Monoliths with chiral surface functionalization for enantioselective capillary electrochromatography

The state-of-the-art in CEC enantiomer separations with monolithic capillary columns is comprehensively reviewed. The various types of monolithic columns comprising in situ organic polymer monoliths, molecularly imprinted polymer (MIP) monoliths, silica monoliths and monoliths made from particles are discussed with a focus on materials’ synthesis, chemistry and properties as well as column aspects. Monolithic MIP-type porous layer open-tubular (PLOT) columns are treated herein as well. From this survey of the literature, the authors come to the conclusion that monolithic silica capillaries appear to become the preferred column type for CEC enantiomer separations of low-molecular drugs and other chiral pharmaceuticals or chemicals.     

Retinal astrocyte differentiation mediated by leukemia inhibitory factor in cooperation with bone morphogenetic protein 2

Retinal astrocytes and their precursor cells migrate from the optic nerve. Interleukin 6 family cytokines, whose signal transduction requires gp130, promote astrocyte differentiation in the optic nerve, though the mechanism of astrocyte differentiation in the retina has not been clarified. We found that GFAP-positive astrocytes were significantly decreased in number but that a considerable number of astrocytes were still present in gp130-deficient mouse retina. These findings suggest that gp130-dependent signaling pathways play essential roles in retinal astrocyte differentiation and that retinal astrocyte differentiation can also be promoted by other signaling pathways. We found that leukemia inhibitory factor, bone morphogenetic proteins, and their receptors are expressed in P0 retina. In addition, leukemia inhibitory factor and bone morphogenetic protein 2 synergistically promote astrocyte differentiation of retinal precursor cells isolated from P0 mouse retina. These observations demonstrated that not only gp130-dependent signaling but also bone morphogenetic proteins play essential roles in retinal astrocyte differentiation.     

Zinc-mediated neuronal death is dependent on Trk activation

Zinc release is a primary mediator of neuronal death. Here we show that zinc-mediated death of neurons in vitro is dependent on nerve growth factor (NGF) stimulation and does not occur in response to exposure to leukemia inhibitory factor. NGF priming is regulated, not by the traditional neurotrophin death receptor, p75NTR, but by TrkA, in a protein- and mRNA synthesis-dependent manner. Furthermore, Trk signaling promotes raised free intracellular zinc, mediating neuronal death after extracellular application of zinc. Thus, regulators of Trk signaling provide attractive targets for future treatment of zinc-associated neurological diseases, including stroke, epilepsy and brain trauma.     

Increase in dopaminergic neurons from mouse embryonic stem cell-derived neural progenitor/stem cells is mediated by hypoxia inducible factor-1alpha

A reliable method to induce neural progenitor/stem cells (NPCs) into dopaminergic (DAergic) neurons has not yet been established. As well, the mechanism involved remains to be elucidated. To induce DAergic differentiation from NPCs, a cytokine mixture (C-Mix) of interleukin (IL)-1beta, IL-11, leukemia-inhibitory factor (LIF), and glial-derived neurotrophic factor or low oxygen (3.5% O(2): L-Oxy) was used to treat embryonic stem (ES) cell-derived NPCs. Treatment with C-Mix increased the number of tyrosine hydroxylase (TH)-positive cells compared with controls (2.20-fold of control). The C-Mix effect was induced by mainly LIF or IL-1beta treatment. Although L-Oxy caused an increase in TH-positive cells (1.34-fold), the combination of L-Oxy with C-Mix did not show an additive effect. Increases in DA in the medium were shown in the presence of C-Mix, LIF, and L-Oxy by high-performance liquid chromatography. Gene expression patterns of neural markers [tryptophan hydroxylase (TPH), GAD67, GluT1, beta-tubulin III, glial fibrillary acidc protein, and TH] were different in C-Mix and L-Oxy treatments. Because increases in hypoxia-inducible factor (HIF)-1alpha protein were found in both treatments, we investigated the effect of HIF-1alpha on differentiation of NPCs to DAergic neurons. Inhibition of HIF-1alpha by the application of antisense oligodeoxynucleotides (ODNs) to NPCs caused a decrease in TH-positive cells induced by LIF treatment. Gene expressions of TH, GAD67, and GluT1 were decreased, and those of TPH, beta-tubulin III, and S-100beta were increased by treatment with just ODNs, indicating the importance of the endogenous effect of HIF-1alpha on neuronal differentiation. These data suggest that enhanced differentiation into DAergic neurons from ES cell-derived NPCs was induced by C-Mix or L-Oxy mediated by HIF-1alpha.     

