Természetes ölő (NK) T lymphocyták légúti gyulladásokban = Natural killer (NK) T lymphocytes in airway inflammation

1.A természetes ölősejtek által keltett légúti gyulladás szteroid gyulladásgátlóval szemben rezisztens. 2.Ebben a modellben csökken az allergiával szembeni tolerancia és fokozódik egy viszonylag újabban felfedezett gyulladáskeltő mediátor, az interleukin-17 (IL-17) szintézise a tüdőben. 3. Az IL-17 hiánya a fenti modellben szteroid rezisztenssé teszi a légúti hyperreaktivitást. 4. Szteroid rezisztens légúti allergia (asthma) modellünkben microarray technikával találtunk mintegy 23 olyan gént, melyeknek a szteroid rezisztencia kialakulásában szerepe lehet. 5. Terhes asthmás betegekben igazoltuk, hogy a Treg sejtek számbeli fokozódása elmarad, mely egészséges terhességben egyébként jellemző. Az anyai asthma tehát csökkenti a terhesség alatti immuntoleranciát. 6. Ugyanerre utalt a szérum HSP70 koncentráció, valamint a Th17/Treg sejtarány emelkedése is asthmás terhesekben. 7. Egészséges terhesekben összefügg a Treg sejtek számának fokozódása (immuntolerancia) a magzati növekedés fiziológiás mértékével. Asthmás terhesekben a Treg szám nem nő és nincs összefüggés a Treg szám és a magzati születési súly között. 8.Számos eredmény született a dohányzás által kiváltott kísérletes pulmonalis hypertonia pathomechanizmusáról, a cisplatinnal kapcsolatos nephropathia kockázati télnyezőiről, valamint az asthma és a tüdőrák különféle biomarkereiről. | 1.Airway inflammation induced by the activation of natural killers proved to be resistant to treatment by steroid antiinflammatory agents. 2.In this model, tolerance against the development of allergies is decreased and the synthesis of interleukin-17 (IL-17), a recently discovered proinflammatory mediator, is increased. 3.Absence of IL-17 in this model of asthma makes airway inflammation steroid resistant. 4.In our earlier, steroid resistant airway allergy model, using microarray technique, we have identified 23 genes possibly responsible for steroid resistance. 5.The increase of Treg cells in healthy pregnancy is absent in pregnant patients suffering from asthma. Thus, asthma interferes with natural immunotolerance of pregnancy. 6.The same conclusion can be drawn basen on the increase of heat-shock protein-70 and the Th17/Treg ratio in asthmatic pregnants. 7.There is a relationship between the abundance of maternal Tregs and the birth weight of newborns in healthy pregnants. This relationship is absent in asthmatic pregnants as is the abundance of Tregs. 8. Many new findings have been published by us about the mechanism of experimental pulmonary hypertension induced by smoking and nephropathy induced by cisplatin (in lung cancer patients). New biomarkers (in the exhaled breath) were identified in asthmatics and lung cancer patients

Inzulin-túlérzékenységi reakció vagy valami más? Tanulságok egy eset kapcsán = Lessons from a case of suspected insulin allergy

Today, insulin hypersensitivity reactions are rare side effects of insulin therapy. In two-thirds of the suspected insulin allergy cases, the clinical symptoms are not related to insulin. The authors report the case of a 64-year-old female patient, by whom lymphocyte tarnsformation test (LIT) has been used to elucidate the background of allergic symptoms developed during insulin therapy. The performed LTT did not support hypersensitivity to insulin, however, the positive protamine test raised the suspicion of fish allergy. Complementary immunoserology also highlighted the coexistence of previously unrevealed thyroid disease. To our knowledge, this is the first documented case report in Hungary that attempts to address the real cause of a suspected hypersensitivity reaction to insulin by using LTT

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria

Correction to: Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report

Abstract Following publication of the original article [1], the authors requested a correction to the details of one of the co-authors

Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report

Abstract Background Defects of the slow myosin heavy chain isoform coding MYH7 gene primarily cause skeletal myopathies including Laing Distal Myopathy, Myosin Storage Myopathy and are also responsible for cardiomyopathies. Scapuloperoneal and limb-girdle muscle weakness, congenital fiber type disproportion, multi-minicore disease were also reported in connection of MYH7. Pathogeneses of the defects in the head and proximal rod region of the protein are well described. However, the C-terminal mutations of the MYH7 gene are less known. Moreover, only two articles describe the phenotypic impact of the elongated mature protein product caused by termination signal loss. Case presentation Here we present a male patient with an unusual phenotypic variant of early-onset and predominant involvement of neck muscles with muscle biopsy indicating myopathy and sarcoplasmic storage material. Cardiomyopathic involvements could not be observed. Sequencing of MYH7 gene revealed a stop-loss mutation on the 3-prime end of the rod region, which causes the elongation of the mature protein. Conclusions The elongated protein likely disrupts the functions of the sarcomere by multiple functional abnormalities. This elongation could also affect the thick filament degradation leading to protein deposition and accumulation in the sarcomere, resulting in the severe myopathy of certain axial muscles. The phenotypic expression of the detected novel MYH7 genotype could strengthen and further expand our knowledge about mutations affecting the structure of MyHCI by termination signal loss in the MYH7 gene

Cellular and molecular mechanisms of allergic asthma

Asthma is a chronic disease of the airways, which affects more than 350 million people worldwide. It is the most common chronic disease in children, affecting at least 30 million children and young adults in Europe. Asthma is a complex, partially heritable disease with a marked heterogeneity. Its development is influenced both by genetic and environmental factors. The most common, as well as the most well characterized subtype of asthma is allergic eosinophilic asthma, which is characterized by a type 2 airway inflammation. The prevalence of asthma has substantially increased in industrialized countries during the last 60 years. The mechanisms underpinning this phenomenon are incompletely understood, however increased exposure to various environmental pollutants probably plays a role. Disease inception is thought to be enabled by a disadvantageous shift in the balance between protective and harmful lifestyle and environmental factors, including exposure to protective commensal microbes versus infection with pathogens, collectively leading to airway epithelial cell damage and disrupted barrier integrity. Epithelial cell-derived cytokines are one of the main drivers of the type 2 immune response against innocuous allergens, ultimately leading to infiltration of lung tissue with type 2 T helper (TH2) cells, type 2 innate lymphoid cells (ILC2s), M2 macrophages and eosinophils. This review outlines the mechanisms responsible for the orchestration of type 2 inflammation and summarizes the novel findings, including but not limited to dysregulated epithelial barrier integrity, alarmin release and innate lymphoid cell stimulation