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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 289 records · Page 16Linked to original sources
PubMed1997

Acyl-GPC and alkenyl/alkyl-GPC:acyl-CoA acyltransferases.

In mammalian tissues, phosphatidylcholine, or 1,2-diacyl-glycerophosphocholine (GPC), is the most abundant form of choline-containing phospholipids. In some electrically active tissues, a significant portion of the choline-containing phospholipids is 1-alkenyl-2-acyl-GPC (plasmenylcholine). The 1-alkyl-2-acyl-GPC is found in significant amounts in circulating cells such as neutrophils and macrophages but in low amounts in other tissues. Structural studies of phosphatidylcholine indicate that there is an asymmetric distribution of acyl groups on the molecule. Saturated fatty acids are usually esterified at the sn-1 position of the glycerol backbone, whereas unsaturated fatty acids are esterified at the sn-2 position. Similarly, unsaturated acyl groups are usually found in the sn-2 position of plasmenylcholine. The remodelling of the sn-2 acyl group in phosphatidylcholine by the deacylation-reacylation process has been demonstrated in a number of tissues. Phospholipase A2 is responsible for the hydrolysis of the acyl group at the sn-2 position, whereas 1-acyl-GPC:acyl-CoA acyltransferase is responsible for the reacylation reaction. The acyltransferase is located in the microsomal fraction and displays specificity towards the polyunsaturated acyl groups. The enzyme can be solubilized by detergent, but the enzyme activity in soluble form is difficult to maintain. The acyltransferase for the reacylation of 1-alkenyl-GPC is also located in the microsomal fraction and is somewhat specific towards polyunsaturated acyl groups. In guinea pig heart mitochondria, however, a new form of 1-alkenyl-GPC acyltransferase was identified which appeared to be different from the microsomal form. The acyltransferase for the acylation of 1-alkyl-GPC into platelet-activating factor has been studied in several tissues including human neutrophils. At present, the contribution of the acyltransferase in attaining the observed molecular composition of the choline-containing phospholipids in the tissue has not been defined. We postulate that the intrinsic acyl-CoA specificity of the acyltransferase, the flux of 1-acyl-GPC, 1-alkenyl-GPC and 1-alkyl-GPC, as well as the pool size of acyl-CoA are major factors in producing the final composition of the molecular species of the choline-containing phospholipids.

Acylation↗
PubMed1997

On the mechanism of the losartan-mediated inhibition of phosphatidylcholine biosynthesis in H9c2 cells.

Phosphatidylcholine is the major phospholipid in mammalian tissues and the biosynthesis of phosphatidylcholine in H9c2 cells was previously shown to be stimulated by angiotensin II. In this study, we used the potent AT1 receptor antagonist, losartan, to determine if the angiotensin II-mediated stimulation of phosphatidylcholine biosynthesis was mediated by AT1 receptors. H9c2 cells were incubated with angiotensin II in the absence or presence of various concentrations of losartan. The cells were then incubated with [methyl-3H]choline for an additional 60 min and the radioactivity incorporated into phosphatidylcholine and its choline-containing metabolites determined. Losartan at concentrations which block AT1 receptors did not effect phosphatidylcholine biosynthesis mediated by angiotensin II. In contrast, higher concentrations of losartan inhibited radioactivity incorporated into phosphatidylcholine and its metabolites and this was due to a losartan-mediated reduction in choline uptake. Kinetic studies revealed that the losartan-mediated inhibition of choline uptake was competitive. High concentrations of losartan caused a translocation of CTP:phosphocholine cytidylyltransferase from the cytosolic (inactive) to the membrane (active) fraction likely as a compensatory mechanism for the losartan-mediated reduction in new phosphatidylcholine biosynthesis. Incubation of cells with PD123319, a potent AT2-receptor antagonist, did not block the angiotensin II-mediated stimulation of phosphatidylcholine biosynthesis. The results suggest that angiotensin II stimulates phosphatidylcholine biosynthesis independent of AT1- and AT2-receptor activation and losartan inhibits phosphatidylcholine biosynthesis by reducing choline uptake in H9c2 cells.

