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Biomedical subjects

J Stott

Publications and source records attributed to J Stott.

At least 19 recordsLinked to original sources
PubMed2004

The detection of psychological problems by General Practitioners--influence of ethnicity and other demographic variables.

BACKGROUND: Common mental illness in Black Africans and Black Caribbeans has been relatively little studied in the UK. Previous studies of the detection of psychological problems by General Practitioners (GPs) in these groups have been inconclusive. AIMS: The aim of this study was to investigate the prevalence, detection and management of psychological problems in General Practice among Black Caribbeans and Black Africans compared to White English attenders and to examine the relative contribution of other sociodemographic factors to these main outcome variables. METHOD: Consecutive attenders aged 16-65 years at 18 General Practitioners in South-East London completed the General Health Questionnaire (GHQ-12) before seeing the GP. The GPs rated the current emotional state of the patients at the end of each consultation. Comparison of the GHQ and GP ratings was used to compute the detection indices. RESULTS: A total of 1211 patients aged 16-65 years were approached to take part in the study. Of the patients, 75 (6%) declined or were not able to complete the GHQ. In all, 994 individuals had both GP and GHQ ratings. There was an overall probable prevalence of 37%, of which 73% were identified as cases by the GPs. Black African patients had lower rates of common mental disorders, were less likely to be detected as psychiatric cases by the GP and less likely to receive active management for their psychological problems than Black Caribbean and White English patients. Rates of prevalence, detection and management were similar between Black Caribbean and White English patients. In the multivariate analysis, ethnicity, employment and age all played a significant independent role in predicting probable prevalence. The patients' reported decision to talk to their GP about psychological problems was the main predictor of detection. Ethnicity did not independently predict detection, but Black African cases were less likely to say that they would talk to their GP about psychological problems. GPs' identification indices mirrored probable prevalence, suggesting that GPs were more sensitive to detecting psychiatric illness in individuals belonging to groups which commonly presented as symptomatic. CONCLUSIONS: The findings suggest that in General Practice the prevalence of common mental disorders, their detection and management in Black Caribbeans are similar to those in White English, but that Black Africans have lower prevalence, are less likely to be detected and are less likely to receive active management. The study of GP consulters presents problems for the interpretation of these results and it may be that Black Africans with psychological problems are less likely than their Caribbean and English counterparts to attend their GP, and less willing to speak to them about these problems when they do. Future similar studies should distinguish Black African and Black Caribbean subjects in their analyses, as categories such as 'Afro-Caribbean' may mask important differences in attitudes and illness behaviour.

Adolescent↗
PubMed2002

Resuspension of DNA sequencing reaction products in agarose increases sequence quality on an automated sequencer.

We are investigating approaches to increase DNA sequencing quality. Since a majorfactor in sequence generation is the cost of reagents and sample preparations, we have developed and optimized methods to sequence directly plasmid DNA isolated from alkaline lysis preparations. These methods remove the costly PCR and post-sequencing purification steps but can result in low sequence quality when using standard resuspension protocols on some sequencing platforms. This work outlines a simple, robust, and inexpensive resuspension protocol for DNA sequencing to correct this shortcoming. Resuspending the sequenced products in agarose before electrophoresis results in a substantial and reproducible increase in sequence quality and read length over resuspension in deionized water and has allowed us to use the aforementioned sample preparation methods to cut considerably the overall sequencing costs without sacrificing sequence quality. We demonstrate that resuspension of unpurified sequence products generated from template DNA isolated by a modified alkaline lysis technique in low concentrations of agarose yields a 384% improvement in sequence quality compared to resuspension in deionized water. Utilizing this protocol, we have produced more than 74,000 high-quality, long-read-length sequences from plasmid DNA template on the MegaBACET 1000 platform.

Cell Fractionation↗
PubMed2001

Specific proliferative T cell responses and antibodies elicited by vaccination with simian immunodeficiency virus Nef do not confer protection against virus challenge.

The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated. Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef. Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein. This immunization protocol elicited anti-Nef antibodies in all of the vaccinates as well as specific proliferative responses. However, specific cytotoxic T cell responses were not detected before virus challenge. All vaccinates were challenged intravenously with 10 MID(50) of SIVmacJ5 along with four controls. All eight subjects became infected after SIV challenge and there were no group-specific differences in virus load as measured by virus titration and vRNA analysis. The results of this study support indirectly the report from Gallimore and colleagues (Nat Med 1995;1:1667) suggesting that CD8(+) T lymphocyte responses are required for Nef-based vaccines to restrict SIV infection. If Nef-based vaccines are to be beneficial in controlling infection with immunodeficiency viruses, then it will be necessary to develop more effective immunization protocols that elicit potent CD8(+) cell responses reproducibly.

