即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

海洛因成瘾与学习记忆

海洛因成瘾是我国发病最高,危害最大的一种成瘾性疾病,而其中枢机制则是解决临床预防和治疗的关键,至今仍不清楚。既往工作表明,学习记忆功能在海洛因成瘾的中枢机制中居于重要的中心环节。本文在总结既往海洛因成瘾研究工作基础上联系学习记忆功能,试图从系统整合层次分析相关领域研究工作的不足和今后工作的发展方向。     

Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer

The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance and cell function perspectives. We also discuss analysis methods to access IF, which enables quantification of the cellular microenvironment; such methods have demonstrated, for example, that there can be dramatic gradients from tissue to plasma during inflammation and that tumor IF is hypoxic and acidic compared with subcutaneous IF and plasma. Accumulated recent data show that IF and its convection through the interstitium and delivery to the lymph nodes have many and diverse biological effects, including in ECM reorganization, cell migration, and capillary morphogenesis as well as in immunity and peripheral tolerance. This review integrates the biophysical, biomechanical, and biological aspects of interstitial and lymph fluid and its transport in tissue physiology, pathophysiology, and immune regulation.     

Change and reciprocity in adolescent aggressive and rule-breaking behaviors and parental support and dysfunctional discipline

This study examined how the development of aggressive/rule-breaking behaviors (9-17 years) is related to the development of overreactive and warm parenting, and explored gender differences in development and interrelations. Externalizing was assessed using combined mother/father reports of the Child Behavior Checklist (N = 516). Overreactivity was assessed using self-reports of the Parenting Scale; warmth was measured using self-reports of the Parenting Practices Questionnaire. All constructs were assessed three times across 6 years. The interrelated development of externalizing and parenting was examined by cohort-sequential multigroup latent growth models. Timing of effects was investigated using multigroup cross-lagged models. The results from latent growth models suggest that boys and girls change similarly in the extent to which they show externalizing behaviors, and indicate that mothers and fathers show somewhat different parenting toward boys than girls. No gender differences were found for interrelations between externalizing and parenting. Initial levels of aggression were related to changes in overreactivity and warmth, and vice versa. Changes in externalizing were related to changes in parenting. Cross-lagged models showed that relations between overreactivity and aggression/rule breaking were reciprocal. Together, results from this study show that adolescent externalizing and parenting affect each other in important ways, regardless of the gender of the child or the parent.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.     

国产与进口雷帕霉素洗脱支架治疗应用远期安全性与有效性

背景：药物洗脱支架治疗冠状动脉粥样硬化性心脏病能有效降低术后中远期冠状动脉再狭窄和远期心脏不良事件的发生率。 目的：对比国产与进口雷帕霉素洗脱支架治疗冠状动脉粥样硬化性心脏病的安全性和有效性。 方法：按照循证医学要求全面检索国内外近5年来有关国产和进口雷帕霉素洗脱支架治疗冠状动脉粥样硬化性心脏病的随机对照或临床对照试验,对符合纳入标准的文献进行Meta分析。 结果与结论：共纳入16篇临床对照试验,其中2 603例使用国产雷帕霉素洗脱支架,2 646例使用进口雷帕霉素洗脱支架。国产雷帕霉素洗脱支架组与进口雷帕霉素洗脱支架组主要心脏不良事件、靶血管血运重建、心源性死亡、心肌梗死、支架内血栓发生率差异均无显著性意义。显示从目前临床研究看,国产雷帕霉素洗脱支架在安全性和有效性方面不亚于进口雷帕霉素洗脱支架。     

Ethics and health. Challenges and reflections

In this essay, the concepts of ethics, bioethics, and professional ethics are reviewed. In addition, we analyzed the relationship between ethics and medicine, the conditions that can be source of ethical dilemmas, and the influence of ethics in the doctor-patient relationship, in the clinical work of the physician, and in an individual and institutional process of decision-making. Some factors that result from the interrelationship between ethics and health care, in particular the need for preserving and increasing the human dimension in medical practice, are discussed. Finally, the idea is supported that to achieve the purpose previously mentioned, three challenges must to be overcome: to defeat reductionism in analysis of medical matters, to accept the uncertainty of medical work and the attempt to reach adequate levels of equity in the development of health services.     

MMP-2、bFGF在子宫内膜异位症和子宫腺肌病中的表达及意义

目的：探讨基质金属蛋白酶－2（MMP－2）和碱性成纤维生长因子（bFGF)在子宫内膜异位症发生发展中的作用。方法：应用免疫组织化学法（SABC法），检测70例异位内膜组织和30例正常子宫内膜组织（对照组）中MMP－2和bFGF的表达。结果：在异位内膜组和对照组中，MMP－2的阳性表达率分别为71．43％和40．00％，强阳性表达率分别为40．00％和6．67％（P＜0．01）；bFGF的阳性表达率分别为65．71％和40．00％，强阳性表达率别为20．0％和0％（P＜0．01）。而MMP－2和bFGF在卵巢子宫内膜异位症和子宫腺肌症中的肌性表达率，两组间差异均无显著性（P＞0．05）。结论：异位内膜组织中MMP－2的过度表达与异位内膜组织的侵袭力有关，bFGF与子宫内膜异位症的血管生成密切相关，提示MMP－2和bFGF在子宫内膜异位症的发生发展中发挥作用。     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

