Silicone rubber and natural rubber as biomaterials

The roles of silicone rubber and natural rubber as biomaterials are contrasted, with silicone rubber being widely used and natural rubber having, as yet, found limited application. Relevant properties of both elastomers are described, applications are discussed and possible future developments are considered.     

HLA-C revisited

During the past 10 years knowledge about the interactions between major histocompatibility complex (MHC) class I molecules and the T-cell receptor (TCR) complex of cytotoxic T-cells (CTL) has developed dramatically. But the primary interest, both with respect to structure as well as function, has concentrated on HLA-A and -B molecules because of their high sequence polymorphism and their dominating presence at the cell surface. In contrast, HLA-C molecules seemed to be of only minor importance in the cascade of immune reactions owing to their more limited polymorphism and reduced levels of surface expression. The inability to define a number of antigen specificities had the result that HLA-C molecules were often neglected in studies of immune response, transplantation, and disease association. More recently a new function has been identified for HLA class I molecules where they act as inhibitors of the lytic capacity of natural killer (NK) cells and non-MHC-restricted T-cells. Moreover, the understanding of this novel mode of negative regulation of cytotoxicity was remarkably influenced by HLA-C since these were the first HLA class I molecules found to have such inhibitory potential. With this new inhibitory function serving as an essential component of the immune system, HLA-C molecules can no longer be neglected.     

Regulation of human natural killer (NK) cell function: Induction of killing of an NK-resistant renal carcinoma cell line

Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), -interferon (IFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E₂ (PGE₂) duringin vitro activation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE₂. Removal of Leu 11b(+), OKM1(+), orl-leucylleucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.     

16例染色体异常核型分析

目的与方法本文对189例自然流产、闭经、发育不全患者进行细胞遗传学检查,结果发现异常核型16例,异常核型涉及1、3、4、5、6、7、8、9、10、 15、X、Y染色体.其中平衡易位10例,性染色体异常3例,大Y染色体3例.结论染色体异常是导致流产、闭经、性发育异常的重要遗传因素,应引起临床医师的高度重视.     

Molecular characterization of a novel pattern recognition protein from nonspecific cytotoxic cells: sequence analysis, phylogenetic comparisons and anti-microbial activity of a recombinant homologue

Nonspecific cytotoxic cells (NCC) are the first identified and most extensively studied killer cell population in teleosts. NCC kill a wide variety of target cells including tumor cells, virally transformed cells and protozoan parasites. The present study identified a novel evolutionarily conserved oligodeoxynucleotide (ODN) binding membrane protein expressed by channel catfish (Ictalurus punctatus) NCC. Peptide fingerprinting analysis of the ODN binding protein (referred to as NCC cationic anti-microbial protein-1/ncamp-1) identified a peptide that was used to design degenerate primers. A catfish NCC cDNA library was used as template with these primers and the PCR-amplified product was sequenced. The translated sequence contained 203 amino acids (molecular mass of 22,064.63 Da) with characteristic lysine rich regions and a pI=pH 10.75. Sequence comparisons of this protein indicated similarity to zebrafish (51.2%) histone family member 1-X and (to a lesser extent) to trout H1. A search of EST databases confirmed that ncamp-1 is also expressed in various tissues of channel catfish as well as zebrafish. Inspection for signature repeats in ncamp-1 and comparisons with histone-like peptides from different species indicated the presence of multiple lysine based motifs composed of AKKA or PKK repeats. The novel protein was cloned, expressed in E. coli and the recombinant was used to generate rabbit anti-serum. The recombinant ncamp-1 bound GpC and CpG ODNs and was detected with homologous anti-ncamp-1 polyclonal antibodies. Western blots of NCC membranes using anti-ncamp-1 serum detected a 29 kDa protein. Binding competition experiments demonstrated that anti-ncamp-1 antibodies and GpC bound to the same protein on NCC. Two different truncated forms of ncamp-1 as well as the full-length recombinant protein exhibited anti-microbial activity. The present study demonstrated the expression by NCC of a new membrane protein that may participate in the recognition of bacterial DNA and as such participate in innate anti-microbial immune responses in teleosts.     

