一株可识别胸腺基质内上皮细胞与血管系统的单链抗体

胸腺是Ｔ细胞分化和发育的主要场所〔1〕,胸腺前体细胞进入胸腺以后通过不断的迁移与胸腺微环境中各种成分相互作用 ,经历阳性选择和阴性选择形成功能成熟的Ｔ细胞〔2〕。胸腺微环境是一个高度异质化的环境 ,成分复杂 ,包括基质细胞、细胞外基质、细胞因子、激素等等。每种成分在Ｔ细胞的发育中可能起着不同的作用。噬菌体抗体库中存在对各种各样抗原特异的抗体 ,ｖａｎＥｗｉｊｋ实验室应用半合成的抗体库对胸腺的基质进行了研究 ,并得到了 3个针对不同基质细胞的单链抗体〔3〕。在重新筛选和分析抗体库的过程中我们获得了一个新的单链抗体…     

Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation

We measured the formation of a Staphylococcus aureus biofilm in vitro on unloaded and gentamicin-loaded bone cements (CMW3 and Palacos R) and related the formation to antibiotic release rates. All experiments were done in triplicate. Microbial growth on gentamicin-loaded cements occurred despite the release of antibiotic. Biofilm formation on gentamicin loaded CMW3 bone cement was one fourth to one fifth less than on the unloaded bone cement, while biofilm formation on Palacos R bone cement was not significantly affected by antibiotic loading. More gentamicin was released from CMW3 (79 mg) than from Palacos R (70 mg), but the percentage gentamicin released after one week relative to the total amount incorporated was significantly lower for CMW3 (4.7%) than for Palacos R (8.4%). After one day, subinhibitory concentrations of antibiotics were eluted from the cements. We concluded that antibiotic-loaded bone cement does not necessarily inhibit the formation of an infectious biofilm in vitro.     

远端器官预缺血改善冠状动脉缺血再灌注时心肌血供及减少心律失常发生率

远端器官缺血性预处理 (RPC)可减少缺血再灌注后心肌坏死范围。本研究旨在观察RPC对缺血再灌注心脏不同部位血流及心律失常发生率的影响。方法 :19头成年绵羊随机分为对照组 (n =9)及RPC组 (n =10 )。RPC组动物接受 3次左侧股动脉阻断 (5min)及再灌注 (5min) ,随后两组动物均分别依次阻断左冠状动脉前降支 (LAD) 10min ,再灌注 10min ;左冠状动脉第一分支 (D1)阻断及再灌注 10min后阻断左旋支 (LCX) 10min ,再灌注后观察 12 0min。结果 :LCX再灌注 10min时RPC组左室心内膜前壁、间隔及心外膜间隔心肌血流量 (分别为 0 .86± 0 .2 7,1.10±0 .34及 1.2 0± 0 .5 1ml·min-1·g-1)显著高于对照组 (分别为 0 .6 4± 0 .2 8,0 .6 9± 0 .2 3及 0 .5 8± 0 .2 6ml·min-1·g-1) ,P <0 .0 5。RPC显著减少再灌注后心室纤颤的发生率 (对照组 8/ 9,RPC组 2 / 10 ,P <0 .0 1)。冠状动脉阻断及再灌注后对照组主动脉平均压低于RPC组 ,但差异无显著性 (P >0 .0 5 )。结论 :RPC显著减少心肌缺血及再灌注期心室纤颤的发生 ,其机制可能与RPC显著改善心内膜血液供应有关。     

Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy

We have evaluated the potential usefulness of radiolabelled [DTPA⁰,Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide as radiopharmaceuticals for somatostatin receptor–targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [¹¹¹In-DTPA⁰] octreotide. Comparing different peptide–chelator constructs, [DTPA⁰,Tyr³]octreotide and [DOTA⁰, Tyr³]octreotide were found to have a higher affinity than [DTPA⁰]octreotide for subtype 2 somatostatin receptors (sst₂) in mouse AtT20 pituitary tumour cell membranes (all IC₅₀ values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both ¹¹¹In-labelled [DOTA⁰,Tyr³]octreotide and [DTPA⁰,Tyr³]octreotide in sst₂-expressing tissues than after injection of [¹¹¹In-DTPA⁰]octreotide, showing that substitution of Tyr for Phe at position 3 in octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of ¹¹¹In-labelled [DTPA⁰]octreotide, [DTPA⁰,Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled octreotide/rat, indicating specific binding to sst₂. Comparing different radionuclides, [⁹⁰Y-DOTA⁰,Tyr³]octreotide had the highest uptake in sst₂-positive organs, followed by the [¹¹¹In-DOTA⁰,Tyr³]octreotide, whereas [DOTA⁰, ¹²⁵I-Try³]octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of ¹¹¹In-labelled [DTPA⁰]octreotide, [DTPA⁰, Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide was reduced over 50% by an i.v. injection of 400 mg/kg d-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected. Int. J. Cancer 75:406–411, 1998. © 1998 Wiley-Liss, Inc.     

