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1.
Toxicol In Vitro ; 100: 105902, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39025159

RESUMEN

Epidemiological studies indicate that electromagnetic fields (EMF) are associated with cancer in humans. Exposure to mobile phone specific high frequency fields (HF-EMF) may lead to increased glioma risks, while low frequency radiation (LF-EMF) is associated with childhood leukemia. We studied the impact of HF-EMF (1950 MHz, UMTS signal) on DNA stability in an astrocytoma cell line (1321N1), and the effect of LF-EMF (50 Hz) in human derived lymphoma (Jurkat) cells. To find out if these fields affect chemically induced DNA damage, co-exposure experiments were performed. The cells were exposed to HF-EMF or LF-EMF and treated simultaneously and sequentially with mutagens. The compounds cause DNA damage via different molecular mechanisms, i.e. pyrimidine dimers which are characteristic for UV light (4-nitroquinoline 1-oxide, 4NQO), bulky base adducts (benzo[a]pyrene diolepoxide, BPDE), DNA-DNA and DNA-protein cross links and oxidative damage (NiCl2, CrO3). DNA damage was measured in single cell gel electrophoresis (comet) assays. We found a moderate reduction of basal and 4NQO-induced DNA damage in the astrocytoma line, but no significant alterations of chemically induced DNA migration by the HF and LF fields under all other experimental series. The biological consequences of the moderate reduction remain unclear, but our findings indicate that acute mobile phone and power line specific EMF exposures do not enhance genotoxic effects caused by occupationally relevant chemical exposures.


Asunto(s)
Teléfono Celular , Daño del ADN , Campos Electromagnéticos , Exposición Profesional , Humanos , Campos Electromagnéticos/efectos adversos , Línea Celular Tumoral , Exposición Profesional/efectos adversos , Mutágenos/toxicidad , Ensayo Cometa
2.
Clin Cancer Res ; 30(18): 4044-4054, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39028916

RESUMEN

PURPOSE: A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA). PATIENTS AND METHODS: Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated. RESULTS: A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52-14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01-9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells. CONCLUSIONS: HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.


Asunto(s)
Vacunas contra el Cáncer , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Femenino , Persona de Mediana Edad , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Masculino , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/uso terapéutico , Vacunas de Subunidad/inmunología , Resultado del Tratamiento , Estadificación de Neoplasias , Anciano de 80 o más Años
3.
Mutat Res Rev Mutat Res ; 794: 108510, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004337

RESUMEN

Micronucleus (MN) assays with buccal cells are at present widely used to investigate occupational exposures to genotoxic carcinogens. This article describes their use for the monitoring of metal exposed workers. We found in total 73 relevant articles, in the majority (97 %) increased MN and/or other nuclear anomalies were reported. Most studies were realized in South East Asia and South America. A variety of different occupations was studied including welders, electroplaters, painters, workers in battery recycling and production, tannery workers, dental technicians, miners, workers in foundries and smelters, and also subjects working in waste recycling, glass, aluminum and steel production. In many investigations the effects increased with the duration of the working period. The quality of individual studies was evaluated with a quality score tool. The number of cells was in most studies sufficient and DNA-specific stains were used. However, many studies have shortcomings, e.g. they focused solely on MN formation and did not evaluate anomalies, which provide additional information about the stability of the genetic material and acute cytotoxic effects. Only 35 % of the investigations contain quantitative information about exposures to metals and other toxicants. In 6 of these studies, correlations were observed between the concentrations of specific metals (As, Pb, Cr, Cd) in body fluids and MN frequencies. Taken together, the available data indicate that the MN assay can be used to detect chromosomal damage in metal exposed groups; furthermore, it enables also comparisons between subgroups differing in regard to their exposure and allows an estimation of the efficiency of protective measures. The exposure of workers to metals is currently controlled with chemical analytical measurements only, MN assays with buccal cells could contribute to further improve the safety at workplaces as they reflect the biological consequences including synergistic and antagonistic interactions between toxicants.

4.
Vaccines (Basel) ; 12(7)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39066432

RESUMEN

Immunity against respiratory pathogens is often short-term, and, consequently, there is an unmet need for the effective prevention of such infections. One such infectious disease is coronavirus disease 19 (COVID-19), which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on 11 March 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, contained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred, and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and, thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus' transmission is warranted. In this review, we present the status of the systemic vaccines, both the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell peptide-based vaccination applied by a prime-boost schedule to elicit both systemic and mucosal immunity.

5.
Allergy ; 79(9): 2482-2501, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39003594

RESUMEN

BACKGROUND: SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system. METHODS: We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). RESULTS: Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3-CD56+ NK and CD19+CD27+ B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. CONCLUSIONS: COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.


