Below are some highlights of recent scientific activities from Clinical Center departments. For more complete descriptions of these and other research projects, see the Clinical Center's Annual Report of Clinical Research Activities and Lectures.
Recent Clinical Center Research Activities include . . .
Radiology and Imaging Sciences
State-of-the-Art Imaging Equipment Procurement
To continually provide cutting-edge imaging technologies for clinical research, a number of state-of-the-art imaging equipment purchases are being made: a PET/CT scanner with a 128-slice CT scanner combined with a 2mm spatial resolution PET scanner; multiple 3T MRI units operating at 32 channels; 320 and 256-slice CT scanners as well as dual source MDCT; a 3D ultrasound unit; focused ultrasound at 3T, and a combined robotic CT-angiography unit. The configuration of much of this equipment is not commercially available and will provide the Clinical Center with state-of-the-art imaging.
Immune Cell Harvesting
The use of donor natural killer (NK) cells in the setting of genetically different blood cell transplantation is being investigated. Evidence suggests that NK cells may have anti-leukemia or anti-tumor properties and do not appear to cause graft-versus-host disease. This means there may be a role for NK cells as part of the transplant regimen. Work is being conducted to develop methods for isolating, manipulating, storing, and assaying the NK cells. This project is being done in collaboration with the National Heart, Lung, and Blood Institute.
Increasing Red Cell Availability
Under a research protocol, persons with the inherited disorder of iron absorption, hereditary hemochromatosis, are being studied as potential blood donors. Collecting blood from these individuals is the standard treatment for iron overload. However systems to assure safety of this blood for transfusion, and safe and easy methods of following iron depletion have been lacking. The Clinical Center Department of Transfusion Medicine has developed a model system that addresses all of these issues. The first 100 research subjects entered now supply 10 percent of the red blood cells used for transfusion. Applying such a system nationwide should help address blood shortages in the United States.
Islet Cell Harvesting
A laboratory service has been established to isolate pancreatic islets from cadaver organ donors. The process isolates islets, which contain beta cells that produce insulin, and transplants those islets into the livers of patients with Type 1 diabetes. The islet transplant is done through an injection using interventional radiology. The outcome may free Type 1 diabetes patients from being insulin dependent or decrease the amount of insulin they require. This program is led by the National Institute of Diabetes and Digestive and Kidney Diseases and is supported by the Clinical Center.
More than 30,000 units of platelets for transfusion are collected annually by the Department of Transfusion Medicine in about 4,500 procedures. About 10 percent of these transfusions have limited clinical success, meaning minimal or no increase in platelet count. A molecular complex on the surface of most cells, Human Leukocyte Antigen (HLA), is responsible for rejection of transplants. A genetic analysis study is underway to determine if there is a benefit to platelet survival by increasing the resolution of donor/recipient matching. If so, donors can be selected not only for platelet transfusions but also for other forms of transfusion and transplantation where histocompatibility could be increased through better matching. This study is being undertaken with collaborators at the University of Pittsburgh and the French National Transfusion Service.
Transfusion recipients will be followed for years to determine whether they have developed infections from transfusions and what impact this might have on their future health. Previous studies conducted by the department of Transfusion Medicine have defined the clinical importance of post-transfusion Hepatitis B and C and HIV.
Critical Care Medicine
Sickle Cell Anemia and Pain
Sickle cell anemia pain occurs when blood vessels are blocked by sickled red blood cells. Researchers from the Clinical Center's Department of Critical Care Medicine believe this blockage may be exacerbated by an over-abundance of hemoglobin in the blood produced by faulty red blood cells, and they have found a connection between freely-circulating hemoglobin and the pain associated with the disease. In persons with sickle cell anemia, normally disc-shaped red blood cells become crescent-shaped due to an inherited abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a vital protein that carries oxygen from the lungs to the body tissues. For those with the mutation, red blood cells don't work properly but break down and release large amounts of hemoglobin directly into the blood stream. This study has discovered that the chronic release of cell-free hemoglobin into the blood stream overwhelms the systems in place to remove it by rapidly destroying nitric oxide, a short-lived gas produced by cells lining the blood vessels, and that the excess cell-free hemoglobin reacts with the gas 1,000 times more rapidly than it would if the hemoglobin were in a red blood cell. Destruction of the nitric oxide leads to constricted blood vessels, high blood pressure in the lungs and the restricted flow of oxygen and nutrients to vital tissues and organs. Nitric oxide inhalation therapy and a set of highly sensitive assays were used by the scientists in this study to show that nitric oxide scavenging by the cell-free hemoglobin may play a major role in sickle cell disease. The nitric oxide therapy used in the study inactivated the cell-free hemoglobin, a mechanism that might reduce the severity or duration of pain crisis. The research team includes investigators from the National Institute of Diabetes, Digestive, and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the Medical College of Wisconsin.
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