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Biomedical subjects

Ralph Nanan

Publications and source records attributed to Ralph Nanan.

12 recordsLinked to original sources
PubMed2006

Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells.

Abnormalities in CD4(+)CD25(+)Foxp3(+) regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the alpha chain of the interleukin-7 receptor, allows an unambiguous flow cytometry-based distinction to be made between CD127(lo) T reg cells and CD127(hi) conventional T cells within the CD25(+)CD45RO(+)RA(-) effector/memory and CD45RA(+)RO(-) naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25(+)CD127(lo) cells comprised 6.35 +/- 0.26% of CD4(+) T cells, of which 2.05 +/- 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127(lo) phenotype were highly correlated within the CD4(+)CD25(+) population. Moreover, both effector/memory and naive CD25(+)CD127(lo) cells manifested suppressive activity in vitro, whereas CD25(+)CD127(hi) cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.

Adult↗
PubMed2006

Chronic gingivitis in a new BTK mutation.

A 5-yr-old Caucasian boy with a new mutation in Bruton's tyrosine kinase (BTK) is described. Full sequencing of the BTK gene revealed a point mutation in exon 17 resulting in an amino acid change from tryptophan to serine at location 581 of the tyrosine kinase domain. Clinically the child presented with chronic gingivitis and had no prior history of bacterial infections. Whereas serum immunoglobulin M (IgM) levels were undetectable, IgG levels were in the low normal range. The gingivitis completely resolved after intravenous immunoglobulin therapy. Lymphocyte phenotyping revealed 0.05% B cells in his peripheral blood, which were IgG(-), IgM(+), IgD(+), CD38(+), CD20(+), CD27(-). However, 40% of the B cells also expressed CD5. This subpopulation of B cells has not previously been described in X-linked agammaglobulinaemia (XLA) patients. We suggest that the occurrence of CD5(+) B cells could correlate with a late onset and mild clinical presentations of XLA.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2006

Sleep disturbances in the disabled child--a case report and literature review.

Sleep disturbances in children are common. In children with intellectual disabilities sleeping problems are more common. This may result in increased burden of illness, additional parental stress, and day time behavioural difficulties. This article illustrates the problems that sleep disturbances create for children with disabilities and discusses methods for managing sleep problems.

Anticonvulsants↗
PubMed2005

Persistence of naive CD45RA+ regulatory T cells in adult life.

Regulatory T cells (TREGs) constitutively expressing CD4, CD25, and the transcription factor Foxp3 can prevent a wide range of experimental and spontaneous autoimmune diseases in mice. In humans, CD4+CD25bright T cells, predominantly within the CD45RO+ activated/memory subset in adults and the CD45RA+ naive T-cell subset in infants, are considered to be the equivalent subset. Using novel combinations of monoclonal antibodies (mAbs), we examined expression of CD25 in human infant thymus, cord blood, adult peripheral blood, lymph node, and spleen. In addition to the CD4+CD25bright T cells, subfractionation on the basis of CD45 splice variants indicated that all samples contained a second distinct population of cells expressing a slightly lower level of CD25. In adult peripheral blood, this population expressed a naive CD45RA+ phenotype. The corresponding population in lymph node, spleen, and cord blood showed some evidence of activation, and expressed markers characteristic of TREGs, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Sorted CD4+CD25+CD45RA+ T cells from both cord and adult blood expressed very high levels of mRNA for Foxp3 and manifested equivalent suppressive activity in vitro, indicating that they are bone fide members of the regulatory T-cell lineage. Targeting naive TREGs in adults may offer new means of preventing and treating autoimmune disease.

Aging↗
PubMed2005

Therapeutic potential of stem cells in perinatal medicine.