Anxiety disorders in later life: a report from the longitudinal aging study Amsterdam

Objective. To study the prevalence and risk factors of anxiety disorders in the older (55–85) population of The Netherlands. Method. The Longitudinal Aging Study Amsterdam (LASA) is based on a random sample of 3107 older adults, stratified for age and sex, which was drawn from the community registries of 11 municipalities in three regions in The Netherlands. Anxiety disorders were diagnosed using the Diagnostic Interview Schedule in a two-stage screening design. The risk factors under study comprise vulnerability, stress and network-related variables. Both bivariate and multivariate statistical methods were used to evaluate the risk factors. Results. The overall prevalence of anxiety disorders was estimated at 10·2%. Generalized anxiety disorder was the most common disorder (7·3%), followed by phobic disorders (3·1%). Both panic disorder (1·0%) and obsessive compulsive disorder (0·6%) were rare. These figures are roughly similar to previous findings. Ageing itself did not have any impact on the prevalence in both bivariate and multivariate analyses. The impact of other factors did not change much with age. Vulnerability factors (female sex, lower levels of education, having suffered extreme experiences during World War II and external locus of control) appeared to dominate, while stresses commonly experienced by older people (recent losses in the family and chronic physical illness) also played a part. Of the network-related variables, only a smaller size of the network was associated with anxiety disorders. Conclusions. Anxiety disorders are common in later life. The risk factors support using a vulnerability–stress model to conceptualize anxiety disorders. Although the prevalence of risk factors changes dramatically with age, their impact is not age-dependent. The risk factors indicate which groups of older people are at a high risk for anxiety disorders and in whom active screening and treatment may be warranted.Copyright © 1998 John Wiley & Sons, Ltd.     

Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2

Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (self) epitopes for which tolerance has not been established, while simultaneously providing the necessary adjuvant activity. The resulting response type is influenced by the genotype of exposed individuals and relates to susceptibility to the adverse immune effects of the chemicals. Here, we assessed the modulatory role of the chemical compounds themselves. A single injection of streptozotocin (STZ) increased the number of CD8⁺ cells, macrophages, apoptotic cells, and IFN-γ-producing T helper and T cytotoxic cells, whereas the number of CD4⁺ cells and B cells was reduced in the draining lymphnode. Coinjection with the reporter antigen TNP-OVA resulted in primary and secondary production of TNP-specific antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA. Injection of HgCl₂ on the other hand, reduced the number of IFN-γ-producing cells, induced accumulation of B cells and CD4⁺ and CD8⁺ T cells, enhanced IgG1 and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production as well as for DTH reactions. Together these results indicate that a single injection of STZ stimulates type-1 responses, whereas HgCl₂ enhanced mixed type-1 and −2 responses in BALB/c mice. These response types match the (auto)immune effects elicited to unknown (auto)antigens following multiple injections of these chemicals.     

APC mutations in human colorectal adenomas: analysis of the mutation cluster region with temperature gradient gel electrophoresis and clinicopathological features

To date, the earliest mutations in colorectal adenomas have been found in the adenomatous polyposis coli (APC) gene, considered the ‘gatekeeper’ in tumourigenesis. To study the types of APC gene mutations and their relation to clinicopathological features which are associated with malignant potential, the mutation cluster region of the APC gene was analysed in a series of 32 human sporadic colorectal adenomas from 22 patients. DNA was extracted from frozen sections and two overlapping fragments which cover the mutation cluster region were amplified using the polymerase chain reaction (PCR). Mutations were screened with temperature gradient gel electrophoresis and identified by DNA sequencing. Mutations were found in 14 samples (44 per cent) from 11 patients. The changes could be characterized as point mutations (n=7), deletions of one or more nucleotides (n=6), and insertions (n=1). From five patients, multiple adenoma samples were obtained and the adenomas from two of these patients showed a heterogeneous mutation pattern in the APC gene. All detected mutations are predicted to result in a truncated APC protein. Genetic alterations in the mutation cluster region of the APC gene occurred significantly more frequently in large adenomas and showed a trend towards an increase in villous adenomas and adenomas with moderate and severe dysplasia. It is concluded that an increased proportion of APC gene mutations were found in the adenomas showing clinicopathological features associated with increased proliferation but not with characteristics of malignant potential. The results suggest that in a significant proportion of adenomas, other (genetic) alterations are involved in early tumourigenesis. © 1998 John Wiley & Sons, Ltd.