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Biomedical subjects

R H Lee

Publications and source records attributed to R H Lee.

At least 73 records · Page 4Linked to original sources
PubMed1990

Cyclic GMP and photoreceptor function.

A single photon can be detected by a rod photoreceptor cell. The absorption of light by rhodopsin triggers a cascade of reactions that amplifies the photon signal and results in ion channel closure with hyperpolarization of the rod photoreceptor cell. Light-induced conformational changes in rhodopsin facilitate the binding of a guanosine nucleotide-binding protein, transducin, which then undergoes a GTP-GDP exchange reaction and dissociation of the transducin complex. A subunit of transducin then activates a phosphodiesterase complex that hydrolyzes cyclic GMP. In darkness, cyclic GMP binds to cation channels of the photoreceptor plasma membrane, maintaining them in an open configuration. The light-induced reduction in cyclic GMP concentration dissociates the bound cyclic GMP, resulting in channel closure and hyperpolarization. Down-regulation of the cascade involves other proteins that block the interaction of transducin with rhodopsin and another protein that may interfere with transducin recycling. Cone photoreceptors possess a light-activated cascade that follows the rod format, but it is composed of proteins that are homologous to those of rod photoreceptors. Phototransduction in invertebrate photoreceptors uses rhodopsin to activate a cascade that uses phosphoinositides and calcium ion to regulate membrane polarization.

Antigens↗
PubMed1988

Evaluation of left ventricular contractility indexes for the detection of symptomatic and silent myocardial ischemia.

This study evaluated the role of left ventricular (LV) ejection fraction and systolic blood pressure (BP) to end-systolic volume ratio to detect symptomatic and silent myocardial ischemia. The sensitivity and diagnostic accuracy of these contractility indexes were compared with angina and ST depression during exercise. Thirty consecutive patients referred for chest pain performed symptom-limited bicycle exercise and had coronary angiography within 3 months. Twenty-two had angiographically significant coronary artery disease and 8 had normal coronary anatomy. Systolic BP was measured by sphygmomanometry; LV ejection fraction and end-systolic volume were obtained by nuclear ventriculography. Normal values for contractility indexes were defined as LV ejection fraction greater than 52% at rest and increment of greater than or equal to 5% during exercise, and systolic BP to end-systolic volume ratio greater than 2.2 mm Hg/ml at rest and greater than 3.0 mm Hg/ml during exercise. The sensitivity of systolic BP to end-systolic volume ratio to identify patients with coronary artery disease at rest was 71 vs 33% for LV ejection fraction. During exercise, each contractility index had a sensitivity of 95% and there was a combined sensitivity of 100%. This compares with 71% for ST depression and 48% for exercise-induced angina. Thus, 52% had no angina and 36% of them were also silent by electrocardiography. Among the patients with symptomatic ischemia, 20% had no ST-segment depression. Measurement of contractility indexes enhanced the detection of silent myocardial ischemia and provided information on LV function vital to prognosis and management of patients with coronary artery disease.

Adult↗
PubMed1988

The photoreceptor-specific 33 kDa phosphoprotein of mammalian retina: generation of monospecific antibodies and localization by immunocytochemistry.

The distribution in mouse retina of a 33,000 Da phosphoprotein (33 kDa) that complexes with the beta/gamma subunits of transducin (T beta gamma) and undergoes light-induced dephosphorylation was determined by immunocytochemistry. An antiserum containing antibodies for the 33 kDa protein and beta-transducin of mouse and bovine retinas was generated against the purified 33 kDa-T beta gamma complex from bovine retina. The antiserum reacts with beta-transducin derived from either 33 kDa-T beta gamma complex or transducin complex (T alpha beta gamma), but not with the alpha- or gamma-transducin. It also reacts with both the phosphorylated and unphosphorylated form of the 33 kDa-T beta gamma complex. Antibodies, monospecific for the 33 kDa and beta-transducin subunits respectively, were purified from the antiserum by immunoadsorption and used in immunocytochemical analysis of the respective antigens. The 33 kDa protein was found to be associated exclusively with the photoreceptor cells of the retinas, with the most intense staining in the inner and outer segments' layers and lighter staining in the synaptic terminal layers. beta-Transducin also is found in the photoreceptors, but some T beta immunoreactivity exists within the inner plexiform layer. The specific localization of the 33 kDa protein together with its light-modulated phosphorylation suggest that the 33 kDa-T beta gamma complex is involved in light-regulated activities of the rod photoreceptor cells.

