Relationship Between Architecture and Adhesion in Polyurethane‐Based Copolymers, 2

Summary: This study describes the chain extension, with polycaprolactone diols, of polyurethane‐graft‐poly(butyl acrylate)s which were first prepared by the step growth polymerization of a mixture of diphenylmethane‐4,4′‐diisocyanate (MDI) and α,α′‐dihydroxyl‐poly(butyl acrylate)s. The success of the chain extension reaction was studied and confirmed by ¹H NMR, SEC and DSC analysis. The incorporation of polycaprolactone sequences in the polyurethane chains modified their specific adhesive properties, bringing cohesion to the material, as demonstrated by tack measurements.

PUR‐graft‐PBA extended with PCL.     

Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics

Chronic alcoholics are frequently immunodeficient, have polyclonal hypergammaglobulinaemia, and often have autoantibodies. Recent work in other diseases has shown that functional distinctions of possible relevance to autoimmunity and immunodeficiency can be found among the B cell subsets defined by differential expression of the surface markers CD5 and CD45RA. Therefore, we have evaluated the CD5,CD45RA B cell subsets of both chronic alcoholics without evidence of active liver disease (AWLD), and alcoholics admitted for acute alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry in 20 patients and 29 controls revealed a sharp decrease in the percentage of alcoholics’ B cells which were CD5⁺, 37·6% versus 16·3%, P<0·00001; absolute CD5⁺ B cell numbers were similarly reduced (58·9 cells/μl versus 20·9; P =0·0012). In addition to the loss of CD5⁺ B cells, there was a reduction in the percentage of B cells which are CD5⁻CD45RA^hi, leaving many patients with a B cell profile which was predominantly CD19⁺CD5⁻CD45RA^lo. This subset appears phenotypically similar to the IgM-producing CD5⁻CD45RA^lo subset described by others, and may be enriched for autoantibody-producing cells. One outlier patient was an ALD with 61% of B cells which were CD5⁺, which also is a profile consistent with increased autoantibody production.     

Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA)

Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2⁺ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.     

Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice

Disruption of cell polarity is seen in many cancers; however, it is generally considered a late event in tumor progression. Lethal giant larvae (Lgl) has been implicated in maintenance of cell polarity in Drosophila and cultured mammalian cells. We now show that loss of Lgl1 in mice results in formation of neuroepithelial rosette-like structures, similar to the neuroblastic rosettes in human primitive neuroectodermal tumors. The newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally. A large proportion of Lgl1(-/-) neural progenitor cells fail to exit the cell cycle and differentiate, and, instead, continue to proliferate and die by apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack of differentiation. These results reveal a critical role for mammalian Lgl1 in regulating of proliferation, differentiation, and tissue organization and demonstrate a potential causative role of disruption of cell polarity in neoplastic transformation of neuroepithelial cells.     

Histiocytosis X arising in Hodgkin's disease: immunophenotypic characterization with a panel of monoclonal antibodies

Summary This report describes the antigenic profile of the proliferating cells of pulmonary histiocytosis X (HX) in a patient treated with chemotherapy for Hodgkin's lymphoma; the association of pulmonary HX and Hodgkin's disease has rarely been described in the literature. The histopathological diagnosis of HX was confirmed with the aid of monoclonal antibodies (mAbs) to CD4, CD1a, and polyclonal serum anti S-100 protein. The phenotype of HX cells has been analysed using a panel of mAbs against HLA class I A, B, C monomorphic determinants, locus A and B,2-microglobulin, HLA class II distinct monomorphic determinants, DP, DQ, DR, intercellular adhesion molecule-1 (ICAM-1) and vitronectin receptors. Our results indicate that HX cells express HLA class I and II, including locus A, locus B and DP, DQ, DR, like their normal counterpart (represented by Langerhans cells) and detectable levels of ICAM-1 but not vitronectin receptors. We would like to stress the possibility of the association of HX and Hodgkin's lymphoma extending the immunophenotypic profile of HX cells.     

