Plant allergens and pathogenesis-related proteins. What do they have in common?

In the recent past a great number of proteins causing type 1 allergic reactions in humans have been isolated and characterised. The main sources containing allergens are plants, mites, fungal spores and insects. Plant-derived allergens may either be taken in from the upper respiratory tract or they are present in a vast range of plant food causing food allergic reactions. Compared to the enormous amount of different plant proteins only a small number out of them are identified as a an allergen at present. Looking at the allergen encoding sequences, relationships by sequence similarity can be found quite frequently to a restricted number of plant protein families. Predominantly, these protein families are seed storage proteins, structural proteins and proteins involved in the defence-related system - pathogenesis-related proteins. In the following, a short overview of a number of pathogenesis-related protein families is presented in relation to the already known homologous plant allergens.     

Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common?

Until recently, dogma dictated that the immune system and the central nervous system (CNS) live mostly separate, parallel lives, and any interactions between the two were assumed to be limited to extreme cases of pathological insult. It was only a decade ago that T cells in the injured brain were shown to play a protective rather than a destructive role. In this article, we explore the role of the immune system in the healthy brain, focusing on the key function that T lymphocytes have in the regulation of cognition. We discuss candidate mechanisms underlying T cell-mediated control of cognitive function in human cognitive diseases associated with immune decline, such as age- and HIV-related dementias, 'chemo-brain' and others.     

What they are, how they work and why they do what they do? The story of SV40-derived gene therapy vectors and what they have to offer

The natural function of viruses is to deliver their genetic material to cells. Among the most effective of viruses in doing that is Simian Virus-40 (SV40). The properties that make SV40 a successful virus make it an attractive candidate for use as a gene delivery vehicle: high titer replication, infectivity for almost all nucleated cell types whether the cells are dividing or resting, potential for integration into cellular DNA, a peculiar pathway for entering cells that bypasses the cells' antigen processing apparatus, very high stability, and the apparent ability to activate expression of its own capsid genes in trans. Exploiting these and other characteristics of wild type (wt) SV40, increasing numbers of laboratories are studying recombinant (r) SV40-derived vectors. Among the uses to which these vectors have been applied are: delivering therapy to inhibit HIV, hepatitis C virus (HCV) and other viruses; correction of inherited hepatic and other protein deficiencies; immunizing against lentiviral and other antigens; treatment of inherited and acquired diseases of the central nervous system; protecting the lung and other organs from free radical-induced injury; and many others. The effectiveness of these vectors is a reflection of the adaptive evolution that produced their parent virus, wt SV40. This article explores how and why these vectors work, their strengths and their limitations, and provides a functional model for their exploitation for experimental and clinical applications.     

Manic symptoms in psychiatrically hospitalized children--what do they mean?

OBJECTIVE: To examine the clinical implications of manic symptoms in psychiatrically hospitalized children aged 5-12. METHODS: DSMIIIR manic symptoms, along with symptoms of other psychiatric disorders, were rated by parents and teachers on the Child Symptom Inventory IIIR prior to hospitalization. The Child Behavior Checklist (CBCL; was also completed. During hospitalization children were evaluated by structured interview (K-SADS-E), and numerous rating scales weekly. Children with symptoms of mania (mania criteria with/without episodes) were compared to those without mania. Severity of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), depression, CBCL factors, and comparable factors from teacher and parent inpatient rating scales were examined. Finally, a subgroup of both groups of children treated with stimulants were compared at baseline and at least two weeks of treatment. RESULTS: Children with manic symptoms had more severe ADHD, ODD and depression symptoms. CBCL scores on aggression, social and thought problems were higher. Teachers and nursing staff made similar observations. Time in hospital was greater for children with manic symptoms. Both groups improved significantly on stimulant medication though reduction in overall psychopathology was often modest. CONCLUSIONS: Manic symptoms, regardless of whether or not they represent bipolar disorder, are a marker of serious psychopathology and treatment resistance.     

What do asthmatics have to fear from food and additive allergy?

International studies report marked increases in the prevalence of food allergy, along with increases in hospital admissions and emergency presentations for severe allergic reactions due to foods. The prevalence of self‐reported food allergy is common, but generally exceeds that which can be verified from challenge studies, although nut allergies appear to be an important exception to this rule. Studies examining food allergy deaths suggest that those who die of food allergy usually have co‐existent asthma. Adolescents and young adults are at most risk, and adrenaline auto‐injectors are sub‐optimally used. Food chemical sensitivity is very commonly reported but not usually verified by challenge testing. However, the exception to this is sulphite sensitivity, which can elicit reproducible reactions in some. The increasing prevalence of severe food allergies and awareness of its risk in those with asthma demands an especially rigorous approach to the diagnosis and management of co‐existent food allergy and asthma, especially in young people who appear to be at most risk from death from severe food allergy. Cite this as: A. Gillman and Jo A. Douglass, Clinical & Experimental Allergy, 2010 (40) 1295–1302.     