Asunto(s)
Inmunidad Adaptativa , Anticuerpos Antivirales , COVID-19 , Citocinas , Inmunidad Innata , SARS-CoV-2 , Células TH1 , Células Th2 , Humanos , COVID-19/inmunología , COVID-19/sangre , SARS-CoV-2/inmunología , Masculino , Citocinas/sangre , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Células Th2/inmunología , Inmunidad Adaptativa/inmunología , Adulto , Células TH1/inmunología , Células TH1/metabolismo , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Estudios Longitudinales , Proteínas de la Nucleocápside de Coronavirus/inmunología
6.
Front Immunol ; 15: 1379833, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911871

RESUMEN

Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.


Asunto(s)
Alérgenos , Reacciones Cruzadas , Inmunoglobulina E , Polen , Profilinas , Salsola , Humanos , Profilinas/inmunología , Profilinas/química , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Alérgenos/genética , Salsola/inmunología , Femenino , Polen/inmunología , Masculino , Reacciones Cruzadas/inmunología , Adulto , Proteínas Recombinantes/inmunología , Rinitis Alérgica Estacional/inmunología , Persona de Mediana Edad , Basófilos/inmunología , Basófilos/metabolismo , Antígenos de Plantas/inmunología , Antígenos de Plantas/genética , Adulto Joven , Adolescente , Proteínas de Plantas/inmunología , Proteínas de Plantas/genética
7.
Vaccines (Basel) ; 12(5)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38793769

RESUMEN

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs.

8.
Bioelectromagnetics ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778512

RESUMEN

Potential differential and non-differential recall error in mobile phone use (MPU) in the multinational MOBI-Kids case-control study were evaluated. We compared self-reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702 subjects aged between 10 and 24 years in eight countries. Spearman rank correlations, Kappa coefficients and geometric mean ratios (GMRs) were used. No material differences in MPU recall estimates between cases and controls were observed. The Spearman rank correlation coefficients between self-reported and recorded MPU in the most recent 3 months were 0.57 and 0.59 for call number and for call duration, respectively. The number of calls was on average underestimated by the participants (GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59). Country, years since start of using a mobile phone, age at time of interview, and sex did not appear to influence recall accuracy for either call number or call duration. A trend in recall error was seen with level of self-reported MPU, with underestimation of use at lower levels and overestimation of use at higher levels for both number and duration of calls. Although both systematic and random errors in self-reported MPU among participants were observed, there was no evidence of differential recall error between cases and controls. Nonetheless, these sources of exposure measurement error warrant consideration in interpretation of the MOBI-Kids case-control study results on the association between children's use of mobile phones and potential brain cancer risk.

9.
Environ Int ; 187: 108665, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677087

RESUMEN

Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations predominating the search for brain tumor risks of mobile phone use since the late 1990 s were deemed unresolvable by further investigations of that type. Indeed, prospective cohort studies typically have the advantage of being not or less affected by differential exposure misclassification, recall and selection bias, and, as they proceed in the direction of the time arrow, results are more easily interpreted in terms of causation. However, results of the COSMOS study published now in this journal are not of help for the risk assessment of mobile phone use and do not support the conclusions of the authors that their findings "suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma".


Asunto(s)
Neoplasias Encefálicas , Teléfono Celular , Neoplasias Encefálicas/epidemiología , Humanos , Teléfono Celular/estadística & datos numéricos , Estudios Prospectivos , Estudios de Cohortes , Sesgo , Medición de Riesgo , Glioma/epidemiología , Meningioma/epidemiología , Neuroma Acústico/epidemiología , Exposición a la Radiación/estadística & datos numéricos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano
10.
Clin Microbiol Infect ; 30(6): 816-821, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38432432

RESUMEN

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.


Asunto(s)
Cultivo de Sangre , Candida , Candidemia , Sensibilidad y Especificidad , Humanos , Candidemia/diagnóstico , Candida/aislamiento & purificación , Candida/clasificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Cultivo de Sangre/métodos , Adulto , Anciano de 80 o más Años , Unidades de Cuidados Intensivos , Imagen por Resonancia Magnética
11.
Environ Res ; 251(Pt 1): 118634, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38452915

RESUMEN

Several human studies indicate that mobile phone specific electromagnetic fields may cause cancer in humans but the underlying molecular mechanisms are currently not known. Studies concerning chromosomal damage (which is causally related to cancer induction) are controversial and those addressing this issue in mobile phone users are based on the use of questionnaires to assess the exposure. We realized the first human intervention trial in which chromosomal damage and acute toxic effects were studied under controlled conditions. The participants were exposed via headsets at one randomly assigned side of the head to low and high doses of a UMTS signal (n = 20, to 0.1 W/kg and n = 21 to 1.6 W/kg Specific Absorption Rate) for 2 h on 5 consecutive days. Before and three weeks after the exposure, buccal cells were collected from both cheeks and micronuclei (MN, which are formed as a consequence of structural and numerical chromosomal aberrations) and other nuclear anomalies reflecting mitotic disturbance and acute cytotoxic effects were scored. We found no evidence for induction of MN and of nuclear buds which are caused by gene amplifications, but a significant increase of binucleated cells which are formed as a consequence of disturbed cell divisions, and of karyolitic cells, which are indicative for cell death. No such effects were seen in cells from the less exposed side. Our findings indicate that mobile phone specific high frequency electromagnetic fields do not cause acute chromosomal damage in oral mucosa cells under the present experimental conditions. However, we found clear evidence for disturbance of the cell cycle and cytotoxicity. These effects may play a causal role in the induction of adverse long term health effects in humans.


