Natural history and clinical significance of arrhythmias after acute cardiac infarction.
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Adams-Stokes Syndrome↗
Biomedical subjects
E Olsen
Publications and source records attributed to E Olsen.
[A study on the use of Wing's rating scale for Danish schizophrenia patients].
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Adult↗
A qualitative and quantitative protein database approach identifies individual and groups of functionally related proteins that are differentially regulated in simian virus 40 (SV40) transformed human keratinocytes: an overview of the functional changes associated with the transformed phenotype.
A qualitative and quantitative two-dimensional (2-D) gel database approach has been used to identify individual and groups of proteins that are differentially regulated in simian virus 40 (SV40) transformed human keratinocytes (K14). Five hundred and sixty [35S]methionine-labeled proteins (462 isoelectric focusing, IEF; 98 nonequilibrium pH gradient electrophoresis, NEPHGE), out of the 3038 recorded in the master keratinocyte database, were excised from dry, silver-stained gels of normal proliferating primary keratinocytes and K14 cells and the radioactivity was determined by liquid scintillation counting. Two hundred and thirty five proteins were found to be either up- (177) or down-regulated (58) in the transformed cells by 50% or more, and of these, 115 corresponded to known proteins in the keratinocyte database (J.E. Celis et al., Electrophoresis 1993, 14, 1091-1198). The lowest abundance acidic protein quantitated was present in about 60,000 molecules per cell, assuming a value of 10(8) molecules per cell for total actin. The results identified individual, and groups of functionally related proteins that are differentially regulated in K14 keratinocytes and that play a role in a variety of cellular activities that include general metabolism, the cytoskeleton, DNA replication and cell proliferation, transcription and translation, protein folding, assembly, repair and turnover, membrane traffic, signal transduction, and differentiation. In addition, the results revealed several transformation sensitive proteins of unknown identity in the database as well as known proteins of yet undefined functions. Within the latter group, members of the S100 protein family--whose genes are clustered on human chromosome 1q21--were among the highest down-regulated proteins in K14 keratinocytes. Visual inspection of films exposed for different periods of time revealed only one new protein in the transformed K14 keratinocytes and this corresponded to keratin 18, a cytokeratin expressed mainly by simple epithelia. Besides providing with the first global overview of the functional changes associated with the transformed phenotype of human keratinocytes, the data strengthened previous evidence indicating that transformation results in the abnormal expression of normal genes rather than in the expression of new ones.
Autoradiography↗
Reference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions.
A highly reproducible, commercial and nonlinear, wide-range immobilized pH gradient (IPG) was used to generate two-dimensional (2-D) gel maps of [35S]methionine-labeled proteins from noncultured, unfractionated normal human epidermal keratinocytes. Forty one proteins, common to most human cell types and recorded in the human keratinocyte 2-D gel protein database were identified in the 2-D gel maps and their isoelectric points (pI) were determined using narrow-range IPGs. The latter established a pH scale that allowed comparisons between 2-D gel maps generated either with other IPGs in the first dimension or with different human protein samples. Of the 41 proteins identified, a subset of 18 was defined as suitable to evaluate the correlation between calculated and experimental pI values for polypeptides with known composition. The variance calculated for the discrepancies between calculated and experimental pI values for these proteins was 0.001 pH units. Comparison of the values by the t-test for dependent samples (paired test) gave a p-level of 0.49, indicating that there is no significant difference between the calculated and experimental pI values. The precision of the calculated values depended on the buffer capacity of the proteins, and on average, it improved with increased buffer capacity. As shown here, the widely available information on protein sequences cannot, a priori, be assumed to be sufficient for calculating pI values because post-translational modifications, in particular N-terminal blockage, pose a major problem. Of the 36 proteins analyzed in this study, 18-20 were found to be N-terminally blocked and of these only 6 were indicated as such in databases. The probability of N-terminal blockage depended on the nature of the N-terminal group. Twenty six of the proteins had either M, S or A as N-terminal amino acids and of these 17-19 were blocked. Only 1 in 10 proteins containing other N-terminal groups were blocked.
Amino Acid Sequence↗
A canine model for global control of the reimplanted larynx. A potential avenue for human laryngeal transplantation.
Previous attempts at laryngeal transplantation have failed because the grafted organ could not be dynamically rehabilitated. Nerve-muscle pedicles were used to reinnervate each of the principal intrinsic laryngeal muscles in 20 dogs after autotransplantation with conservation of the essential nutrient vessels. Afferent information obtained by sensors fixed to the chest (a strain gauge and transthoracic impedance electrode) was channeled to an electronic package for coordinated stimulation of pedicles reinnervating the posterior cricoartenoideus (opening), the cricothyroideus (elongation) and the thyroarytenoideus (closure of the vocal cords) by perineural electrodes. Corresponding vocal cord motion was videotaped on the same screen as sensor displacements and stimulating currents (approximately 2 V, 60 Hz, and 4 msec pulse width). Clear responses were recorded in all evaluable animals (n = 8), but contraction was stronger with longer reinnervation time (3-7 weeks). Based on this feasibility study, chronic experiments are planned that will set the ground work for possible future human laryngeal transplantation.
