Torsades de pointes during intravenous pentamidine isethionate therapy.
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Biomedical subjects
Publications and source records attributed to M Kiess.
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Equipment used in space for the cultivation of mammalian cells does not meet the usual standard of earth bound bioreactors. Thus, the development of a space worthy bioreactor is mandatory for two reasons: First, to investigate the effect on single cells of the space environment in general and microgravity conditions in particular, and second, to provide researchers on long term missions and the Space Station with cell material. However, expertise for this venture is not at hand. A small and simple device for animal cell culture experiments aboard Spacelab (Dynamic Cell Culture System; DCCS) was developed. It provides 2 cell culture chambers, one is operated as a batch system, the other one as a perfusion system. The cell chambers have a volume of 200 microliters. Medium exchange is achieved with an automatic osmotic pump. The system is neither mechanically stirred nor equipped with sensors. Oxygen for cell growth is provided by a gas chamber that is adjacent to the cell chambers. The oxygen gradient produced by the growing cells serves to maintain the oxygen influx by diffusion. Hamster kidney cells growing on microcarriers were used to test the biological performance of the DCCS. On ground tests suggest that this system is feasible.
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The relative value of exercise electrocardiography and computer analyzed thallium-201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion.
Increased thallium lung uptake during exercise correlates with an exercise-induced elevation in left ventricular filling pressure. This finding was analyzed in 48 patients with 1-vessel left anterior descending (LAD) coronary artery disease (CAD) before and after percutaneous transluminal coronary angioplasty. Patients were separated into 2 groups: 13 (27%) patients with increased (group 1) and 35 patients with normal thallium lung uptake (group 2). Compared with group 2, group 1 patients had more severe LAD luminal diameter narrowing (90 +/- 6% vs 81 +/- 11% [mean +/- standard deviation], p less than 0.003); slower clearance of thallium from the LAD territory segments (half-life 13.5 +/- 8.0 vs 6.5 +/- 5.0 hours, p less than 0.007); and more abnormal thallium segments per patient by quantitative criteria (p less than 0.02). After angioplasty, thallium lung uptake became normal in 12 of 13 patients in whom it was previously elevated. Increased thallium lung uptake after exercise occurs in 1-vessel LAD disease, and is related to the severity of ischemia by thallium scan and the severity of stenosis by angiography. Therefore, increased thallium lung uptake identifies a subset of patients with 1-vessel CAD with a greater amount of myocardium at risk.
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Tryparedoxin has recently been discovered as a constituent of the trypanosomal peroxidase system catalysing the reduction of a peroxiredoxin-type peroxidase by trypanothione [Nogoceke et al. (1997) Biol. Chem. 378, 827-836] and has attracted interest as a potential molecular target for the development of trypanocidal agents. Here we describe the first isolation of a novel gene from Crithidia fasciculata encoding a different tryparedoxin designated tryparedoxin II. The deduced amino acid sequence of tryparedoxin II (accession number AF055986) differs substantially from the partial sequence reported for the tryparedoxin described previously and now renamed tryparedoxin I. It shares the sequence motif Vx3FSAxWCPPCR shown to represent the catalytic site in tryparedoxin I [Gommel et al. (1997) Eur. J. Biochem. 248, 913-918] with mouse nucleoredoxin (accession number X92750), and a thioredoxin-like gene product of Caenorhabditis elegans (accession number U23511). Depending on which ATG is considered functional as translation start codon, tryparedoxin II, with 150 or 165 amino acid residues, is 50% larger than the typical thioredoxins. The tryparedoxins appear phylogenetically related to the thioredoxins, but sequence similarities are restricted to the active site motifs and their intimate neighbourhood. His-tagged tryparedoxin II expressed in E. coli exhibited ping-pong kinetics in the trypanothione:peroxiredoxin assay with kinetic parameters (KM peroxiredoxin = 4.2 microM, KM trypanothione = 33 microM, Vmax/[E] = 952 min(-1)) similar to those reported for tryparedoxin I [Gommel et al. (1997) Eur. J. Biochem. 248, 913-918]. The co-existence of two distinct tryparedoxins in C. fasciculata suggests diversified biological roles of this novel type of protein, which in trypanosomatids may substitute for the pleiotropic redox catalyst thioredoxin.
From September 1986 to September 1987 percutaneous balloon valvuloplasty was performed in 20 patients with critical aortic stenosis. The mean age was 74, range 54 to 90 years. Two patients were NYHA class II, 10 patients were functional class III and eight were class IV. After percutaneous balloon valvuloplasty, using 15, 18 or 20 mm diameter balloon catheters via a 14F vascular sheath from the femoral artery, one patient was class I, 11 class II and seven were class III. One patient, who had only minimal reduction of aortic valve gradient from 120 to 100 mmHg, remained in class IV. The systolic gradient was reduced by 50% from 70 +/- 26 (+/- SD) to 35 +/- 22 mmHg (P less than 0.001) after valvuloplasty and the aortic valve area increased by 43% from 0.51 +/- 0.12 to 0.73 +/- 0.25 cm2 (P less than 0.001). There were no procedural or 30 day deaths nor any embolic events. Percutaneous balloon valvuloplasty is a relatively safe and effective treatment for the older adult with symptomatic aortic stenosis.
The HIV-1-specific virus protein U (Vpu) is an amphipathic membrane-associated phosphoprotein that probably possesses an N-terminal hydrophobic membrane anchor and a hydrophilic moiety. Because of an as yet undefined cytotoxic effect and the low concentration of Vpu in host cells, it has not been possible to obtain sufficient quantities of this protein for biochemical and structural investigations. We describe the synthesis, in two forms, of 50-residue peptides representing the polar cytoplasmic domain of Vpu: pVpu, comprising the wild-type Vpu sequence of HIV-1, strain HTLVIIIB, from position Ile32 to Leu81, and a mutant, pVpum2/6, with replacement of Ser52-56 with Asn. This mutation affects the two phosphorylation sites of Vpu for casein kinase-2 (CK-2), the enzyme that phosphorylates Vpu in HIV-1-infected cells. The peptides were purified to homogeneity and characterized by N-terminal sequencing, mass spectrometry and SDS-PAGE. Furthermore, both peptides were immunologically characterized by Western blot and ELISA using Vpu-specific monoclonal and polyclonal antibodies. Recombinant human CK-2 caused in vitro phosphorylation of pVpu, but had no effect on the mutant pVpum2/6. Investigation of the peptides by circular dichroism showed that addition of trifluoroethanol stabilized the alpha-helical secondary structure. Preliminary 1H NMR spectroscopic data indicated that, in the presence of trifluoroethanol, both peptides in solution have stable secondary structures with considerable alpha-helical content.