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1.
Allergy ; 72(5): 731-736, 2017 May.
Article in English | MEDLINE | ID: mdl-27659406

ABSTRACT

BACKGROUND: Inappropriate dietary eliminations may impair quality of life, affect children's growth and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food-avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. This study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC. METHODS: A prospective study was conducted involving 81 mothers of children with IgE-mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State-Trait Anxiety Inventory on the day of OFC and 6 months later. RESULTS: In total, 11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants' characteristics or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC. CONCLUSIONS: Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food.


Subject(s)
Feeding Behavior , Food Hypersensitivity/epidemiology , Food , Health Knowledge, Attitudes, Practice , Adult , Allergens/immunology , Anxiety , Child , Child, Preschool , Female , Food/adverse effects , Food Hypersensitivity/immunology , Humans , Immunoglobulin E/immunology , Male , Middle Aged , Mothers/psychology , Population Surveillance , Prospective Studies , Surveys and Questionnaires
2.
Allergy ; 72(7): 1054-1060, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27886387

ABSTRACT

BACKGROUND: Food allergy is major public health concern affecting nearly 15 million Americans and 80 million Europeans. Risk of anaphylaxis and implications for social activities affect patients' quality of life and psychological well-being. We previously found that young patients reported higher levels of alexithymia (difficulty in recognizing and expressing emotions) compared with healthy peers and may influence affect, management style and clinical outcomes. This study aimed to explore links between coping strategies, alexithymia and anxiety among food-allergic adolescents and young adults. METHODS: Ninety-two patients with IgE-mediated food allergy (mean age 18.6 years) completed Coping Orientation to Problems Experienced Inventory, Toronto Alexithymia Scale and Trait Anxiety subscale of State-Trait Anxiety Inventory. Multivariate analyses of variance assessed differences and associations between subgroups on the scales. RESULTS: Significant differences found between alexithymia levels in coping style were explained by Avoidance strategies. 'Avoidance' had the highest contribution in explaining alexithymia, followed by trait anxiety, age, anaphylaxis and social support. Respondents with higher alexithymia use avoidance as coping strategy over and above other coping strategies such as problem-solving and positive thinking, are younger, will have experienced anaphylaxis and will have lower social support. CONCLUSIONS: Recognizing the specific role of affect regulation in health behaviours may constitute an important step in supporting patients to explore more adaptive strategies.


Subject(s)
Adaptation, Psychological , Affective Symptoms , Anxiety , Food Hypersensitivity/psychology , Adolescent , Adult , Age Factors , Female , Food Hypersensitivity/diagnosis , Food Hypersensitivity/immunology , Humans , Immunoglobulin E/immunology , Male , Quality of Life , Young Adult
3.
Allergy ; 71(11): 1575-1584, 2016 11.
Article in English | MEDLINE | ID: mdl-27059671

ABSTRACT

BACKGROUND: A major drawback of oral immunotherapy for food allergy is the possibility of severe side-effects. We assessed both safety and efficacy of a low allergenic hydrolysed egg (HydE) preparation used in a double-blind placebo-controlled randomized study in egg allergic children. METHODS: In a pilot multicentre study, 29 egg allergic patients (aged 1-5.5 years) were administered daily for 6 months 9 g HydE or placebo in a blinded, randomized manner. Safety was verified by oral food challenge to assess tolerance towards HydE at the start and efficacy by an open oral food challenge (OFC, primary outcome) at the end. Additionally, changes in basophil activation and specific IgE and IgG4 were assessed. RESULTS: All egg allergic patients randomized to HydE (n = 15) tolerated the full dose at day 1 and received the maintenance dose from the start at home. No statistically significant difference was observed on the final OFC (36% and 21% had a negative OFC in the treatment and placebo groups, respectively). Specific IgG4 levels increased, while both CD203c+ and CD63+ basophils decreased significantly more over time in the treatment than in the placebo group. CONCLUSIONS: HydE can be regarded as a safe, low allergenic product to use in children allergic to egg. Although not significant, HydE given for 6 months increased numerically the proportion of patients becoming tolerant to egg. HydE induced a modulation of the immune response towards better tolerance. A longer treatment period and/or a higher dose may improve the clinical outcome and should be evaluated.