Asunto(s)
Teléfono Celular , Citocinesis , Mucosa Bucal , Humanos , Mucosa Bucal/efectos de la radiación , Mucosa Bucal/citología , Adulto , Masculino , Citocinesis/efectos de la radiación , Muerte Celular/efectos de la radiación , Adulto Joven , Femenino , Aberraciones Cromosómicas/efectos de la radiación , Pruebas de Micronúcleos , Campos Electromagnéticos/efectos adversos , Micronúcleos con Defecto Cromosómico/efectos de la radiación
14.
EBioMedicine ; 96: 104788, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37672867

RESUMEN

BACKGROUND: Patients with inflammatory bowel disease (IBD) and healthy controls received primary SARS-CoV-2-mRNA vaccination and a booster after six months. Anti-TNF-α-treated patients showed significantly lower antibody (Ab) levels and faster waning than α4ß7-integrin-antagonist recipients and controls. This prospective cohort study aimed to elucidate the underlying mechanisms on the basis of circulating T-follicular helper cells (cTfh) and B memory cells. METHODS: We measured SARS-CoV-2- Wuhan and Omicron specific Abs, B- and T-cell subsets at baseline and kinetics of Spike (S)-specific B memory cells along with distributions of activated cTfh subsets before and after primary and booster vaccination. FINDINGS: Lower and faster waning of Ab levels in anti-TNF-α treated IBD patients was associated with low numbers of total and naïve B cells vs. expanded plasmablasts prior to vaccination. Along with their low Ab levels against Wuhan and Omicron VOCs, reduced S-specific B memory cells were identified after the 2nd dose which declined to non-detectable after 6 months. In contrast, IBD patients with α4ß7-integrin-antagonists and controls mounted and retained high Ab levels after the 2nd dose, which was associated with a pronounced increase in S-specific B memory cells that were maintained or expanded up to 6 months. Booster vaccination led to a strong increase of Abs with neutralizing capacity and S-specific B memory cells in these groups, which was not the case in anti-TNF-α treated IBD patients. Of note, Ab levels and S-specific B memory cells in particular post-booster correlated with the activation of cTfh1 cells after primary vaccination. INTERPRETATIONS: The reduced magnitude, persistence and neutralization capacity of SARS-CoV-2 specific Abs after vaccination in anti-TNF-α-treated IBD patients were associated with impaired formation and maintenance of S-specific B memory cells, likely due to absent cTfh1 activation leading to extra-follicular immune responses and diminished B memory cell diversification. These observations have implications for patient-tailored vaccination schedules/vaccines in anti-TNF-α-treated patients, irrespective of their underlying disease. FUNDING: The study was funded by third party funding of the Institute of Specific Prophylaxis and Tropical Medicine at the Medical University Vienna. The funders had no role in study design, data collection, data analyses, interpretation, or writing of report.

15.
Allergy ; 78(12): 3136-3153, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37701941

RESUMEN

BACKGROUND: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail. OBJECTIVE: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation. METHODS: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG1 and IgG4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients. RESULTS: IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG1 and IgG4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation. CONCLUSION: IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.


Asunto(s)
Hipersensibilidad a los Alimentos , Polen , Ratas , Animales , Humanos , Epítopos , Antígenos de Plantas , Alérgenos , Inmunoglobulina G , Inmunoglobulina E , Péptidos , Proteínas de Plantas , Proteínas Recombinantes
16.
Mutagenesis ; 38(4): 227-237, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37418160