Increasing evidence suggests that stem cells have tremendous potential to facilitate repair of damaged tissue and to exert protective influences that limit the extent of damage. Their inherent capacity to respond to signals generated by damaged tissue, migrate to these regions and either replace dead tissue or deliver protection by secretion of specific growth hormones and protective factors, suggests that they might have unrivalled therapeutic potential in perinatal medicine. A further potential of stem cells is their use in gene repair strategies for genetic disorders; an application which is exceedingly interesting from a perinatal perspective. Because of the relatively small size of infants and their capacity for future growth, stem cell therapy could be more successful in newborns than in older children or adults. In practical terms, the placenta, with its large reservoir of fetal blood, offers the ideal source of autologous stem cells. This affords the opportunity for stem cells to be collected and used, either directly ex vivo or after in vitro modulation, both for disorders in the neonatal period and for those arising later in life. The organs most affected from tissue damage in the neonatal period are the brain and the lung. So far, the most promising application of stem cells might be in the treatment of neurological injury. In this review we discuss recent research findings with adult stem cell therapy and their potential use in perinatal medicine. Furthermore, specific animal models suitable to explore the patho-physiological mechanisms of stem cell transplantation after neurological injury will be discussed. This review gives an overview of basic science findings and their possible role for clinical application with regards to the therapeutic potential of stem cells in perinatal medicine. Medline was searched for journal selection in peer-reviewed journals with high impact scores, which were relevant to this topic. All articles were in English and the search was not limited by publication year. However, the oldest publication was dated 1988 (reference 1).

Animals↗
PubMed2003

Expansion of human gamma/delta T cells in vitro is differentially regulated by the measles virus glycoproteins.

Impaired proliferative response of lymphocytes after mitogenic stimulation ex vivo is a key feature of the generalized immunosuppression induced by measles virus (MV). Compelling evidence suggests that negative signalling by the MV glycoprotein (gp) complex and the surface of uninfected lymphocytes is essential for this effect. So far, the inhibitory activity of this complex applied to all lymphocyte subpopulations irrespective of the mode of stimulation and could not be overcome by external stimulation. This study shows that the isopentenyl pyrophosphate (IPP)/IL-2-stimulated expansion of human gamma/delta T cell receptor (TCR) T cells from peripheral blood mononuclear cells (PBMCs) is inhibited efficiently when the MV gp complex is expressed on the surface of persistently MV-infected T or monocytic cells. In contrast, persistently infected B cells or infected human dendritic cells (DCs) do not interfere with expansion of gamma/delta TCR T cells from PBMCs. These particular two cell populations, however, efficiently inhibit IPP/IL-2-stimulated expansion of gamma/delta TCR T cells from purified T cells and this is reverted by resubstitution with monocytes. As revealed by filter experiments, cocultivation with B cells and DCs empower monocytes, at least partially by soluble mediators, to provide membrane contact-dependent costimulatory signals that neutralize the inhibitory effect of the MV gp complex. Thus, gamma/delta TCR T cells are sensitive to MV gp-mediated inhibition; however, this is overcome efficiently by signals delivered from monocytes conditioned by B cells and DCs.

B-Lymphocytes↗
PubMed2003

Effect of antenatal corticosteroid administration on Doppler flow velocity parameters in pregnancies with absent or reverse end-diastolic flow in the umbilical artery.

OBJECTIVE: Evaluation of alterations of Doppler flow velocity waveforms after antenatal corticosteroid therapy. METHODS: Pulsatility index of the umbilical artery, middle cerebral artery and ductus venosus waveforms was measured in high-risk pregnancies complicated by umbilical AREDV directly prior to and within 24 or 48 hours after application of the first dose of a steroid treatment course. RESULTS: Return of a positive end-diastolic flow after umbilical AREDV or conversion of REDV into zero-flow was detected in 9 of 20 (45%) pregnancies after steroid application. Neither in the group which showed altered umbilical end-diastolic flow nor in the total of patients investigated was there any significant change in the PI of the umbilical artery or the ductus venosus waveforms. In contrast, there was an overall drop of pulsatility in the middle cerebral artery. CONCLUSIONS: Antenatal corticosteroid administration could increase cerebral perfusion but has no influence on umbilical and venous blood flow.

Adrenal Cortex Hormones↗
PubMed2002

Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: correlation with short-term perinatal outcome.