Subject(s)
Allergens/administration & dosage , Allergens/immunology , Desensitization, Immunologic , Egg Hypersensitivity/immunology , Egg Hypersensitivity/therapy , Eggs/adverse effects , Administration, Oral , Basophils/immunology , Basophils/metabolism , Child, Preschool , Desensitization, Immunologic/methods , Egg Hypersensitivity/diagnosis , Female , Humans , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Immunophenotyping , Infant , Male , Phosphoric Diester Hydrolases/metabolism , Pyrophosphatases/metabolism , Skin Tests , Tetraspanin 30/metabolism , Treatment Outcome
4.
Psychol Health Med ; 20(6): 732-41, 2015.
Article in English | MEDLINE | ID: mdl-25531062

ABSTRACT

Maternal stress in fetal and early life has been associated with the development of respiratory allergies, but no studies exist about food allergy. Stressful events and the quality of caregiving provided, as they affect the emotional and physiologic regulation of the infant, could alter the hypothalamic-pituitary-adrenal and immune system, facilitating an increased allergic response. This study aimed to investigate the influence of perinatal stress, as perceived by mothers, on developing food allergy in childhood. A survey on pregnancy and the first three months after giving birth was submitted to 59 Italian mothers of at least one child suffering from severe food allergy and one completely healthy child, for a total of 118 children examined. The presence of stressful events and the quality of perinatal period for each child were assessed retrospectively. The food allergic children's data were compared to siblings' data through inferential statistics. The results showed a significantly higher number of stressful events occurred during patients' perinatal period, compared to siblings, in particular bereavements in pregnancy and parenting difficulties in postpartum. Mothers reported harder pregnancies and more stressful, harder, and, in general, worse postpartum when referring to their food-allergic children, in comparison with their siblings (p < .05). Psychological aspects are demonstrated to be involved in the development of allergic diseases. This study constitutes the first step to examine the role of early stress and perinatal psychosocial factors in the pathogenesis of food allergy; further studies are necessary to understand individual psychological impact and its relations with genetic and biological factors.


Subject(s)
Food Hypersensitivity/epidemiology , Mothers/psychology , Postpartum Period/psychology , Pregnancy Complications/psychology , Prenatal Exposure Delayed Effects/epidemiology , Stress, Psychological/psychology , Adolescent , Adult , Case-Control Studies , Child , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pregnancy , Retrospective Studies , Self Report , Surveys and Questionnaires
5.
Genomics ; 93(3): 196-204, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18950699

ABSTRACT

We have engineered a set of useful tools that facilitate targeted single copy knock-in (KI) at the hypoxanthine guanine phosphoribosyl transferase 1 (Hprt1) locus. We employed fine scale mapping to delineate the precise breakpoint location at the Hprt1(b-m3) locus allowing allele specific PCR assays to be established. Our suite of tools contains four targeting expression vectors and a complementing series of embryonic stem cell lines. Two of these vectors encode enhanced green fluorescent protein (EGFP) driven by the human cytomegalovirus immediate-early enhancer/modified chicken beta-actin (CAG) promoter, whereas the other two permit flexible combinations of a chosen promoter combined with a reporter and/or gene of choice. We have validated our tools as part of the Pleiades Promoter Project (http://www.pleiades.org), with the generation of brain-specific EGFP positive germline mouse strains.


Subject(s)
Gene Expression Profiling/methods , Gene Knock-In Techniques/methods , Genetic Vectors/genetics , Genomics/methods , Hypoxanthine Phosphoribosyltransferase/genetics , Promoter Regions, Genetic/genetics , Animals , Base Sequence , Cytomegalovirus/genetics , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Female , Humans , Male , Mice , Mice, Transgenic , Molecular Sequence Data , Reproducibility of Results , Sequence Alignment , Sequence Deletion
6.
Mol Psychiatry ; 13(1): 65-73, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17519929

ABSTRACT

Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P<0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.


Subject(s)
Birth Weight/drug effects , Infant Behavior/drug effects , Maternal-Fetal Exchange , Prenatal Exposure Delayed Effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonin Plasma Membrane Transport Proteins/genetics , Adaptation, Physiological/drug effects , Adult , Anxiety Disorders/blood , Anxiety Disorders/drug therapy , Apgar Score , Case-Control Studies , Chi-Square Distribution , Cohort Studies , Depressive Disorder/blood , Depressive Disorder/drug therapy , Female , Gestational Age , Humans , Infant Behavior/physiology , Infant, Newborn , Male , Polymorphism, Genetic , Pregnancy , Pregnancy Outcome , Reference Values , Risk Assessment , Serotonin Plasma Membrane Transport Proteins/drug effects , Selective Serotonin Reuptake Inhibitors/blood , Selective Serotonin Reuptake Inhibitors/therapeutic use
7.
Genes Brain Behav ; 6(6): 503-16, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17054721