RESUMEN

The aim of this study was to investigate if age and body mass of humans have an impact on the DNA-damaging properties of high-frequency mobile phone-specific electromagnetic fields (HF-EMF, 1950 MHz, universal mobile telecommunications system, UMTS signal) and if this form of radiation has an impact on the genotoxic effects of occupationally relevant exposures. Pooled peripheral blood mononuclear cells (PBMC) from three groups [young normal weight, young obese (YO), and older age normal weight individuals] were exposed to different doses of HF-EMF (0.25, 0.5, and 1.0 W/kg specific absorption rate-SAR) and simultaneously or sequentially to different chemicals which cause DNA damage (CrO3, NiCl2, benzo[a]pyrene diol epoxide-BPDE, and 4-nitroquinoline 1-oxide-4NQO) via different molecular mechanisms. We found no difference in regard to the background values in the three groups but a significant increase of DNA damage (81% without and 36% with serum) in cells from old participants after radiation with 1.0 W/kg SAR 16 h. In combined treatment experiments we found no impact of the UMTS signal on chemically induced DNA damage in the different groups in general. However, a moderate decrease of DNA damage was seen in simultaneous treatment experiments with BPDE and 1.0 W/kg SAR in the YO group (decline 18%). Taken together our findings indicate that HF-EMF cause DNA damage in PBMC from older subjects (69.1 years). Furthermore, they show that the radiation does not increase induction of DNA damage by occupationally relevant chemicals.


Asunto(s)
Teléfono Celular , Campos Electromagnéticos , Humanos , Campos Electromagnéticos/efectos adversos , Leucocitos Mononucleares , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido , Daño del ADN , Demografía
17.
BMJ ; 381: 1111, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37220942
18.
Euro Surveill ; 28(17)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37103786

RESUMEN

Following an increase in diphtheria cases in Europe since 2022, we retrospectively estimated the prevalence of seroprotection against diphtheria and tetanus in 10,247 Austrian residents (population: 8,978,929) voluntarily tested between 2018 and 2022. Lack of seroprotection against diphtheria was found in 36% compared with 4% against tetanus. The geometric mean antibody concentration against tetanus was 7.9-fold higher compared with that for diphtheria. Raising awareness of regular booster vaccinations against diphtheria in combination with tetanus and pertussis is urgently needed.


Asunto(s)
Difteria , Tétanos , Tos Ferina , Humanos , Difteria/epidemiología , Difteria/prevención & control , Tétanos/epidemiología , Tétanos/prevención & control , Austria/epidemiología , Estudios Retrospectivos , Anticuerpos Antibacterianos , Inmunización Secundaria , Tos Ferina/prevención & control , Europa (Continente)/epidemiología
19.
Eur Clin Respir J ; 10(1): 2194165, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37006411

RESUMEN

Background: The American Academy of Pediatrics Children's Health Survey for Asthma (CHSA) is a widely used instrument to assess various aspects of health and well-being in relation to asthma. There is a parent and a child version of this questionnaire and little is known about the concordance between these versions. Method: In a cross-sectional study conducted in 13 facilities, hospitals and outpatient clinics covering all areas of Kosovo, children with asthma aged 7-16 years were enrolled. Information about asthma diagnosis was obtained from the treating physician. Children and parents answered the CHSA, parent or child version (CHSA-C) as well as a number of questions about environmental conditions, health insurance and socio-demographic characteristics. Results: The survey included 161 Kosovar children with asthma and their caregivers. Although there were significant differences between parents and child versions regarding physical health, child activity and emotional health, with parents rating physical and emotional health higher and child activity lower, there were significant correlations (R > 0.7) for physical and child activity scales but only a low one (R = 0.25) for emotional health. Inspection of concordance for single items revealed very high correlations (>0.9) for all disease events, but a significant underestimation of the number of wheezing episodes by parents. Good agreement was found for statements about disease severity. Conclusions: The high correlation between information about children's health obtained from parents and children underlines the usefulness of parents as source of information on child's asthma. Impact of the disease on emotional health is, however, underestimated by parents.

20.
Mutat Res Rev Mutat Res ; 791: 108458, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37031732

RESUMEN

The single cell gel electrophoresis technique is based on the measurement of DNA migration in an electric field and enables to investigate via determination of DNA-damage the impact of foods and their constituents on the genetic stability. DNA-damage leads to adverse effects including cancer, neurodegenerative disorders and infertility. In the last 25 years approximately 90 human intervention trials have been published in which DNA-damage, formation of oxidized bases, alterations of the sensitivity towards reactive oxygen species and chemicals and of repair functions were investigated with this technique. In approximately 50% of the studies protective effects were observed. Pronounced protection was found with certain plant foods (spinach, kiwi fruits, onions), coffee, green tea, honey and olive oil. Also diets with increased contents of vegetables caused positive effects. Small amounts of certain phenolics (gallic acid, xanthohumol) prevented oxidative damage of DNA; with antioxidant vitamins and cholecalciferol protective effects were only detected after intake of doses that exceed the recommended daily uptake values. The evaluation of the quality of the studies showed that many have methodological shortcomings (lack of controls, no calibration of repair enzymes, inadequate control of the compliance and statistical analyses) which should be avoided in future investigations.


Asunto(s)
Antioxidantes , Dieta , Humanos , Ensayo Cometa , Antioxidantes/farmacología , Estrés Oxidativo , Daño del ADN/genética , ADN
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