Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells.

Anandamide (N-arachidonylethanolamide) is an endogenous cannabinoid that mimics the pharmacologic effects of Delta(9)-tetrahydrocannabinol, the major bioactive substance in marijuana. Anandamide appears to be synthesized, released, and inactivated by mechanisms similar to those for other neurotransmitters. Of interest to the present studies are reports that anandamide undergoes carrier-mediated uptake into neuronal or glial cells after release, followed by rapid intracellular degradation by the intracellular fatty acid amidohydrolase.

Long-term variations of man-made radionuclide concentrations in a bio-indicator Mytilus galloprovincialis from the French Mediterranean coast.

Results from a 14-year monitoring (1984-1997) of man-made radionuclide (137Cs and 106Ru) levels in Mytilus galloprovincialis collected monthly on the French Mediterranean coast are presented. In this area sources of man-made radionuclides are on the one hand atmospheric fallout from both the past nuclear testings and the Chernobyl accident and on the other hand discharges from nuclear installations located on the Rhône River banks, especially those from the spent nuclear fuel reprocessing plant in Marcoule. Long-term variations of radionuclide concentrations in Mytilus demonstrated seasonal variations which are linked to the reproductive cycle of these organisms as well as to variations in land-based inputs of man-made radionuclides.

The role of CD80 and CD86 in enhancing CD8(+) cell suppression of HIV replication.

CD8(+) cells activated in the presence of autologous macrophages (Mphi) have an increased ability to suppress HIV replication compared to the same cells stimulated in the absence of Mphi. Blocking the B7 molecules decreases the ability of Mphi to increase CD8(+) cell antiviral activity. In the present study CD8(+) cells exposed to purified forms of both the CD80 and the CD86 molecules during stimulation with anti-CD3 antibodies (Ab) had a greater ability to suppress HIV replication than CD8(+) cells exposed to anti-CD3 Ab alone.

Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter.

Mutation of a conserved Asp (D98) in the rat serotonin (5HT) transporter (rSERT) to Glu (D98E) led to decreased 5HT transport capacity, diminished coupling to extracellular Na+ and Cl-, and a selective loss of antagonist potencies (cocaine, imipramine, and citalopram but not paroxetine or mazindol) with no change in 5HT Km value. D98E, which extends the acidic side chain by one carbon, affected the rank-order potency of substrate analogs for inhibition of 5HT transport, selectively increasing the potency of two analogs with shorter alkylamine side chains, gramine, and dihydroxybenzylamine. D98E also increased the efficacy of gramine relative to 5HT for inducing substrate-activated currents in Xenopus laevis oocytes, but these currents were noticeably dependent on extracellular medium acidification.

Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease.

To test the hypothesis that the angiotensin converting enzyme (ACE) genotype is associated with chronic beryllium disease (CBD) and disease severity, we studied 50 cases of CBD and compared their ACE genotype to that of two different control groups, consisting of: (1) 50 participants from a beryllium machining facility; and (2) 50 participants from a non-beryllium-associated workplace. We found no statistically significant difference in the frequency of the I or D allele or of the DD genotype among cases of CBD and either control group. The odds ratio (OR) for the CBD DD genotype as compared with the non-DD genotype was 1.

CD8+ cell-derived anti-human immunodeficiency virus inhibitory factor.

CD8+ cells in human immunodeficiency virus (HIV)-infected individuals develop the ability to control HIV replication not only by destruction of the infected cells but also by controlling the virus in a noncytotoxic fashion that leaves the infected cell functionally intact. The CD8+ noncytotoxic response is mediated by a novel soluble factor known as CD8+ cell antiviral factor (CAF). CAF suppresses HIV replication in the infected cell at the level of viral transcription by interrupting the ability of Tat or host cellular factors to interact with the HIV long terminal repeats.

Differential effects of CD28 costimulation on HIV production by CD4+ cells.

We have observed that CD28 costimulation of CD4+ cells can have differential effects on HIV replication. Triggering the CD28 molecule on peripheral blood CD4+ cells during stimulation with anti-CD3 Abs enhances virus production following acute infection with HIV. Endogenous virus production in CD4+ cells from HIV-infected individuals is also increased by this procedure.

