The history of cyclosporin A (Sandimmune®) revisited: Another point of view

The immunosuppressant cyclosporin A (Sandimmune^®) has become the first line treatment for preventing rejection of transplanted organs and for certain, autoimmune diseases. The discovery of that drug and its preclinical development are described, and it is shown that most earlier accounts of the history of this compound are, in important respects, incorrect and misleading.     

Endothelial cells as antigen-presenting cells: role in human transplant rejection

The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’ positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection. Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998     

Rip it up and start again: The rejection of a characterization of a phenomenon

In this paper, I investigate the nature of empirical findings that provide evidence for the characterization of a scientific phenomenon, and the defeasible nature of this evidence. To do so, I explore an exemplary instance of the rejection of a characterization of a scientific phenomenon: memory transfer. I examine the reason why the characterization of memory transfer was rejected, and analyze how this rejection tied to researchers’ failures to resolve experimental issues relating to replication and confounds. I criticize the presentation of the case by Harry Collins and Trevor Pinch, who claim that no sufficient reason was provided to abandon research on memory transfer. I argue that skeptics about memory transfer adopted what I call a defeater strategy, in which researchers exploit the defeasibility of the evidence for a characterization of a phenomenon.     

What's new in the field of cancer vaccines?

The observation that in some cases tumors undergo spontaneous regression concomitantly with autoimmune manifestations has been interpreted as an indication of the involvement of the immune system in tumor rejection. This raised the conceptual possibility that the immune system could be used against the tumor. However, since tumor cells are poorly immunogenic by themselves, early attempts to develop immune-based approaches for cancer therapy saw the use of tumor cells transduced with genes coding for cytokines or costimulatory molecules to enhance in vivo immunity. The identification of cytotoxic T lymphocyte (CTL)-defined tumor associated antigens has allowed the development of new strategies for cancer immunotherapy. Novel adjuvants have been identified, and different modes of antigen delivery were devised which aim at inducing efficient CTL responses in patients. This review will discuss some of what is currently considered as relevant aspects of antitumor immunization.Received 19 July 2002; received after revision 11 December 2002; accepted 13 December 2002     

Trials of mixed grafts of 5 cell lines from human brain tumors in athymic nude mice]

Five established lines derived from human brain tumors were mixed in pairs and injected into athymic nude Mice. The observation of mixed tumors and patterns of rejection obtained after inoculation enabled us to classify these five lines according to their aggressiveness in a heterologous host. In addition, the SA 52 line induced an inhibitory effect on graft growth (or a facilitation of rejection).     

Xenoreactive natural antibodies

Shortages of human organs for transplantation have made it necessary to examine the possibility of using nonhuman organs for xenotransplantation the transplantation of tissues between different species. Pigs are now regarded as the most likely species to serve as donors for clinical xenotransplantation. However, rejection of pig tissues and organs, mediated by the host's immune system, remains a major barrier to successful xenotransplantation. The primary immunological hurdle to overcome is rejection mediated by antibodies in the host that recognize antigens present on xenogeneic tissues. Since these antibodies are produced naturally in the host without immunization, they are termed natural antibodies. Here, we review the nature of xenoreactive natural antibodies directed toward pig tissues, and summarize recent progress in the field of xenotransplantation directed at overcoming humoral rejection of porcine xenografts.     

Possible involvement of the phloem sealing system in the acceptance of a plant as host by an aphid

Possible reasons for the rejection of some lines ofTriticum monococcum (Tm44 and Tm46) by the aphidSitobion avenae were explored. In allT. monococcum lines studied, whether unfavourable (non-host/resistant plant) or favourable (host/susceptible plant), the concentrations of hydroxamic acids, a family of aphid-resistance factors in cereals, were significantly lower than the levels in the favourable host-plantTriticum aestivum cv. Therefore, hydroxamic acids did not account for the host/non-host patterns observed. Phloem sap was collected by stylectomy from young seedlings of favourable and unfavourable plants. In non-aphid-resistant genotypes, the success in stylectomy, the proportion of amputated stylets resulting in long (>1 min) exudations, the average duration of exudation, and the final volume of sap exuded, were higher than in the aphid-resistant genotypes. It is concluded that aphid interference with the phloem sealing system of the plant is a likely mechanism of rejection ofT. monococcum lines Tm44 and Tm46 as hosts byS. avenae.     

