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Biomedical subjects

L Borysiewicz

Publications and source records attributed to L Borysiewicz.

11 recordsLinked to original sources
PubMed2001

Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer.

Cervical cancer is the second most common cause of cancer death in women worldwide. It is almost invariably associated with infection with human papilloma virus (HPV) particularly types 16 and 18. The ubiquitous expression of E6 and E7 oncogene products has been recognised as an attractive target for CTL-mediated immunotherapy. In-vivo expansion of an HPV oncogene product specific MHC class 1 restricted response has been demonstrated using intradermally administered live vaccinia virus HPV 16 and 18 E6/E7 gene construct (TA-HPV, Cantab Pharmaceuticals). Responses have been seen in 1/3 evaluable patients with advanced cervical cancer, and 3/12 CIN3 volunteers, and in 4/29 patients with early invasive cervical cancer (Rankin et al. Proceedings of 91st AACR Meeting, San Francisco, April 2000). In addition, the adoptive transfer of ex vivo HPV 16 or 18 positive autologous tumour lysate pulsed dendritic cells is currently being tested as an alternative means of expanding HPV specific CTL in advanced cervical cancer patients. So far an HLA-A*O201 restricted CD8 T cell response has been recorded in the single HLA-A*O201 patient whose tumour was shown to be HPV16 positive. It appears therefore feasible to induce HPV specific CTL responses in patients with cervical cancer using several vaccine strategies. However, further clinical trials are needed to determine the full anti-tumour potential of this vaccine based immunotherapy.

Adoptive Transfer↗
PubMed1999

Acute fatigue in chronic fatigue syndrome patients.

BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding. METHODS: Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks. RESULTS: CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session. CONCLUSIONS: The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease.

Acute Disease↗
PubMed1996

Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome.

BACKGROUND: There is a need for a valid self-rating questionnaire to screen for psychiatric morbidity in patients with chronic fatigue syndrome (CFS). This study had the aim of assessing the utility and validity of two commonly used measures. METHOD: Scores obtained on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were compared with various diagnostic and severity ratings obtained via a validating clinical interview, the Schedules for the Clinical Assessment of Neuropsychiatry (SCAN) in 95 consecutively referred subjects at a medical out-patient clinic who fulfilled standard criteria for CFS, and 48 healthy controls. Outcome measures were validating coefficients and receiver operating characteristics (ROC) for different thresholds and scoring on GHQ and BDI and index of definition (ID) as measured by SCAN; and Pearson and point by serial correlation coefficients for different diagnostic groups derived via SCAN and defined according to ICD-10 and DSM-III-R. RESULTS: GHQ and BDI perform poorly as screeners of psychiatric morbidity in CFS subjects when compared with various SCAN derived ratings although results for controls are comparable with other studies. CONCLUSIONS: Neither the GHQ nor BDI alone can be recommended as screeners for psychiatric morbidity in CFS subjects.

Fatigue Syndrome, Chronic↗
PubMed1995

Neuraesthenia revisited: ICD-10 and DSM-III-R psychiatric syndromes in chronic fatigue patients and comparison subjects.

BACKGROUND: Different definitions of chronic fatigue syndrome (CFS) have different psychiatric exclusion criteria and this affects the type and frequency of associated psychiatric morbidity found. The operational criteria for neuraesthenia in ICD-10 vary in this and other respects from the Centers for Disease Control and Prevention (CDC) criteria for CFS. Neuraesthenia and associated psychiatric morbidity in CDC-defined CFS are evaluated. METHOD: CFS subjects and controls were interviewed with the Schedule for the Clinical Assessment of Neuropsychiatry (SCAN). The computerised scoring program for SCAN (CATEGO5) facilitates the assignment of operational definitions according to DSM-III-R and ICD-10. Subjects were re-interviewed with SCAN an average of 11 months later. No specific treatments or interventions were given during this period. RESULTS: The majority of subjects fulfilled ICD-10 operational criteria for neuraesthenia and had two and a half times the rate of psychiatric morbidity as the healthy comparison group according to the CATEGO5 Index of Definition (ID). Approximately 80% of subjects fulfilled both DSM-III-R and ICD-10 criteria for sleep disorders. There was a significant fall in the number of subjects fulfilling criteria for depression and anxiety disorders and a significant increase in the number of subjects with no diagnosis for DSM-III-R criteria over time. There were no significant changes over time for any diagnosis according to ICD-10 criteria or for overall levels of psychopathology as reflected in CATEGO5 ID levels. CONCLUSIONS: The ICD-10 'neuraesthenia' definition identifies almost all subjects with CDC-defined CFS. Fifty percent of CFS subjects also had depressive or anxiety disorders, some categories of which remit spontaneously over time.

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↗
PubMed1990

Induction of immunoglobulin G Fc receptors by recombinant vaccinia viruses expressing glycoproteins E and I of herpes simplex virus type 1.

Glycoprotein E (gE) of herpes simplex virus type 1 (HSV-1) will bind immunoglobulin G (IgG) (Fc) affinity columns (R. B. Bauke and P. G. Spear, J. Virol. 32:779-789, 1979), but recent evidence suggests that the HSV-1 Fc receptor is composed of a complex of gE and glycoprotein I (gI) and that both gI and gE are required for Fc receptor activity (D. C. Johnson and V. Feenstra, J. Virol. 61:2208-2216, 1987; D. C. Johnson, M. C. Frame, M. W. Ligas, A. M. Cross, and N. D. Stow, J. Virol. 62:1347-1354, 1988). We have expressed gE and gI, either alone or in combination, on the surface of HeLa cells by using recombinant vaccinia viruses and have measured Fc receptor activity by Fc-rosetting or IgG-binding assays. Expression of gE alone resulted in the induction of Fc receptor activity, while expression of gI alone gave no detectable Fc binding. Coexpression of gE and gI resulted in higher levels of IgG binding than did expression of gE alone, despite the fact that under conditions of coexpression, the levels of surface gE were reduced. We propose that gE and gI together form a receptor of higher affinity than gE alone and that HSV-1 therefore has the potential to induce two Fc receptors of different affinities.

Animals↗
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↗
PubMed1987

Circulating T-cell populations during mercuric chloride-induced nephritis in the Brown Norway rat.

Fluorescence-activated cell sorter analysis was used to study the peripheral lymphocyte populations during mercuric chloride (HgCl2)-induced autoimmune nephritis in the Brown Norway (BN) rat. Sequential studies showed a transient loss of T cells from peripheral blood attributable to decreases in the percentage of T-helper cells. In addition, there was a decrease in the percentage of T-cytotoxic/suppressor cells prior to the appearance of circulating anti-GBM antibodies, followed by elevated levels of T-suppressor cells during down-regulation of the response. This method may allow closer inspection of the events linking changes in T-cell populations and induction and termination of an autoimmune response.

Animals↗