Animals↗
PubMed1988

Characterization of a phosphodiesterase-immunoreactive polypeptide from rod photoreceptors of developing rd mouse retinas.

In the inherited retinal degeneration of rd mice, cyclic GMP accumulates in affected rod photoreceptors prior to their degeneration. A deficiency in the activity of the visual cell phosphodiesterase apparently results in the accumulation of cyclic GMP. The cyclic GMP phosphodiesterase (PDE) of normal mouse photoreceptors is a heteromeric protein complex of about 170 kDa, consisting of the alpha beta catalytic unit and the gamma inhibitory unit. The isolated complex has low enzyme activity but it can be activated by incubation with histone. Affinity-purified polyclonal antibodies against the PDE complex of bovine rod outer segments were prepared and used to identify in retinas of both normal and rd mice PDE-immunoreactive polypeptides which comigrated on SDS-polyacrylamide gels with the large subunits (88 kDa) of the normal PDE complex. During development of normal retinas, the 88 kDa immunoreactive component of the PDE complex were detected by day 7, with immunoreactivity increasing throughout the second postnatal week. In rd retinas, the 88 kDa immunoreactivity increased after 9 postnatal days, decreased during rod photoreceptor degeneration, and was undetectable in mature rd retinas. Under nondenaturing conditions, the PDE-immunoreactive polypeptide of rd retinas sedimented on sucrose gradients with a sedimentation coefficient of 5.6S and an apparent molecular mass of about 105 kDa; no associated histone-activated PDE activity was detected. These findings show that PDE-immunoreactive polypeptides are synthesized in immature rd photoreceptors and that the PDE-immunoreactive polypeptides fail to form a PDE complex which is comparable to that of normal photoreceptors.

Animals↗
PubMed1988

Tic disorders of childhood.

Tic disorders may be classified as simple tics, chronic motor tics or Tourette syndrome, the most severe of the three types. Tourette syndrome is rather uncommon and is often misdiagnosed. Tic disorders of childhood probably have an organic etiology and a genetic component. An increased incidence of obsessive-compulsive behavior, attention deficit disorder and other abnormalities have been reported in Tourette patients. Haloperidol is often useful in controlling severe tic symptoms, while stimulant drugs may worsen the symptoms.

Attention Deficit Disorder with Hyperactivity↗
PubMed1987

A novel complex from bovine visual cells of a 33,000-dalton phosphoprotein with beta- and gamma-transducin: purification and subunit structure.

Photoreceptors of mammalian retinas contain a 33-kDa (33K) protein that is phosphorylated, in vitro, by cyclic nucleotide dependent protein kinases. The 33K protein is phosphorylated in the dark, in situ, and dephosphorylated upon illumination. The soluble 33K protein from bovine retinas has been purified to near homogeneity by extraction at pH 5.7 and chromatography on ion-exchange, gel filtration, and hydroxylapatite columns. In the native conformation, the 33K protein is associated with a 37-kDa (37K) and a 10-kDa (10K) protein, forming a trimeric complex with a sedimentation coefficient of 4.9 S and an apparent molecular mass of 77 kDa. The 33K protein can be dissociated from the 37K/10K complex by centrifugation in the presence of high pH and high salt; the subunits reassociate to form the trimeric complex upon recentrifugation in an isotonic buffer with neutral pH. The 33K protein is phosphorylated rapidly by exogenous kinase, in vitro, whereas the 37K and 10K subunits remain unphosphorylated. The 37K and 10K subunits cross-react with antibodies prepared against the beta- and gamma-subunits, respectively, of bovine transducin, indicating that the 37K and 10K subunits are immunologically identical with beta- and gamma-transducin, respectively. No immuno-cross-reactivity was observed between the 33K protein and an antibody against the alpha-subunit of bovine transducin. The 33K-beta-/gamma-transducin complex exhibits striking similarity to transducin in its subunit structure and mode of subunit interaction, suggesting it may play an important role in the metabolism and function of rod photoreceptor cells.

Animals↗
PubMed1987

Immunological determination of transducin content in retinas exhibiting inherited degeneration.