BACKGROUND: High perinatal morbidity and mortality rates have been reported in association with absent or reverse end-diastolic flow velocities in the umbilical artery. Doppler of fetal venous blood flow might be a helpful instrument for predicting fetal outcome. However, clinical data addressing this issue are rare. Thus, the aim of this study was to evaluate arterial and ductus venosus blood flow velocities as a predictor of short-term outcome in fetuses with umbilical absent or reverse end-diastolic flow velocities. METHODS: Thirty-five high-risk single pregnancies complicated by umbilical absent or reverse end-diastolic flow velocities were monitored by serial measurement of the pulsatility index of the umbilical artery, middle cerebral artery, and ductus venosus waveforms over a period of 1-75 days. RESULTS: The mean observation period between first detection of an umbilical absent or reverse end-diastolic flow velocity and delivery was 8.9 days. A significant correlation was found between parameters of short-term perinatal outcome (art. pH, art. base excess, development of intraventricular hemorrhage, mortality) and end-diastolic flow velocity waveform or pulsatility index of the ductus venosus waveform, but not with arterial Doppler parameters. Gestational age proved to be the best predictor for duration of assisted ventilation and development of respiratory distress syndrome. CONCLUSIONS: Our results indicate that in high-risk pregnancies with umbilical absent or reverse end-diastolic flow velocities, determination of blood flow velocities in the ductus venosus is a useful additional parameter for prediction of fetal outcome and for timing delivery.

Blood Flow Velocity↗
PubMed2002

T cell responses in acute measles.

Immune containment of measles virus (MV) infection has long been a focus of interest for investigators. An emerging theme is that MV immunity is conferred by appropriately polarized antiviral CD4+ and CD8+ T cell populations. Recent technological advances permit the analysis of the composition and dynamics of these CD4+ and CD8+ T cell responses at the single cell level, and of the molecular events responsible for their induction. Novel insights into these issues for measles are discussed in the light of their importance for the development of an improved vaccine.

Antigen Presentation↗
PubMed2001

Measles virus and canine distemper virus target proteins into a TAP-independent MHC class I-restricted antigen-processing pathway.

After infection of CEM174.T2 cells [deficient for the transporter of antigen presentation (TAP)] with measles virus (MV) the nucleocapsid protein is recognized by L(d)-restricted cytotoxic T cells in a TAP-independent, chloroquine-sensitive fashion. Presentation via the TAP-independent pathway requires virus replication. During MV infection of the cell the nucleocapsid as well as the matrix protein enter the endolysosomal compartment as indicated by colocalization with the lysosomal-associated membrane protein 1 (LAMP-1). Similarly, the nucleocapsid protein of canine distemper virus (CDV) is recognized in a TAP-independent fashion. In addition, a recombinant MV expressing bacterial beta-galactosidase protein is able to introduce the recombinant antigen into the TAP-independent pathway whereas a vaccinia virus expressing beta-galactosidase is not. These data and a report about TAP-independent recognition of parainfluenza virus type 1 suggest that members of the Paramyxoviridae family regularly introduce viral proteins into the TAP-independent antigen-processing pathway.

Animals↗
PubMedDate not supplied

Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: longitudinal analysis.

OBJECTIVE: To evaluate alterations of arterial and ductus venosus blood flow velocities during deterioration and their interdependence. METHODS: 37 high-risk pregnancies complicated by umbilical absent or reverse end-diastolic flow velocities (AREDV) were monitored by measurement of the pulsatility index of the umbilical artery, middle cerebral artery and ductus venosus waveforms. RESULTS: The mean observation period was 16.5 days. There was a significant change in the pulsatility of waveforms in all vessels over the observation period. Compared with the ductus venosus, pulsatility of waveforms in the middle cerebral artery diverged from the normal range 2.2 weeks earlier. Increase in pulsatility in the umbilical artery was concomitant with venous but not with cerebral flow alterations. In addition, there was a correlation between the increase of venous but not arterial pulsatility and perinatal acidemia. Variability of pulsatility index values of the umbilical artery and the ductus venosus but not of the middle cerebral artery increased towards delivery. CONCLUSIONS: Ductus venosus Doppler allows detection of further deterioration in centralized fetuses with umbilical AREDV. However, striking short-term variability has to be taken into account when considering this parameter.

Blood Flow Velocity↗