Induction Of Symptoms Research Articles

Immunogenicity of Milk Protein-Containing Hydrophilic Gel Patch for Epicutaneous Immunotherapy for Milk Allergy.

Epicutaneous immunotherapy (EPIT) involving the skin's immune system is easy to use, painless and has a low risk of systemic side effects; it can be applied to food allergies that have a high morbidity rate in children. In this study, we evaluated the safety and efficacy of hydrophilic gel patch (HG) for EPIT. Milk protein concentrate (MPC)-containing HG was applied to the skin that maintained a barrier function or formed puncture holes with microneedle, and MPC-specific antibodies were measured. The clinical study was conducted involving patients with severe milk allergy. No specific immune response was induced when immunizing to intact skin, and antibody production was observed by forming puncture holes. It was suggested that MPC contained in HG has immunogenicity and a very small amount of MPC was delivered to intact skin. In the clinical study, the symptom induction threshold increased in four of eight subjects, allowing them to consume milk and switch to oral immunotherapy. Although local skin reactions and temporary elevation of specific IgE antibodies were observed, no systemic side effects appeared throughout the study. EPIT using HG is a safe method to enable oral administration even in patients with severe milk allergies.

Profilin is a marker of severity in allergic respiratory diseases.

The capacity of profilin to induce allergic symptoms in patients with respiratory allergy has been questioned. In this sense, the aim of this study was to investigate the correlation between profilin exposure and induction of symptoms in a prospective case-control study. The concentration of profilin as well as pollen levels in the air was measured. A diary score of symptoms was collected from allergic patients. Seventy-nine individuals were included in the study; fifty cases and 28 controls were positive or negative to profilin, respectively. Conjunctival and bronchial provocation tests were performed with purified profilin (Pho d 2) in a subgroup of cases and controls. Profilin was detected in the environment on 133days (maximum peak of 0.56ng/m3 ). A positive correlation between profilin and pollen count of Olea and Poaceae was observed (ρ=0.24; P<.001). Intensity of total, nasal and ocular symptoms was statistically higher in cases than in controls (P<.001). The risk of suffering symptoms, measured by the percentage of patients who presented any of the symptoms each day, was also higher in cases than in controls. The provocation test was positive in 95% of bronchial and 90% of conjunctival challenges in cases, and negative in all controls. Profilin was detected in the environment and had the ability to induce a specific allergen response. Patients sensitized to this panallergen showed more symptoms and were more likely to have symptoms. Therefore, sensitization to profilin seems to be a marker of severity in patients with rhinoconjunctivitis and asthma mediated by pollen.

Effect of processing of bovine milk on gastrointestinal symptoms and intestinal pressure in sensitive individuals

AbstractOver the last years, the consumption of unpasteurised milk has increased in popularity in the Western countries, despite the known risks associated with food-borne pathogens. Some people appear to experience milk-related gastrointestinal symptoms even when tested negative for lactose intolerance and milk allergy. In such cases, processing of milk, most often homogenisation or heat treatment, has been suggested to be involved in the induction of the gastrointestinal symptoms. Commercial milk is generally homogenised for the purpose of physical stability. Homogenisation reduces the size of fat droplets. Breaking of the fat globules creates new interface, which is covered with denaturated proteins. Further denaturation level of the proteins depends on the severity of the heat treatment. In this study entity, the effect of processing of bovine milk on the gastrointestinal symptoms in self-reported milk sensitive individuals was tested in two separate double blind crossover trials. Tested milks included raw milk (unprocessed), pasteurized milk, pasteurized and homogenized milk, and UHT treated and homogenized milk thus including milks at both end of commercially approved liquid milks in Finland. All milks came from the same herd of cows, which nulled the effect of genetic background and feeding of the cows. Ingestible pH-, pressure and temperature measuring probe was used to investigate gastrointestinal pressure. Self-reported diaries were used to measure perceived gastrointestinal symptoms. Additionally inflammation markers were studied from the plasma. In the first trial no significant difference was found in the amount of gastrointestinal symptoms or in the intestinal pressure after the consumption of native and processed milk. However, the obtained results on pressure in the large intestine (P = 0.068) as well as reported symptoms (P = 0.103) suggested that further studies in this area were needed. However, in the second trial where pasteurised, pasteurised and homogenised, and UHT -treated and homogenized milks were compared, the amount, severity or duration of the reported symptoms did not differ. This study demonstrates that the ingestible pressure-, pH and temperature measuring probe provided a novel possibility to study intestinal pressure in nutrition trials. The results of the present studies do not support the hypothesis that cows’ milk processing would induce gastrointestinal symptoms in milk sensitive but lactose tolerant subjects.

An initial investigation of serum cytokine levels in patients with gadolinium retention.