Animals↗
PubMed2001

'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo.

BACKGROUND: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use. METHODS: Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 x 104 50% tissue culture infectious doses (TCID)50 of SHIV(89.6PD). RESULTS: D2S, P2K, GD and N9 all inhibited SHIV(89.6PD) in vitro. In vivo, three out of four control macaques were infected as judged by viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four out of eight macaques pre-treated with P2K, two out of four pre-treated with D2S, one out of four pre-treated with N9, two out of four pre-treated with GD and four out of four pre-treated with D2S + GD, a combination additive in vitro. INTERPRETATION: D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence of protection in vivo, comparable to that seen with the virucide, N9. These data, together with the results of phase I and phase II studies in healthy women which have shown minimal toxicity, support plans for a phase III efficacy trial of chemically simple inhibitors of HIV entry with low toxicity, for the prevention of HIV infection in women.

Administration, Intravaginal↗
PubMed2001

The Interdisciplinary Generalist Project at the University of Nebraska Medical Center.

The Interdisciplinary Generalist Curriculum (IGC) Project at the University of Nebraska College of Medicine (Nebraska) had three goals: (1) to increase first- and second-year students' exposure to primary care practice in the community; (2) to develop specific educational programs introducing these students to the principles and practices of primary care medicine; and (3) to establish a generalist coordinating council to provide leadership and to nurture generalist educational initiatives in the College of MEDICINE: Students at Nebraska were already required to spend three half-days a semester in a longitudinal clinical experience (LCE) and to complete a three-week primary care block experience in the summer between the first and second years. IGC Project funds were used increase the number of required LCE visits to five a semester and to develop curricular enhancements that would maximize the educational potential of community-based clinical experiences for first- and second-year students. Curricular elements developed included a focus on faculty development for preceptors and development of the Primary Care Introduction to Medicine Curriculum, an eight-week, interdisciplinary module scheduled late in the first year to help prepare students for intensive summer rotations. Other developments were the implementation of a pediatric physical examination experience for first-year students and the implementation of instruction in community-oriented primary care in the second year. Lessons learned are related to: (1) the value and power of early clinical experiences; and (2) the enhancing effect of a holistic, longitudinal view of the curriculum on the planning of early clinical experiences.

Curriculum↗
PubMed2001

Mechanisms of protection induced by live attenuated simian immunodeficiency virus: III. Viral interference and the role of CD8+ T-cells and beta-chemokines in the inhibition of virus infection of PBMCs in vitro.

In this study, we investigated whether a type of retroviral interference might be one mechanism that mediates the powerful protection induced by live attenuated SIVC8. Our results show that retroviral interference could be demonstrated between SIV and SHIV-HXBc2 in human T-cell lines chronically infected with either SIVC8 or SIVJ5. Lymphocytes from macaques infected with live attenuated SIVC8 were significantly less sensitive (P < 0.05) to in vitro infection by virulent SIVJ5 and SHIV-HXBc2 than were lymphocytes from naive controls. However, this significant difference in the sensitivity of lymphocytes to virus infection was not observed for more efficiently replicating viruses such as SHIVSF33 and SIVsm3. Virus growth was significantly enhanced (P < 0.01) by depletion of CD8+ T-cells, suggesting a role for these cells in the control of SIV replication, both in vitro and in vivo. We found that levels of the beta-chemokines regulated upon activation, normal T-cell expressed and secreted, macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta did not correlate with inhibition of virus replication. Taken together, our findings do not support the hypothesis that retroviral interference is the mechanism by which live attenuated SIVC8 induces protection.

Animals↗
PubMed1999

Live attenuated SIV--a model of a vaccine for AIDS.

The experimental infection of macaques with simian immunodeficiency virus (SIV) has provided strong evidence that it may be possible to develop a vaccine against AIDS. Live attenuated SIV vaccines have been found to confer the most potent protection against challenge with a variety of pathogenic viruses. This article summarizes the work performed at NIBSC to characterize the protection conferred by live attenuated SIV and to identify mechanisms of vaccine protection. The results of these experiments are discussed in conjunction with observations from related studies made by other groups.

AIDS Vaccines↗
PubMed1998

Mechanisms of protection induced by attenuated simian immunodeficiency virus. II. Lymphocyte depletion does not abrogate protection.

