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Biomedical subjects

P Sissons

Publications and source records attributed to P Sissons.

12 recordsLinked to original sources
PubMed2002

Randomized controlled trial of the Alexander technique for idiopathic Parkinson's disease.

OBJECTIVE: To determine whether the Alexander Technique, alongside normal treatment, is of benefit to people disabled by idiopathic Parkinson's disease. DESIGN: A randomized controlled trial with three groups, one receiving lessons in the Alexander Technique, another receiving massage and one with no additional intervention. Measures were taken pre- and post-intervention, and at follow-up, six months later. SETTING: The Polyclinic at the University of Westminster, Central London. SUBJECTS: Ninety-three people with clinically confirmed idiopathic Parkinson's disease. INTERVENTIONS: The Alexander Technique group received 24 lessons in the Alexander Technique and the massage group received 24 sessions of massage. MAIN OUTCOME MEASURES: The main outcome measures were the Self-assessment Parkinson's Disease Disability Scale (SPDDS) at best and at worst times of day. Secondary measures included the Beck Depression Inventory and an Attitudes to Self Scale. RESULTS: The Alexander Technique group improved compared with the no additional intervention group, pre-intervention to post-intervention, both on the SPDDS at best, p = 0.04 (confidence interval (CI) -6.4 to 0.0) and on the SPDDS at worst, p = 0.01 (CI -11.5 to -1.8). The comparative improvement was maintained at six-month follow-up: on the SPDDS at best, p = 0.04 (CI -7.7 to 0.0) and on the SPDDS at worst, p = 0.01 (CI -11.8 to -0.9). The Alexander Technique group was comparatively less depressed post-intervention, p = 0.03 (CI -3.8 to 0.0) on the Beck Depression Inventory, and at six-month follow-up had improved on the Attitudes to Self Scale, p = 0.04 (CI -13.9 to 0.0). CONCLUSIONS: There is evidence that lessons in the Alexander Technique are likely to lead to sustained benefit for people with Parkinson's disease.

Activities of Daily Living↗
PubMed2000

Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors.

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8(+) T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8(+) T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in "fresh" killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.

CD8-Positive T-Lymphocytes↗
PubMed1996

Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors.

The cellular sites and mechanisms of human cytomegalovirus (HCMV) latency are still poorly defined. Although evidence suggests that peripheral blood monocytes are one site of latency in the healthy carrier, it is unlikely that monocytes represent a site of primary HCMV infection. Consequently, we have analysed CD34+ bone marrow progenitors, precursors of monocytes, to determine whether they are a site of HCMV carriage in normal virus carriers. For the first time, we demonstrate the presence of endogenous HCMV within bone marrow progenitors in the absence of HCMV lytic gene expression. These findings are consistent with previous evidence showing that the permissiveness of myeloid cells for HCMV is critically dependent on the differentiation state of the cell.

Antigens, CD34↗
PubMed1996

Analysis of the human env-specific cytotoxic T-lymphocyte (CTL) response in natural human immunodeficiency virus type 1 infection: low prevalence of broadly cross-reactive env-specific CTL.

Major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to persistent virus infections. Candidate vaccines against human immunodeficiency virus type 1 (HIV-1) should elicit broad cross-reactive immunity to confer protection against different strains of HIV-1. As it is likely that candidate vaccines will include the envelope gene product Env, we determined the proportion of CTL clones which recognized variable and conserved determinants in three env variants during natural infection. Limiting dilution analysis was used to characterize numerous short-term CTL clones derived from peripheral blood of HIV-1-infected subjects, using split-well analysis to assay cytotoxicity against target cells expressing gp160env of HIV-1 strains IIIB, MN, and RF. In 9 of 12 HIV-1-infected subjects, at the clonal level most env-specific CTL recognized determinant(s) within one env variant but not in the other variants. In some subjects, CTL recognized multiple nonconserved determinants in different variants. The pattern of recognition of different env variants was relatively stable over time. In most of the patients studied, the proportion of CTL which showed cross-recognition of conserved determinants shared among the three strains was low. Two novel CTL epitopes within gp41 were identified by using 15-mer peptides of the HIV-SF2 sequence. When specific peptide was used to stimulate CTL precursors in vitro, the frequency of peptide-specific CTL precursors was very high, but the CTL elicited by this stimulation were highly strain specific. We conclude that the use of a single HIV env variant to detect CTL activity can underestimate the magnitude and complexity of the env-specific CTL response. The low prevalence of CTL clones which show cross-recognition of conserved determinants may have implications for immunization strategies based solely on env; to elicit broadly cross-reactive CTL other, more conserved viral antigens are likely to be needed in addition to env. Because of its capacity to distinguish CTL responses against different virus strains, limiting dilution analysis is particularly appropriate to quantitate the immune responses generated by candidate env-based vaccines.

Adult↗
PubMed1996

Latent and persistent infections of monocytes and macrophages.

