Changes in dendritic cell migration and activation during SIV infection suggest a role in initial viral spread and eventual immunosuppression

Dendritic cells (DC) serve an essential function in linking the innate and acquired immune responses to antigen. Peripheral DC acquire antigen and migrate to draining lymph nodes, where they localize to the T cell-rich paracortex and function as potent antigen presenting cells. We examined the effects of human immunodeficiency virus (HIV) infection on DC function in vivo using the rhesus macaque/simian immunodeficiency virus (SIV) model. Our data show that during acute SIV infection, Langerhans cell density is reduced in skin and activated DC are increased in proportion in lymph nodes, whereas during AIDS, DC migration from skin and activation within lymph nodes are suppressed. These findings suggest that changes in DC function at different times during the course of infection may serve to promote virus dissemination and persistence: early during infection, DC mobilization may facilitate virus spread to susceptible lymph node T cell populations, whereas depressed DC function during advanced infection could promote generalized immunosuppression.     

In vitro multiplication of Quercus leucotrichophora and Q. glauca: Important Himalayan oaks

Multiple shoots of Quercus leucotrichophora L. and Q. glauca Thunb. were induced from the intact embryos (decoated seeds) as well as from the cotyledonary nodes (with attached cotyledons but without radicle and primary shoot) of 3-weeks old in vitro grown seedlings on Woody Plant (WP; Lloyd and McCown, 1980) and Murashige and Skoog (MS; 1962) media supplemented with 6-benzyladenine (BA), either alone or in combination with gibberellic acid (GA₃)/ indole-3-butyric acid (IBA). BA (22.19 M) was effective for induction of multiple shoots and addition of GA₃ to the medium further enhanced the shoot number and shoot height but resulted in shoot thinness. High frequency shoot multiplication was achieved using cotyledonary nodes. Shoots were further multiplied from the original explant on WP medium supplemented with BA (22.19 M). Nearly 78% and 67% rooting was obtained in Q. leucotrichophora and Q. glauca microshoots (3–4 cm high), respectively on 1/2 strength WP medium supplemented with IBA (14.76 M). However, this was associated with basal callus formation. Treatment with IBA (25–100 M) for 24 or 48 h followed by transfer to PGR free 1/2 strength WP medium not only improved the rooting percentage but also avoided basal callus formation. IBA at 100 M for 24 h was most effective (90% and 100% rooting in Q. leucotrichophora and Q. glauca, respectively). In vitro rooted plants were hardened and established in garden soil.Growth performance of 6-month-old in vitro raised plants was compared with ex vitro plants (seedlings) of the same age. The photosynthesis and transpiration rates of eight months old in vitro and ex vitro raised plants of both species were measured under different light (0, 600, 900, 1200, 1500 and 2000 mol m^–2s^–1) and temperature (20, 25, 30, 35 and 40 °C). Light optimum for photosynthesis was around 2000 mol m^–2s^–1 in Q. leucotrichophora and around 1500 mol m^–2s^–1 in Q. glauca whereas optimum temperature for photosynthesis was 25 °C in Q. leucotrichophora and 30 °C in Q. glauca. The rate of transpiration at different temperatures (20–40 °C), in the two species, increased with increase in the light intensity up to the highest level, i.e., 2000 mol m^–2s^–1. Temperatures beyond 35 °C adversely affected the rate of transpiration in in vitro raised as well as ex vitro plants of both the species. In vitro raised and hardened plants of both the species were comparable to ex vitro plants in terms of gas and water vapour exchange characteristics, within the limits of this study.     

Autoantibody to DNA binding protein B as a novel serologic marker in systemic sclerosis

Systemic sclerosis is a systemic disease that is characterized by tissue fibrosis, small-vessel vasculopathy, and an autoimmune response associated with autoantibodies. We performed serological analysis of cDNA expression library (SEREX) to identify autoantibodies associated with systemic sclerosis. We identified 4 clones that react with sera of patients with SSc but not with those of healthy donors. These clones are phosphoglycerate mutase, centromere autoantigen C, U1 small nuclear ribonucleoprotein, and DNA binding protein B (dbpB). We chose to study autoantibody to DNA binding protein B. Immunoreactivity against recombinant dbpB was detected in 40.5% (15/37) of patients with SSc, 14.6% (6/41) of patents with systemic lupus erythematosus, 6.7% (1/15) of patients with rheumatoid arthritis, 0% (0/12) of patients with Sjogren syndrome, and 5.9% (1/17) of patients with polymyositis/dermatomyositis. The frequency of anti-dbpB was significantly higher in the SSc patients (15/37, 40.5%) compared to the healthy controls (3/41, 7.3%, p=0.0005 by chi(2) test). Eleven patients (11/20, 55%) with the diffuse cutaneous type of SSc had anti-dbpB and 4 patients (4/17, 23.5%) with the limited cutaneous type had anti-dbpB. The presence of anti-dbpB was significantly associated with the diffuse cutaneous type (p=0.00003 by chi(2) test). This is the first report to suggest that autoantibody to dbpB can be used as a serologic marker of systemic sclerosis.     