To determine the role that cellular immune responses play in the protection conferred by vaccination with attenuated SIVmac32H (pC8), we have attempted to deplete macaques of their CD8+ cells prior to challenge with wild-type SIVmac32H (pJ5). In two of four pC8-infected macaques, N109 and N112, a transient partial depletion of CD8+ cells by antibody treatment was achieved. On the day of challenge peripheral CD2+CD4-CD8+ cell counts were reduced by 92 and 95%, respectively, in animals N109 and N112 and their lymph nodes revealed a 46 and 58% reduction, respectively, in CD2+CD4-CD8+ cells. Two other pC8-immunized macaques, N110 and N111, treated in the same way, did not show significant depletion of CD8+ cells. None of these four pC8-immunized animals became infected when challenged with 50 MID50 of pJ5. Treatment of a further four pC8-infected and protected macaques and two naive control animals with Campath-1H antibody successfully depleted peripheral CD3+ cell counts by >99% in all treated animals. Campath-1H depletion resulted in enhanced, longer lasting lymphoid depletion. Yet subsequent challenge with 20 MID50 of pJ5 still failed to infect the pC8-immunized animals. All eight of the naive controls, including two Campath-1H-treated animals, became infected following challenge. In summary, partial depletion of circulating CD8+ cells or total lymphocytes prior to challenge failed to abrogate the protection conferred by vaccination with pC8.

Animals↗
PubMed1998

A clinically relevant HIV-1 subunit vaccine protects rhesus macaques from in vivo passaged simian-human immunodeficiency virus infection.

OBJECTIVES: To investigate whether immunization with recombinant HIV-1 envelope protein derived from a clinical isolate could protect macaques from infection with an in vivo passaged chimeric simian-human immunodeficiency virus (SHIV). DESIGN AND METHODS: A total of 16 animals were studied from which three groups of four animals were immunized with vaccine formulations of the CC-chemokine receptor-5-binding recombinant gp120 of HIV-1W6.1D. Four weeks after the last immunization, all 16 animals were intravenously challenged with in vivo passaged SHIV derived from the same HIV-1 group B clinical isolate (W6.1D) as the vaccines. RESULTS: Vaccine protection from infection was demonstrated in 10 out of 12 macaques immunized with recombinant gp120. Complete protection from infection was achieved with all of the animals that received the SBAS2-W6.1D formulation, a potent inducer of both T-cell and humoral immune responses. Partial protection was achieved with SBAS1-W6.1D, a formulation based on immunomodulators known to induce T-cell responses in humans. In vaccinated animals that were infected, virus load was reduced and infection was delayed. CONCLUSIONS: In a relatively large number of primates, vaccine efficacy was demonstrated with a clinically relevant HIV-1 vaccine. These results reveal that it is possible to induce sterilizing immunity sufficient to protect from infection with SHIV which was passaged multiple times in vivo. Our findings have implications for current HIV-1 clinical vaccine trials and ongoing efforts to develop safe prophylactic AIDS vaccines.

AIDS Vaccines↗
PubMed1998

Candidate vaccines protect macaques against primate immunodeficiency viruses.

The preclinical evaluation of the efficacy of potential vaccines against AIDS requires challenge models. The experimental infection of macaques with simian immunodeficiency virus, human immunodeficiency virus type 2 (HIV-2) or chimeric viruses have proven to be most valuable. The progress made using simian models to assess the efficacy and identify the correlates or mechanism of protection by whole inactivated virus, live attenuated virus or recombinant sub-unit vaccines is reviewed. It is possible to conclude from these studies that an effective AIDS vaccine is feasible. Furthermore, it is likely that these different vaccine approaches protect through distinct mechanisms. These results provide a scientific basis for the development and selection of suitable candidate human AIDS vaccines for testing in humans.

AIDS Vaccines↗
PubMed1997

Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric simian/human immunodeficiency viruses in Macaca mulatta.

