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At least 703 records · Page 39Linked to original sources
PubMed1981

T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases.

Progressive growth of the P815 mastocytoma in semisyngeneic mice evokes the generation of a T cell-mediated mechanism of immunosuppression that inhibits the capacity of passively transferred, tumor-sensitized T cells from regressing this tumor in recipient mice. This conclusion is based on two findings: (a) that it is possible to demonstrate adoptive T cell-mediated regression of established tumors, but only if the tumors are growing in T cell-deficient recipients, and (b) that adoptive T cell-mediated regression of tumors in these recipients can be inhibited by the infusion of splenic T cells from T cell-intact, tumor-bearing donors. The results of additional experiments designed to measure the effect of decreasing the number of suppressor cells and the time that they are infused, relative immune cells, indicate that the function of suppressor cells in this model is to inhibit the replication of passively transferred immune T cells. The results obtained with the P815 mastocytoma are similar to those obtained previously with a chemically induced fibrosarcoma. They show, in addition, that passively transferred immune cells are capable of destroying already seeded metastases in T cell-deficient recipients.

Animals↗
PubMed2001

Reservoirs of human immunodeficiency virus type 1: the main obstacles to viral eradication.

Highly active antiretroviral therapy (HAART) has led to profound decreases in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected persons, at least in the developed world. Many infected persons have plasma levels of HIV-1 RNA that are less than the limits of detection of most clinical assays as a result of combination antiretroviral therapy. Nonetheless, HIV-1 has not been eradicated by HAART. This has been shown to be because of latent HIV-1 replication-competent provirus in resting CD4+ T lymphocytes, cryptic viral replication below the limits of detection of most clinical assays, and, possibly, the presence of viral sanctuary sites. An understanding of these reservoirs for HIV-1 in the setting of virally suppressive HAART will be critical for the development of new approaches to induce HIV-1 remissions and for the exploration of the possibility of viral eradication in the future.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Prospects for a group A streptococcal vaccine: rationale, feasibility, and obstacles--report of a National Institute of Allergy and Infectious Diseases workshop.

Infections due to group A streptococci (GAS) represent a public health problem of major proportions in both developing and developed countries. Currently available methods of prevention are either inadequate or ineffective, as attested to by the morbidity and mortality associated with this ubiquitous pathogen worldwide. Advances in molecular biology have shed new light on the pathogenesis of GAS infections and have identified a number of virulence factors as potential vaccine targets. Therefore, the National Institute of Allergy and Infectious Diseases convened an expert workshop in March 2004 to review the available data and to explore the microbiologic, immunologic, epidemiologic, and economic issues involved in development and implementation of a safe and effective GAS vaccine. Participants included scientists and clinicians involved in GAS research, as well as representatives of United States federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, Department of Defense, and National Institute of Allergy and Infectious Diseases), the World Health Organization, and the pharmaceutical industry. This report summarizes the deliberations of the workshop.

Developed Countries↗
PubMed2005

Microbicides to prevent HIV transmission: overcoming obstacles to chemical barrier protection.

BACKGROUND: Microbicides are topical compounds that could prevent sexually transmitted infections. Several compounds have demonstrated activity both in vitro and in animal models, but none has been approved for use in humans. METHODS: A review of >100 recent publications from MEDLINE (through October 2005) and abstracts presented at recent conferences was undertaken to describe the current status of microbicide research and to delineate why microbicides are not yet available. RESULTS: More than 15 candidate microbicides are currently being studied in clinical trials. Their mechanisms of action include disruption of the viral membrane by surfactants, maintenance of an acidic vaginal pH, binding to the viral envelope to block receptor binding, and blocking of receptors; they may also be combined with antiretroviral drugs. The development of safe and effective microbicides has been delayed by limitations in understanding the biological processes of human immunodeficiency virus (HIV) transmission, difficulties in extrapolation from animal models, lack of established correlates of protection, and the need to enroll and follow large cohorts of high-risk participants for several years in order to demonstrate efficacy. CONCLUSIONS: Safe and effective topical microbicides are biologically plausible. Several trials that are under way may demonstrate the ability of microbicides to protect against transmission of HIV, but multiple challenges remain.

Administration, Intravaginal↗
PubMedDate not supplied

Vaccines: obstacles and opportunities from discovery to use.

