While maternal drug use and HIV did not have adverse effects on child health and development, these findings highlight the social implications for children affected by the heterosexual spread of HIV.

Adult↗
PubMed1996

CD4 and CD8 lymphocytes in diagnosis and disease progression of pediatric HIV infection.

Vertical infection with human immunodeficiency virus-1 (HIV-1) causes profound changes in the proportions of subpopulations of lymphocytes in the peripheral circulation. In this study the percentages in whole blood of CD4 and CD8 cells, and of immunologically important subpopulations, were measured in 19 HIV-infected children over periods of up to 4 years and compared to our recently published ranges for normal children of various ages. The rate of CD4 decline and of CD8 increase differed between clinically fast and slow progressors. On CD8 cells, cytotoxic, memory (CD11abright and CD45R0), and activation (HLA-DR) markers were raised soon after birth to levels outside the normal range, and compared favorably with HIV culture as a method for early diagnosis of HIV infection. Mean levels of naive (CD45RA) and memory (CD45R0, CD29) markers on CD4 cells became significantly altered after 48 months of age, suggesting that these are markers of more advanced disease. Despite different ages of enrollment into the study, in the cohort as a whole, the levels of the lymphocyte subpopulations studied changed consistently. Thus, their measurement could be useful both in the diagnosis and prognosis of HIV infection in individual children. This is the first report showing that lymphocyte subpopulation analysis can play a major role in the diagnosis of pediatric HIV infection.

Biomarkers↗
PubMed1994

Age-related ranges of memory, activation, and cytotoxic markers on CD4 and CD8 cells in children.

The expression of markers defining functional subpopulations on the surface of CD4 and CD8 cells changes with disease. To monitor these changes in children, it is important to establish the age-related normal changes in marker expression due to maturation of the immune system. We have studied the expression of several functionally important molecules on both CD4 and CD8 cells in 168 children (aged 0-122 months) using monoclonal antibodies and flow cytometry. Our results show that the percentage of CD4 cells decreases with age, while the CD8 percentage increases, resulting in a decrease in the CD4/CD8 ratio. The expression of CD45RO and CD29 increases with age, while CD45RA expression decreases, both on CD4 and CD8 cells. The expression of HLA-DR on both CD4 and CD8 cells, and of CD11a and CD57 on CD8 cells, is less clearly age dependent. The relationships between the marker percentages and age were not straightforward; the standard deviations and the skewness, as well as their mean values, varied as a function of age. The changes were modeled for each marker and age-specific centiles are presented.

Aging↗
PubMed1994

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection.

HIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CD8 lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any, between CTL activity and CD8 subpopulations. We have measured CTL activity against four HIV gene products (gag, tat, pol and env) and expression of CD45RO, CD45RA, HLA-DR, CD29, S6F1, and CD57 surface markers on CD8 cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HIV-gag, -pol and -tat, and the other to HIV-pol. All the HIV-infected and two uninfected children had abnormal proportions of CD8 subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CD8 subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CD8 cells, an expansion of HLA-DR+ CD8 cells and a loss of CD45RA+ CD8 cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1994

Cytotoxic T lymphocyte activity in children infected with HIV.

Of the Edinburgh cohort of approximately 130 children born to HIV-infected women, 9 are infected and alive. This article describes results from the first 18 months of a natural history study of seven of these, and two adopted children, studying the CD8 T cell-mediated cytotoxicity against HIV proteins (Gag, Tat, Pol, and Env), over time, and relating it to clinical progression and viral activity. Autologous EBV cell lines infected with vaccinia-HIV constructs were used as target cells, and bulk-cultured peripheral blood mononuclear cells as effector cells. The children ranged in age from 0 to 93 months, with six of the nine showing CTL activity to one or more HIV proteins. The specificity of the response was directed against Tat in the younger children, switching to Pol, then Gag or Env. Preliminary analysis of virological data showed no association between CTL and virus activity. The children with CTLs tended to be well clinically, but the cohort needs to be studied longer before conclusions can be made about CTL activity and HIV disease progression. Cytotoxic T lymphocyte activity has also been observed in two children diagnosed as HIV uninfected. These results show the importance of looking at CTL specificity, and may have implications in vaccine design.

Child↗
PubMed1993

Ewing's sarcoma in a child with human immunodeficiency virus (type 1) infection.

A male child with vertically transmitted human immunodeficiency virus type 1 (HIV) infection developed a Ewing's sarcoma of the left fibula at 6.1 years of age. We report the antitumour chemotherapy given and the response of the tumour. Six months after tumour diagnosis the child died of probable HIV encephalopathy. This is the first reported case of Ewing's sarcoma in an HIV-infected child.

AIDS Dementia Complex↗
PubMed1993

Measles, mumps and rubella immunisation in children at risk of infection with human immunodeficiency virus.

A retrospective serological study of 81 children at risk of HIV (II HIV-infected, 70 HIV-negative) was performed to assess susceptibility to measles, mumps and rubella and response to measles, mumps and rubella (MMR) immunisation. There was no difference in the initial serological response between the HIV-infected and HIV-negative children. Repeat serology should be performed on HIV-infected children as during follow-up antibodies may be lost. Reimmunisation should be considered for the seronegative.

Antibodies, Viral↗
PubMed1993

Cardiac dysfunction in paediatric HIV infection.

