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Biomedical subjects

S Crowe

Publications and source records attributed to S Crowe.

14 recordsLinked to original sources
PubMed1992

Antigen-mediated effects on epithelial function.

In summary, immediate hypersensitivity reactions to luminal antigens occur in the intestine and result in pathophysiology including increased permeability and ion secretion. The mechanism involves activation of mast cells with neural amplification (FIG. 5). Released mediators/neurotransmitters may act independently or synergistically on the epithelium to elicit Cl ion secretion. In addition, a cyclooxygenase product of arachidonic acid metabolism, possibly of mesenchymal cell origin, may be a common mediator. However, additional effector cell(s) besides mast cells are undoubtedly involved. This system demonstrates undeniably the concept of neuro-immuno-physiology of gut mucosa.

Animals↗
PubMed1992

Primary and secondary human in vitro T-cell responses to soluble antigens are mediated by subsets bearing different CD45 isoforms.

A culture system has been developed which consistently supports in vitro proliferative responses to conventional soluble antigens by human CD4+ T cells from non-immunized donors. T cells exposed to an antigen in primary cultures could be restimulated in vitro in an antigen-specific manner to give secondary responses with greater magnitudes and a more rapid onset than the initial reaction. To characterize further the responding T-cell population in primary compared with secondary reactions, T cells were depleted of CD45RA+ or CD45RO+ cells and stimulated with recall and non-recall antigens. It was found that the soluble non-recall antigen keyhole limpet haemocyanin did not stimulate CD45RO+ T cells, yet induced strong proliferative responses from CD45RA+ T cells. Conversely, it was confirmed that human CD45RO+ T cells respond to the recall antigen-purified protein derivative from Mycobacterium tuberculosis. Cell mixing experiments indicated that CD45RO+ T cells are unlikely to have any suppressive effect on the reactivity of CD45RA+ cells to non-recall antigens. These data provide new support for the hypothesis that CD45RA+ represents the naive and CD45RO+ the memory phenotype of human CD4+ T cells.

Antigens↗
PubMed1991

Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.

Adult↗
PubMed1989

GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage.

GLQ223 is a highly purified, formulated preparation of trichosanthin, a 26-kDa plant-derived ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus (HIV) in vitro. The compound produced concentration-dependent inhibition of HIV replication in acutely infected cultures of T-lymphoblastoid cells (VB cell line). Treatment with GLQ223 selectively reduced levels of detectable viral proteins compared to total cellular protein synthesis and produced a selective decrease in levels of viral RNA relative to total cellular RNA in acutely infected cells. Substantial inhibition of viral replication was observed at concentrations of GLQ223 that showed little inhibition of parallel uninfected cultures. Selective anti-HIV activity was also observed in cultures of primary monocyte/macrophages chronically infected with HIV in vitro. When freshly drawn blood samples from HIV-infected patients were treated with a single 3-hr exposure to GLQ223. HIV replication was blocked for at least 5 days in subsequently cultured monocyte/macrophages, without further treatment. The anti-HIV activity of GLQ223 in both acutely and chronically infected cells and its activity in cells of both lymphoid and mononuclear phagocytic lineage make it an interesting candidate as a potential therapeutic agent in HIV infection and AIDS.

Antigens, Viral↗
PubMed1989

Serum beta 2-microglobulin decreases in patients with AIDS or ARC treated with azidothymidine.

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

AIDS-Related Complex↗
PubMed1989

Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi's sarcoma: a randomized, double-blind trial.

The effect of recombinant tumor necrosis factor-alpha (rTNF), injected directly into the tumor, was evaluated in a Phase I/II study of 27 patients with AIDS-associated Kaposi's sarcoma (KS). The maximally tolerated intralesional dose was less than 100 micrograms/m2 and the recommended intralesional dose was 25 micrograms/m2. In a double-blind, randomized, placebo-controlled study, rTNF reduced the cross-sectional area of 15 of 16 (94%) of the injected KS lesions and caused complete disappearance of 3 of 16 (19%) lesions. Only injected lesions showed a response. Rigors and fever were common dose-dependent side effects and were attenuated by meperidine. There were no changes in human immunodeficiency virus (HIV) activity as determined by serum p24 antigen levels. While biologically active, the systemic toxicity of rTNF as well as the lack of distant antitumor effects in noninjected lesions limits its clinical usefulness under the conditions employed in this trial.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo.

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The future of antiviral chemotherapy.

This article has reviewed the principal antiviral agents and their application in the therapy and prevention of viral diseases. Only acyclovir, amantadine, ribavirin, zidovudine, and vidarabine have received FDA approval for therapy of systemic viral infections. Although ganciclovir, phosphonoformate, the acyclovir prodrugs, disoxaril, and the interferons are now being used only on an investigational basis, it is likely that at least some of these agents will soon be licensed. The search for more effective and safer antivirals continues, and with increasing academic and industrial interest, the prospects for this branch of chemotherapy appear promising.

Antiviral Agents↗
PubMed1987

Quantitative immunocytofluorographic analysis of CD4 surface antigen expression and HIV infection of human peripheral blood monocyte/macrophages.

HIV infection of CD4-bearing lymphocytes alone does not fully explain the immune dysfunction of AIDS. Monocyte/macrophages infected with HIV may serve as a reservoir of HIV, may function abnormally and may transmit infection to other susceptible cells, thus playing a central role in the development of the immunodeficiency of AIDS. Quantitative analysis of surface antigens and measurement of HIV antigens in infected cells have been difficult using the conventional approach of immunofluorescent staining of cells on slides. We have developed a system that maintains monocyte/macrophages in suspension culture for at least four months. Through immunocytofluorographic single cell analysis we have shown that CD4 antigen is present on monocytes, and that a tenfold increase in expression occurs during the first two weeks in culture. In contrast, LeuM3 antigens decreased to background levels in the course of long-term culture. Using anti-HIV p24 antibody, we have demonstrated that monocyte/macrophages can be infected with HIV. Up to 70% of cells from individual donors could be infected. The techniques herein described allow in vitro quantitation of some of the mechanisms by which HIV infection of monocyte/macrophages may contribute to the immunodeficiency states associated with AIDS.

Antibodies, Monoclonal↗
PubMed1986

Prevalence of delta infection in the western Pacific region.

The prevalence of coinfection and superinfection with the delta agent was studied in 2,645 hepatitis B surface antigen (HBsAg)-positive subjects from six countries and nine islands in the Western Pacific region. The study group comprised 262 patients with acute hepatitis B and 2,383 chronic carriers of HBsAg, of whom 278 were suffering from chronic liver disease or primary hepatocellular carcinoma. While major foci of infection were observed in Nauru, Niue, and Western Samoa, delta infection appears to be uncommon in other parts of the region.

Asia, Southeastern↗