Characterization and functionality of cell surface molecules on human mesenchymal stem cells.

We have characterized adhesion molecules on the surface of multipotential human mesenchymal stem cells (hMSCs) and identified molecules whose ligands are present on mature hematopoietic cells. Flow cytometric analysis of hMSCs identified the expression of integrins: alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta4, in addition to ICAM-1, ICAM-2, VCAM-1, CD72, and LFA-3. Exposure of hMSCs to IL-1alpha, TNFalpha or IFNgamma up-modulated ICAM-1 surface expression, whereas only IFNgamma increased both HLA-class I and -class II molecules on the cell surface.

Outcomes of pregnancies diagnosed with Klinefelter syndrome: the possible influence of health professionals.

Objective: To describe the association between the outcomes of pregnancies diagnosed with Klinefelter syndrome (KS) and the specialty of the health professional providing pre- and post-diagnostic counselling.

Method: Data were extracted from the case notes of the 111 cases of KS diagnosed prenatally between 1986 and 1997 in eight geographical regions in five European countries. The data extracted included: outcome of pregnancy, maternal age, social class, parity, gestational age at diagnosis, year of diagnosis and specialties of the health professionals conducting pre- and post-diagnosis consultations.

Counselling following the Prenatal Diagnosis of Klinefelter Syndrome: Comparisons between Geneticists and Obstetricians in Five European Countries.

Objective: To describe and compare the information obstetricians and geneticists in five European countries report they would give following the prenatal diagnosis of Klinefelter syndrome. Methods: 388 obstetricians and 269 geneticists from Germany, the Netherlands, Portugal, Spain and the UK completed a brief questionnaire assessing two variables: the information they reported providing to parents following the prenatal diagnosis of Klinefelter syndrome (categorized as positive or negative); and their perceptions of the quality of life with the condition. Results: Geneticists were more likely than obstetricians to report providing more positive than negative information about Klinefelter syndrome than equal amounts of positive and negative information or more negative than positive information about the condition (excess positive information).

Evaluation of coxsackievirus infection in children with human immunodeficiency virus type 1-associated cardiomyopathy.

In a matched case-control study of the association between coxsackieviruses and cardiac impairment, 24 human immunodeficiency virus (HIV) type 1-infected children with cardiac impairment were compared with 24 HIV-1-infected control subjects. Serologic evidence of coxsackievirus infection was present in all children, with no significant difference in geometric mean antibody titers between case patients and control subjects. Conditional logistic regression to test for an association between coxsackievirus antibody titer and the presence or absence of cardiac impairment, by any indicator, showed an odds ratio of 1.

Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV transmission.

A case-control design study was used to investigate the association of maternal HIV-1 phenotype in MT-2 cells at or near the time of delivery with perinatal transmission of HIV-1, controlling for maternal CD4 percentage and duration of rupture of membranes, in 48 transmitting and 96 non-transmitting HIV-1-infected mothers who gave birth between 1990 and 1995. The non-syncytium-inducing (NSI) phenotype was more commonly seen in transmitting mothers compared with non-transmitting mothers (90% vs. 75%, p =.

Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy.

Background: Human immunodeficiency virus (HIV)-infected children often suffer from impaired growth. Highly active antiretroviral therapy (HAART) successfully reduces HIV 1 (HIV-1) RNA to 400 copies/mL or less in many children.

Objectives: To determine if age- and sex-adjusted growth z scores correlate with HIV-1 RNA level and if control of viral load for 48 and 96 weeks results in improved growth in children receiving highly active antiretroviral therapy.

Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection.

Background: The efficacy and tolerance of switching from zidovudine (ZDV) and lamivudine (3TC) in clinically stable HIV-infected children with incomplete viral suppression to stavudine (d4T), nevirapine (NVP) and ritonavir (RTV) has not been determined. Aim. To evaluate the safety, tolerance, antiviral activity and immunologic changes after the change to a three drug combination.

Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.

Objective: Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various components of the marrow microenvironment, such as bone, adipose, and stromal tissues. The bone marrow microenvironment is vital to the development, differentiation, and regulation of the lymphohematopoietic system. We hypothesized that the activities of MSCs in the bone marrow microenvironment might also include immunomodulatory effects on lymphocytes.

Mesenchymal stem cells: stealth and suppression.

Human post-natal bone marrow contains mesenchymal stem cells (MSCs), which are capable of giving rise to multiple mesenchymal cell lineages. Large quantities of human MSCs can be readily obtained following a simple bone marrow aspiration procedure and subsequent expansion over a million-fold in culture. This extensive capacity for clinical scale expansion in vitro has facilitated the development of preclinical models as well as clinical studies designed to assess the safety, feasibility, and efficacy of transplanting allogeneic MSCs for a variety of indications.

Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation.

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia.

Establishment of Arabidopsis thaliana ribosomal protein RPL23A-1 as a functional homologue of Saccharomyces cerevisiae ribosomal protein L25.

Arabidopsis thaliana ribosomal protein (r-protein) RPL23A-1 shows 54% amino acid sequence identity to the Saccharomyces cerevisiae equivalent r-protein, L25. AtRPL23A-1 also shows high amino acid sequence identity to members of the L23/L25 r-protein family in other species. R-protein L25 in S.

