A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.     

鱼类染色体G—显带的Brd U—BSG方法及白鲢G—带模式图的初步建立

本文报道了一种显示鱼类染色体G-带的BrdU-BsG方法。采用肾细胞短期培养,收获前12小时加入BrdU,使终浓度为10μg/ml。制片经HCl、Ba(OH)_2处理,4×SSC温育。Giemsa染色,显示出白鲢的G-带。其带纹细致清晰,一个细胞的单倍染色体上显示带纹达200条以上,是目前已报道的鱼类多重带中带纹最多的,且反差明显,带纹有特征性,结果较稳定。根据实验结果初步建立了白鲢的G-带模式图。     

A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation

A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies'' chaperone-like function.     

Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models

Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS lymphoma. POM should be further evaluated in clinical trials.     

Amyloidogenicity of naturally occurring full‐length animal IAPP variants

The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP.     

The rattan trade of Northern Myanmar: Species, supplies, and sustainability

Although Myanmar exports millions of dollars of rattan cane each year, the last systematic treatment of rattans in this country was done over 100 years ago, and virtually nothing has been written about the collection and trade of this important forest resource. Here we report the results from a study of rattans in the Hukaung Valley Tiger Reserve in northern Myanmar. A total of 15 species of rattan were encountered; seven species are new records for Myanmar and two species are new to science. Inventory transects revealed that the density of commercial rattans in local forests averages 40.5 canes ≽4m long/hectare. Populations of all species appear to be actively regenerating. The current pattern of rattan exploitation, however, is largely uncontrolled and will eventually lead to resource depletion unless some form of management is implemented.     

The descending branch of the superficial circumflex artery supplying anteromedial thigh skin

This report presents an extended groin flap design that consists of a conventional skin paddle in the groin region and a vertical extension in the anteromedial thigh region, based on the superficial iliac circumflex artery and an unnamed descending branch, respectively. The inferior branch of the superficial iliac circumflex artery that supplies the thigh extension of the flap, spanning approximately the upper half of the thigh region, was found to originate approximately 2 cm from the origin of the superficial iliac circumflex artery. A total of six free and four local flaps were used in 10 patients with ages ranging from 10 to 60 years (average, 45 years). There were six male and four female patients. The free flaps were required for total facial resurfacing, through-and-through cheek defect, and burn scar contractures and traumatic defects of the lower extremity. The local flaps were used for reconstruction of scrotum defect, trochanteric decubitus ulcer, and lower abdominal skin and fascia defects. All 10 flaps survived completely. The groin flap with anteromedial thigh extension offers the following advantages: (1) it is very easy and quick to elevate; (2) a significantly increased volume of tissue is available for reconstruction, based on one axial vessel and being completely reliable; (3) the flap offers two skin paddles that are independently mobile; (4) there is no need for positional change and a two-team approach is possible; and (5) it can be raised as a vertical skin island only. The authors conclude that the groin flap with anteromedial thigh extension is a useful modification for reconstruction of both distant and local defects.