A child under long term surveillance for vertically acquired HIV-I infection developed respiratory symptoms. Dilated cardiomyopathy was diagnosed. Clinical and echocardiographic assessment of six other children with symptomatic HIV disease showed no evidence of cardiac dysfunction. The exact prevalence of this complication in paediatric HIV infection is unknown, but the potential diagnostic difficulties are highlighted.

Cardiomyopathy, Dilated↗
PubMed1993

Infrequent vertical transmission of hepatitis C virus.

The rate of vertical transmission of hepatitis C virus (HCV) was determined by a combination of assays for anti-HCV antibody and the polymerase chain reaction (PCR) in 66 children born to infected mothers. Only 4 children showed evidence of infection with HCV, being positive for anti-HCV in all samples collected from 6 months to 5 years of age. All samples from the remaining 62 children were repeatedly anti-HCV-negative on screening by two second-generation antibody assays. Furthermore, samples collected at age 12 months from 30 antibody-negative children born of HCV-infected mothers were uniformly PCR-negative, showing that "seronegative" infection with HCV was rare or absent in this study group. Serologic reactivity to HCV-encoded antigens in samples from infected children was largely confined to the HCV core protein. Infection with human immunodeficiency virus in the mother was not a significant cofactor for mother-to-child transmission of HCV.

Child, Preschool↗
PubMed1993

Dizygotic twins discordant for HIV and hepatitis C virus.

Twin girls were born at 37 weeks' gestation to a mother infected by HIV and hepatitis C virus. Twin 1 had symptomatic HIV infection by 9 months but was negative for hepatitis C virus antibody and RNA. Twin 2 became HIV antibody negative by 15 months but was positive for antihepatitis C virus and RNA.

Child↗
PubMed1992

Virus infections of the respiratory tract in HIV-infected children.

In order to determine whether the rates of respiratory viral infection and the severity of respiratory symptoms in HIV-infected children were higher than those in noninfected children, nose and throat swabs for viral isolation were taken at 3-month intervals during the first 2 years of life from 50 children born to HIV-infected women. Similar samples were obtained during the first year of life from 19 control children born to HIV seronegative mothers. Of the 50 children, five proved to be HIV-infected while 45 were presumed to be uninfected. HIV-infected children had significantly more respiratory symptoms and a higher proportion of samples from which viruses were isolated than the non-HIV-infected children. Also, more infected episodes required admission to hospital in the HIV-infected group. There was no such difference between the non-HIV-infected and the control children. Three HIV-infected children received intravenous immunoglobulin therapy. Among these the proportion of positive samples for viral isolation was greater before than after treatment began. These results suggest that HIV-infected children are more susceptible to recurrent viral infection and that passive immunotherapy may be of benefit to such children.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Vertical transmission.

Since AIDS was first described in children, much has been learnt about the epidemiology, clinical presentations and natural history of perinatally acquired HIV disease. As yet, several questions remain unanswered about the pathogenesis of vertical transmission, the relative risk associated with each mode of transmission, the rate of transmission from mother to child, and the factors that might contribute to the efficiency of transmission. Data presented thus far suggest that intrauterine exposure poses the greatest risk, but more recent reports have reopened speculation that infection could occur at or around the time of delivery. The prospects for intervention, to stop transmission from mother to child, rest on the ability to identify HIV-infected women; the knowledge of how and when the virus infects the fetus; and how to identify, as early as possible, those truly infected infants. Resources should therefore be set aside for routine screening for HIV in antenatal women. There is also a need to quantify the contribution made by intrauterine versus intrapartum events. Lastly, promising new techniques designed to detect neonatal HIV infection must be properly evaluated against standard methods, and correlated with clinical outcome. Only then can the efficacy of antiretroviral therapy be tried, to prevent vertical transmission.

Female↗
PubMed1992

Maternal antibodies to gp120 V3 sequence do not correlate with protection against vertical transmission of human immunodeficiency virus.

A retrospective study of sera from mothers infected with human immunodeficiency virus (HIV-1) was undertaken to investigate whether the titers or affinities of antibodies against the third hypervariable region (V3 loop) of gp120 correlated with transmission of the virus from mother to child. The cohort comprised 7 mothers who transmitted HIV-1 to their children and 20 who did not. Sera were screened for reactivity against two synthetic peptides, one encompassing the entire V3 loop of gp120 (amino acids 297-330) and the other containing an immunodominant epitope from gp41 (amino acids 596-614). Doubling dilutions of sera were tested to obtain antibody titers against both peptides: Anti-gp41 titers were used to normalize the anti-V3 titers. Maternal sera were also screened for the presence of high-affinity antibodies against the V3 peptide. No differences were observed in either titers or affinities of maternal antibodies to the V3 sequence from transmitters and nontransmitters.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Zidovudine therapy in combination with intravenous immunoglobulin in HIV infected children.

There is little published data on concomitant use of zidovudine and intravenous immunoglobulin (IV IgG). In this paper we review our experience of four HIV-1 infected children treated with zidovudine for periods of 19-33 months (mean 26.5 months) subsequent to starting IV IgG for period of 18-20 months (mean 19 months). In these children the only clear benefit we found was in one child who had developed HIV encephalopathy which resolved after starting zidovudine. The respective roles of zidovudine and intravenous immunoglobulin in HIV-1 infected children need to be clarified in larger comparative trials.

CD4-Positive T-Lymphocytes↗