PubMed Health⌕ Search

Biomedical subjects

D Benjamin

Publications and source records attributed to D Benjamin.

At least 145 records · Page 8Linked to original sources
PubMed1993

Increased protein kinase C activity in human memory T cells.

A number of T cell surface antigens including CD45R0, CD58, CD11 alpha, CD29, CD44, and CD26 are present on differentiated T cells and identify T cell populations that respond to recall antigens. To further study the biochemical basis for this immune memory, we used an anti-CD26 mAb to identify the memory T cell population. We have previously shown that CD26+ T cells display an increased proliferative response to anti-CD3 and anti-CD2 mAbs and furthermore have significantly greater PMA-induced phosphorylation of the invariant gamma and delta chains of the T cell receptor (TCR)/CD3 complex when compared to CD26-T cells. This suggested that differential distribution of protein kinase C (pkC) in the CD26 subsets may be related to the reduced activation requirements observed in memory T cells upon recall antigen challenge. We now directly demonstrate that when peripheral blood T cells are sorted into CD26+ and CD26- T cells the majority of pkC activity can be recovered from the cytosol fraction of the memory (CD26+) T cell population. When activated through the TCR/CD3 pathway, the CD2 pathway, or directly by the phorbol ester, PMA, the memory (CD26+) T cells showed an increased proliferative response that was inhibited by the pkC inhibitor, staurosporine. When CD26+ T cells were cultured in the presence of PMA, which depletes pkC activity, CD26 antigen expression was down-regulated. PMA was also able to inhibit phytohemagglutinin (PHA)-induced expression of the CD26 antigen in CD26- T cells. These data demonstrate a relation between CD26 expression and pkC activity and suggest that enhanced pkC activity is associated with memory T cell function.

Alkaloids↗
PubMed1993

Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Childrens Cancer Group pilot study.

PURPOSE: Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue. RESULTS: One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis. CONCLUSION: Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.

Actuarial Analysis↗
PubMed1993

Anxiogenic effect of disulfiram evaluated in an animal model.

The present experiment was designed to determine whether disulfiram produced an interoceptive discriminative stimulus (IDS) in rats similar to that exhibited by the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate PTZ (20 mg/kg IP) from saline, according to an FR10 schedule of food reinforcement. After training criteria had been met, discrimination testing revealed that disulfiram (100 mg/kg, IP) produced a PTZ-like IDS that fully substituted for PTZ 4 hours after injection, decaying to baseline values by the third day. The metabolite of disulfiram, diethyl dithiocarbamate (100 mg/kg, IP), followed much the same temporal pattern, but only showed partial substitution for PTZ. When ethanol (1 g/kg, gavage) or the monoamine oxidase inhibitor pargyline (50 mg/kg, IP) were administered in combination with disulfiram, no significant change of the PTZ-like stimulus was observed. Pargyline (100 mg/kg, IP) or acetaldehyde (200 mg/kg, IP), given alone, did not significantly substitute for PTZ. These data show that disulfiram produces an IDS in rats similar to that produced by other anxiogenic drugs. These data also suggest that the mechanism by which disulfiram produces its anxiogenic effect may not be entirely based upon the disulfiram metabolite diethyl dithiocarbamate, elevated acetaldehyde levels or stimulation of the catecholaminergic system.

Acetaldehyde↗
PubMed1993

Ethanol prevents desensitization of 5-HT2 receptor-mediated responses consequent to defeat in territorial aggression.

The effect of intruder status in territorial aggression on behavior in the elevated plus-maze, the open field and on 5-HT2 receptor-mediated behaviors was evaluated in male Long-Evans hooded rats. Intruders (350 g) were placed in the home cages of aggressive resident rats (475-600 g) and removed after 20 roll-tumble fights. On the following day, the rats were tested on the elevated plus-maze, and behavior in the open field was evaluated after injection with the 5-HT2/1C receptor agonist, DOI (1.0 mg/kg). The number of headshakes following DOI injection are thought to be an indicator of 5-HT2 receptor function. Although several other stressors were evaluated, only defeat in territorial aggression caused a significant decrement in the number of headshakes following DOI injection. To determine if ethanol (ET) could decrease the behavioral consequences of defeat, the effect of ET (1.25 g/kg) given before and immediately after aggression on behavior 24 hours later was evaluated. Although ET treatment had no effect on the control group that did not experience aggression, the ET treatment attenuated the desensitization of 5-HT2 receptor-mediated responses induced by aggression and severely exacerbated the anxiety-like effects as measured in the elevated plus-maze. These data suggest that (1) 5-HT2 receptor sensitivity decreases as a consequence of defeat, but not after several other stressors; (2) defeat in territorial aggression results in significant anxiety-like effects in the elevated plus-maze 24 hours later; and (3) these anxiety-like effects are exacerbated when ET is given before, and immediately after, the aggression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1992

Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10.

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV-positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV-negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV-positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Interferon-gamma gene expression in human B-cell lines: induction by interleukin-2, protein kinase C activators, and possible effect of hypomethylation on gene regulation.

Human interferon-gamma (IFN-gamma) is an important immunomodulatory protein produced predominantly by T cells and large granular lymphocytes (LGLs). Whereas large amounts of data have been accumulated regarding IFN gamma gene expression in these two cell types, little information about IFN gamma expression in other cell types exists. In this study, we have analyzed the production of IFN gamma by the Epstein-Barr virus (EBV)-positive B-cell line, JLP(c), derived from a patient with Burkitt's lymphoma, and another human B-cell line, PA682BM-1, which was derived from an acquired immunodeficiency syndrome patient. Southern blot analysis indicates the presence of an Ig heavy chain gene rearrangement, but no rearrangement of the T-cell receptor beta chain gene or IFN gamma gene in these B-cell lines. Both cell lines were found to express surface IgD and other B-cell surface markers, thus confirming their B-cell lineage. Analysis for surface Ig, cytoplasmic Ig, and secreted Ig indicates that the two cell lines are in relatively early stages of the B-cell differentiation pathway. We now report that PA682BM-1 can be triggered by the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate (PMA) and (-)Indolactam-v, to secrete IFN gamma, whereas JLP(c) cells spontaneously produce low levels of IFN gamma that can be enhanced by PKC activators and interleukin-2 (IL-2). After activation of the cell lines with IL-2, (-)Indolactam-v, and PMA, increases in cytoplasmic messenger RNAs (mRNAs) of IFN gamma and the IL-2 receptor chains were also observed. The induction of IFN gamma mRNA and protein by IL-2 was completely blocked by a monoclonal antibody to IL-2 receptor p75 (beta chain), but not by the monoclonal antibody to p55 (alpha chain). Analysis of IFN gamma genomic DNA indicates that the gene is not amplified, but that hypomethylation in the 5' noncoding region of the IFN gamma gene has occurred in the B-cell line from the Burkitt's lymphoma patient that spontaneously produces IFN gamma. This finding suggests that the methylation state of the promoter region may play an important role in the control of IFN gamma gene expression in B cells.

Acquired Immunodeficiency Syndrome↗