ObjectiveTo determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms.Materials and MethodsTwenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms.ResultsSerum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms' intensity were not confirmed.ConclusionThe statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms.

Journey of begomovirus betasatellite molecules: from satellites to indispensable partners.

Betasatellites are a group of circular, single-stranded DNA molecules that are frequently found to be associated with monopartite begomoviruses of the familyGeminiviridae. Betasatellites require their helper viruses for replication, movement, and encapsidation and they are often essential for induction of typical disease symptoms. The βC1 protein encoded by betasatellites is multifunctional that participates in diverse cellular events. It interferes with several cellular processes like normal development, chloroplasts, and innate immune system of plants. Recent research has indicated βC1 protein interaction with cellular proteins and its involvement in modulation of the host's cell cycle and symptom determination. This article focuses on the functional mechanisms of βC1 and its interactions with other viral and host proteins.

The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study

Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.

Bioactive Ingredients in Rice (Oryza sativa L.) Function in the Prevention of Type 2 Diabetes.

Diabetes mellitus (DM) greatly impacts human health worldwide as over 400 million patients suffer from DM-related symptoms. Type 2 DM accounts for more than 90% of DM and is caused mainly by unhealthy lifestyles, such as high-calorie and high-fat diets. Such undesirable eating habitats induce resistance to insulin resulting in high blood sugar levels that cause induction of various symptoms and complications of DM. Therefore, management of blood sugar levels is important for preventing DM. Our group has recently found that rice (Oryza sativa L.) contains anti-diabetes compounds. Here, we summarize the effect of the bioactive ingredients in rice on preventing type 2 DM.

Construction and biological characterization of an Agrobacterium-mediated infectious cDNA of squash mosaic virus

Squash mosaic virus (SqMV), a member of the species Squash mosaic virus in the genus Comovirus (family Comoviridae), is an important seed-borne virus that causes serious economic losses in cucurbit crops. Here, we constructed infectious cDNA clones of SqMV genomic RNAs (RNA1 and RNA2) under the control of the cauliflower mosaic virus (CaMV) 35S promoter by Gibson assembly. The infectious cDNA clones of SqMV could infect zucchini squash (Cucurbita pepo) plants systemically by agrobacterium-mediated inoculation. The virus progeny from the infectious clones showed no difference from the wild type in terms of pathogenicity and symptom induction. It could be mechanically transmitted to zucchini squash (Cucurbita pepo), pumpkin (Cucurbita moschata), cucumber (Cucumis sativus), and muskmelon (Cucumis melo) but not watermelon (Citrullus lanatus) or Nicotiana benthamiana. This is the first report of construction of a SqMV infection clone and will facilitate the investigation of viral pathogenesis and host interactions.

Peach Tree Pollen and Prunus persica 9 Sensitisation and Allergy in Children and Adolescents

Background: Although plant and fruit pollens are entomophilous and relevant in exposed workers, we have shown a high frequency of sensitisation and symptoms induction of peach tree pollen (PTP) and Prunus persica 9 (Pru p 9) in adults from areas of peach cultivars. Methods: We studied the sensitisation and clinical relevance of PTP and Pru p 9 in a large group of children and adolescents aged 3–19 years. A detailed questionnaire plus skin prick testing to prevalent allergens, PTP, and Pru p 9 were carried out. The clinical relevance was established by nasal provocation test (NPT) and symptom score index. Results: We evaluated 685 children (mean age 8.75 ± 3.3 years, median 9 years), 52% of them female. Sensitisation to PTP occurred in 20% of the cases following olive tree (33%) and Phleum pratense (26%). In a randomly selected subgroup of subjects sensitised to PTP, 30% were skin prick test-positive to Pru p 9. Most cases had rhinitis or rhinoconjunctivitis. NPT showed the relevance of PTP and Pru p 9 in the induction of symptoms. Conclusion: PTP and Pru p 9 are relevant in the induction of sensitisation and respiratory symptoms in children and adolescents. This allergen should be evaluated in children living in regions of peach tree cultivars.

Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease

Background and Objectives: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. Methods: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4–5, 5–6, and 6–7. Results: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4–5 (19%) was much higher than in that of pH 5–6 (11%) and pH 6–7 (12%). In the reflux at pH 4–5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5–6 and pH 6–7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. Conclusion: Reflux at pH <5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.

Emerging Treatment Targets for Migraine and Other Headaches.

