Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward‐driven behaviors, which can result in life‐altering morbidity. The mesocorticolimbic dopamine network guides reward‐motivated behavior; however, its role in this treatment‐related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward‐learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD‐fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex‐matched PD patients with (n = 19) or without (n = 18) ICB. An incentive‐based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole‐brain voxelwise analyses and region‐of‐interest‐based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala‐to‐midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum‐to‐subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment‐avoidance learning. These data indicate that PD‐ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward‐based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509–521, 2018. © 2017 Wiley Periodicals, Inc.     

Monocyte-mediated antibody-dependent cell-mediated cytotoxicity: the role of the metabolic burst

Human monocytes respond to opsonized microorganisms with a "metabolic burst" composed of an increase in oxygen consumption, an increase in hexose monophosphate shunt (HMPS) activity, and the generation of reactive oxygen species (ROS). We investigated the role of the metabolic burst in antibody-dependent cell-mediated cytotoxicity (ADCC) by human monocytes toward anti-D coated erythrocyte target cells because recent studies suggested a role for oxygen-dependent bactericidal mechanisms in ADCC. In normal monocytes, we found that ADCC was nearly halved under hypoxic conditions. Several agents known to impair activation of the burst, such as vincristine, cation chelators, and a sulfhydryl reagent, all decreased cytotoxicity if added before initiation of contact between target and effector cells. Cytotoxicity was inhibited by 2-deoxyglucose but not fluoride, suggesting a nonglycolytic role for glucose in ADCC, perhaps in the HMPS pathway. Although these data suggested a role for the metabolic burst in ADCC, scavengers of ROS did not impair cytotoxicity, and monocytes from chronic granulomatous disease (CGD) patients who had a defective metabolic burst had normal levels of ADCC. We conclude that ADCC toward anti-D coated erythrocyte target cells was the result of at least two independent but closely related cytotoxic pathways. Although one of these pathways appeared to involve the metabolic burst, the potentially cytotoxic reactive oxygen species did not appear to play a role in this system.     

Identification of T lymphocytes in human mixed hemopoietic colonies

The addition of a T-cell growth-promoting medium (PHA-TCM) to culture conditions that support growth of multi-lineage hemopoietic colonies enhances the proliferation of cells with lymphoid morphology within these colonies. These cells were identified as T lymphocytes by their ability to form rosettes with SRBC and their reaction with monoclonal antibodies (OKT3, OKT4) directed against T-cell-specific surface components. They continue to proliferate extensively under the influence of PHA-TCM after transfer of mixed colonies into liquid suspension culture. Supportive evidence for a common progenitor of myeloid and lymphoid cells within single mixed colonies is provided by Y-chromatin body analysis of E-rosette positive and negative cells in colonies grown in cocultures of male and female bone marrow cells.     

Storage of platelet concentrates using ion exchange resin charged with dibasic phosphate.

Platelet concentrates were prepared at twice the normal concentration and stored at room temperature for 7 days in either standard bags (controls) or bags to which 1 or 2 g of Amberlite resin beads charged with dibasic phosphate had been added. The resin beads served as a buffer system by providing a "slow release" form of phosphate ions as well as by binding CO2 produced during platelet metabolism. Control platelets demonstrated rapid falls in pH, ATP content, morphology score, and thrombin-induced nucleotide release after 24 hr of storage with a fall in pH to less than 6.0 by day 3. Profound ultrastructural changes and a rise in pO2, suggesting loss of platelet viability, accompanied these changes. In contrast, the resin-stored platelets remained near normal after 24 hr of storage, with preservation of discoid morphology, 95% of ATP levels, excellent ultrastructural appearance, and evidence of continued oxygen consumption after 3 days of storage. Even after 7 days of storage, ATP levels remained greater than 50% of baseline and ultrastructurally intact platelets were seen. In the 1-g resin bags the pH remained at baseline levels (6.9-7.0), while there was a rise in pH in the 2-g resin bags. These results demonstrate the beneficial effects of maintaining a higher pH during platelet storage and provide a new approach to studying the metabolic changes that occur during longer term storage.     

Long-term follow-up patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized

Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.     

几丁糖与人工骨联合应用预防椎板切除术后硬膜外粘连的实验研究

目的:观察椎板切除术后用几丁糖(CHT)的同时在椎板缺损处植入磷酸三钙人工骨(TCP)预防硬膜外瘢痕粘连的效果。方法:40只纯种日本大耳白兔随机分成A、B、C、D四组,制作L4椎板损伤模型。A组硬膜外涂布生理盐水,B组硬膜外涂布几丁糖,C组硬膜外覆盖人工骨,D组硬膜外涂布几丁糖的同时加人工骨覆盖。术后12周对椎板切除部位进行大体观察、组织学观察及生化检查,比较各组间瘢痕形成和粘连情况。结果:B、C、D组的改良Rydell-Balazs粘连韧度评分、胶原含量及改良Nussvaum组织学评分均优于A组(P<0.01),D组优于B组与C组(P<0.05),B组与C组无显著性差异(P>0.05)。结论:联合应用几丁糖和人工骨能有效预防硬膜外瘢痕粘连的形成,比单独应用几丁糖和人工骨预防效果好。     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.     

Cytomegalovirus-seronegative blood components for the prevention of primary cytomegalovirus infection after marrow transplantation. Considerations for blood banks

The authors report 2.5 years' experience with the use of cytomegalovirus (CMV)-seronegative blood components for the prevention of primary CMV infection after allogeneic marrow transplantation from seronegative marrow donors to 104 CMV-seronegative patients. Patients and blood donors were screened for CMV-seronegativity by a combination of passive latex agglutination, complement fixation, and indirect hemagglutination CMV antibody screening methods. Changes in blood banking procedures necessary to provide CMV-seronegative components are detailed. Providing CMV-seronegative components was a considerable undertaking; a mean, per patient, of 19 units of red cells and 105 units of platelets was required. Twenty percent of the platelet support was provided by family members and 80 percent by volunteer donors. CMV-infection was eliminated in all but one patient not considered infected at the time of transplantation. The capability to provide CMV-seronegative components depends on an adequate supply of seronegative donors, a sensitive and practical screening method for CMV antibody, a major commitment by the blood bank, and close communication between the blood bank and the patients' physicians.