[Acute pulmonary embolism with negative D-dimers].
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Biomedical subjects
Publications and source records attributed to E Ferrari.
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Using a strand displacement assay we have followed DNA helicase activities during the simultaneous isolation of several enzymes from calf thymus such as DNA polymerases alpha, delta, and epsilon, proliferating cell nuclear antigen, and replication factor A. Thus we were able to discriminate and isolate four different DNA helicases called A, B, C, and D. DNA helicase A is identical with the enzyme described earlier (Thömmes, P., and Hübscher, U. (1990) J. Biol. Chem. 265, 14347-14354). The four enzymes can be distinguished by (i) their putative molecular weights after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (ii) glycerol gradient sedimentation under low and high salt conditions, (iii) sensitivity to salt, (iv) binding to DNA, (v) nucleoside- and deoxynucleoside 5'-triphosphate requirements, and (vi) by their direction of movement. DNA helicase A unwinds in the 3'----5' direction on the DNA it was bound to, while DNA helicases B, C, and D do so in the 5'----3' direction. DNA helicase D, and to some extent DNA helicases B and C, are able to unwind long substrates of more than 400 nucleotides. Replication factor A, a single-stranded heterotrimeric DNA binding protein involved in cellular DNA replication and DNA repair stimulates the DNA helicases. The stimulatory effect is most pronounced on DNA helicase A, where replication factor A enables this helicase to unwind longer substrates. DNA helicases B, C, and D are also stimulated by replication factor A. The effect of replication factor A appears to be specific since corresponding single-stranded DNA binding proteins from Escherichia coli and bacteriophage T4 have no or even a negative effect on the four DNA helicases. Heterologous human replication factor A has no stimulatory effect on any of the four DNA helicases suggesting a species specificity of these interactions. Thus it appears that mammalian cells possess, as does E. coli, a variety of different enzymes that can transiently abolish the double helical DNA structure in the cell.
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A 33-year old male Tunisian developed, without any apparent cause, an abscess of the brainstem which was shown by various mycological investigations to be due to a Blastomyces dermatitidis infection. This case is of interest not only because of the exceptional location of the abscess in the brainstem, but also because of its treatment: this was the first case where the fluconazole-flucytosine combination was used against blastomycosis with fully satisfactory results after a 28-month follow-up.
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Nine patients with aortic aneurysm undergoing arterial reconstruction with temporary aortic occlusion were studied. Since a typical condition of ischemia-reperfusion of the muscles of the lower limbs was created during this surgery, muscle biopsies from the right femoral quadriceps as well as blood samples from the homolateral saphenous vein were taken: (1) before clamping of the aorta, (2) just before declamping, and (3) 30 minutes after reperfusion. Light microscopy revealed a consistent granulocyte infiltration in the ischemic and reperfused skeletal muscle. Ultrastructural damage to the muscle fibers was seen during ischemia and became more severe upon reperfusion. The recruitment of granulocytes into the muscle tissue paralleled the activation of the blood complement system and an increase in circulating neutrophils. Although a spontaneous superoxide anion (O2-) generation from such granulocytes cannot be proved, upon stimulation with formyl-methionyl-leucyl-phenylalanine neutrophils showed a reduced ability in O2 free radical production at the end of ischemia and enhanced O2- generation at reperfusion as compared with the controls. All these findings indicate an active role of granulocytes in the genesis of reperfusion-induced tissue injuries.
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Interferon, a fairly recent drug, is used in some cancers and other diseases. The adverse effects include cardiotoxicity which was recognized from phase-I trials. Some of these complications are very common and not serious at the dose levels administered: transient hypotension at the beginning of the treatment, atrial extrasystole. Other effects are less common and not dangerous: low-level conduction impairment or reversible hypertension as the authors recalled. There are also a much more serious forms of toxicity which may be life-threatening, one of which seems to be dose-dependent and consists of the onset of cardiomyopathy, which is usually reversible when treatment is stopped, the other is uncontrollable and usually occurs in high-risk cardiac patients from the first few injections and results in sudden death induced by acute coronary artery failure and/or serious ventricular arrhythmia. The physiopathology of this cardiotoxicity remains unknown, but as it is known to exist, rigorous cardiological monitoring of all patients receiving this treatment is necessary.
The efficacy and tolerability of nimesulide were assessed in a randomized study versus diclofenac sodium in the treatment of 50 patients affected with acute superficial thrombophlebitis. Both drugs, administered in a dose of 1 tablet b.i.d. for 10 days, evidenced a prompt and effective analgesic and anti-inflammatory activity. Particularly, the tolerability of nimesulide was excellent.
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