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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Sarns centrifugal pump for repair of thoracic aortic injury: case reports.

A new centrifugal pump (Sarns), originally designed for ventricular assist, was successfully used in two patients during repair of traumatic pseudoaneurysm of the descending thoracic aorta. The distal thoracic aorta was perfused without heparinization to avoid spinal cord and visceral ischemia, reduce afterload on the heart, and avoid clamp injury to the aorta. Distal mean aortic pressure was maintained above 50 mm Hg with a mean pump flow of 1.75 liter/minute. Proposed structural advantages of the Sarns centrifugal pump for perfusion of the distal thoracic aorta without heparin are resistance to thrombus formation, air embolus, and hemolysis.

Accidents, Traffic↗

Developing a comprehensive mechanical support program.

As cardiac surgery centers appreciate that ventricular assist devices (VAD) can dramatically impact patient survival as a bridge to transplant or recovery, and possibly permanent therapy, increasing numbers will desire to establish mechanical support programs. A number of vital elements must be put in place in order to operate a successful mechanical support program. Of utmost importance is the assembly of a dedicated team focused on comprehensive care of critically ill patients in need of circulatory support. An ongoing commitment from anesthesiologists, cardiologists, nephrologists, and other support staff is essential. Selection of complementary assist devices should be made to cover the spectrum of required support scenarios, both short- and long-term. Outpatient therapy has become increasingly important in mechanical cardiac assistance and establishment of an office where "LVAD coordinators" see outpatients facilitates this aspect of the program. Critically ill patients in need of cardiac assistance may benefit from specialized medical therapies such as: (1) intravenous arginine vasopressin for vasodilatory hypotension; (2) inhaled nitric oxide for right heart failure; (3) aprotinin to reduce hemorrhage; and (4) early enteral feeding in an effort to reduce infectious complications and improve rehabilitation following VAD implantation. A regional network with spoke hospitals centered around a hub hospital with long-term VAD and heart transplant programs can improve survival of patients with postcardiotomy cardiogenic shock via early transfer to the hub hospital. In this article, we describe the components of our mechanical support program that have allowed us to successfully support patients with heart failure in need of circulatory support.

Assisted Circulation↗

Effects of artificial circulation by pulsatile and non-pulsatile flow on brain tissues.

We examined the effects of artificial circulation by pulsatile and non-pulsatile flow on microcirculation in the brain from the viewpoints of circulation and metabolism in the brain. A centrifugal pump was fixed in the bypass in the right heart of 10 pigs. In 5 of the 10 pigs, a pulsatile flow pump was fixed in the bypass in the left heart (P group), and in the remaining 5 pigs, a centrifugal pump was fixed in the bypass in the left heart (NP group). Hemodynamics were periodically monitored for 3 hours while maintaining about 100 mmHg of the mean aortic pressure. Intracranial pressure (ICP), cerebral tissue blood flow and cerebral blood flow (CBF) were measured and compared with the initial values. As the parameters of metabolism in the brain, the cerebral oxygen consumption and lactic acid - pyruvic acid ratio were evaluated. If the cerebral blood flow was reduced by cardiogenetic shock, we suggest that blood circulation and metabolism in the brain were maintained by artificial circulation. It also indicated that there was no significant difference in blood circulation and metabolism in the brain between artificial pulsatile and non-pulsatile flow circulation.

Animals↗

Experience in reducing the hemolysis of an impeller assist heart.

Blood trauma has been one of the main problems of centrifugal pumps. The difficulties in reducing hemolysis are many, and all the factors causing excessive hemolysis always act together, making them difficult to discover and distinguish. Furthermore, error could occur at many points during hemolysis testing, making it difficult to repeat results. In developing the low hemolysis pulsatile and nonpulsatile impeller pumps the authors established an experimental method for investigating and searching for the hemolysis factors. In this study two pumps with only one differing factor were compared or only one factor on one pump was changed in the middle of the test period. In this way the effect of the individual factor on pump hemolysis could be seen and some factors have been thus confirmed as important reasons for hemolysis: 1) the drift of the pump output (including the volume and efficiency) from the design point; 2) impeller vane angles, i.e., the radial logarithmic spiral angle and the axial helical spiral angle; 3) roughness of vane surface and other blood contacting surfaces of the sealing box and pump housing; 4) vibration of the rotor resulting from dynamic disequilibrium; and 5) prerotation swirl at the inlet of the pump. The blood pressure to be pumped has been shown to have no influence on pump hemolysis. After eliminating the hemolysis factors, the blood trauma of the impeller heart has been reduced remarkably. The index of hemolysis of the nonpulsatile pump is 0.015, about one fifth of a clinically used roller made in Shanghai and two sevenths of one Sarns 7,000 Roller; the index of hemolysis of the pulstile pump is 0.020, about one sixth of a self-made diaphragm pump and one thirteenth of the Polystan pulsa tile pump.

Assisted Circulation↗

[The results of bypass with the BioPump in the surgery of traumatic rupture of the thoracic aorta without heparin].

In surgery of the traumatic rupture of descending thoracic aorta, external shunt without systemic heparinization is commonly employed to avoid the bleeding of other injured organs as well as the ischemic injury of spinal cord. However, it provides no means of controlling the flow. We employed the BioPump without heparinization in 2 cases of traumatic rupture of descending thoracic aorta and additional 2 cases of aneurysm of thoracic aorta. Significant platelet loss occurred immediately after operation, however, there was no postoperative evidence of the organ failures due to microembolization. Heparinless bypass with the BioPump is considered to be safe and simple as an adjunct means in surgery of the traumatic rupture of thoracic aorta.

Adolescent↗

Current status of external counterpulsation.

This article traces the development of external counterpulsation from its beginnings to the present. Initially, counterpulsation was carried out by cannulating the femoral artery. The hemodynamic goals were to reduce the afterload of the left ventricle, and to raise or augment the diastolic pressure. This gave rise to the term "counterpulsation." The intra-aortic balloon is capable of producing these salutary effects because of its proximity to the outlet of the left ventricle. The same hemodynamic effects can be obtained by external counterpulsation. However, one must produce a negative pressure during cardiac systole, and ensure that this is applied to the lower extremities. The only clinical study in which this was done was in the treatment of patients in cardiogenic shock by Soroff and colleagues. The results of the clinical studies reviewed are all suggestive of benefits derived from external counterpulsation in a variety of clinical settings. These studies suggest the following avenues for improvement in the equipment used to carry out external counterpulsation: 1. Inclusion of the vascular bed of the buttocks to be subjected to the external pressures, as advocated by Zheng. 2. Inclusion of a negative pressure blanket, as advocated by Soroff. 3. Further investigation of graded-sequential external counterpulsation, using the buttocks and negative pressure. 4. Application of external counterpulsation earlier in cardiogenic shock and for at least 4 hours in acute myocardial infarction. Our evaluation is that this method has not been studied in a way that demonstrates its full potential. We feel that it is on the threshold of being shown to be useful in all of the clinical settings reviewed, and we hope that the necessary equipment will be created to allow investigators to establish its proper place in our therapeutic armamentarium.

Acute Disease↗