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Biomedical subjects

A H Rook

Publications and source records attributed to A H Rook.

At least 109 records · Page 6Linked to original sources
PubMed1984

NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations.

The acquired immunodeficiency syndrome is a new disease whose cause is unknown but is almost surely due to a transmissible agent, most likely a virus. The disease is clearly spread by sexual contact, particularly homosexual activity. Blood-borne transmission constitutes the other major recognized form of spread of the disease, although it is highly likely that the disease is not readily spread through casual, nonsexual, non-blood-borne routes. Although the disease is still highly concentrated in the United States, it is now seen in several countries throughout the world. The common denominator of the disease is a profound suppression of cell-mediated immunity, specifically a quantitative and qualitative defect in the T4 inducer or helper subset of T lymphocytes. Hyperactivity of B lymphocytes is also characteristic. The clinical manifestations are those of severe and life-threatening opportunistic infections and unusual neoplasms, particularly Kaposi's sarcoma. The mortality may well approach 100%, making this one of the most extraordinary transmissible diseases in history.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Comparative virulence and immunogenicity of the Towne strain and a nonattenuated strain of cytomegalovirus.

The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks). None of the four seronegative subjects receiving the Towne strain developed systemic infection, but all developed delayed local reactions at the injection sites. All subjects developed cytotoxic lymphocyte responses specific to cytomegalovirus, usually HLA-restricted, but these were of greater magnitude and duration in the Toledo-1 recipients. The latter also developed natural killer cell and interferon responses, atypical lymphocytosis, inversion of helper/suppressor cell ratios, and depressed responses to T-cell mitogens, none of which occurred in Towne strain recipients. The results further substantiate the avirulence and immunogenicity of the Towne strain cytomegalovirus.

Adult↗
PubMed1984

Use of interleukin-2 in patients with acquired immunodeficiency syndrome.

Twelve patients with acquired immunodeficiency syndrome were treated with a natural product, highly purified human interleukin-2. Doses ranged from 250 to 250,000 units. No clinical responses were seen. Minimal toxicity was noted and consisted of mild prolongation of partial thromboplastin time and proteinuria. Immunologic changes during the study included a decrease in the number of circulating T8 lymphocytes, increased skin test reactivity, and a decline in serum immunoglobulin levels.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Treatment of intraocular inflammatory disease with cyclosporin A.

Eight patients with bilateral sight-threatening posterior uveitis of non-infectious aetiology that had not responded to corticosteroid or cytotoxic therapy were given cyclosporin A. Seven of the eight responded with improvement in visual acuity and disappearance of ocular inflammatory activity. The seven included two with Behçet's disease, who also had improvement in non-ocular symptoms. Peripheral blood lymphocytes from the seven cyclosporin A responsive patients, but not those from the non-responder, gave positive in-vitro blastogenic responses to the retinal S-antigen, a highly uveitogenic organ-specific material. In four patients OKT4/OKT8 ratios fell after the start of therapy, as the result of an increase in the OKT8 fraction. In the other four patients the fall was preceded by an increase in the OKT4/OKT8 ratio. Cyclosporin A did not influence natural killer cell activity. Side-effects ascribed to cyclosporin A were tolerated or disappeared with continued therapy, sometimes at a lower dosage. No neoplasms were observed. Cyclosporin A seems to be effective treatment for selected patients with severe bilateral uveitis of non-infectious aetiology.

Adult↗
PubMed1983

Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome.

The recently described acquired immune deficiency syndrome (AIDS) is characterized by the occurrence of severe opportunistic infections and an aggressive form of Kaposi's sarcoma. A variety of profound defects in cell-mediated immunity have been reported in association with the AIDS, including deficiencies in natural killer (NK) cell activity and cytomegalovirus (CMV)-specific cytotoxicity. In the present study, the in vitro effects of interleukin-2 (IL-2) and interferon beta (IFN Beta) on these abnormalities were examined to assess the potential use of these lymphokines in the immunotherapeutic treatment of this syndrome. The peripheral blood lymphocytes (PBL) from six male homosexuals with AIDS and an active CMV infection exhibited markedly depressed NK cell and CMV-specific cytotoxic lymphocyte responses compared with uninfected, heterosexual control subjects. Incubation of PBL with IFN Beta enhanced the NK cell activity and the CMV-specific cytotoxicity of only one of six and neither of two AIDS patients, respectively, while enhancing the NK cell activity of all six control subjects. In contrast, IL-2 dramatically enhanced both the NK cell and the CMV-specific cytotoxic lymphocyte activities of all of the patients. These results indicate that IL-2 can substantially potentiate the depressed cytotoxic effector functions of PBL from AIDS patients, while IFN Beta has little effect.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Cytotoxic t cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients.