Immunotherapy against antigenic tumors: a game with a lot of players

Our understanding of how immune responses are generated and regulated drives the design of possible immunotherapies for cancer patients. For that reason, we first describe briefly the actual immunological theories and their common perspectives about cancer vaccine development. Second, we describe cancer vaccines that are able to induce tumor-specific immune responses in cancer patients. However, these responses are not always followed by tumor rejection. At the end of the review, we discuss two possible reasons that might explain this dichotomy of cancer immunology. First, the immune response generated, although detectable, may not be quantitatively sufficient to reject the tumor. Second, the tumor microenvironment may modulate tumor cell susceptibility to the systemic immune response induced by the immunization. Finally, we discuss what, in our opinion, might be the best way to improve cancer vaccine strategies and how the relationship between the tumor and its surroundings might be studied in more details. Received 21 June 2001; received after revision 15 August 2001; accepted 15 August 2001     

Allotransplantation of rat parathyroid glands: effects of organ culture and transplantation into the adrenal gland.

Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB2) to Fischer rats (AgB1) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.     

The ‘Darwin-Marx correspondence’: a correction and revision

The logical links between the Judaeo-Christian doctrine of creation and the practice of natural philosophy on the one hand, and the rejection of belief in demonic agency on the other, were made explicit in the seventeenth century by, among others, Balthasar Bekker (1634–98), whose ideas I argue to have been not without influence. In section 1, I present the accounts of three historians of the opposition to belief in witchcraft and of the decline of the witch-persecution, Hugh Trevor-Roper, Keith Thomas, and Brian Easlea. In section 2, I maintain that Bekker has been underestimated both by Trevor-Roper and by Easlea. In section 3, I investigate more generally some of the connections between the new natural philosophy and belief in supernatural interventions, cast doubt on the view that rejection of belief in witchcraft and the devil requires rejection of belief in creation, and thus supplement or qualify the accounts of Trevor-Roper, Thomas, and Easlea of why belief in witchcraft faded away.     

Allotransplantation of rat parathyroid glands: Effects of organ culture and transplantation into the adrenal gland

Summary Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB²) to Fischer rats (AgB¹) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.Acknowledgments. The authors thank Mrs Barbara Lovett for her secretarial assistance.     

Causally productive activities

This paper suggests and discusses an answer to the following question: What distinguishes causal from non-causal or coincidental co-occurrences? The answer derives from Elizabeth Anscombe’s idea that causality is a highly abstract concept whose meaning derives from our understanding of specific causally productive activities (e.g., pulling, scraping, burning), and from her rejection of the assumption that causality can be informatively understood in terms of actual or counterfactual regularities.     

Vitamin A and tumor immunity

Summary Intraperitoneal administration of vitamin A into the BALB/c mice inoculated with a syngeneic fibrosarcoma, Meth A, caused a remarkable augmentation of tumor rejection. A cell-depletion technique revealed that the primary effector cells responsible for the augmented rejection were Thy-1 positive, Lyt-1 negative, Lyt-2 positive lymphocytes, suggesting the involvement of cytotoxic lymphocytes.This work was supported in part by a Grant-in-Aid for scientific research from the Ministry of Education, Science and Culture, Japan, and in part by a Grant-in-Aid for cancer research from the Fukuoka Cancer Society, Japan.We thank Mr M. Fujiki and Miss A. Maeda for excellent technical assistance.     