The glycosylphosphatidyl inositol-anchored adhesion molecule F3/contactin is required for surface transport of paranodin/contactin-associated protein (caspr)

Paranodin/contactin-associated protein (caspr) is a transmembrane glycoprotein of the neurexin superfamily that is highly enriched in the paranodal regions of myelinated axons. We have investigated the role of its association with F3/contactin, a glycosylphosphatidyl inositol (GPI)-anchored neuronal adhesion molecule of the Ig superfamily. Paranodin was not expressed at the cell surface when transfected alone in CHO or neuroblastoma cells. Cotransfection with F3 resulted in plasma membrane delivery of paranodin, as analyzed by confocal microscopy and cell surface biotinylation. The region that mediates association with paranodin was mapped to the Ig domains of F3 by coimmunoprecipitation experiments. The association of paranodin with F3 allowed its recruitment to Triton X-100-insoluble microdomains. The GPI anchor of F3 was necessary, but not sufficient for surface expression of paranodin. F3-Ig, a form of F3 deleted of the fibronectin type III (FNIII) repeats, although GPI-linked and expressed at the cell surface, was not recovered in the microdomain fraction and was unable to promote cell surface targeting of paranodin. Thus, a cooperative effect between the GPI anchor, the FNIII repeats, and the Ig regions of F3 is required for recruitment of paranodin into lipid rafts and its sorting to the plasma membrane.     

生物体衰老与复制衰老--体内与体外研究

体外连续培养的细胞在有人数的细胞分裂后,更新换代合成ＤＮＡ及分裂的能力,最后导致增殖能力的丧失,但基本代谢过程仍能维持,这种现象称为复制衰老。本文讨论了复制衰老现象存在的普遍性,描述了衰老细胞伯特征,对复制衰老和生物体衰老之间的联系进行了重点分析。现有的研究虽然还不完全,但都提示复制衰老是生物体衰老在细胞水平上的反映,并充分肯定了复制衰老是一个较好的研究机体衰老的模型。     

Propagation of Dalbergia sissoo Roxb. through in vitro shoot proliferation from cotyledonary nodes

A protocol is presented for micropropagation of an economically important timber-yielding forest tree, Dalbergia sissoo Roxb. (Sissoo). Multiple shoots were induced from cotyledonary nodes derived from 1-week-old axenic seedlings on Murashige and Skoog's medium containing either N ⁶-benzyladenine (BA), kinetin (Kn), isopentenyladenine (2iP) or thidiazuron (TDZ), with BA being the most effective growth regulator. High-frequency shoot proliferation (99%) and maximum number of shoots per explant (7.9 shoots) were recorded with BA at an optimum level of 8.9 μM. Concentrations of all cytokinins tested above the optimum level markedly reduced the frequency of shoot proliferation. A proliferating shoot culture was established by repeatedly subculturing the original cotyledonary node on shoot multiplication medium after each harvest of the newly formed shoots. Primary shoots were multiplied as nodal explants, and from each stem node 2 or 3 shoots developed. Thus, 60–70 shoots were obtained in 3 months from a single cotyledonary node. About 91% of the shoots developed roots following transfer to half-strength MS medium containing a combination of 5.7 μM indole-3-acetic acid, 4.9 μM indole-3-butyric acid and 5.3 μM indole-3-propionic acid. Eighty percent of the plantlets were successfully acclimatized and established in soil. Received: 1 October 1997 / Revision received: 31 March 1998 / Accepted: 7 April 1998     

Determinants of Intestinal Detoxication of Lipid Hydroperoxides

It has long been recognized that hydroperoxides are agents of cytotoxicity. However, in recent years, it is increasingly apparent that lipid hydroperoxide may play an important role in mediating cellular and molecular events in degenerative pathophysiological processes that lead to intestinal disorders, such as cancer. Yet, surprisingly, little is known of the intestinal disposition of peroxidized lipids and of the metabolic factors that determine mucosal peroxide elimination. The present paper summarizes the evidence for the pivotal role of reductant (GSH and NADPH) availability in intestinal peroxide detoxication. This information will provide important insights into the relationship between luminal lipid hydroperoxides and intestinal GSH redox homeostasis, and is pertinent to understanding how dietary oxidants like lipid peroxides, can impact intestinal integrity with implications for genesis of gut pathology.     

2型糖尿病的系统性血管保护治疗策略

在最新研究发现的系统性血管保护的优化治疗策略表明,血管损伤机制与胰岛素抵抗、糖尿病肾病及外周动脉疾病(PAD)的发病机理相关。胰岛素抵抗机制在血管损伤方面主要表现为大血管和微血管病变。系统性动脉硬化性疾病的及时诊断和干预是至关重要的。并且,治疗方面不仅仅是改善现有疾病状况,也应注意减少心血管事件的风险。这些努力有助于降低心血管事件的风险和死亡率。PAD的治疗包括药物治疗、血管内治疗和血管重建,以及运动疗法。经典治疗药物包括血管舒张剂,如贝前列素和抗血小板药物。值得注意的是,贝前列素除血管舒张活性外还有几个其他治疗作用,包括保护血管内皮、抗血小板和抗炎作用。最近的前期临床研究表明,贝前列素不仅通过其舒张血管活性改善四肢缺血,同时改善了影响血管内皮功能的胰岛素抵抗。贝列前素的应用,在早期疾病阶段维持血管内皮功能,减少血管事件的发生率,发挥其系统性血管保护作用。这样,贝列前素最终将有助于改善患者的生存质量并可能增加PAD患者的寿命。