We studied 58 recipients of bone-marrow transplants to evaluate immune responses to cytomegalovirus infection. Such infection developed in 43 patients; it was fatal in 12, nonfatal in 23, and present at death from other causes in eight. All patients had low or absent cytomegalovirus-specific cytotoxic lymphocyte activity before the onset of infection. Cytomegalovirus-specific cytotoxic responses developed in all survivors, whereas only two patients with fatal infection had even low-level cytomegalovirus-specific cytotoxic responses. Natural and antibody-dependent killer-cell activities were depressed both before and during infection in patients with fatal infections, but not in those who survived. The outcome of the infection did not correlate with the nature of the underlying disease, the type of transplant received, the pretransplantation cytomegalovirus-antibody status, or lymphocyte-proliferation responses to cytomegalovirus antigens or concanavalin A. The correlation between effective virus-specific cytotoxic response and recovery from infection indicates that these effector cells probably mediate recovery from cytomegalovirus infection.

Antibodies, Viral↗
PubMed1982

Natural killer cells and interferon responses in patients with systemic lupus erythematosus.

Natural killer (NK) cell activity was studied in 23 patients with systemic lupus erythematosus (SLE). The overall NK activity was lower in patients with SLE than in normal female individuals. Patients with clinically active SLE disease had slightly lower NK activity than the patients with inactive disease. Other clinical parameters as well as treatment status did not correlate with NK activity. Interferon (IFN) enhanced the NK activity of normal individuals and of 11 SLE patients, while it did not enhance in the remaining 12 patients. The patients whose NK activity was enhanced by beta-IFN had significantly higher initial activity than those who did not respond to beta-IFN. Furthermore, peripheral mononuclear cells (MNC) from IFN responders produced gamma-IFN after stimulation with concanavalin A (Con A) in titres comparable to those of normals. In contrast, peripheral MNC from beta-IFN non-responders failed to produce significant titres of gamma-IFN after stimulation with Con A. These results indicate that certain patients with SLE have low NK activity, which is generally paralleled by an inability to respond to exogenous beta-IFN and by blunted production of gamma-IFN after stimulation with Con A.

Cells, Cultured↗
PubMed1981

HLA restricted virus-specific cytotoxic T-lymphocyte responses to live and inactivated influenza vaccines.

36 young adult volunteers were given either virus, or inactivated surface-antigen influenza vaccine, containing influenza A (H1N1) antigen. Their peripheral-blood lymphocytes were analysed to determine whether cytotoxic T lymphocytes (CTL) were induced by these vaccines. All three vaccines induced HLA-restricted T-lymphocyte responses specific for influenza A virus. This CTL response was found in 28 of 30 volunteers who showed antibody responses and in 3 of 6 who did not develop antibodies. Virus infected target cells showing certain HLA antigens (A1, A9, and B8) were less susceptible to lysis by HLA-matched cytotoxic T effector cells than target cells which matched effectors at other HLA loci.

Adult↗
PubMedDate not supplied

Interleukin 2 therapy in infectious diseases: rationale and prospects.

Clinical trials using interleukin 2 as a therapeutic immunomodulating agent in patients with acquired immunodeficiency syndrome have recently begun. In this article we present data from studies which indicate the ability of interleukin 2 in vitro to augment clinically important cytotoxic immune responses in lymphocytes from these patients. These studies provide both a rationale for the current trials and a model for evaluating the potential for use of interleukin 2 in other infectious diseases. We outline the types of infectious diseases in which interleukin 2 may prove to be useful and the therapeutic strategies in which it may play a role.

Acquired Immunodeficiency Syndrome↗