Elevated troponin T levels in a female carrier of Duchenne muscular dystrophy with normal coronary angiogram: a case report and review of the literature

We present the case of a 48-year-old female carrier of Duchenne muscular dystrophy (DMD) with repeatedly documented levels of elevated troponin T without arguments for cardiac ischaemia. Elevated levels of troponin T are frequently reported in DMD patients and may function as a useful cardiac index to assess dystrophic degeneration of the myocardium in a subclinical stage. Cardiac troponins may help the clinician to diagnose myocardial damage in a very early stage of cardiac impairment independently from skeletal muscle degeneration.     

Individual nuclear uptake patterns for adriamycin and daunomycin in human leukemia and lymphoma cells

Summary Since both cytotoxicity and resistance towards the anthracycline derivatives adriamycin and daunomycin have been related to cellular uptake and intranuclear retention, the nuclear concentrations of these antibiotics were separately determined in various human leukemia cells after standardised in-vitro exposure. The study included analyses of cells from 31 patients (AML, 12; AUL, 7; T-cell leukemias, 4; leukemic B-cell lymphomas, 2; CML blast crisis, 5; CLL, 1). In all samples studied the uptake was concentrative with intranuclear concentrations exceeding the concentrations in the medium by factors of 4-10 for adriamycin and 6-13 for daunomycin. After 90 min of incubation, when daunomycin incorporation had reached steady state and 90% of the steady state concentrations was reached in the case of adriamycin, the comparative nuclear anthracycline concentrations showed a marked patient-to-patient variation without any relation to the cytological or cytochemical classification. Striking differences were noted in the ratios of DNM/ADM intranuclear concentrations ranging from 1.0 to 5.5. The DNM/ADM ratio was low in three cases with prior DNM treatment and, vice versa, increased in a case of CML blast crisis from 1.8 to 2.7 following ADM treatment.These results suggest that the processes involved in cellular uptake and intranuclear concentration of the two conventional anthracyclines may be different.Although more detailed analyses will be necessary the data could explain the clinical observation that in the chemotherapy of human leukemias daunomycin and adriamycin do not behave fully cross-resistant.Supported by Deutsche Forschungsgemeinschaft, SFB No. 102, Project C2     

Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27 antibody

Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens presented on foetal platelets cause their immune destruction. Whether human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a patient was described who suffered from a NAIT caused by an HLA-B27 antibody. Sera from the mother and the newborn were tested for human platelet antigen antibodies and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies against cluster designation (CD)109 and platelet glycoproteins of the father were found in patient's and mother's serum. However, HLA ELISA was used to identify HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing results showed that the father descended HLA-B27 antigen on patient and his brother. The mother was HLA-B27 negative. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-B27 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented.     

Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes

This study focused on the development and initial psychometric evaluation of a set of online, webcam-collected, and artificial intelligence-derived patient performance measures for neurodevelopmental genetic syndromes (NDGS). Initial testing and qualitative input was used to develop four stimulus paradigms capturing social and cognitive processes, including social attention, receptive vocabulary, processing speed, and single-word reading. The paradigms were administered to a sample of 375 participants, including 163 with NDGS, 56 with idiopathic neurodevelopmental disability (NDD), and 156 neurotypical controls. Twelve measures were created from the four stimulus paradigms. Valid completion rates varied from 87 to 100% across measures, with lower but adequate completion rates in participants with intellectual disability. Adequate to excellent internal consistency reliability (α = 0.67 to 0.95) was observed across measures. Test–retest reproducibility at 1-month follow-up and stability at 4-month follow-up was fair to good (r = 0.40–0.73) for 8 of the 12 measures. All gaze-based measures showed evidence of convergent and discriminant validity with parent-report measures of other cognitive and behavioral constructs. Comparisons across NDGS groups revealed distinct patterns of social and cognitive functioning, including people with PTEN mutations showing a less impaired overall pattern and people with SYNGAP1 mutations showing more attentional, processing speed, and social processing difficulties relative to people with NFIX mutations. Webcam-collected performance measures appear to be a reliable and potentially useful method for objective characterization and monitoring of social and cognitive processes in NDGS and idiopathic NDD. Additional validation work, including more detailed convergent and discriminant validity analyses and examination of sensitivity to change, is needed to replicate and extend these observations.     

Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.

Human platelet-derived growth factor (PDGF) stimulated prostaglandin (PG) E2 synthesis in the cell cycle of Swiss 3T3 cells at two distinct time intervals, with a first plateau within 10 min and a second plateau within 2-4 h after addition of PDGF. At 4 h, the concentration of PGE2 in PDGF-stimulated cultures exceeded the quiescent control cells by a factor of 10-15. Quiescent cells incubated with up to 16 microM exogenous arachidonic acid (AA) synthesized only small amounts of PGE2. In contrast, 4 h after addition of PDGF, the concentration of PGE2 synthesized from exogenous AA exceeded that in quiescent cultures by a factor of 28. The effect of PDGF stimulation on PG synthesis from exogenous AA could not be explained by growth factor-mediated increase in the cellular free AA pool as shown in experiments using [14C]AA. PDGF also stimulated synthesis of PGI2 (prostacyclin), thromboxane, and PGF2 alpha from exogenous AA. While inhibition of protein synthesis by 10 micrograms/ml cycloheximide had no effect on the early increase in PGE2 synthesis, the second increase was completely prevented. Additionally, cycloheximide treatment at 6 h after PDGF stimulation resulted in rapid decline of PGE2 synthesis from exogenous AA. Quiescent cultures pretreated with 100 microM aspirin and stimulated by PDGF thereafter recovered from cyclooxygenase inhibition within 180 min. Our results suggest that phospholipase activation and resultant AA release is not sufficient to induce the burst of PG synthesis observed in PDGF-stimulated cells. Instead, PDGF stimulates PG synthesis by direct effects on the PG-synthesizing enzyme system, one involving a protein synthesis-independent mechanism and another that requires rapid translation of cyclooxygenase.