ABSTRACT

Nuclear receptor 2E1 (NR2E1) is expressed in human fetal and adult brains; however, its role in human brain-behavior development is unknown. Previously, we have corrected the cortical hypoplasia and behavioral abnormalities in Nr2e1(-/-) mice using a genomic clone spanning human NR2E1, which bolsters the hypothesis that NR2E1 may similarly play a role in human cortical and behavioral development. To test the hypothesis that humans with abnormal brain-behavior development may have null or hypomorphic NR2E1 mutations, we undertook the first candidate mutation screen of NR2E1 by sequencing its entire coding region, untranslated, splice site, proximal promoter and evolutionarily conserved non-coding regions in 56 unrelated patients with cortical disorders, namely microcephaly. We then genotyped the candidate mutations in 325 unrelated control subjects and 15 relatives. We did not detect any coding region changes in NR2E1; however, we identified seven novel candidate regulatory mutations that were absent from control subjects. We used in silico tools to predict the effects of these candidate mutations on neural transcription factor binding sites (TFBS). Four candidate mutations were predicted to alter TFBS. To facilitate the present and future studies of NR2E1, we also elucidated its molecular evolution, genetic diversity, haplotype structure and linkage disequilibrium by sequencing an additional 94 unaffected humans representing Africa, the Americas, Asia, Europe, the Middle East and Oceania, as well as great apes and monkeys. We detected strong purifying selection, low genetic diversity, 21 novel polymorphisms and five common haplotypes at NR2E1. We conclude that protein-coding changes in NR2E1 do not contribute to cortical and behavioral abnormalities in the patients examined here, but that regulatory mutations may play a role.


Subject(s)
Cerebral Cortex/metabolism , Intellectual Disability/genetics , Microcephaly/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Regulatory Elements, Transcriptional/genetics , Animals , Case-Control Studies , Cerebral Cortex/abnormalities , Ethnicity/genetics , Evolution, Molecular , Female , Genetic Testing , Haplotypes , Humans , Intellectual Disability/complications , Intellectual Disability/metabolism , Male , Matched-Pair Analysis , Microcephaly/complications , Microcephaly/metabolism , Mutation , Orphan Nuclear Receptors , Pedigree , Primates/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Reference Values
8.
Croat Med J ; 42(4): 473-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11471203

ABSTRACT

Gene therapy of cancer has become a major interest of medical research since more than 60% of the ongoing gene therapy protocols today involve cancer patients. To increase the therapeutic index of cancer gene therapy, targeting strategies have been developed to ensure that the expression of therapeutic genes is restricted exclusively to the tissue of interest. An attractive approach lies in the possibility to control the expression of therapeutic genes at the transcriptional level by the introduction of tissue-specific or tumor-specific enhancers/promoters offers. We have developed transcriptionally targeted vectors for gene therapy of solid tumors, including malignant gliomas and epithelial thyroid tumors. The choice of these tumor types relies on their clinical impact, ie, morbidity and mortality, the lack of effective conventional therapeutic strategies, and the ability of these tumors to express tissue/tumor-specific genes, whose transcriptional control elements (enhancer/promoter) may be used for achieving selective transgene expression. Here we report our clinical and preclinical experience in gene therapy of brain and thyroid tumors, and review the literature published on this topic.


Subject(s)
Brain Neoplasms/therapy , Gene Targeting , Genetic Therapy , Glioblastoma/therapy , Brain Neoplasms/genetics , Glioblastoma/genetics , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/therapy , Transcription, Genetic
9.
Eur J Endocrinol ; 143(4): 447-66, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11022190

ABSTRACT

Gene therapy for endocrine diseases represents an exciting new type of molecular intervention that may be a curative one. Endocrine disorders that might be treated by gene therapy include monogenic diseases, such as GH deficiency and hypothalamic diabetes insipidus, and multifactorial diseases, such as diabetes mellitus, obesity and cancer. Premises seem promising for endocrine tumours, but many combined approaches of cell and gene therapy are foreseeable also for other endocrine disorders. This review outlines the principles of gene therapy, describes the endocrine disorders that might take advantage of gene transfer approaches, as well as the gene therapy interventions that have already been attempted, their major limitations and the problems that remain to be solved.


