610 Medizin und Gesundheit
Refine
H-BRS Bibliography
- yes (19)
Departments, institutes and facilities
Document Type
- Article (17)
- Part of a Book (1)
- Conference Object (1)
Year of publication
- 2018 (19) (remove)
Keywords
- 3-hydroxy-n-butyric acid (1)
- Angiogenesis (1)
- Graft material (1)
- Ketoacidosis (1)
- Ketoasidoz (1)
- Kozak-sequence (1)
- MCT (1)
- MOCS1 (1)
- MSCs (1)
- Moco deficiency (1)
This paper presents the outcomes of an exploratory field study that examined the social impact of an ICT-based suite of exergames for people with dementia and their caregivers. Qualitative data was collected over a period of 8 months, during which time we studied the daily life of 14 people with dementia and their informal and professional caregivers. We focus on the experiential aspects of the system and examine its social impact when integrated into the daily routines of both people with dementia themselves and their professional and family caregivers. Our findings indicate that relatives were able to regain leisure time, whilst people with dementia were able to recapture certain aspects of their social and daily activities that might otherwise have been lost to them. Results suggest that the system enhanced social-interaction, invigorated relationships, and improved the empowerment of people with dementia and their caregivers to face daily challenges.
Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.
In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.
Once aberrantly activated, the Wnt/βcatenin pathway may result in uncontrolled proliferation and eventually cancer. Efforts to counter and inhibit this pathway are mainly directed against βcatenin, as it serves a role on the cytoplasm and the nucleus. In addition, speciallygenerated lymphocytes are recruited for the purpose of treating liver cancer. Peripheral blood mononuclear lymphocytes are expanded by the timely addition of interferon γ, interleukin (IL)1β, IL2 and anticluster of differentiation 3 antibody. The resulting cells are called cytokineinduced killer (CIK) cells. The present study utilised these cells and combine them with drugs inhibiting the Wnt pathway in order to examine whether this resulted in an improvement in the killing ability of CIK cells against liver cancer cells. Drugs including ethacrynic acid (EA) and ciclopirox olamine (CPX) were determined to be suitable candidates, as determined by previous studies. Drugs were administered on their own and combined with CIK cells and then a cell viability assay was performed. These results suggest that EAtreated cells demonstrated apoptosis and were significantly affected compared with untreated cells. Unlike EA, CPX killed normal and cancerous cells even at low concentrations. Subsequent to combining EA with CIK cells, the potency of killing was increased and a greater number of cells died, which proves a synergistic action. In summary, EA may be used as an antihepatocellular carcinoma drug, while CPX possesses a high toxicity to cancerous as well as to normal cells. It was proposed that EA should be integrated into present therapeutic methods for cancer.
Amaç: Keton cisim oluşumu (ketogenez) bozuklukları; mitokondriyel 3-hidroksi-3metil glutaril CoA sentaz (Mhs) ve 3-hidroksi-3-metil glutaril CoA liyaz (HL) enzim eksiklikleri sonucu oluşur. Keton cisim yıkımı (ketoliz) bozuklukları ise suksinil CoA: 3 oksoasit CoA transferaz (SCOT) ve asetoasetil CoA thiolaz-beta ketotiolaz (MAT) enzim eksiklikleri sonucu oluşmaktadır. Keton metabolizma bozukluğu tanısıyla izlenen hastaların klinik ve laboratuvar bulguları ile değerlendirilmesi amaçlandı.
Yöntem: Keton metabolizması bozukluğu tanısıyla izlenen hasta verileri retrospektif olarak incelendi.
Bulgular: Dört hastada HL eksikliği, 3 hastada MAT eksikliği ve 2 hastada SCOT eksikliği tanısı mevcuttu. Hastaların ortanca yaşı 5 yıl (6 ay-15,5 yıl), ilk metabolik dekompanzasyon atak yaşı ortalama 7,7 ay (22 gün-19 ay) idi. MAT eksikliği olan bir hasta, kardeş taraması ile asemptomatik dönemde tanı aldı. İki hastada spastik tetraparezi gibi ağır nörolojik defisit gelişti. Dekompanzasyon ataklarının beslenememe, kusma ve gastroenterit gibi infeksiyon sonrası geliştiği görüldü.
Sonuç: Açıklanamayan metabolik asidoz atakları durumunda keton metabolizma bozuklukları akılda tutulmalıdır. Akut dekompanzasyon değişik yaşlarda ortaya çıkabilir, klinik şiddeti değişken olabilir. Erken tanı ve uygun tedavi mortalite ve morbidite açısından çok önemlidir.
Major progress occurred in understanding inborn errors of ketone body transport and metabolism between the International Congresses on Inborn Errors of Metabolism in Barcelona (2013) and Rio de Janeiro (2017). These conditions impair either ketogenesis (presenting as episodes of hypoketotic hypoglycemia) or ketolysis (presenting as ketoacidotic episodes); for both groups, immediate intravenous glucose administration is the most critical and (mHGGCS, HMGCS2) effective treatment measure.
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL-negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR-ABLp190+Pax5+/- mice developed pB-ALL with shorter latencies, 90% incidence, and accumulation of genomic alterations in the remaining wild-type Pax5 allele. Mechanistically, the Pax5-deficient leukemic pro-B cells exhibited a metabolic switch towards increased glucose utilization and energy metabolism. Transcriptome analysis revealed that metabolic genes (IDH1, G6PC3, GAPDH, PGK1, MYC, ENO1, ACO1) were upregulated in Pax5-deficient leukemic cells, and a similar metabolic signature could be observed in human leukemia. Our studies unveil the first in vivo evidence that the combination between Sca1-BCR-ABLp190 and metabolic reprogramming imposed by reduced Pax5 expression is sufficient for pB-ALL development. These findings might help to prevent conversion of BCR-ABLp190 preleukemic cells.