Differences in HIV replication in CD4+ lymphocytes are not related to beta-chemokine production.

CD4+ T lymphocytes from different donors vary in their ability to replicate different isolates of HIV. Beta-chemokines have been shown to reduce the rate of HIV replication in cultured cells. We now demonstrate, using CD4+ cells from 19 different donors, that the variations in viral replication observed in CD4+ lymphocytes are not due to endogenous production of beta-chemokines by the cells.

Rapid-staged strategy for concomitant critical carotid and left main coronary disease with left ventricular dysfunction: IABP use.

Background: Few reports address the high-risk patient population with concomitant critical carotid and left main coronary disease with left ventricular dysfunction. To decrease the risks involved with the simultaneous and traditional staged surgical approaches, we developed a rapid staging strategy using an intraaortic balloon pump.

Methods: Between 1992 and 1996, 20 patients presented with a high-risk "triad" defined by greater than 70% stenosis of the left main coronary artery, ejection fraction less than 0.

Virological and immunological features of long-term human immunodeficiency virus-infected individuals who have remained asymptomatic compared with those who have progressed to acquired immunodeficiency syndrome.

Infection with the human immunodeficiency virus (HIV) leads to a decrease in CD4(+) T cells and disease progression within a decade of seroconversion. However, a small group of infected people, despite being infected by HIV for 10 or more years, remain clinically asymptomatic and have stable CD4(+) cell counts without taking antiretroviral medication. To determine why these individuals, known as long-term survivors (LTS), remain healthy, the hematological profiles, viral load and properties, HIV coreceptor genotype, and anti-HIV immune responses of these people were compared with those of individuals who have progressed to disease (Progressors) over the same time period.

High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol.

Human and Drosophila melanogaster serotonin (5-HT) transporters (SERTs) exhibit similar 5-HT transport kinetics and can be distinguished pharmacologically by many, but not all, biogenic amine transporter antagonists. By using human and Drosophila SERT chimeras, major determinants of potencies of two transporter antagonists, mazindol and citalopram, were tracked to the amino-terminal domains encompassing transmembrane domains I and II. Species-scanning mutagenesis, whereby amino acid substitutions are made switching residues from one species to another, was employed on the eight amino acids that differ between human and Drosophila SERTs in this region, and antagonist potencies were reassessed in 5-HT uptake assays.

Primary CD8+ cells from HIV-infected individuals can suppress productive infection of macrophages independent of beta-chemokines.

The productive infection of human monocyte-derived macrophages (Mphi) by HIV was suppressed by primary CD8+ cells from asymptomatic HIV-infected individuals. This anti-HIV response was noncytotoxic; removal of the CD8+ cells from the infected Mphi leads to virus production. CD8+ cells inhibited HIV replication when separated from the infected Mphi by a transwell filter insert, indicating a diffusible factor made by the CD8+ cells suppressed productive infection of Mphi.

Speech perception results for children with implants with different levels of preoperative residual hearing.

Objective: Many reports have established that hearing-impaired children using the Nucleus 22-channel cochlear implant may show both significant benefits to lipreading and significant scores on open-set words and sentences using electrical stimulation only. These findings have raised questions about whether severely or severely-to-profoundly deaf children should be candidates for cochlear implants. To study this question, postoperative results for implanted children with different levels of preoperative residual hearing were evaluated in terms of speech perception benefits.

CD28 costimulation increases CD8+ cell suppression of HIV replication.

A subset of CD8+ T lymphocytes that expresses CD28, a membrane receptor for B7 differentiation Ags found on APCs, is primarily responsible for the noncytotoxic suppression of HIV replication in CD4+ cells of HIV-infected individuals. Optimal inhibition of HIV production by CD8+ cells occurs after triggering the CD28 molecule on the cells with anti-CD28 Abs during stimulation. Blocking the interaction of the CD28 and B7 molecules with a CTLA4Ig fusion protein abrogates the ability of autologous macrophages to enhance this CD8+ cell antiviral activity.