Nodular bleomycin toxicity

Pulmonary interstitial fibrosis, a well-known toxic effect of bleomycin therapy, usually presents radiographically as diffuse reticularity. The authors report an unusual case of biopsy-proven bleomycin toxicity that presented as pulmonary nodules mimicking metastatic tumor. The histologic findings resembled those seen in the diffuse form of toxicity but notably also included foci of bronchiolitis obliterans.     

Strain‐dependent induction of allergic rhinitis without adjuvant in mice

BACKGROUND: To date, no murine models have been reported to show the induction of both antigen-specific IgE and nasal eosinophilia, two of the major hallmarks of allergic rhinitis, after local sensitization in the absence of adjuvants, a phenomenon which reflects natural exposure. In this report, we attempted to establish a murine model representing an initiation of allergic rhinitis. METHODS: BALB/c, CBA/J, and C57BL/6 mice were sensitized intranasally to Schistosoma mansoni egg antigen (SEA) solely. After repeated sensitization, serum Ab titers, nasal eosinophilia, and cytokine production by nasal lymphocytes were determined. RESULTS: BALB/c mice produced SEA-specific IgE after repeated sensitization. High-dose sensitization to SEA induced IgE production in CBA/J mice, while C57BL/6 mice did not show the production throughout the period observed, suggesting that IgE production was regulated genetically. BALB/c mice also exhibited nasal eosinophilia after the nasal challenge. In addition, nasal lymphocytes sensitized with SEA intranasally produced significant amount of IL-5 in vitro. CONCLUSIONS: These results suggest that intranasal sensitization with SEA in the absence of adjuvants induces a Th2 immune reaction, reflecting the hallmarks of the initiation of allergic rhinitis both in vivo and in vitro, which is genetically regulated.     

Large French-Canadian family with Lewy body parkinsonism: exclusion of known loci.

The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French-Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two-point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well-documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of alpha-synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome-wide screen has been undertaken in an effort to identify a novel PD gene.     

Glucocorticoids potentiate kainic acid-induced seizures and wet dog shakes

Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes.     

Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.     

乳腺癌患者保乳术联合腔镜腋窝淋巴结清扫术的临床研究

目的 探讨保乳手术联合腔镜腋窝淋巴结清扫术(MALND)对乳腺癌患者上肢功能、应激反应及血管细胞黏附分子-1 (VCAM-1)、细胞间黏附分子-1(ICAM-1)水平的影响。方法 回顾性分析98例乳腺癌患者的临床资料,依据手术方式的不同分为研究组53例和对照组45例。对照组行保乳手术联合传统腋窝淋巴结清扫术(CALND),研究组行保乳手术联合MALND。比较2组术前、术后6个月上肢功能;收集2组患者术前、术后12 h焦虑自评量表(SAS)、抑郁自评量表(SDS)评分以及心率(HR)、平均动脉压(MAP)水平,并对比2组应激反应程度;比较2组患者术前、术后5 d VCAM-1、ICAM-1水平。结果 术后6个月,研究组前屈、后伸、内收、外展、内旋、外旋活动角度大于对照组,差异有统计学意义(P<0.05);术后12 h,研究组SAS、SDS评分及HR、MAP水平低于对照组,差异有统计学意义(P<0.05);术后5 d,研究组VCAM-1、ICAM-1水平低于对照组,差异有统计学意义(P<0.05)。结论 保乳手术联合MALND对乳腺癌患者上肢功能影响小,术后应激反应程度轻...     

Prolonged alterations in the serotonin neural system following the cessation of adolescent anabolic-androgenic steroid exposure in hamsters (Mesocricetus auratus)

In hamsters (Mesocricetus auratus), anabolic-androgenic steroid (AAS) exposure during adolescence facilitates offensive aggression that is modulated, in part, by serotonin (5-HT) signaling and development and by signaling and expression of 5-HT1B receptors. To examine whether these effects are persistent or reversible, the authors administered AAS to hamsters, then examined them for aggression at 1, 4, 11, 18, or 25 days following cessation of AAS treatment. Then, 1 day later, hamsters were killed by transcardial perfusion and examined for 5-HT afferents to and 5-HT1B receptor-containing neuronal puncta and somata in areas of the brain altered by AAS, namely, the anterior hypothalamus, ventrolateral hypothalamus, and medial amygdala. Although aggression resulting from AAS exposure returned to control, nonaggressive levels by 18 days following cessation of AAS treatment, alterations in 5-HT afferent innervation and 5-HT1B receptor localization were observed throughout the extended time period examined. These data suggest that adolescent AAS exposure may have long-term, irreversible effects on 5-HT neural systems and that return to nonaggressive behavioral phenotypes following adolescent AAS exposure may not be a function of plasticity in central 5-HT systems.     

1140919448CD200-dependent suppression of human NK activity by IVIG requires CD200 receptor type 2

Problem: IVIG prepared from plasma of stored human blood can be efficacious in improving pregnancy success in a selected subgroup of patients but RCTs using an IVIG showing inferior suppression of NK activity in vitro have been negative (J Assist Reprod Genet 2006). A significant component of NK suppression by IVIG appears to be due to CD200 released into plasma from PBL during storage at 4C. CD200 receptors (CD200R) are expressed at the fetomaternal interface prior to onset of abortion; CD200R1 mediates direct effects on gamma‐delta T cell development and suppresses alpha‐beta T cell responses in vitro, whereas CD200R2 alters DC so as to facilitate development of alpha‐beta Treg cells. Which receptor(s) mediate NK cell suppression? Methods: Purified human PBL or the CD56⁺ NK cell subset of PBL were used to lyse 51Cr‐labeled K562 cells in vitro. Different IVIG preparations were tested for suppressive ability, and suppression was blocked by either anti‐huCD200 mAb or rabbit anti‐huCD200R1 or R2 antibodies. Results: CD200‐dependent IVIG NK suppressive potency differed among IVIG types (Gammagard>Gamunex>>Gamimmune). CD200‐dependent suppression was blocked by anti‐CD200R antibody able to react with the type 2 receptor. K562 cells did not express receptor, and purified CD56⁺ NK cells were suppressed effectively without the need for non‐NK cells. Conclusions: IVIG may directly express NK cell activity via CD200 binding to CD200R2.