卫星导航接收机抗欺骗干扰极大似然检测性能分析

欺骗干扰给卫星导航接收机带来巨大威胁,而现有的文献均把欺骗干扰识别作为抗欺骗干扰的主要研究方向,而涉及欺骗干扰抑制方面的文献很少.本文针对卫星导航接收机抗产生式欺骗干扰问题,根据接收机具有不同干扰先验信息的3种情形,分别提出并证明了3个命题.这些命题给出了极大似然检测器在干扰背景下对真实卫星数据的检测性能界.命题表明,在具备干扰信道先验信息时,极大似然检测器具有良好的抗产生式欺骗干扰性能.仿真实验验证了理论分析的正确性和有效性.     

Speed and consistency of human decisions to swallow or spit sweet and sour solutions.

Measurements of the frequency and speed of spitting or swallowing citric acid, sodium saccharin, or mixture solutions, using the taste of one of them as the definition of what was to be spit, revealed that 'correct' spits occurred on > or = 70% of trials with equal reliability and latency among the liquids, indicating that recognition-based rejection decisions in adult humans are as rapid and consistent for an arbitrary sweet taste as for a sour or mixed taste.     

Euler, vis viva, and equilibrium

Euler’s ‘On the force of percussion and its true measure’, published in 1746, shows that not only had the issue of vis viva not been settled, but that the concepts of inertia and even force were still very much up for grabs. This paper details Euler’s treatment of the vis viva problem. Within those details we find differences between his physics and that of Newton, in particular the rejection of empty space and reduction of all forces to the operation of inertia through contact. One can further see how Euler’s philosophy of science embraced explanation through mechanisms and equilibrium conditions.     

Cicero's demarcation of science: A report of shared criteria

The problem of establishing intensional criteria to demarcate science from non-science, and in particular science from pseudoscience, received a great amount of attention in the 20th century philosophy of science. It remains unsolved. This article compares demarcation criteria found in Marcus Tullius Cicero’s rejection of genethliac astrology and other pseudo-divinatory techniques in his De divinatione (44 BCE) with criteria advocated by a broad selection of modern philosophers of science and other specialists in science studies. Remarkable coincidences across two millennia are found on five basic criteria, which hints at a certain historical stability of some of the most fundamental features of a concept of “science” broadly construed.     

犬高危穿透性角膜移植术后使用1％RAPA滴眼液对体内TNF-α含量的影响

目的通过观察肿瘤坏死因子-α（tumornecrosisfactor-α，TNF-α）变化情况，评价犬高危穿透性角膜移植后RAPA滴眼液抗免疫排斥反应效果。方法选择36只健康犬建立角膜高危病理模型后进行高危穿透性角膜移植手术，并分组用复方氯化钠或1％RAPA点眼，4次／d，18只未手术犬为空白对照组。同时进行外周血和角膜组织中TNF—α含量检测。结果术后7～42d复方氯化钠组和治疗组TNF-α浓度明显比对照组高（P〈0．01），在术后28d治疗组TNF-α浓度逐渐降低，复方氯化钠组仍维持较高含量。结论RAPA滴眼液能降低角膜移植手术后TNF-α含量，有效抗免疫排斥反应。     

Von der Mathematik der nervösen Ordnungsleistung

Summary An exact analysis of the coordination of movements in arthropods and vertebrates leads to the rejection of older explanations in terms of reflex physiology and to a dynamic conception of the process in the central nervous system, which admits of representation by a physical model (as well as of a mathematical formulation). This conception carries with it the implication that locomotion is caused by automatic elements that work in the rhythm of locomotion and are prior to the motor elements.This view stands in close relation to the physiology of the nervous system and to Gestalt psychology.     

Effect of acetylsalicylate on surgical bleeding, postoperative mortality and allograft survival in rats undergoing heart transplantation.

18 rats were treated with L-ASA before heart transplantation and daily thereafter until death or rejection. 22 animals acted as controls. A significantly higher post-operative mortality rate, without any significant modification of the transplant survival time, was found in L-ASA-treated group.