Migraine is a complex disorder that is characterized by an assortment of neurological and systemic effects. While headache is the most prominent feature of migraine, a host of symptoms affecting many physiological functions are also observed before, during, and after an attack. Furthermore, migraineurs are heterogeneous and have a wide range of responses to migraine therapies. The recent approval of calcitonin gene-related-peptide based therapies has opened up the treatment of migraine and generated a renewed interest in migraine research and discovery. Ongoing advances in migraine research have identified a number of other promising therapeutic targets for this disorder. In this review, we highlight emergent treatments within the following biological systems: pituitary adenylate cyclase activating peptdie, 2 non-mu opioid receptors that have low abuse liability - the delta and kappa opioid receptors, orexin, and nitric oxide-based therapies. Multiple mechanisms have been identified in the induction and maintenance of migraine symptoms; and this divergent set of targets have highly distinct biological effects. Increasing the mechanistic diversity of the migraine tool box will lead to more treatment options and better patient care.

Phytotoxins produced by pathogenic fungi of agrarian plants

This review, covering the literature from 1965 to present (2018), treats of phytotoxins produced by fungi responsible of heavy diseases of important agrarian crops, including legumes, cereals, fruit trees, vegetables and crops for oil seed production. The symptoms induced on the infected plants are reported and the heavy economical losses caused by the diseases were also described. The chemical characterization and biological activity of the fungal phytotoxins, belonging to the different classes of natural compounds, is reported. In some cases, the probable role played by phytotoxins in the induction of plant disease symptoms is described as well as the results of structure–activity relationship and mode of action studies. The potential application in agriculture and in medicine for some of them is also discussed highlighting the increase in safety and the practical advantages.

Topical Triamcinolone-Induced Psychosis

Topical Triamcinolone-Induced Psychosis

In vitro symptom induction of Colletotrichum abscissum infection in detached sweet orange flowers

The citrus industry is economically important in several countries around the world, and its primary challenges include pests and diseases, especially in Brazil. Post-bloom fruit drop (PFD), caused by Colletotrichum abscissum, a fungus that belongs to the C. acutatum species complex, is one of the most severe citrus crop diseases, causing damage to blossoms and interfering in the fruit viability, consequently contributing to early drop of the fruit. Little is known about the pathogenic mechanisms of C. abscissum in the flowers of citrus species, so finding an experimental model to study symptom development and gene function under controlled conditions is essential. However, the complexity of the PFD pathosystem in the field does not allow adequate experimental control, and due to regulations, evaluating genetically modified fungi under natural environmental conditions requires prior approval. Studies of gene function can be performed by knockdown, knockout, or deletion in C. abscissum mutants with a focus on symptom development in flowers. We developed a reliable in vitro system as an alternative for symptom induction of C. abscissum infection in detached citrus flowers. Inoculated citrus flowers were placed on Petri dishes with a water-agar substrate and kept in BOD chambers for 72 h. All C. abscissum inoculations resulted in the typical symptoms of PFD, proving the effectiveness of this large-scale screening system, which is fast and reliable and requires less space than that required for greenhouse or open-field experiments.

Identification of 16SrIII-J phytoplasma effectors using a viral vector

The pathogenicity mechanisms of phytoplasmas has been documented for several ribosomal groups, but there is a lack of information for the 16SrIII group. Phytoplasmas in this ribosomal group were detected in most of the countries of South America, in different crops, from herbaceous to woody species. This works aimed to verify if the in planta transient expression of putative phytoplasma effector proteins allow to observe symptoms related to those associated with phytoplasma diseases. Plants infected with Tobacco mosaic virus vector carrying 16SrIII-J phytoplasma SAP54 and SAP05 ortologous genes, showed flowering abnormalities in comparison to those not infected or infected with the viral vector alone indicating a putative role of these proteins in 16SrIII-J phytoplasma symptom induction.

Use of the cotton leaf curl Multan alphasatellite as a silencing or expression vector.

Alphasatellites, formerly known as DNA 1, are a satellite-like components associated with begomoviruses (the family Geminiviridae) that require betasatellite for symptom induction but depend on DNA-A for systemic movement. We have converted alphasatellite into gene-silencing vector (modified alphasatellite (∆DNA 1)) by deleting its A-rich region that does not affect the replication nor the movement of the helper virus. Insertion of a transgene green florescence protein (GFP) into ∆DNA 1 resulted in the silencing g of the cognate gene in Nicotiana benthamiana. The silencing persisted for more than one and half month and was associated with the decreased level of mRNA of the target gene. This satellite-like DNA vector induced gene silencing (VIGS) promises to be applicable to other begomovirus/alphasatellite systems, thereby providing the powerful approach to gene discovery and the analysis of gene functions in malvaceous crops. Keywords: cotton; begomovirus; alphasatellite; RNAi.