中枢神经系统感染患者血清NSE和sICAM-1的改变

目的 :探讨中枢神经系统感染患者血清中NSE和sICAM 1水平的改变。方法 :采用ELISA法检测了 30例CNS感染的患者和 2 0例正常健康人血清中的NSE和sICAM 1水平。结果 :在CNS感染患者血清中NSE( 12 5 .6 8± 14 .38μg/L)和sICAM 1( 4 48.94± 96 .70μg/L)显著高于正常对照组的NSE( 6 .6 6± 1.2 5 μg/L)和sICAM 1( 2 91.78± 39.18μg/L) ,P <0 .0 1。在CNS感染各组中病毒性脑炎患者的NSE亦显著高于其他各组 ;sICAM 1在CNS感染各组间无显著性差异 ,P >0 .0 5。结论 :提示NSE和ICAM 1可作为CNS损害和感染的监测指标     

HSP70对大鼠肝脏局部缺血再灌注后炎症反应的影响

目的：通过热应激预处理诱导HSP70表达，探讨其对肝脏缺血再灌注损伤后炎症反应的影响。方法:采用大鼠局部缺血再灌注模型（IR组），并在热应激预处理（H+IR组）及槲皮素＋热应激预处理（Q+H+IR组）条件下观察肝脏缺血再灌注后HSP70、ICAM-1的表达及MPO的活性；测定血清ALT和AST的活性；电镜观察肝细胞结构的改变。结果:在H+IR组检测的各时点HSP70表达均明显高于其它两组、对肝脏进行缺血再灌注后，肝细胞损伤较轻，血清ALT、AST升高不明显(P<0.01)；肝组织中ICAM-1表达增加，以再灌注后6 h最显著，MPO活性升高以12 h最为显著，但两者变化均低于IR组和Q+H+IR组(P<0.01)。结论：〖HTSS〗热应激预处理诱导产生HSP70蛋白能够降低大鼠肝脏缺血再灌注损伤过程ICAM-1的表达和MPO活性的改变，进而抑制炎症反应引起的肝脏损伤。     

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.     

The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.     

Microscopic analysis of the cellular events during scatter factor/hepatocyte growth factor-induced epithelial tubulogenesis

Scatter factor/hepatocyte growth factor (SF/HGF), a large multifunctional polypeptide growth and motility factor, is known to play important roles during embryonic development, adult tissue growth and repair. In an established three-dimensional type I collagen model, SF/HGF induces Madin-Darby canine kidney (MDCK) epithelial cysts to form long, branching tubules (tubulogenesis). In addition, the composition of the surrounding extracellular matrix (ECM) has been shown to modulate SF/HGF-induced morphogenesis, where tubulogenesis was completely abrogated in Matrigel basement membrane. Many cellular events that occur during SF/HGF-mediated remodelling, and its modulation by the ECM, remain unclear. We have investigated these mechanisms through microscopic examination of the time-course of SF/HGF-induced responses in MDCK cysts cultured in type I collagen or Matrigel. We found that early responses to SF/HGF were matrix-independent. Changes included increased paracellular spacing between normally closely apposed lateral membranes, and the formation of filopodial processes, indicating a partial motile response. Cell-cell contact was maintained, with the persistence of cell junctions. Therefore, while one or a number of ECM components are preventing SF/HGF-primed cells from undergoing an invasive and/or migratory programme, non-permissive matrices are not preventing SF/HGF signalling to the cell. Later matrix-dependent responses, which occurred in type I collagen but not Matrigel, included the formation of basal protrusions that comprise two or more neighbouring cells, which extend to form nascent tubules. Modified polarity of cells comprising the basal protrusions was evident, with a marker for the apical membrane being found in the same region as adherens junctions and desmosomes, typically localized at lateral membranes. We propose a model for SF/HGF-induced tubulogenesis in which tubules form from basal protrusions of adjacent cells. This mechanism of in vitro tubule formation has many similarities to reported in vivo epithelial tubulogenesis.