Hepatocellular carcinoma and estrogen receptors: Polymorphisms and isoforms relations and implications

Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver. Estrogen way of action is mediated by estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), that belong to a family of nuclear receptors that may regulate the expression of many genes. The ER subtypes exert a variety of roles in many stages of liver disease and may play a part in the process of signal transduction, according to some studies. However, the many functions of ER subtypes in hepatic diseases, in special of the ERβ, are yet to be clarified.The genetic modifications related to HCC are not yet fully clarified and accumulation of multiple genetic alterations appears to have an important role in carcinogenesis of HCC. The presence of some certain single nucleotide polymorphism (SNP) may have a functional repercussion related to final product of a gene, which can be measured and may participate in some alterations related to a pathological condition.Our hypothesis is based on the fact that liver tissue express ER and its different variants exert multiple functions in various stages of liver disease and participate in an extremely complicated signal transduction process, therefore we believe that the presence of one or more SNPs of ESR1 and ESR2 genes may be related with the increase of risk in developing and the severity of HCC, as well as in the response to different treatments. The confirmation of our hypothesis by scientific studies may provide knowledge of markers that act as prognostic factors of this disease, as well as enabling alternatives to development of anti tumoral therapies.     

Control and assessment of the uterus and cervix during pregnancy and labour

Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.     

Religious beliefs and practices and Catholic couples' management of anger and conflict

Grounded theory techniques and Repertory Grids were used in a qualitative study to generate and analyse material from 20 Catholics each interviewed twice. Religious practices increased the amount of intrapersonal ‘space’ available by acting physiologically, cognitively and affectively to reduce the intensity of anger experienced and to support couples in taking responsibility for their own part in a conflict. Couples could also regulate the interpersonal space between them by detouring their anger to God, and by finding support for both the avoidance and confrontation of conflict through religious beliefs. The relationship with God had an interactive and compensatory role in relation to the marital relationship. Changes in religious beliefs or marital relationship dynamics were not always neatly integrated and ambivalence over anger and conflict sometimes resulted and manifested in discordance between the spousal and God relationships. Copyright © 2000 John Wiley & Sons, Ltd.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Chromogranins A and B and secretogranin II: evolutionary and functional aspects

Chromogranins/secretogranins or granins are a class of acidic, secretory proteins that occur in endocrine, neuroendocrine, and neuronal cells. Granins are the precursors of several bioactive peptides and may be involved in secretory granule formation and neurotransmitter/hormone release. Characterization and analysis of chromogranin A (CgA), chromogranin B (CgB), and secretogranin II (SgII) in distant vertebrate species confirmed that CgA and CgB belong to related monophyletic groups, probably evolving from a common ancestral precursor, while SgII sequences constitute a distinct monophyletic group. In particular, selective sequences within these proteins, bounded by potential processing sites, have been remarkably conserved during evolution. Peptides named vasostatin, secretolytin and secretoneurin, which occur in these regions, have been shown to exert various biological activities. These conserved domains may also be involved in the formation of secretory granules in different vertebrates. Other peptides such as catestatin and pancreastatin may have appeared late during evolution. The function of granins as propeptide precursors and granulogenic factors is discussed in the light of recent data obtained in various model species and using knockout mice strains.     

microRNA与肿瘤侵袭转移

microRNA (miRNA)是一类长度为17~25 nt的单链非编码RNA,通过与靶基因mRNA互补位点的结合在转录后水平调控靶基因的表达.miRNA作为调控基因表达的重要分子在肿瘤侵袭转移中的作用越来越受到重视,阐明miRNA在肿瘤侵袭和转移中的作用机制具有重要的理论意义,同时也可以为肿瘤的诊断和治疗提供新方法.文章综述了miRNA在鼻咽癌、乳腺癌、肺癌、肝癌、结直肠癌和前列腺癌侵袭转移过程中作用机制的研究进展.     

Ghrelin and the short- and long-term regulation of appetite and body weight

Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues. Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from insulin surges. Consequently, ingested lipids suppress ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation, ghrelin also fulfills established criteria for an adiposity-related hormone involved in long-term body-weight regulation. Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to body-weight alterations. Ghrelin crosses the blood-brain barrier and stimulates food intake by acting on several classical body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic ghrelin administration increases body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the ghrelin or ghrelin-receptor gene causes resistance to diet-induced obesity, and pharmacologic ghrelin blockade reduces food intake and body weight. Ghrelin levels are high in Prader-Willi syndrome and low after gastric bypass surgery, possibly contributing to body-weight alterations in these settings. Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders.     

Resilience and variability in pathogens and hosts

Adaptability by means of phenotype variability in host-pathogen systems is studied using a model that resembles a class of array systems known as cellular automata. Each automaton in this model is characterized by a network of n x m processors that process the information contained in levels 0 to m. The effect of the automaton's architecture on its ability to satisfy variations in constraints is analysed, and automata-evolution experiments are described. Increasing the number of organization levels in the automaton is shown to increase its efficiency in buffering external changes, and the mechanism of modulating the processing rules appears more efficient than the mechanism of controlling the mutation rate. Analogy with biological systems suggests that hosts and pathogens evolve towards increasing modulation of their genomic information processing and that single mature lymphocytes should be able to generate more than one antigen receptor. These hypotheses can provide an explanation for the sequential ordered expression of different antigen genes in trypanosomes, as well as for immunosuppression and autoimmune phenomena.