Modulation of arabinosyladenine metabolism by 2'-deoxycoformycin in the therapy of human acute leukemia.
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Biomedical subjects
Publications and source records attributed to B Nowak.
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Two serologically distinguishable primate herpesviruses, Herpesvirus aotus type 1 and type 3, were examined with regard to their genomes and structural polypeptides. The duplex DNA genomes of these two viruses were found to be essentially identical in molecular weight (Mr approximately equal to 145 X 10(6)) and guanine plus cytosine composition (55%). Both contained unique and inverted repeat nucleotide sequences of the same size and arrangement, which, as judged by DNA-DNA hybridization and restriction enzyme analyses, were at least 95% homologous. In addition, no differences were observed in electrophoretic profiles of virion polypeptides. Because of their great similarity with respect to these criteria, the two viruses ought to be considered independent isolates (or strains) of a single virus, which should be designated H. aotus type 1. The elevated molecular weight and presence of two sets of inverted repeat sequences closely resemble the structure of the human cytomegalovirus genome. However, no sequence homology (less than 5%) nor similarity in virion polypeptides was detected between H. aotus type 1 and human cytomegalovirus.
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Subclasses of simian virus 40 large T antigen in simian virus 40-transformed and -infected cells separated by zone velocity sedimentation in sucrose density gradients have been characterized. Three forms of large T antigen were distinguished: a 5 to 6S form, a 14 to 16S form, and a 23 to 25S form. These forms appeared to differ biochemically and biologically. Differential labeling experiments suggested that the 5 to 6S form was less highly phosphorylated than the faster-sedimenting forms. The 23 to 25S form which was complexed with one or more host phosphoproteins, as reported recently (D. P. Lane and L. V. Crawford Nature [London] 268:261-263, 1979; F. McCormick and E. Harlow, J. Virol. 34: 213-224, 1980), was prominent in extracts of transformed cells, but was also detected in productively infected cells. Pulse-chase experiments suggested that the 5 to 6S large T antigen is a precursor of the more stable, faster-sedimenting forms of T antigen. Monkey cells infected with a tsA mutant of simian virus 40 at 41 degrees C contained only 5 to 6S large T antigen, implying that this form is not active in the initiation of simian virus 40 DNA replication. In pulse-chase, shift-down experiments, DNA replication resumed, and the 5 to 6S large T antigen which had accumulated at 41 degrees C was partially converted at 33 degrees C to a fast-sedimenting form. However, shift-up experiments demonstrated that the fast-sedimenting large T antigen, once formed, remained stable at 41 degrees C, although it was unable to function in initiation. These experiments suggest that different biological functions of large T antigen may be carried out by different subclasses of this protein.
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Two cases of Prinzmetal's variant angina are presented in which coronary spasm was documented by electrocardiographic evidence obtained in the coronary care unit during provocative testing with ergonovine maleate after the arteriographic demonstration of anatomically normal coronary arteries. The rationale and risks of provocative testing for spasm in patients with chest pain and anatomically normal coronary arteries are reviewed. The advantages of performing provocative testing in the coronary care unit after arteriography rather than in the catheterization laboratory during coronary arteriography are discussed.
The paper presents results of evaluation of exposure to xylene of workers employed in paint workshops of the Agricultural Machines Factory "Rofama". The evaluation has been made basing on the measurements of urinary methylhippuric acid. It was found that spray painting exerts the most harmful effect on the health of workers exposed to xylene.
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Haploidentical transplant is now established as a procedure of choice for patients who lack a compatible donor. However, they are still referred too late, heavily pretreated, at very advanced stages. We initiated a three-step phase I study trying improve transplant-related mortality, relapse rate, and immunity: G-CSF + DLI, GM-CSF + DLI, patient- and disease-adapted strategy. Thirty-three consecutive leukemia patients, aged 18-55, were investigated (20 very poor risk, 11 poor risk, and 2 better risk). GvH type NK alloreactivity was chosen when possible (18/33) and balanced across the three groups. In the first nine patients, G-CSF was used and escalated prophylactic DLI started at month 1. Thus, G-CSF and 1-3 DLI (10(4) CD3/kg) is safe. It results in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (10(4) CD3/kg) at day 30 unless aGVHD (3 patients). The comparison between the two first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD: 0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD > 1: 9/12, price to pay: GVHD resulting in five deaths in total. Step 3 (13 patients) consists of a patient-adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK alloreactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mug) is given the follow-up of these 13 patients, although promising is currently short (median 5 months). Overall, TRM at day 100 is 3/29, reflecting the good tolerance of the conditioning in a heavily pretreated population (median age: 43). NRR mortality (8/26) at 1 year is greater in the GM-CSF + DLI group, reflecting the impact of severe aGVHD. We conclude that the third strategy might improve the outcome without exposing patients to unnecessary severe GVHD.
PURPOSE: Radioactive stents have been proposed as endovascular irradiation device to prevent in-stent restenosis by inhibiting neointimal proliferation. 32P-stents have been used in several studies so far, but require large-scale labeling procedures and endovascular barotrauma for stent expansion supporting the development of edge restenosis. Purpose of this study was to establish dosimetry of a self-expanding nitinol stent for peripheral vascular disease, which was radiolabeled with 188rhenium (188Re) by a dip coating technique. METHODS AND MATERIALS: The surface of nitinol Memotherm FLEXX stents was polymer-coated providing functional NH(2) groups for diethylenetriaminepentaacetic acid (DTPA) binding, providing the ligand for the complexation of 188Re onto the stent surface. Stability of radiolabeling was tested over 48 h using an in vitro blood circulation (Chandler Loop). Radial and longitudinal dose distributions of a radiolabeled stent were obtained with a plastic scintillator dosimetry system. RESULTS: Stents with a length of 30 mm and a diameter of 8 mm were labeled with up to 33 MBq 188Re. A total of 69+/-4% of the labeled 188Re remained stable on the stent surface after 48 h. Ninety-five percent of the infinitely accumulated dose was supplied to the target tissue within 72 h. Including correction for radioactivity washout from the stent, the infinitely accumulated dose at 1 mm radial distance from the stent surface was 1.85+/-0.19 Gy/MBq 188Re/cm stent length. CONCLUSIONS: We developed a technique for radiolabeling of self-expanding nitinol stents with 188Re by dip coating and formation of 188Re chelate complexes. We provide dosimetry data useful for application of this beta-emitting stent for endovascular brachytherapy in peripheral vascular occlusive disease.
One- and two-dimensional echocardiography are the most reliable methods of detecting mitral stenosis. Planimetry of the mitral valve area allows a reliable assessment of the degree of stenosis in 75% of all patients. Doppler echocardiography offers the possibility of measuring the transmitral pressure gradient and to determine pressure half-time, from which the mitral valve area can be calculated. The transmitral pressure gradient, however, undergoes considerable day-to-day variations and therefore its value for quantification is limited. The pressure half-time and planimetry of the mitral valve area are supplementary methods, for they allow the determination of the functional and the anatomic mitral valve area. These combined techniques allow a reliable quantification of the degree of mitral stenosis in about 90% of all patients. Doppler and color-coded Doppler echocardiography are sensitive tools in detecting accompanying disorders as mitral and aortic regurgitation or aortic stenosis. Subsequent disorders of mitral stenosis such as pulmonary hypertension or relative tricuspid incompetence can be assessed. In selected cases mitral valve surgery may be performed without prior catheterization.
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