Since smallpox, vaccine-development programs have varied, yet common elements exist. Investment in vaccine research and development depends on epidemiology, market size, funding, and liability. Fear of liability inhibits innovation, adaptation of existing methods, and regulatory decision-making. Vaccine evaluation proceeds from animal and in vitro studies to controlled human clinical trials. Successive stages provide the information base necessary for decisions on vaccine approval for general use, but sociopolitical forces can affect the process. The World Health Organization establishes nonbinding international norms for vaccine acceptability that are adopted by many countries. Concerns for purity and safety need to be addressed along with cost and vaccine availability. For example, replacement of brain tissue-derived rabies vaccine in developing countries with a continuous cell line-derived vaccine is possible if purity is balanced in relation to safety. Substantially reducing the toll of infectious diseases will require cooperation and common-sense decisions.

Animals↗
PubMed2003

Obstacles to implementing research outcomes in community settings.

PURPOSE: In contrast to controlled laboratory- or clinic-based research that can fail to capture the real-world behaviors of older adults, field research offers the best opportunity for ecological validity. However, the tradeoff inherent in field studies is the potential sacrifice of scientific rigor. Applied research presents a unique set of challenges that vary with context. This article discusses these challenges along with possible solutions. DESIGN: Examples are drawn from an ongoing, longitudinal Roybal Center study of driving competence that is being conducted in Department of Motor Vehicles field sites. The challenges faced at each stage of the project are discussed. METHOD: Methodological issues include identifying field collaborators, approaching administrators with the research proposal, producing a battery that is manageable and acceptable while maintaining scientific merit, training indigenous personnel to administer this battery, introducing the research and consenting potential participants, and managing large data sets offsite. Additional issues include quality control, the importance of distinguishing between individuals who consent and those who decline participation, and the collection of follow-up data via telephone. IMPLICATIONS: The use of field research in changing public perceptions, medical practice, and public policy is discussed.

Aged↗
PubMed2002

Implementation of a teacher-delivered sex education programme: obstacles and facilitating factors.

Interventions are unlikely to achieve their desired aims unless they are implemented as intended. This paper focuses on factors that impeded or facilitated the implementation of a specially designed sex education programme, SHARE, which 13 Scottish schools were allocated to deliver in a randomized trial. Drawing on qualitative and quantitative data provided by teachers, we describe how this intervention was not fully implemented by all teachers or in all schools. Fidelity to the programme was aided by intensive teacher training, compatibility with existing Personal and Social Education (PSE) provision, and senior management support. It was hindered by competition for curriculum time, brevity of lessons, low priority accorded to PSE by senior management, particularly in relation to timetabling, and teachers' limited experience and ability in use of role-play. The nature of the adoption process, staff absence and turnover, theoretical understanding of the package, and commitment to the research were also factors influencing the extent of implementation across and within schools. The lessons learned may be useful for those involved in designing and/or implementing other teacher-delivered school-based health promotion initiatives.

Adolescent↗
PubMed1991

beta-Lactamase produced by a highly beta-lactam-resistant strain of Bacteroides fragilis: an obstacle to the chemotherapy of experimental mixed infections.

A strain of Bacteroides fragilis, which produces a metallo-beta-lactamase, was inoculated into pouches on the backs of rats together with a beta-lactamase-negative Escherichia coli highly sensitive to beta-lactam antibiotics. The mixed infection rat pouch model was treated with either flomoxef (susceptible to hydrolysis by the beta-lactamase produced by B. fragilis), or cefmetazole (relatively resistant to hydrolysis). In this model of mixed infection flomoxef showed weak in-vivo activity against E. coli, although showing the same strong activity in a model of single infection with E. coli. On the other hand, cefmetazole showed strong activity against E. coli, even in the model of mixed infection. The concentrations of both drugs in the pouches were decreased in infections with the strain of B. fragilis. There was a greater decrease in the concentration of flomoxef than of cefmetazole. Flomoxef was unstable whereas cefmetazole was relatively stable in the pouch exudates that had been infected with B. fragilis. These experimental data suggest that bacteria that produce a metallo-beta-lactamase decrease the in-vivo efficacy of beta-lactam antibiotics against other co-infecting bacteria. Thus, it is suggested that it is important in the chemotherapy of mixed bacterial infections that include these highly resistant beta-lactamase-producing bacteria to use antibiotics that are stable to hydrolysis by these enzymes.

Animals↗