Evolution and transmission of stable CTL escape mutations in HIV infection.

Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression.

Population pharmacokinetics of dapsone in children with human immunodeficiency virus infection.

Background: Previous studies of dapsone pharmacokinetics in children have been too small to allow assessment of the relationships between dapsone pharmacokinetic parameters and patient characteristics or markers of efficacy and toxicity.

Methods: We used population analysis to estimate dapsone pharmacokinetic parameters in children participating in a phase I/II study of daily and weekly dapsone in children with human immunodeficiency virus (HIV) infection. With use of the program NONMEM and a 1-compartment open model, the influence of demographic and clinical characteristics on oral clearance (CL/F) and oral volume of distribution (V/F) were examined.

The effect of protease inhibitor therapy on growth and body composition in human immunodeficiency virus type 1-infected children.

Objective: To determine the effect of protease inhibitors (PIs) on growth and body composition in children with human immunodeficiency virus type 1 (HIV-1) infection.

Background: HIV-1-infected children have chronic problems with both linear growth and weight gain. Viral load may directly influence growth and nutritional status of HIV-1-infected children with reduction of viral load improving the nutritional condition.

Localization of ulnar neuropathy with conduction block across the elbow.

We performed short segment incremental stimulation on 13 consecutive patients with ulnar neuropathy across the elbow (UNE) and conduction block. Conduction block occurred proximal to the medial epicondyle in 62%, at the epicondyle in 23%, and below the elbow in 15%. The ulnar nerve may be more prone to external compression above the elbow than previously recognized.

Evaluation of immune survival factors in pediatric HIV-1 infection.

Peripheral blood CD4+ and CD8+ T cells, CD19+/20+ B cells, and serum immunoglobulins (Igs) have been implicated as survival factors for pediatric HIV-1 infection. To determine which of these immune factors might be important in predicting survival, we studied HIV-1 vertically infected (HIV-1+) children over a 5-year period. Peripheral blood lymphocytes and Igs were measured in 298 HIV-1+ children, who were classified as survivors or nonsurvivors, and in 463 HIV-1 vertically exposed and noninfected (HIV-1-) children.

Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and children.

The highly sensitive quantitation of virus-specific CD8(+) T cells using major histocompatibility complex-peptide tetramer assays has revealed higher levels of cytotoxic T lymphocytes (CTLs) in acute and chronic virus infections than were recognized previously. However, studies in lymphocytic choriomeningitis virus infection have shown that tetramer assays may include measurement of a substantial number of tetramer-binding cells that are functionally inert. Such phenotypically silent CTLs, which lack cytolytic function and do not produce interferon (IFN)-gamma, have been hypothesized to explain the persistence of virus in the face of a quantitatively large immune response, particularly when CD4 help is impaired.

A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators.

Background: The optimal duration of zidovudine administration to prevent perinatal transmission of human immunodeficiency virus type 1 (HIV-1) should be determined to facilitate its use in areas where resources are limited.

Methods: We conducted a randomized, double-blind equivalence trial of zidovudine starting in the mother at 28 weeks' gestation, with 6 weeks of treatment in the infant (the long-long regimen), which is similar to protocol 076; zidovudine starting at 35 weeks' gestation, with 3 days of treatment in the infant (the short-short regimen); a long-short regimen; and a short-long regimen. The mothers received zidovudine orally during labor.

Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group.

Background: Perinatal exposure to zidovudine may cause cardiac abnormalities in infants. We prospectively studied left ventricular structure and function in infants born to mothers infected with the human immunodeficiency virus (HIV) in order to determine whether there was evidence of zidovudine cardiac toxicity after perinatal exposure.

Methods: We followed a group of infants born to HIV-infected women from birth to five years of age with echocardiographic studies every four to six months.

Prospective 5-year study of peripheral blood CD4, CD8, and CD19/CD20 lymphocytes and serum Igs in children born to HIV-1 women. The P(2)C(2) HIV Study Group.

Background: Peripheral blood CD4(+) and CD8(+) T cells, CD19(+)/20(+) B cells, and serum Igs are known to be altered by the progression of pediatric HIV-1 infection, but their evaluation as predictors of survival needs further definition.

Objective: To determine the natural history of these immune factors and their importance in predicting survival, we studied 298 HIV-1 vertically infected (HIV-1(+)) children over a 5-year period.

Methods: These immune factors and serum HIV-1 RNA levels were measured in two groups: (1) a birth cohort of children enrolled up to age 28 days postnatally, including 93 HIV-1(+) and 463 HIV-1 uninfected infants (HIV-1(-)), and (2) an older cohort of 205 HIV-1(+) children enrolled after the age of 28 days, who were classified as survivors or nonsurvivors.

Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay.

Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays.

Characterization of a novel respiratory syncytial virus-specific human cytotoxic T-lymphocyte epitope.

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in childhood worldwide. The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. This HLA B7-restricted epitope in nucleoprotein (NP) was detectable in four healthy, B7-positive adult subjects using B7-RSV-NP tetrameric complexes to stain CD8(+) T cells.