Interleukin-2 and interferon alpha 2 combination

We have studied activity and toxicity of subcutaneous recombinant interleukin-2 and interferon alpha 2b in a series of 14 patients with advanced renal cell carcinoma. No objective response was observed, and the median survival was 16 months (range 3-19); toxicity was acceptable. All the patients had poor prognostic factors and were pretreated with interferon.     

Autonomic cardiovascular alterations as therapeutic targets in chronic kidney disease

Clinical Autonomic Research - The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. We reviewed the...     

Prediction of unexpected sudden death among healthy dogs by a novel marker of autonomic neural activity

BACKGROUND: Unexpected sudden death among apparently healthy individuals remains a daunting problem. We have previously shown that autonomic modulation of cardiac arrhythmias and autonomic markers, such as baroreflex sensitivity (BRS) and heart rate variability (HRV), carry predictive power after myocardial infarction. OBJECTIVE: We tested the hypothesis that a parameter combining BRS and HRV could predict risk for ventricular fibrillation (VF) during a first ischemic episode in otherwise healthy dogs. METHODS: In 43 fully instrumented dogs, BRS and frequency domain analysis of HRV were determined, as well as the occurrence (n = 10, high-risk) or absence (n = 33, low-risk) of VF during 2 minutes of myocardial ischemia superimposed on submaximal exercise. TARVA (Tonic and Reflex Vagal Activity), expressed in units, is the parameter resulting from the multiplication of BRS by HF/LF (an index of tonic vagal activity). RESULTS: High-risk dogs had markedly lower TARVA values, reflecting lower cardiac vagal activity, than low-risk animals (12 +/- 5 versus 56 +/- 43 units, P < .001). The area under the receiver-operator characteristic curve for TARVA was 0.96 (95% confidence interval 0.86 to 0.99); its optimal cutoff had a 100% sensitivity and a 88% specificity with positive and negative predictive values of 71% and 100%, respectively. CONCLUSION: Differences in cardiac autonomic activity, present in healthy dogs, allow prediction of arrhythmic risk during a first ischemic episode. Increased risk is associated with reduced vagal activity. If confirmed in humans, this finding would open the way to the identification of those apparently healthy subjects at risk for sudden cardiac death during their first episode of myocardial ischemia.     

Checkpoint-mediated control of replisome-fork association and signalling in response to replication pausing

The replication checkpoint controls the integrity of replicating chromosomes by stabilizing stalled forks, thus preventing the accumulation of abnormal replication and recombination intermediates that contribute to genome instability. Checkpoint-defective cells are susceptible to rearrangements at chromosome fragile sites when replication pauses, and certain human cancer prone diseases suffer checkpoint abnormalities. It is unclear as to how the checkpoint stabilizes stalled forks and how cells sense replication blocks. We have analysed the checkpoint contribution in controlling replisome-fork association when replication pauses. We show that in yeast wild-type cells, stalled forks exhibit stable replisome complexes and the checkpoint sensors Ddc1 and Ddc2, thus activating Rad53 checkpoint kinase. Ddc1/Ddc2 recruitment on stalled forks and Rad53 activation are influenced by the single-strand-binding protein replication factor A (RFA). rad53 forks exhibit a defective association with DNA polymerases alpha, epsilon and delta. Further, in rad53 mutants, stalled forks progressively generate abnormal structures that turn into checkpoint signals by accumulating RFA, Ddc1 and Ddc2. We suggest that, following replication blocks, checkpoint activation mediated by RFA-ssDNA filaments stabilizes stalled forks by controlling replisome-fork association, thus preventing unscheduled recruitment of recombination enzymes that could otherwise cause the pathological processing of the forks.     

Phagocyte function and immunological findings in a Wiskott-Aldrich syndrome long-term survivor

The case reported concerns a 19-year-old man who presented with clinical and laboratory findings compatible with the Wiscott-Aldrich Syndrome. Our patients is the eighth reported case of a long-term survivor with this syndrome. Immunologic studies revealed, in spite of a normal lymphocyte number, an impaired delayed hypersensitivity and a failure of response to mitogens and irradiated allogeneic cells. IgE and IgA levels were high while IgM levels were low. Studies of phagocytic cells showed normal phagocytosis, candidacidal activity, IgG receptors and phagocytic metabolic burst. However, the patient's neutrophils and monocytes responded poorly to chemoattractants and the serum generated less chemotactic activity than normal sera. Detailed studies revealed the presence in the patient's serum of 2 different inhibitors of chemotaxis: a cell-directed inhibitor and an inhibitor of chemotactic factors.     

Evaluation of a 2D UNet-Based Attenuation Correction Methodology for PET/MR Brain Studies

Journal of Digital Imaging - Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps,...