RESUMEN
A 55-year-old patient had spent 12 years with unexplained seizures, initially diagnosed as epilepsy and then as a psychiatric disorder. When she was admitted with hypoglycaemia, a fasting test was performed showing blood sugar levels as low as 1 mmol/L with symptoms of neuroglycopenia. Insulinoma was suspected and an MRI showed a large tumour in the tail region of the pancreas. A Dodecanetetraacetic acid-Tyr3-octreotate (DOTATATE) positron emission tomography CT indicated no malignancy and showed no signs of metastasis. The patient underwent surgery, leaving her asymptomatic.
Asunto(s)
Epilepsia , Insulinoma , Neoplasias Pancreáticas , Errores Diagnósticos , Femenino , Humanos , Insulinoma/diagnóstico por imagen , Insulinoma/cirugía , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Exposure of gastric epithelial cells to the bacterial carcinogen Helicobacter pylori causes DNA double strand breaks. Here, we show that H. pylori-induced DNA damage occurs co-transcriptionally in S-phase cells that activate NF-κB signaling upon innate immune recognition of the lipopolysaccharide biosynthetic intermediate ß-ADP-heptose by the ALPK1/TIFA signaling pathway. DNA damage depends on the bi-functional RfaE enzyme and the Cag pathogenicity island of H. pylori, is accompanied by replication fork stalling and can be observed also in primary cells derived from gastric organoids. Importantly, H. pylori-induced replication stress and DNA damage depend on the presence of co-transcriptional RNA/DNA hybrids (R-loops) that form in infected cells during S-phase as a consequence of ß-ADP-heptose/ ALPK1/TIFA/NF-κB signaling. H. pylori resides in close proximity to S-phase cells in the gastric mucosa of gastritis patients. Taken together, our results link bacterial infection and NF-κB-driven innate immune responses to R-loop-dependent replication stress and DNA damage.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Helicobacter pylori/patogenicidad , FN-kappa B/metabolismo , Proteínas Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Bacterianas/metabolismo , Línea Celular Tumoral , ADN/química , ADN/genética , Daño del ADN , Replicación del ADN/efectos de los fármacos , Floxuridina , Glicosiltransferasas/metabolismo , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/metabolismo , Interacciones Huésped-Patógeno/fisiología , Humanos , Lipopolisacáridos/metabolismo , Mutación , FN-kappa B/genética , Proteínas Quinasas/genética , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
Male osteoporosis often remains unrecognised. Osteoporotic fractures occur approximately 10 years later in men than in women due to higher peak bone mass. However, 30% of all hip fractures occur in men. Risk factors of osteoporotic fractures can be grouped into primary and secondary causes. We present the case of a 53-year-old man, who suffered a compression fracture of a lumbar vertebra after a generalised seizure and an atraumatic rib fracture 5 months later. We could exclude secondary causes of bone mineral loss such as primary hyperparathyroidism, glucocorticoid use and hypogonadism. However, a heterozygous missense mutation of the COL1A1 gene in exon 48 in further search of a secondary cause was found. Therapy was changed from bisphosphonate treatment to teriparatide. Considering the lack of other osteogenesis imperfecta (OI) symptoms and signs, the patient's illness can be classified as mild. OI should be considered as differential diagnosis in unexplained cases with osteoporosis.