The inherited disorders of rd mice and affected Irish setter dogs are characterized by the accumulation of cyclic GMP (cGMP). Since the cGMP level in normal retinal rods is regulated by a light-activated enzyme cascade involving rhodopsin, transducin, and phosphodiesterase, an abnormality associated with any of these three proteins would cause cGMP accumulation. In order to determine the relationship between different forms of retinal degeneration and the transducin content in the affected retinas, affinity-purified antibodies directed against the individual subunits of bovine transducin were prepared. These antibodies, which recognized transducin in many vertebrate species, were used to compare the retinal content of this protein at various stages of inherited photoreceptor degeneration. In each of the disorders studied (rd and rds mice, RCS rat, and affected Irish setter dog), retinas at early stages of degeneration displayed two characteristics similar to those of normal control retinas. First, all three subunits of transducin were detected and found to have normal electrophoretic mobility, suggesting that these disorders are unlikely to be due to changes in the composition of transducin subunits. Second, the amount of cross-reactive T beta always exceeded those of T alpha and T gamma. This disproportionately higher amount of T beta-like protein became more pronounced as the visual cells degenerated. In retinas which had undergone complete photoreceptor degeneration, cross-reactive T alpha and T gamma were undetectable. In contrast, anti-T beta gamma antibodies detected an amount of T beta-like polypeptide corresponding to 10-25% of the control. Since our anti-T beta gamma antibodies recognize the beta subunit of the GTP-binding N proteins of the adenylate cyclase system, this finding suggests that this residual T beta-like protein, which is not part of transducin, may be associated with other GTP-binding regulatory proteins.

Animals↗
PubMed1987

Residency positions offered in three specialties.

Many believe that the changing economic environment might have dramatic effects on the quality or quantity of graduate medical training, yet the evidence is scant. This article assesses the impact of economic factors on the number of residency positions offered by teaching hospitals in surgery, in medicine, in pathology, and in the hospital as a whole. It first outlines in a nontechnical way the policy and empirical implications of an economic approach to residency training. The empirical analysis then compares results from three separate data sets, using both hospitalwide and department-specific information. The article closes by using the estimates to attempt an assessment of the likely impact of cost control and increased competition on training opportunities.

Cost Control↗
PubMed1986

A 7 year experience with low anterior sigmoid resections using the EEA stapler.

The EEA stapler was used in 205 patients over a 7 year period with 19 complications (9 percent) and 1 death (0.5 percent). Meticulous attention to technique and familiarization with the EEA stapler are necessary to achieve such results. The use of mechanical and oral antibiotic bowel preparation, perioperative systemic antibiotics, povidone-iodine irrigation of the rectal ampulla, and meticulous surgical technique have combined to lower the complication rate of this procedure to a minimum. The EEA stapler has greatly improved the safety and ease of anterior sigmoid resections and now provides a frequent alternative to abdominoperineal resection in many patients with midrectal and even low rectal lesions.

Adenocarcinoma↗
PubMed1986

Rod photoreceptor cells dissociated from mature mice retinas.

Intact rod photoreceptors were dissociated from pronase-treated whole retinas of adult mice by repeated passage through a plastic pipette tip. Hemocytometer counts of the cell suspensions indicate that, during a series of ten dissociation steps, a total of about 1-2 million intact photoreceptor cells are dissociated from one adult mouse retina, with less than 5% contamination from Müller cells and neurons of the inner retina. Visual cells with rod outer segments (ROS) and synaptic terminals are released in each step, but they occur in the greatest number during the sixth to ninth steps; detached ROS are released most frequently in the early steps, and neurons of the inner retinal layers appear in the later steps of dissociation. Nuclei are found in each step. Cell intactness was estimated by Trypan blue and Erythrosin B exclusion and by microscopic analysis using differential interference optics or scanning electron microscopy. The cells bind lectins (concanavalin A, Ricinis communis, and wheat germ agglutinin but not peanut agglutinin), displaying surface topography like that observed in situ. The metabolic capacity of dissociated cells was assessed by measuring the utilization of 32P inorganic phosphate for the synthesis of phospholipids and for the light-dependent phosphorylation of rhodopsin. Mature photoreceptor cells were estimated to contain, on average, 6.4 X 10(-12) g DNA, 2.3 X 10(-12) g RNA and 42-64 X 10(-12) g protein. The dissociation procedure provides a population of photoreceptor cells that appears suitable for microscopic, electrophysiological, and biochemical analysis.

Animals↗