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Biomedical subjects

J M Dwyer

Publications and source records attributed to J M Dwyer.

At least 19 recordsLinked to original sources

A preliminary study to determine the effect of an infusion of cryopreserved autologous lymphocytes on immunocompetence and viral load in HIV-infected patients.

Therapeutic measures aimed at boosting the immunity of HIV-infected patients are a critical component of strategies for effective therapy of HIV and AIDS. To improve immunocompetence in patients with progressive disease, autologous lymphocytes that were collected and cryopreserved earlier in the course of HIV-infection were reinfused. None of the 12 patients receiving cell infusions experienced any adverse effects. Improvements in immunologic parameters (CD4+ counts, CD8+ counts, or both; HIV-specific cytotoxic T-lymphocyte (CTL) activity; or viral load) were seen in seven patients. Restoration of the CD4+ count to the level recorded at the time of cell harvest was achieved in two patients with less advanced disease. Plasma HIV RNA was reduced by >0.5 logs in two of the four patients tested. These preliminary results suggest that cellular immunotherapy using cryopreserved autologous lymphocytes has the potential to improve some measures of immunity in patients with HIV/AIDS and warrants further investigation.

Adult

Suppression of HIV replication in vitro by CD8+ T-cells from HIV-infected and HIV-seronegative individuals.

The inhibitory effect of CD8+ T-cells from HIV-infected or HIV-seronegative individuals on HIV replication in the naturally-infected CD4+ T-cells in vitro was examined. Not only autologous CD8+ T-cells from HIV-infected individuals but also allogeneic CD8+ T-cells from HIV-seronegative individuals prevented or delayed HIV replication, even in transwell cocultures using a semi-permeable 0.45 micron filter. The level of the inhibitory effect of allogeneic CD8+ T-cells from the HIV-seronegative individuals on the HIV replication was varied among CD4+ T-cells obtained from HIV-infected individuals used. The results suggested that CD8+ T-cells from HIV-seronegative individuals as well as HIV-infected individuals could produce some cytokine(s) which suppress HIV replication in vitro. The sensitivity to the cytokine(s) might be variable among HIV strains, depending on differences in the nucleotide sequence of different HIV-1 strains. Further studies of control of HIV replication by CD8+ anti-HIV cytokine(s) should provide new strategies for the therapy of HIV infection.

CD8-Positive T-Lymphocytes

Challenge and response: HIV in Asia and the Pacific.

Inexorably, the epicentre of the global HIV pandemic is moving from Africa to Asia. Despite many years of much-publicised analysis of the African epidemic, most countries in Asia and many in the Pacific have not introduced the public health strategies known to minimise the spread of HIV. What must be done now, and how can the developed countries in the region, such as Australia, assist their neighbours?

Asia

Transfer factor in the age of molecular biology: a review.

Current data suggests that the transferring of immunologically specific information by transfer factor molecules requires interaction with a cell that has been genetically programmed to be antigen reactive but at the time of interaction is unprimed. Contact with transfer factor molecules would allow a naive recipient, on a first encounter with antigen, to make a secondary rather than a primary immunological response. Transfer factor molecules for each and every antigenic determinant are thus necessary. Transfer factors made from animals or humans are capable of transferring antigen specificity across a species barrier. Even primitive species have cells from which one can make transfer factors. The molecules are, therefore, well conserved and it is reasonable to suggest that they are important for normal immunological functioning. Proposed mechanisms of action must explain the fact that transfer factors obtained from the cells of high responder animals are capable of transferring delayed hypersensitivity to low responder animals while the reverse is not true. Transfer factor molecules are likely to interact with the variable regions of the alpha and/or beta chain of T cell receptors to change their avidity and affinity for antigen in a way that otherwise would only occur after an encounter with antigen.

Animals

A falls and balance clinic for the elderly.

A Falls and Balance Clinic for the elderly has been developed with the aim of identifying those at risk of subsequent falls, and recommending intervention strategies to reduce this risk. The physical and functional status of 149 clients referred to the Clinic are reported. Neurological and musculoskeletal pathologies were identified as the cause of falls in the majority of clients. Measures of gait velocity and stride length, and ability to stand on one leg were markedly reduced compared with normative data for healthy elderly. A number of other measures of balance, strength, and function are also reported. The results of a questionnaire about home environment indicated that only 28% of those referred had been assessed in their own home in the previous year. Home environment was considered a potential risk in a further 28% of clients and a home visit was instituted in these cases. Other intervention strategies included referral for further investigations (36%), Day Hospital (33%), provision of a home program of balance or strengthening exercises (27%), and medication change (15%). Issues related to the establishment, operation and long term evaluation of the effectiveness of a specialist Falls and Balance Clinic for the elderly are discussed.

