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Biomedical subjects

T E Lee

Publications and source records attributed to T E Lee.

8 recordsLinked to original sources

Emergency medicine in Russia.

Russia has undergone sweeping political and social reforms within the past 5 years. The economic and social reforms heralded by the "new openness" of perestroika have led to a restructuring of medicine as well. Changes include the emergence of "for profit" organizations and acute care facilities, the introduction of private health insurance, modifications in the medical education system, and realignment of health priorities with a new trend toward primary care.

Economics↗

N-type inactivation in the mammalian Shaker K+ channel Kv1.4.

Mammalian voltage-gated K+ channels are oligomeric proteins, some of which may be composed in vivo of subunits derived from several similar genes. We have studied N-type inactivation in the rapidly inactivating Kv1.4 channel and, in specific, heteromultimers of this gene product with Kv1.5 noninactivating subunits. Heteromultimeric channels were analyzed for the stoichiometry of Kv1.4:Kv1.5 subunits by observing shifts in the midpoints of steady-state availability from that of homomultimeric channels. This analysis was employed to examine inactivation of heteromultimeric channels expressed in Xenopus oocytes using two model systems: by expression of a Kv1. 4-Kv1.5 tandem fusion construct and by coexpression of native Kv1.4 and Kv1.5 channels across a wide relative concentration range of microinjected mRNA. Additionally, inactivation was examined in coexpression experiments of N-terminal deletion mutants of Kv1.4. We found that (i) a single inactivating subunit conferred inactivation in all hetero-multimers studied; (ii) the rate of inactivation could not be distinguished in channels containing two inactivating subunits from those containing one inactivating subunit; and (iii) large deletions in the linker region between the N-terminal inactivation region and the first membrane-spanning domain had no effect on the rate of inactivation. These data confirm the importance of the proximal N-terminal region in the inactivation of mammalian Kv1.4 channels, and suggest that the inactivation particle remains in close proximity to the permeation pathway even when the channel is in the open state.

Animals↗

Structural determinant for assembly of mammalian K+ channels.

K+ channel function is regulated through the assembly of channel subunit isoforms into either homo- or heterotetrameric structures each characterized by distinct pharmacologic and kinetic properties. In studying the molecular basis of subunit association in mammalian Shaker-like K+ channels, we constructed deletion mutants of the inactivating K+ channel hKv1.4 alone and in tandem with hKv1.5 and examined the functional properties electrophysiologically in Xenopus oocytes. Deletion of 255 amino acids in the amino-terminal domain of hKv1.4 prevented the formation of hybrid channels within the subfamily but had no effect on homomultimerization or voltage-dependent gating. The amino-terminal deletion mutant of Kv2.1, a noninactivating K+ channel from a distantly related subfamily also forms functional homomultimeric channels. Although members of different K+ channel subfamilies do not coassemble, coexpression of the amino-terminal deletion mutants of hKv1.4 and Kv2.1 resulted in the formation of functional hybrid channels. These results demonstrate that the amino-terminal region of mammalian K+ channels subserves two functions. It provides a recognition site necessary for hetero- but not homomultimeric channel assembly within a subfamily and prevents coassembly between subfamilies.

Animals↗

The hand of the helix of deoxyhemoglobin S fibers.

Electron micrographs of deoxyhemoglobin S fiber cross sections provide an end-on view of the fiber whose appearance is sensitive to small changes in orientation. We have developed a procedure to exploit this sensitivity in order to determine the hand of these particles. In a sickle hemoglobin fiber the hemoglobin molecules form long pitch helical strands which twist about the particle axis with a pitch of about 3000 A. Tilting a 400-A-thick cross section by a few degrees aligns one of the long pitch helices so that it is nearly parallel to the direction of view. When a strand of hemoglobin molecules in a fiber is aligned in this manner it appears as a strongly contrasted bright spot. It is this spot, rather than the fiber axis, which appears to be the apparent center of rotation of the cross section. The direction of the displacement of the spot from the particle axis depends upon the particle hand and tilt direction. We have used this property to determine that sickle hemoglobin fibers are right-handed particles. This method may be applicable to other particles with long pitch helices as well.

Computer Simulation↗

Psychiatric manifestation of systemic lupus erythematosus in Singapore. A cross-cultural comparison.

In a case-control, cross-cultural study of the psychiatric morbidity of systemic lupus erythematosus in an Oriental population, 30 patients suffering from SLE and 29 controls with rheumatoid arthritis were interviewed. The SLE patients in Singapore exhibited greater psychiatric morbidity than their Western counterparts. Significant correlation was observed between psychiatric morbidity and the clinical disease activity. The patient's perception of the severity of arthritis, myalgia and dermatological lesions was an important aetiological factor. Culturally determined, disease-related psychological stresses also contributed to the psychopathology.

Adult↗

A method for binding specificity analysis of anti-DNA autoantibodies in SLE.

A pattern of differential binding between an NZB/NZW mouse-derived monoclonal anti-ssDNA antibody, V'D2, and restriction fragments of plasmid pBR322 DNA was shown by electrophoresis of the fragments through a denaturing agarose gel followed by their transfer onto nitrocellulose membrane and subsequent reaction of the immobilized DNA with the antibody and 125I-protein A. The antibody showed preferential binding to a 328 base pair Alu I + Hinf I fragment (denoted FD) (AT content, 60%), compared with the other fragments (AT contents, 40-56%). In dot blot assays the antibody bound only to poly(dT) and poly(dA,dT), failing to bind to other synthetic deoxyribopolynucleotides even at the highest concentration tested (300 ng). In competition experiments, the ability of unlabeled DNA to inhibit binding of V'D2 to FD increased with AT content of the DNA. It is concluded that V'D2 has preference for AT-rich DNA. In addition, poly(dA,dT) inhibited binding to a greater extent than either poly(dA) or poly(dT), indicating that base sequence may be important in defining the antigenic determinant. The method, appropriately modified, may be applicable to a wide range of natural nucleic acids and monoclonal antibodies, allowing detection and isolation of specific DNA fragments for detailed studies of antigenic determinants.

Animals↗

The hemostatic effect of fibrin glue on graft donor sites.

One of the main uses of topical fibrin glue is hemostasis. Fibrin glue from pooled human plasma has been used in Europe for many years. It was used for fixation of skin grafts as early as 1944. Because of the risk of hepatitis and now of acquired immunodeficiency syndrome, this compound has not been approved by the U.S. Food and Drug Administration for use in the United States. It is now possible to make fibrin glue from a single unit of blood. Many blood banks have this capability, and burn centers in the United States are beginning to report its use in skin grafting procedures performed on patients with burns. In an effort to document a hemostatic effect, a prospective double-blind study was designed. Donor sites of patients with burns undergoing skin grafting were studied to provide a uniform wound; anatomic location varied, particularly with respect to gravity. Half of each donor site was sprayed with thrombin and fibrin glue, and the other half was sprayed with thrombin and placebo. A large absorbent pad was placed over the gauze dressing, and all dressings were collected and weighed by the investigators at 6 and 18 hours after the operation. Ten patients have been studied to date. In five patients slightly more bleeding occurred in the site treated with fibrin. One patient had no difference, and four had slightly less bleeding on the donor site treated with fibrin. No significant difference could be found in this initial study group.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns↗