五种免疫相关性心血管疾病的免疫学研究

对扩张型心肌病、风湿性心脏病，原发性高血压，冠心病及肥厚型心肌病进行外周血清可溶性白细胞介素２受体，Ｔ淋巴细胞亚群及自然杀伤细胞活性的检测，并与健康对照组比较，结果显示：ＤＣＭ组，ＲＨＤ组及ＥＨＴ组的ｓＩＬ－２Ｒ明显高于ＮＣ组，而ＤＣＭ、ＲＨＤ风湿活动组的ＮＫ活性低于ＮＣ组，ＥＨＴ组ＮＫ活性高于ＮＣ组。     

Identification of natural antibodies to interleukin-18 in the sera of normal humans and three nonhuman primate species

Natural antibodies to cytokines can be found in the sera of normal healthy individuals in the absence of specific immunostimulation. However, the function, impact, and purpose of natural antibody development have yet to be fully elucidated. Interleukin (IL)-18 is a cytokine that exerts proinflammatory activities and induces natural killer (NK) cell activity. Recombinant human IL-18 (rHuIL-18) is currently in development as a cancer immunotherapy. In this study, the presence of natural antibodies to IL-18 in the sera of normal humans and three nonhuman primate species was evaluated by electrochemiluminescence immunoassay (ECLIA). Of the human sera tested, 6 of 47 samples were positive for natural antibodies to IL-18. Of the nonhuman primate sera tested, 22 of 80 cynomolgus monkey samples, 4 of 31 rhesus monkey samples, and 2 of 20 chimpanzee samples were positive for natural antibodies to IL-18. Natural anti-IL-18 antibodies were neutralizing in 5 of 22 cynomolgus and 2 of 4 rhesus sera. None of the chimpanzee or human sera were able to neutralize IL-18 induction of interferon (IFN)-gamma in vitro. In vivo activity of rHuIL-18 was compared in IL-18 natural antibody-positive and -negative cynomolgus monkeys. The presence of natural antibodies to IL-18 did not alter rHuIL-18 systemic exposure levels, induction of neopterin, or induction of treatment-induced antibodies following intravenous administration of rHuIL-18. In conclusion, our data indicate that, as has been found with other cytokines, natural anti-IL-18 antibodies are relatively common. Moreover, natural anti-IL-18 antibodies do not appear to influence rHuIL-18 activity in vivo and are not predictive of a heightened immune response, suggesting that natural anti-IL-18 antibodies do not impact IL-18 therapy. Finally, our data suggest that the ability to detect natural anti-cytokine antibodies may be a useful measure of the adequacy of an assay for deployment in clinical trials.     

Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma

Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals (81 patients with liver disease and 42 healthy volunteers). The liver diseases included periportal fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T-cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease ( P<0.01) in CD3 and CD4 T-cells, and a highly significant increase ( P<0.001) in CD57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of liver cirrhosis and HCC.     

Ly49 gene expression in different inbred mouse strains

Mouse natural killer cells express receptors for class IMHC in the form of the Ly49 family of proteins. The Ly49 family contains at least 13 expressed members (A, B, C, D, E, F, G, H, I, J, L, O, and P) and is further subdivided into activating and inhibitory subfamilies based on intracellular and transmembrane characteristics. The level of sequence identity between different members varies dramatically. However, comparison of the extracellular domain has revealed that several of the Ly49 molecules also form “pairs,” where one member is activating and the other is inhibitory. Until recently, most Ly49 molecules described have come from the C57B1/6 strain of inbred mice. Using molecular cloning and immunochemical analysis we have found that different mouse strains express novel Ly49 molecules. Comparison of the allelic forms of some Ly49 molecules has shown that the dividing line between different genes and different alleles is blurred. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-56000. Animal care was provided in accordance with the procedures outlined in A Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication No. 86-23, 1985). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.     

Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients

Summary The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.