输卵管积水对着床窗期子宫内膜人白血病抑制因子(LIF)和转化生长因子(TGF-β_2)表达的影响

目的:探讨输卵管积水对人子宫内膜着床窗期的影响。方法:用免疫组化法检测输卵管积水组(A组)、输卵管阻塞无积水组(B组)和正常组(C组)着床窗期子宫内膜人白血病抑制因子(LIF)和转化生长因子(TGF)-β2的表达。结果:LIF和TGF-β2在3组着床窗期子宫内膜都有表达,A组的LIF和TGF-β2表达均明显低于B组和C组组(P<0.05)。结论:输卵管积水妇女着床窗期子宫内膜LIF和TGF-β2的低表达可能是输卵管积水妇女胚胎种植失败的原因之一。     

Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women

A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56⁺ uNK cells along with a decrease in CD16⁺ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3⁺ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms.     

正常结肠和结肠恶性肿瘤的激光诱发荧光光谱

本试验以氮分子激光作为激发光源,以光学多道分析仪(OMAⅢ)为光谱分析手段,对24例外科手术切除的结肠恶性肿瘤标本进行了研究,光谱分析发现,正常组织和肿瘤组织各具其光谱特征值,以此可作为区分结肠恶性肿瘤的标准。     

Leukocyte migration inhibition factor test as a diagnostic tool for cow's milk allergy

Peripheral blood lymphocytes of children suspected of having cow's milk allergy (CMA) were incubated with cow's milk proteins (β-lactoglobulin, α-lactalbumin and casein) to study release of lymphokines as a result of a specific cell-mediated immunity response to these allergens. LIF (leukocyte migration inhibition factor) production was evaluated by measuring migration areas of leukocytes of healthy donors packed in capillary tubes and added by the the supernatant of whole blood cultures, with and without allergens. Of 57 children studied, 10 were normal controls, 12 had chronic diarrhea, 16 were suspected of CMA not confirmed by milk challenge, 19 had CMA confirmed by one of two milk challenges. LIF Test was positive in 68% of patients with CMA and in 8% of other children. The LIF results are more correlated with the diagnosis than other tests commonly employed. Five patients with CMA reexamined when able to tolerate milk had a decreased production of lymphokines. This study emphasizes the role of cellmediated immunity reactions in the pathogenesis of cow's milk allergy. LIF TEst is proposed as a valid and specific aid for the diagnosis of CMA and as a useful tool in documenting the loss of hypersensitivity.     

Orphan neurones and amine excess: the functional neuropathology of Parkinsonism and neuropsychiatric disease

The aetiology and treatment of Parkinsonism is currently conceptualised within a dopamine (DA) deficiency-repletion framework. Loss of striatal DA is thought to cause motor impairment of which tremor, bradykinaesia and rigidity are prominent features. Repletion of deficient DA should at least minimise parkinsonian signs and symptoms. In Section 2, based on extensive pre-clinical and clinical findings, the instability of this approach to Parkinsonism is scrutinised as the existing negative findings challenging the DA deficiency hypothesis are reviewed and reinterpreted. In Section 3it is suggested that Parkinsonism is due to a DA excess far from the striatum in the area of the posterior lateral hypothalamus (PLH) and the substantia nigra (SN). This unique area, around the diencephalon/mesencephalon border (DCMCB), is packed with many ascending and descending fibres which undergo functional transformation during degeneration, collectively labelled `orphan neurones'. These malformed cells remain functional resulting in pathological release of transmitter and perpetual neurotoxicity. Orphan neurone formation is commonly observed in the PLH of animals and in man exhibiting Parkinsonism. The mechanism by which orphan neurones impair motor function is analogous to that seen in the diseased human heart. From this perspective, to conceptualise orphan neurones at the DCMCB as `Time bombs in the brain' is neither fanciful nor unrealistic [E.M. Stricker, M.J. Zigmond, Comments on effects of nigro-striatal dopamine lesions, Appetite 5 (1984) 266–267] as the DA excess phenomenon demands a different therapeutic approach for the management of Parkinsonism. In Section 4the focus is on this novel concept of treatment strategies by concentrating on non-invasive, pharmacological and surgical modification of functional orphan neurones as they affect adjacent systems. The Orphan neurone/DA excess hypothesis permits a more comprehensive and defendable interpretation of the interrelationship between Parkinsonism and schizophrenia and other related disorders.     

The use of human lymphoid cell line lymphokine preparations (LCL-LK) as working standards in the bioassay of human leucocyte migration inhibition factor (LIF)

The leucocyte migration inhibition test in agarose as described by Clausen (1971) was modified into a statistically designed assay of LIF activity using human polymorphonuclear leucocytes from single blood donors. Individual assays included a laboratory standard of lymphokine with LIF activity prepared from the culture supernatants of the RPMI 1788 human lymphoblastoid cell line (LCL-LK). Analysis of 157 LIF assays revealed simple criteria by which the acceptability of an individual assay could be judged before subjecting it to statistical analysis. The failure of LIF assays to meet these criteria of acceptability was particularly associated with low areas of control polymorph migration in the absence of lymphokine (‘spontaneous migration’).We demonstrate that the statistically designed assay permits the measurement, with precision, of LIF activity in units/ml by reference to a working standard of LCL-LK. We illustrate the use of this assay in the measurement of LIF activity generated by tuberculin-stimulated human peripheral blood lymphocytes.