Human cytomegalovirus (HCMV), like all herpesviruses, persists in the host after primary infection, with reactivation often occurring as a result of immunosuppression. The lack of a model system has made analysis of HCMV latency and reactivation difficult. However, the ability to analyse which specific cell types in vivo carry the virus and the relative levels of permissiveness of these cell types for viral gene expression and productive infection is beginning to help us understand these complex molecular events.

Animals↗
PubMed1994

Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers.

Monocytes are one site of carriage of the human cytomegalovirus (HCMV) genome in healthy human carriers. However, as there are conflicting data detailing the level of HCMV gene expression during persistence in these cells, we have analyzed monocytes for evidence of viral immediate-early, early, and late transcription by using reverse transcription followed by PCR. We were unable to find evidence of HCMV lytic gene transcription in freshly isolated peripheral blood monocytes from HCMV-seropositive subjects. However, as differentiation of monocytes to monocyte-derived macrophages results in increased permissiveness to infection with HCMV in vitro, we examined whether such differentiation could result in reactivation of endogenous viral gene expression. Here we show that in vitro differentiation of monocytes does result in expression of endogenous HCMV immediate-early genes. Although this differentiation led to reactivation of endogenous viral immediate-early expression, we were unable to detect any early or late viral transcription. Cocultivation experiments correlated with this level of gene induction, as no productive infection was detected. These data strongly suggest a mechanism of persistence of HCMV in the peripheral blood that is independent of HCMV lytic gene expression and that initial phases of lytic gene expression in monocytes can be induced by differentiation of these cells to monocyte-derived macrophages.

Adult↗
PubMed1993

Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease.

Major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to human persistent virus infections. Measurements of the frequency and specificity of human immunodeficiency virus type 1 (HIV-1)-specific CTL and their variation with time may indicate their relative importance in modulating the progression of HIV-1 infection. We have used limiting dilution analysis (LDA) to derive quantitative estimates of the frequency of HIV-1-specific CTL precursors in a cross-sectional study of 23 patients at different clinical stages of HIV-1 infection and to compare these with the frequency of CTL precursors specific for another persistent virus (Epstein-Barr virus [EBV]) in the same patients. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous HIV-1-infected lymphoblasts and assayed for cytotoxicity in 51Cr release assays against autologous and MHC-mismatched lymphoblastoid B cells infected with recombinant vaccinia viruses expressing the three HIV-1 structural gene products. The frequency of MHC-restricted precursors was high in asymptomatic HIV-1-infected patients (env-specific CTL precursors up to 73/10(6) PBMC; gag-specific CTL precursors up to 488/10(6) PBMC), although the relative frequency against the different structural gene products varied from patient to patient. The HIV-1-specific CTL precursor frequency was reduced in patients who had more severe (< 400/microliters) CD4+ lymphocyte depletion, while in the majority of such patients the frequency of CTL precursors against EBV was maintained at levels observed in healthy controls. Direct CTL activity in unstimulated PBMC was observed in three of nine patients but no correlation was found between the presence of an activated CTL response and the magnitude of the CTL response detected after stimulation in LDA. Thus, CTL precursors were detected against all three HIV-1 structural gene products in patients with CD4+ lymphocyte counts > 400/microliters, at frequencies that are high compared with those reported for other persistent viruses. A CTL response directed against multiple protein antigens of HIV-1 may protect the patient against epitope variation. The fact that the EBV-specific CTL precursor frequencies were maintained in advanced HIV-1 infection suggests that there may be selective impairment of the HIV-1-specific CTL response associated with disease progression.

Adult↗
PubMed1989

Urokinase: a treatment for relapsing peritonitis due to coagulase-negative staphylococci.

Four consecutive patients with relapsing peritonitis due to coagulase-negative staphylococci have been successfully treated by the addition of urokinase to their treatment regime, having failed to respond to appropriate antibiotic therapy alone. The organisms isolated from each episode of peritonitis in an individual patient were shown to be identical by antibiotic sensitivity, phage typing, slime production and immunoblot analysis. The action of urokinase is unknown but it may act by fibrinolysis, allowing antibiotics access to a source of infection previously protected by fibrin. The technique described is a simple, safe and effective treatment of relapsing peritonitis due to coagulase-negative staphylococci, and its use can markedly reduce the morbidity associated with this infection.

Bacterial Typing Techniques↗
PubMed1987

Immunoaffinity purification of a 72K early antigen of human cytomegalovirus: analysis of humoral and cell-mediated immunity to the purified polypeptide.

An early antigen of human cytomegalovirus (HCMV) was purified from infected cells as a 72K polypeptide by immunoaffinity chromatography using a monoclonal antibody. It was located in both nucleus and cytoplasm, and was non-glycosylated and undetectable on the surface of infected cells. Known seropositive subjects had antibody against the purified protein and it elicited proliferative T cell responses in 10 of 16 subjects. Five of 14 T cell lines established in response to the purified protein were predominantly CD8+ and of these two showed major histocompatibility complex-restricted cytotoxicity against HCMV-infected cells. This provides further evidence that antigens expressed at early times may be targets for the immune response during persistent HCMV infection.

Antibody Formation↗