A plant intron enhances the performance of an infectious clone in planta

Although infectious clones are fundamental tools in virology and plant pathology, their efficacy is often reduced by the instability of viral sequences in Escherichia coli. In this study, we constructed an infectious clone of PepMoV (pPepMoV) in a bacterial binary vector (pSNU1); the clone induces symptoms of PepMoV in agroinfiltrated plants. During its modification and maintenance in E. coli, however, the pPepMoV infectious clone was instable in the bacteria. Manipulation of this unstable clone in the bacterial strain DH10B led to the spontaneous formation of a recombined clone with high stability in the bacteria but with reduced infectivity due to an unwanted insertion of an E. coli sequence in the NIa-protease coding region. Replacement of this sequence with a plant intron restored infectivity and maintained plasmid stability. In addition to restoring plasmid growth in both E. coli and Agrobacterium, the presence of the intron in the PepMoV sequence enhanced the accumulation of PepMoV in agroinfiltrated leaves and resulted in symptom induction in upper systemic leaves that was nearly as strong as with PepMoV sap-inoculation. Plant introns have been previously used to stabilize plasmids in E. coli without any effect or with an unexpected lag in symptom development. In contrast, the current results demonstrated the in vivo enhancement of an infectious clone by a plant intron.

An aromatic amino acid and associated helix in the C-terminus of the potato leafroll virus minor capsid protein regulate systemic infection and symptom expression.

The C-terminal region of the minor structural protein of potato leafroll virus (PLRV), known as the readthrough protein (RTP), is involved in efficient virus movement, tissue tropism and symptom development. Analysis of numerous C-terminal deletions identified a five-amino acid motif that is required for RTP function. A PLRV mutant expressing RTP with these five amino acids deleted (Δ5aa-RTP) was compromised in systemic infection and symptom expression. Although the Δ5aa-RTP mutant was able to move long distance, limited infection foci were observed in systemically infected leaves suggesting that these five amino acids regulate virus phloem loading in the inoculated leaves and/or unloading into the systemically infected tissues. The 5aa deletion did not alter the efficiency of RTP translation, nor impair RTP self-interaction or its interaction with P17, the virus movement protein. However, the deletion did alter the subcellular localization of RTP. When co-expressed with a PLRV infectious clone, a GFP tagged wild-type RTP was localized to discontinuous punctate spots along the cell periphery and was associated with plasmodesmata, although localization was dependent upon the developmental stage of the plant tissue. In contrast, the Δ5aa-RTP-GFP aggregated in the cytoplasm. Structural modeling indicated that the 5aa deletion would be expected to perturb an α-helix motif. Two of 30 plants infected with Δ5aa-RTP developed a wild-type virus infection phenotype ten weeks post-inoculation. Analysis of the virus population in these plants by deep sequencing identified a duplication of sequences adjacent to the deletion that were predicted to restore the α-helix motif. The subcellular distribution of the RTP is regulated by the 5-aa motif which is under strong selection pressure and in turn contributes to the efficient long distance movement of the virus and the induction of systemic symptoms.

Gluten-Free Diet and Its 'Cousins' in Irritable Bowel Syndrome.

Functional disorders are common, with irritable bowel syndrome (IBS) being the commonest and most extensively evaluated functional bowel disorder. It is therefore paramount that effective therapies are available to treat this common condition. Diet appears to play a pivotal role in symptom generation in IBS, with a recent interest in the role of dietary therapies in IBS. Over the last decade, there has been a substantial increase in awareness of the gluten-free diet (GFD), with a recent focus of the role of a GFD in IBS. There appears to be emerging evidence for the use of a GFD in IBS, with studies demonstrating the induction of symptoms following gluten in patients with IBS. However, there are questions with regards to which components of wheat lead to symptom generation, as well as the effect of a GFD on nutritional status, gut microbiota and long-term outcomes. Further studies are required, although the design of dietary studies remain challenging. The implementation of a GFD should be performed by a dietitian with a specialist interest in IBS, which could be achieved via the delivery of group sessions.

Brassica yellows virus\u2019 movement protein upregulates anthocyanin accumulation, leading to the development of purple leaf symptoms on Arabidopsis thaliana

Poleroviruses are widely distributed and often of great economic importance because they cause a variety of symptoms, such as the rolling of young leaves, leaf color changes, and plant decline, in infected plants. However, the molecular mechanism behind these viral-induced symptoms is still unknown. Here, we verified the pathogenicity of the polerovirus Brassica yellows virus (BrYV) by transforming its full-length amplicon into Arabidopsis thaliana, which resulted in many abnormal phenotypes. To better understand the interactions between BrYV and its host, global transcriptome profiles of the transgenic plants were compared with that of non-transgenic Arabidopsis plants. An association between the BrYV- induced purple leaf symptoms and the activation of anthocyanin biosynthesis was noted. Using the transgenic approach, we found that movement protein of BrYV was responsible for the induction of these coloration symptoms. Collectively, our findings demonstrate the BrYV’ pathogenicity and show that the BrYV-induced purple leaf symptom resulted from its movement protein stimulating anthocyanin accumulation.