Perception and recall of interpersonal feedback: Negative bias in depression

Recent research in depression has raised questions concerning the accuracy with which environmental information is processed. The present study was designed to address this issue by examining the perception and recall of evaluative feedback in clinically depressed psychiatric patients in an interpersonal situation. Depressed and nondepressed psychiatric inpatients and nondepressed hospital employees participated in dyadic interactions with age-matched opposite-sex strangers, discussing their responses to a variety of hypothetical situations. Following the interaction, each subject was given a sheet of paper containing ratings on 13 bipolar adjectives, ostensibly an evaluation of the subject completed by an assistant behind a one-way mirror. In fact, all subjects received identical rating sheets. Subjects were asked to indicate their reactions to this evaluation and were subsequently required to reproduce the evaluation from memory on a blank rating sheet. Although no group differences were obtained with respect to the perceived accuracy of the evaluation, the depressed patients considered the assessment to be less favorable overall than did subjects in either of the nondepressed groups. Furthermore, the depressed subjects, to a significantly greater extent than the nondepressed subjects, recalled the evaluation to be more negative than was actually the case. These results are discussed in terms of both cognitive and interpersonal models of depression, and directions for future research are advanced.     

有机磷解毒剂的研究2.吡啶甲醛肟碘甲烷盐(简称2-PAM)的药理作用

2-吡啶甲醛肟碘甲烷盐(2-PAM)为有效的有机磷解毒剂,本文对其药理作用作了初步的观察.证明对乌拉坦麻醉猫在接近临床用量时已能产生拟肾上腺素作用.连续应用多次后出现快速耐受现象.在应用抗肾上腺素药、利血平或切除两侧肾上腺后,2-PAM作用即减弱.C₆即使用至50毫克/公斤,亦不能阻断其作用,而5毫克/公斤的阿托品几能完全取消之.对离体及在位蟾蜍心脏也表现兴奋,此作用可部分地被C₆所阻断.2-PAM对离体豚鼠肠的兴奋作用,亦可被阿托品所取消.文内对其作用机制作了初步分析.     

Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation

The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use in advanced SM with the D816V KIT mutation. We treated a patient with MCL (with an associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD]) based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT-transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM to 40 nM. The patient exhibited a partial response with significant resolution of liver function abnormalities. In addition, PKC412 treatment resulted in a significant decline in the percentage of peripheral blood mast cells and serum histamine level and was associated with a decrease in KIT phosphorylation and D816V KIT mutation frequency. The patient died after 3 months of therapy due to progression of her MDS/MPD to acute myeloid leukemia (AML). This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease.     

Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis

The PTPN11 gene encodes SHP-2 (Src homology 2 domain-containing protein tyrosine Phosphatase), a nonreceptor tyrosine protein tyrosine phosphatase (PTPase) that relays signals from activated growth factor receptors to p21Ras (Ras) and other signaling molecules. Mutations in PTPN11 cause Noonan syndrome (NS), a developmental disorder characterized by cardiac and skeletal defects. NS is also associated with a spectrum of hematologic disorders, including juvenile myelomonocytic leukemia (JMML). To test the hypothesis that PTPN11 mutations might contribute to myeloid leukemogenesis, we screened the entire coding region for mutations in 51 JMML specimens and in selected exons from 60 patients with other myeloid malignancies. Missense mutations in PTPN11 were detected in 16 of 49 JMML specimens from patients without NS, but they were less common in other myeloid malignancies. RAS, NF1, and PTPN11 mutations are largely mutually exclusive in JMML, which suggests that mutant SHP-2 proteins deregulate myeloid growth through Ras. However, although Ba/F3 cells engineered to express leukemia-associated SHP-2 proteins cells showed enhanced growth factor-independent survival, biochemical analysis failed to demonstrate hyperactivation of the Ras effectors extracellular-regulated kinase (ERK) or Akt. We conclude that SHP-2 is an important cellular PTPase that is mutated in myeloid malignancies. Further investigation is required to clarify how these mutant proteins interact with Ras and other effectors to deregulate myeloid growth.