Behavior maintained by intravenous injection of codeine, cocaine, and etorphine in the rhesus macaque and the pigtail macaque

Lever-pressing behavior of two species of macaque, the rhesus macaque ( M. mulatta ) and the pigtail macaque ( M. nemestrina ) was maintained by intravenous injection of codeine, etorphine, or cocaine. Monkeys responded under a fixed-ratio 30 timeout 600 s schedule of drug injection during two daily experimental sessions. Drug-maintained behavior was studied under two access conditions. Under the first condition, selected doses of codeine or cocaine were available for ten consecutive sessions. Under the second condition, responding was maintained by 0.32 mg/kg codeine or 0.32 mg/kg cocaine, and saline and selected doses of codeine, etorphine, and cocaine were substituted during single experimental sessions. Performance varied with drug and injection dose, access condition, and macaque species. For all three drugs, response rate increased and then decreased as injection dose increased. Maximal rates were maintained by 0.10–0.32 mg/kg codeine, 0.0003–0.001 mg/kg etorphine, and 0.10–0.32 mg/kg cocaine. A cocaine dose of 0.32 mg/kg maintained higher rates than any dose of codeine or etorphine, and maintained higher rates when available during consecutive sessions than when substituted for codeine for a single session. Codeine maintained similar rates under all access conditions. The pigtail macaques had short catheter lives, did not readily acquire codeine-maintained responding, and displayed lower rates of drug-maintained lever pressing than the rhesus macaques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46415/1/213_2004_Article_BF00427883.pd

Responding under chained and tandem fixed-ratio schedules

The role of stimuli in chained fixed-ratio schedules of reinforcement was examined. At various ratio values, responding on schedules consisting of three or five equal components, with a different colored light in each component (“block counter”) was compared with responding on tandem or simple fixed-ratio schedules having the same color present throughout the entire ratio. At all ratio values except the smallest, the chain stimuli resulted in longer pauses after reinforcement. The magnitude of this effect became greater as the size of the ratio was increased. Post-reinforcement pause durations were longer under five-component schedules than under three-component schedules. Running rates in the first component were lower on the chained schedules than on the tandem schedules; on both kinds of schedule, rates were lower in the first component than in the rest of the ratio. When the sequence of stimuli was reversed, the duration of the post-reinforcement pause dropped markedly and the running rate in the initial component increased, but these effects gradually disappeared after the first reversal session. When the final chain stimulus was substituted for the first component stimulus but continued to appear in the final chain component as well, the pause duration dropped and remained at this lower level during subsequent sessions

Alteration of humoral, cellular and cytokine immune response to inactivated influenza vaccine in patients with Sickle Cell Disease

info:eu-repo/semantics/publishe

Acute lymphoblastic leukemia in the context of RASopathies

International audienceNoonan syndrome is associated with a range of malignancies including acute lymphoblastic leukemia (ALL). However, little information is available regarding the frequency, natural history, characteristics and prognosis of ALL in Noonan syndrome or RASopathies in general. Cross-referencing data from a large prospective cohort of 1176 patients having a molecularly confirmed RASopathy with data from the French childhood cancer registry allowed us to identify ALL in 6 (0.5%) patients including 4/778 (0.5%) with a germline PTPN11 mutation and 2/94 (2.1%) with a germline SOS1 mutation. None of the patients of our series with CFC syndrome (with germline BRAF or MAP2K1/MAP2K2 mutation - n = 121) or Costello syndrome (with HRAS mutation - n = 35) had an ALL. A total of 19 Noonan-ALL were gathered by adding our patients to those of the International Berlin-Munster-Frankfurt (I-BFM) study group and previously reported patients. Strikingly, all Noonan-associated ALL were B-cell precursor ALL, and high hyperdiploidy with more than 50 chromosomes was found in the leukemia cells of 13/17 (76%) patients with available genetics data. Our data suggest that children with Noonan syndrome are at higher risk to develop ALL. Like what is observed for somatic PTPN11 mutations, NS is preferentially associated with the development of hyperdiploid ALL that will usually respond well to chemotherapy. However, Noonan syndrome patients seem to have a propensity to develop post therapy myelodysplasia that can eventually be fatal. Hence, one should be particularly cautious when treating these patients

Punishment of observing by the negative discriminative stimulus

To determine the effect of a negative discriminative stimulus on the response producing it, two pigeons were each studied in a three-key conditioning chamber. During alternating periods of unpredictable duration, pecking the center (food) key either was reinforced with grain on a variable-interval schedule or was never reinforced. On equal but independent variable-interval schedules, pecking either of the side (observing) keys changed the color of all keys for 30 sec from yellow to either green or red. When the schedule on the center key was variable-interval reinforcement, the color was green (positive discriminative stimulus); when no reinforcements were scheduled, the color was red (negative discriminative stimulus). Since pecking the side keys did not affect grain deliveries, changes in the rate of pecking could not be ascribed to changes in the frequency of primary reinforcement. In subsequent sessions, red was withheld as one of the possible consequences of pecking a given side key. When red was omitted, the rate on that key increased, and when red was restored, the rate decreased. It was concluded that red illumination of the keys, the negative discriminative stimulus, had a suppressive effect on the response that produced it

Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients

Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum immunoglobulin (Ig) M, low IgM antibody production in response to S pneumoniae following nonconjugated immunization, and low blood memory B-cells counts (including marginal zone [MZ] B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from 9 ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1((+)) stromal cells and an excess of DN-Ts. DN-Ts were shown to express MAdCAM-1 ligand, the α4β7 integrin. These observations suggest that accumulating DN-Ts are trapped within stromal cell meshwork and interfere with correct localization of MZ B cells. Similar observations were made in spleens of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody production-specific defect. Splenectomy should be avoided.status: publishe

Autoimmune Lymphoproliferative Syndrome is associated with deficiency in anti-polysaccharide antibodies production and a disorganisation of the spleen marginal zone

Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum IgM, low IgM antibody production in response to S.pneumoniae following non-conjugated immunization and low blood memory B-cells counts (including marginal zone (MZ) B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from nine ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B-cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1 (+) stromal cells and an excess of DN-T cells. DN-T were shown to express MAdCAM-1 ligand, alpha4-beta7 integrin. These observations suggest that accumulating DN T-cells are trapped within stromal cell meshwork and interfere with correct localization of MZ B-cells. Similar observations were made in spleen of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in antipolysaccharide IgM antibody production specific defect. Splenectomy should be avoided.status: publishe