Subject(s)
Endocrine System Diseases/therapy , Genetic Therapy , Animals , Endocrine Gland Neoplasms/therapy , Hormones/deficiency , Humans
10.
Haematologica ; 85(7): 680-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10897118

ABSTRACT

BACKGROUND AND OBJECTIVES: Retroviral vectors are widely used to deliver foreign genes to hematopoietic stem cells (HSC). Improvement of marking protocols needs reporter genes to allow rapid detection and efficient selection of transduced cells. The great potential of EGFP and LNGFR as reporter systems prompted us to compare them simultaneously, using the same retroviral backbone and the same gene transfer procedures. DESIGN AND METHODS: The EGFP and LNGFR coding sequences were separately cloned into the MFG retroviral backbone. A cloning strategy assuring that both genes utilize the same ATG as the start codon was adopted. Marker gene expression, viral titers, transduction efficiency, and vector stability were evaluated in expanded amphotropic packaging clones and human hematopoietic cell lines by flow cytometry and PCR analysis. Vectors were also tested for their ability to transduce CD34+ peripheral blood cells. RESULTS: A significantly larger number of MFG- LNGFR packaging clones were obtained that produced high viral titers. A direct correlation between viral titer and marker gene expression in packaging clones was demonstrated for both constructs. Similar expression kinetics and absence of in vitro toxicity in transduced cells were also observed for both constructs. Successful infection of CD34+ cells was achieved even after a short time of exposure to recombinant viruses. INTERPRETATION AND CONCLUSIONS: Our results demonstrate that EGFP and LNGFR marker genes are equally useful for a rapid, specific and non-toxic detection of transduced cells. The MFG-EGFP construct appears useful to optimize gene transfer protocols in vitro. On the other hand, the MFG-LNGFR construct, for making possible a more efficient selection of high titer producer clones, as well as for safety and adaptability to the in vivo use, is more suitable for clinical applications.


Subject(s)
Gene Transfer Techniques/standards , Luminescent Proteins/genetics , Receptor, Nerve Growth Factor/genetics , Cell Line , Evaluation Studies as Topic , Flow Cytometry , Fluorescent Dyes , Genes, Reporter , Genetic Markers , Genetic Vectors/chemical synthesis , Green Fluorescent Proteins , Hematopoietic Stem Cells/virology , Humans , Pyridinium Compounds , Retroviridae/genetics
11.
Methods Mol Med ; 35: 511-22, 2000.
Article in English | MEDLINE | ID: mdl-21390827

ABSTRACT

Gene therapy of cancer includes strategies for augmentation of immunotherapeutic and chemoterapeutic approaches. These strategies mainly involve ex vivo and in vivo cytokine gene transfer, drug sensitization with genes for prodrug delivery, and the use of drug-resistance genes for protecting bone marrow from high-dose chemotherapy (1). Vector development remains the primary focus for any future research in the field. Retroviral vectors, especially those derived from Moloney murine leukemia virus (MoMLV), remain among the most widely utilized vectors in gene therapy trials.

12.
Intervirology ; 42(1): 1-8, 1999.
Article in English | MEDLINE | ID: mdl-10393497

ABSTRACT

A new restriction fragment length polymorphism (RFLP) analysis has been developed for hepatitis C virus (HCV) typing in the viral 5' non-coding region and contiguous core region. These genomic sequences were chosen for the relative nucleotide homology among different genotypes and for the presence of polymorphic sites. By employing two endonucleases (AccI and MboI) and, in some instances, a third one (EcoRII), we can unambiguously and reproducibly distinguish between genotypes and subtypes 1a, 1b, 1c, 2a, 2c, 2b, 3a, 3b, 4a, 5a and 6a. The method was applied for diagnosing two Italian groups of HCV-infected individuals reflecting a randomly collected population and a group of intravenous drug users. The accuracy of this method has been validated by comparison with INNOLiPA and by sequencing. Our approach represents an improvement over previous RFLP methods, since typing is accurate and simpler.


Subject(s)
Hepacivirus/genetics , Polymorphism, Restriction Fragment Length , Base Sequence , Female , Genotype , Hepacivirus/classification , Hepatitis C/virology , Humans , Male , Molecular Sequence Data , RNA, Viral/genetics
13.
J Biotechnol ; 68(1): 1-13, 1999 Feb 05.
Article in English | MEDLINE | ID: mdl-10036766

ABSTRACT

Gene therapy aims at transferring a therapeutic gene into human somatic cells in order to treat a disease. Originally addressed to hereditary genetic disorders, gene therapy has found therapeutic applications in cancer, infectious diseases and degenerative disorders, particularly those of the nervous system. Although gene transfer into humans has been demonstrated in several clinical trials, with more than 300 currently underway worldwide, there is still no single outcome that undoubtedly showed a consistent benefit for the patient. Nevertheless, the expectations for gene therapy are still high, and the prospects of future clinical success are increasing together with the growing of the field. The development of better delivery systems specifically tailored to individual diseases, with sustained expression of the therapeutic gene in the appropriate cells, will in the end make possible true therapeutic applications of human gene transfer.


Subject(s)
Genetic Diseases, Inborn/therapy , Genetic Therapy , Neoplasms/therapy , Viruses/genetics , Acquired Immunodeficiency Syndrome/therapy , Gene Transfer Techniques , Genetic Vectors , Humans
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