The use of HIV-1 env/SIVmac chimeric viruses expressing divergent HIV-1 envelopes of clinical isolates, facilitates homologous and heterologous evaluation of various recombinant HIV-1 envelope vaccine candidates in lower primates. In this study we compare the in vitro and in vivo infectivity, via intravenous (IV) and intravaginal (IVAG) routes of infection, of stocks of chimeric viruses expressing env from four different clade B HIV-1 isolates. The TCID50/ml was 7.1 x 10(4), 1.0 x 10(4), 6.3 x 10(4), and 1.2 x 10(3) for SHIVsf13, SHIVHan2, SHIVNM-3rn, and SHIVW6.1D, respectively, with a MID50/ml upon IV inoculation of 3.2 x 10(3), 3.2 x 10(4), 3.2 x 10(4), and 3.2 x 10(3), respectively. The same SHIVsf13 stock was infectious after IVAG administration, requiring a 300-fold higher virus dose. Plasma antigenemia and cell-associated viremia were generally highest at weeks 2 or 4 after infection and decreased to subdetectable levels after 8-12 weeks. All infected animals tested developed anti-HIV-1 gp120 antibodies. Inoculated virus dose showed no (linear) quantitative correlation with cellular virus load, duration of viremia, plasma antigenemia, and anti-gp120 antibody titers. No significant changes in peripheral blood CD4 cell levels were observed and none of the animals has shown evidence of disease progression to date (i.e., 13 months postinfection). Four in vivo passages of cell-associated SHIVW6.1D did not result in increased virulence. Vaccine development studies in macaques monkeys have become feasible with the use of various clade B HIV-1 env SHIV chimeras.

Animals↗
PubMed1997

Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection.

Macaques have been protected against infection with human cell-grown SIVmac by immunization with antigens encoded by the human major histocompatibility complex (MHC). Here, we investigated the efficacy of alloimmunization with simian B cells expressing high levels of MHC class I and class II molecules to confer protection against systemic challenge with simian-grown SIVmac. Eight rhesus macaques were vaccinated with glutaraldehyde-fixed and beta-propiolactone-inactivated herpesvirus papio-transformed B cells. Four of the macaques received 5 doses, the others 10. Animals were challenged with rhesus macaque spleen-derived cell-free SIVmac. Allogeneic B cells elicited antibody responses to rhesus MHC class I and II but failed to protect animals against infection. Anti-MHC class I antibodies were restricted in specificity and failed to recognize MHC class I from some B lymphoblastoid cell lines (B-LCLs) including a B-LCL from the animal in whose cells the challenge virus was grown. Vaccinated animals responded to self-MHC class I antigens but not to self-MHC class II antigens from peripheral blood mononuclear cells (PBMCs). Animals that underwent the shorter immunization regimen had transiently enhanced PBMC-associated virus loads after challenge, whereas the average virus-infected cell load was reduced in animals that underwent the more extensive immunization. These results suggest that antibody responses to allogeneic MHC molecules do not protect against infection with immunodeficiency lentiviruses.

Adoptive Transfer↗
PubMed1995

Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques.

In order to develop a successful subunit vaccine against infection with the human immunodeficiency virus (HIV), protective immune effector functions must be identified. Until now, there has been only indirect evidence that HIV-specific cytotoxic T lymphocytes (CTLs) fulfill this role. Using the macaque simian immunodeficiency virus (SIV) model, the protective potential of nef-specific CTLs, stimulated by vaccination, was examined in animals challenged with a high intravenous dose of the pathogenic simian immunodeficiency virus, SIVmac251(32H)(pJ5). An inverse correlation was found between the vaccine-induced nef-specific CTL precursor frequency and virus load measured after challenge. In addition, the early decline in viraemia, observed in both vaccinated and unvaccinated control animals was associated with the development of virus-specific CTL activity and not with the presence of virus-specific neutralizing antibodies. The results imply that vaccines that stimulate strong CTL responses could protect against HIV infection.

Animals↗
PubMed1995

School nursing. A collaborative approach to HIV/AIDS health promotion.

The involvement of school nurses in the planning, presentation and delivery of both general health education and sex education in schools in Wirral has been strengthened by the development since 1990 of the school nurses' HIV/Aids resource group. Ann Taylor and Joan Stott describe how they have worked closely with Wirral education authority personal and social education co-ordinators to devise a health promotion programme for school pupils and college students, and cascade training for school nurse colleagues, teachers and governers.

HIV Infections↗
PubMed1995

Immunization with class I human histocompatibility leukocyte antigen can protect macaques against challenge infection with SIVmac-32H.

OBJECTIVE: To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection. METHODS: HLA class I antigens were immunopurified from a human B-lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell-free SIVmac-32H. Infection was determined by polymerase chain reaction for SIVmac proviral DNA and by virus isolation. Antigen-specific humoral and cellular immune responses were monitored. RESULTS: Macaques immunized with the HLA molecules produced anti-HLA class I antibodies that inhibited SIV replication in vitro and downregulated autologous T-cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected. CONCLUSIONS: This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.

Animals↗