Accidental Falls

The rational use of the HIV antibody test.

The clinical skills of the medical profession can be used to identify unsuspected HIV infection in a cost-effective way. However, other strategies are needed to optimise the detection of HIV infection and achieve the benefits to patients and the community that result from detection.

Cost-Benefit Analysis

Gallium scintigraphy in AIDS.

The acquired immunodeficiency syndrome (AIDS) is a growing problem in Australia: 438 new cases were added in 1988, resulting in the cumulative total of 1562 patients up to November 1989. The cumulative death rate stands at 54%, the majority of deaths being due to secondary infections and malignancies. The clinical presentation of these problems is often non-specific and protean; early diagnosis is the key to successful treatment and survival. Whole body gallium-67 scintigraphy offers an early diagnostic window into many of these infections and malignancies. Although the findings may be non-specific, the procedure is sensitive and may indicate the need for urgent empirical therapy or direct the more definitive investigation. A review of our experience with gallium-67 scanning in 56 AIDS patients at the Prince of Wales/Prince Henry Hospitals confirms its role in presaging significant clinical deterioration in patients with AIDS.

Abdomen

Immunological abnormalities in the chronic fatigue syndrome.

The chronic fatigue syndrome is a disorder of unknown aetiology which is characterized by debilitating fatigue. Recent evidence has suggested that viruses may persist in the tissues of patients with chronic fatigue syndrome. A concurrent immunological disturbance is likely to be associated with the persistence of viral antigens. Therefore, the humoral and cellular immunity of 100 patients who were suffering from chronic fatigue syndrome and that of 100 healthy, age- and sex-matched control subjects were compared. This study documents the frequent occurrence of abnormalities within the cellular and humoral immune systems of patients with well-defined chronic fatigue syndrome. Disordered immunity may be central to the pathogenesis of chronic fatigue syndrome. In patients with chronic fatigue syndrome, a significant (P less than 0.01) reduction was found in the absolute number of peripheral blood lymphocytes in the total T-cell (CD2), the helper/inducer T-cell (CD4) and the suppressor/cytotoxic T-cell (CD8) subsets. A significant (P less than 0.001) reduction also was found in T-cell function, which was measured: in vivo by delayed-type hypersensitivity skin-testing (reduced responses were recorded in 50 [88%] of 57 patients); and in vitro by phytohaemagglutinin stimulation. Reduced immunoglobulin (Ig) levels were common (56% of patients), with the levels of serum IgG3- and IgG1-subclasses particularly (P less than 0.05) affected.

Adolescent

Immunoregulatory activity in supernatants from cultures of normal human trophoblast cells of the first trimester.

Supernatants from isolated trophoblast cell cultures (trophoblastic fluid) derived from first-trimester human placentas were assessed for immunoregulatory activity. Trophoblastic fluid at different days of culture consistently inhibited the blast transformation of allogenic lymphocytes. This suppressor effect had no apparent correlation with biosynthesis of human chorionic gonadotropin by trophoblast cells, since this hormone was secreted into the culture fluid only for the initial 3 days. However, the culture fluids of such purified trophoblast cells contained an immunosuppressive factor, pregnancy-associated plasma protein A, which was measurable throughout the culture period of 8 days. The presence of pregnancy-associated plasma protein A in significant amounts in trophoblastic fluid collected at daily intervals indicated a continuous secretion ability of pregnancy-associated plasma protein A by trophoblast cells in culture parallel to the suppressive immunoregulatory effect of the fluid. Such immunosuppressive effect was absent in the culture fluids of control BeWo malignant trophoblast cells; the BeWo cell culture fluids had markedly reduced levels of pregnancy-associated plasma protein A. The culture supernatant of normal trophoblast cells of placentas from first-trimester pregnancy activated in vitro the generation of a population of suppressor lymphocytes. This effect is generally considered responsible for immunologic tolerance. Therefore demonstration of immunosuppressive effects and the presence of relatively high levels of pregnancy-associated plasma protein A in trophoblastic fluid indicate that such proteins secreted by the trophoblast cells may be important in the local immunoregulatory processes of the fetal allograft.

Cells, Cultured