Avian and simian malaria: do they have a cancer connection?

It has been claimed that infectious agents transmitted by mosquitoes (Diptera: Culicidae) may have a greater connection to cancer then hitherto supposed and that the immune system struggles to recognize and fight some of these infectious agents. One of the claims made is that there is a connection between human malaria and brain cancers in the USA. However, the USA declared itself free of human malaria in the last century, yet cancer incidences remain high, suggesting any overall cancer connection is slight. Two fundamental questions arise from the possible mosquito-cancer connection. Firstly, if mosquitoes are able to vector some pathogens and parasites linked with cancer pathogenesis, why has the fact not been discovered decades ago? Secondly, if there is a connection (other than in relation to Burkett’s lymphoma), what is its extent? The answers may well lie with the various types of malarias known to exist. The discovery in humans of the simian malaria, caused by Plasmodium knowlesi, suggests that other forms of simian or even avian malaria may be capable of survival in humans, albeit at low levels of parasitemia, and humans may be a dead-end host. Other carcinogenic infectious agents transmitted by mosquitoes may also go undetected because either no one is looking for them, or they are looking in wrong anatomical locations and/or with inadequate tools. Research on false negative test results with respect to many infectious agents is sadly lacking, so its extent is unknown. However, electronic and other media provide numerous instances of patients failing to be diagnosed for both human malaria and Lyme’s disease, to take just two examples. This review suggests that to shed light on a potential mosquito-cancer connection, more research is required to establish whether other simian and avian forms of malaria play a part. If so, then they potentially provide unique markers for early cancer detection.     

In a disaster, what should medical technologists at a university hospital do? What do they have?

"Disaster medicine" involves "cases that cannot be supported by the normal medical service system of the hospital because many injuries have occurred by an explosion/chemical pollution/radioactive pollution or a pandemic caused deliberately as well as natural disasters". In "disaster medicine", university hospitals should become the base for advanced medical services and wide area transportation. Also, the clinical laboratory/medical technologists of the university hospital should offer high quality laboratory analysis. On the other hand, one of the advantages of a university hospital is an experimental medicine laboratory (integrated universities also have a Department of Science and Department of Engineering). Development of testing equipment to cover all the functions necessary for disaster medicine may be a possibility. A system to conduct simple testing is expected at the actual location of the emergency, and an identification system must be established. "Emergency medicine" and "disaster medicine" have different aspects, but the essence is the same, and medical technologists must have knowledge/techniques to report and interpret results quickly. Because a university hospital is the core of logistical support, daily training is important.     

Ageing,age-related diseases and oxidative stress: What to do next?

Among other mechanisms, oxidative stress has been postulated to play an important role in the rate of ageing. Oxidative damage contributes to the hallmarks of ageing and essential components in pathological pathways which are thought to drive multiple age-related diseases. Nonetheless, results from studies testing the hypothesis of oxidative stress in ageing and diseases showed controversial results. While observational studies mainly found detrimental effects of high oxidative stress levels on disease status, randomized clinical trials examining the effect of antioxidant supplementation on disease status generally showed null effects. However, re-evaluations of these counterinitiative observations are required considering the lack of reliability and specificity of traditionally used biomarkers for measuring oxidative stress. To facilitate these re-evaluations, this review summarizes the basic knowledge of oxidative stress and the present findings regarding the role of oxidative damage in ageing and age-related diseases. Meanwhile, two approaches are highlighted, namely proper participants selection, together with the development of reliable biomarkers. We propose that oxidized vitamin E metabolites may be used to accurately monitor individual functional antioxidant level, which might serve as promising key solutions for future elucidating the impact of oxidative stress on ageing and age-related diseases.     

Extra-thymically induced regulatory T cells: do they have potential in disease prevention?

Fopx3⁺ Treg safeguard against autoimmune diseases and immune pathology. The extrathymic conversion of naïve T cells into Foxp3⁺ regulatory T cells can be achieved in vivo by the delivery of strong-agonist ligands under subimmunogenic conditions. Tolerogenic vaccination with strong-agonist mimetopes of self-antigen to promote self-antigen specific tolerance may represent the most specific and safest means of preventing autoimmunity. This review discusses the requirements for induction of dominant tolerance exerted by Foxp3⁺ Tregs in autoimmunity with special emphasis on their impact to interfere with T1D. The future goals are the understanding of self-non-self discrimination at the cellular and molecular level, which should then enable investigators to develop clinical vaccination protocols that specifically interfere with unwanted immune responses.     

Neurological soft signs in schizophrenia: are they related to negative or positive symptoms, neuropsychological performance, and violence?

