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Biomedical subjects

D Benjamin

Publications and source records attributed to D Benjamin.

At least 127 records · Page 7Linked to original sources
PubMed1993

Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats.

The effect of the opioid receptor antagonist, naltrexone, on ethanol-induced changes in extracellular dopamine and serotonin in the nucleus accumbens was investigated using in vivo microdialysis in awake, freely moving rats. Locally applied ethanol (5% infused transprobe) resulted in substantial increases in dopamine in dialysate. Administration of naltrexone (cumulative dosing with 0.25-1.0 mg/kg i.p.) during ethanol administration dose-dependently reversed ethanol-induced increases in extracellular dopamine and its metabolite homovanillic acid but not serotonin. These data demonstrate an essential role for the endogenous opioid system in stimulation of dopamine release by ethanol in a brain area associated with reward and support the opioid system as a prime target for pharmacological modulation of the rewarding effects and consumption of ethanol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling.

Microcapillary HPLC electrospray ionization tandem mass spectrometry was used to sequence 15 peptides eluted from HLA-B7. Sequence alignment implicated four peptide positions in specific interactions with the class I molecule, and their importance was confirmed using synthetic peptides. Because no crystal structure for HLA-B7 was available, computer-assisted modeling was used to understand novel aspects of peptide binding specificity and to accurately predict the effect of defined changes in peptide structure. The results demonstrate that mass-spectrometric sequencing coupled with computer-assisted modeling can be used in the absence of a crystal structure to make accurate predictions concerning requirements for peptide binding to class I molecules. These techniques may be valuable to predict or engineer T cell epitopes.

Amino Acid Sequence↗
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↗