Animals↗
Hemodynamic changes with posture in calves with total artificial heart.
Hemodynamic changes with posture, sitting versus standing, were analyzed in five Holstein calves with the Cleveland Clinic-Nimbus TAH. This total artificial heart (TAH) has a left master alternate control mode that adjusts the pump rate and consequently pump flow proportional to the pulmonary venous return to the left pump (AUTO period). However, in this series of experiments, the pump reached its maximum beat rate within 1-5 days post operatively, after which pump flow could not increase (MAX period). Hemodynamic parameters (RAP, LAP, PAP, AoP, and pump flow) were obtained every 15-20 min throughout the experiments for as long as 120 days and averaged for each posture for each period. During the AUTO period, the flow while standing was significantly higher than that while sitting (standing: 8.7 +/- 0.2 L/min; sitting: 7.5 +/- 0.4 L/min; p < 0.05), and the systemic vascular resistance (SVR) was significantly lower (standing: 895 +/- 93 dyne.sec.m-5; sitting: 1,041 +/- 124 dyne.sec.m-5; p < 0.05). During the MAX period, the AoP and SVR standing were significantly lower than those sitting (AoP standing: 91 +/- 7 mmHg; AoP sitting: 98 +/- 7 mmHg; p < 0.05; SVR standing: 652 +/- 75 mmHg; SVR sitting: 730 +/- 96 mmHg; p < 0.05). The Cleveland Clinic-Nimbus TAH responded well to these changes in position, increasing pump flow and maintaining the AoP during the AUTO period.
Animals↗
Effects of PEG-coupled interleukin-2 on rat lung lavage parameters.
The recombinant lymphokine interleukin-2 (IL-2) has activity in renal cell carcinoma, melanoma, and other cancers. A side effect of IL-2 use is a "capillary leak phenomenon" which is purported to be related to endothelial effects of IL-2 itself or to cells activated by IL-2. We studied IL-2 effects on rat lung lavage parameters to determine whether endothelial damage occurred. The specific endpoints were 125I-albumin extravasation, lavage protein, and lavage angiotensin-converting enzyme (ACE) activity. To ensure sensitivity of these endpoints, we used the known endothelial toxicant thiourea, which increases lung lavage protein and lavage ACE. We found that both PEG IL-2 and thiourea increased the amount of protein and 125-I flux into the lavage. However, although thiourea increased lavage ACE, PEG IL-2 did not. These results suggest that PEG IL-2 can increase protein and iodine flux across the endothelium without causing cell injury.
Animals↗
Electrical control of intestinal reservoirs in a chronic dog model.
Pouches constructed from small intestine are used to replace reservoir function after extirpative surgery of the colon. Such pouches empty in an involuntary and uncontrolled fashion. To see whether emptying could be voluntarily controlled, ileal and jejunal reservoirs were constructed in eight dogs under general anesthesia. Four pairs of stainless steel electrodes were attached to the serosa at 5 cm intervals, and the pouches were intubated for pressure measurements with 1.67 mm polyethylene catheters. All lines were brought subcutaneously to the neck where they were maintained under a protective jacket. One to four weeks later, the pouches were stimulated with trains of square wave pulses at frequencies between 3 Hz and 1.67 KHz. The pouches were injected with contrast, and the results were monitored by fluoroscopy. Intrapouch pressure increases as high as 80 mmHg were seen after stimulation at 3 Hz, 100 msec and 6 Hz, 50 msec (10 to 25 mA) and emptying was induced. Pressure increases were also seen after stimulation with 330 Hz, 1 msec and 10 Hz, 1 msec pulse trains, but emptying was not documented. Abdominal wall contraction during stimulation was a problem but could be inhibited by interposing an insulating silastic sheet. The conclusion was made that it is possible to electrically induce emptying of intestinal reservoirs in a chronic dog model.
Animals↗
Effects of a total artificial heart right stroke volume limiter on left-right hemodynamic balance.
In a completely implantable total artificial heart (TAH), the left-right flow difference attributable to higher volumetric efficiency of the right pump and bronchial artery shunting has always been a significant problem. The automatic control of the Cleveland Clinic-Nimbus TAH accommodates for the left-right flow difference when the beat rate is below maximum (AUTO range). However, at its maximum beat rate (MAX), high left atrial pressure (LAP) (greater than 25 mmHg) with relatively low right atrial pressure (RAP) (less than 8 mmHg) were observed both in vitro and in vivo, suggesting the need for a stroke volume limiter (SVL) of the right pump. In vitro volume loading tests showed 10%, 15%, and 20% SVLs prevented a disproportionate increase of LAP. In vivo studies in five Holstein calves also showed a balanced LAP-RAP relationship with 10% and 15% SVLs at MAX. The left pump flow was not affected by this range of SVLs either in vitro or in vivo. Pulmonary function was maintained with either size SVL, with autopsies revealing absence of pulmonary congestion and minimal pleural effusions in two calves surviving for more than 1 month. Although additional studies are needed to determine the appropriate size of the SVL, both 10% and 15% SVLs were effective in maintaining left-right hemodynamic balance in this TAH.
Animals↗