This investigation was carried out on 31 unemployed schizophrenic outpatient men. The general purpose was to explore new aspects of neurological soft signs in schizophrenia. A 108-item version of the Nathan Kline Institute scale of soft signs, the Schedule for Affective Disorders and Schizophrenia psychiatric interview, the negative and positive symptom scale (PANSS), a comprehensive scale of life-time history of violence, and a large set of neuropsychological tests were administered. It was found that "motor" soft signs were significantly more prevalent than "sensory-perceptual" signs, but that each body side manifested equal numbers of neurological signs. Before and after statistical correction for age, education, alcoholism, drug abuse disorder, and daily and cumulative neuroleptic dosage, orbitofrontal-type neuropsychological tasks measuring "impulsivity" related very robustly to the soft signs. Furthermore, before and after the same statistical corrections, right body-side signs correlated significantly with the same neuropsychological tests, whereas left body-side signs did not. The PANSS scores and levels of lifetime violence generally did not correlate significantly with neurological soft signs. The latter negative findings, we think relate to the fact that these were relatively high-functioning (i.e., outpatient) schizophrenics. Overall, the results support notions of frontal lobe and left hemisphere involvement in schizophrenia, these two dysfunctional systems being apparently linked at the level of the orbitofrontal area of the brain.     

Psychological well-being and ill-being: do they have distinct or mirrored biological correlates?

BACKGROUND: Increasingly, researchers attend to both positive and negative aspects of mental health. Such distinctions call for clarification of whether psychological well-being and ill-being comprise opposite ends of a bipolar continuum, or are best construed as separate, independent dimensions of mental health. Biology can help resolve this query--bipolarity predicts 'mirrored' biological correlates (i.e. well-being and ill-being correlate similarly with biomarkers, but show opposite directional signs), whereas independence predicts 'distinct' biological correlates (i.e. well-being and ill-being have different biological signatures). METHODS: Multiple aspects of psychological well-being (eudaimonic, hedonic) and ill-being (depression, anxiety, anger) were assessed in a sample of aging women (n = 135, mean age = 74) on whom diverse neuroendocrine (salivary cortisol, epinephrine, norepinephrine, DHEA-S) and cardiovascular factors (weight, waist-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, total/HDL cholesterol, glycosylated hemoglobin) were also measured. RESULTS: Measures of psychological well-being and ill-being were significantly linked with numerous biomarkers, with some associations being more strongly evident for respondents aged 75+. Outcomes for seven biomarkers supported the distinct hypothesis, while findings for only two biomarkers supported the mirrored hypothesis. CONCLUSION: This research adds to the growing literature on how psychological well-being and mental maladjustment are instantiated in biology. Population-based inquiries and challenge studies constitute important future directions.     

Allergic and autoimmune reactions to xenobiotics: how do they arise?

Induction of allergic and autoimmune reactions by drugs and other chemicals constitutes a major public health problem. Elucidation of the underlying mechanisms might help improve diagnostic tools and therapeutic approaches. Here, Peter Griem and colleagues focus on several aspects of neoantigen formation by xenobiotics: metabolism of xenobiotics into reactive, haptenic metabolites; polymorphisms of metabolizing enzymes; induction of costimulatory signals; and sensitization of T cells.     

Hibernating mammals in sudden cardiac death in epilepsy: What do they tell us?

Epilepsy is the most common neurological disorder; approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency and AED number. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Very recently, our research group was the first to annunciate that winter temperatures may lead a cardiac abnormalities and hence sudden death, become a new potential risk factor to SUDEP. Quite interesting, several mammalian species have evolved to develop a physiological phenomenon called hibernation as a strategy for survival under adverse cold conditions. From cardiovascular point of view, it has been established that hibernating mammals inherited a stable cardiovascular function as a result of adaptation to extreme external and internal environments during hibernation. For instance, hibernating mammals show resistance to hypothermia at a cellular level, the membrane potentials and excitability are more stable in the cardiac cells of these animals (action potentials (60 mV) have been recorded in hibernators myocardium at -5 degrees C), the aortic smooth muscle cells from hibernators are able to maintain ionic gradients upon prolonged exposure to low temperatures, and cardiac myocytes from hibernating mammals maintain constant levels of intracellular free calcium and forceful contractility at 10 degrees C or lower. Taken together, in this paper we postulate that hibernators have some cardiovascular particularities that confer heart protection that could positively influence the cardiovascular system of patients with epilepsy.     

Pigs, do they have their heart in their hand? Anthropological reflections on xenografts

The therapeutic perspectives initiated by xenotransplantations are of interest since they allow a great deal of hope for all patients whose transplant delays decrease in proportion to their prognosis for survival. However, this type of therapy, while resolving the qualitative problem of transplants, could possibly lead to other dilemmas, especially the sociocultural aspects. Besides the potential risk of transmission of a pathogenic agent to the human species, xenotransplants, while creating a symbolic and actual proximity between man and animal, could abolish the ritualized and ancient distance established between the protagonists. It could be pigs or any other type of animal; the central question is one of the relationship between human and animal species. Animal husbandry and slaughtering for food are submitted to very precise cultural codes. But it would be very hasty to think that the use of an animal for therapeutic transplants would be free of all cultural connotations.