Angiotensin II↗
PubMed1997

Prevalence of anti-vif antibodies in HIV-1 infected individuals assessed using recombinant baculovirus expressed vif protein.

A 630 base pair fragment of the HIV-1 genome encompassing the entire vif open reading frame has been produced by the polymerase chain reaction and cloned into the baculovirus transfer vector pAcYM1. Extracts from insect cells infected with a recombinant baculovirus expressing the HIV-1 vif gene product were used in a radioimmunoassay to analyse 238 sera from HIV infected individuals for the presence of anti-vif antibodies. The overall prevalence of anti-vif antibodies in this group of patients was 25.3%. Stratification of the group according to CD4 levels showed that anti-vif antibodies were more prevalent in patients with CD4 counts below the median of the group (155 x 10(6) cells/L; P = 0.005). A significant increase in anti-vif antibodies was observed in patients with CD4 levels less than 280 x 10(6) cells/L (P < 0.01) and in patients with symptomatic HIV infection (P = 0.0003). However, there was no significant difference in the prevalence of anti-vif antibodies in patients stratified according to p24 antigen status. The implications of these findings in the context of HIV replication are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Manual interception of moving targets. I. Performance and movement initiation.

We investigated the capacities of human subjects to intercept moving targets in a two-dimensional (2D) space. Subjects were instructed to intercept moving targets on a computer screen using a cursor controlled by an articulated 2D manipulandum. A target was presented in 1 of 18 combinations of three acceleration types (constant acceleration, constant deceleration, and constant velocity) and six target motion times, from 0.5 to 2.0 s. First, subjects held the cursor in a start zone located at the bottom of the screen along the vertical meridian. After a pseudorandom hold period, the target appeared in the lower left or right corner of the screen and traveled at 45 degrees toward an interception zone located on the vertical meridian 12.5 cm above the start zone. For a trial to be considered successful, the subject's cursor had to enter the interception zone within 100 ms of the target's arrival at the center of the interception zone and stay inside a slightly larger hold zone. Trials in which the cursor arrived more than 100 ms before the target were classified as "early errors," whereas trials in which the cursor arrived more than 100 ms after the target were classified as "late errors." Given the criteria above, the task proved to be difficult for the subjects. Only 41.3% (1080 out of 2614) of the movements were successful, whereas the remaining 58.7% were temporal (i.e., early or late) errors. A large majority of the early errors occurred in trials with decelerating targets, and their percentage tended to increase with longer target motion times. In contrast, late errors occurred in relation to all three target acceleration types, and their percentage tended to decrease with longer target motion times. Three models of movement initiation were investigated. First, the threshold-distance model, originally proposed for optokinetic eye movements to constant-velocity visual stimuli, maintains that response time is composed of two parts, a constant processing time and the time required for the stimulus to travel a threshold distance. This model only partially fit our data. Second, the threshold-tau model, originally proposed as a strategy for movement initiation, assumes that the subject uses the first-order estimate of time-to-contact (tau) to determine when to initiate the interception movement. Similar to the threshold distance model, the threshold-tau model only partially fit the data. Finally, a dual-strategy model was developed which allowed for the adoption of either of the two strategies for movement initiation; namely, a strategy based on the threshold-distance model ("reactive" strategy) and another based on the threshold-tau model ("predictive" strategy). This model provided a good fit to the data. In fact, individual subjects preferred to use one or the other strategy. This preference was allowed to be manifested at long target motion times, whereas shorter target motion times (i.e., 0.5 s and 0.8 s) forced the subjects to use only the reactive strategy.

Adult↗
PubMed1997

Manual interception of moving targets. II. On-line control of overlapping submovements.

We studied the kinematic characteristics of arm movements and their relation to a stimulus moving with a wide range of velocity and acceleration. The target traveled at constant acceleration, constant deceleration, or constant velocity for 0.5-2.0 s, until it arrived at a location where it was required to be intercepted. For fast moving targets, subjects produced single movements with symmetrical, bell-shaped velocity profiles. In contrast, for slowly moving targets, hand velocity profiles displayed multiple peaks, which suggests a control mechanism that produces a series of discrete submovements according to characteristics of target motion. To analyze how temporal and spatial aspects of these submovements are influenced by target motion, we decomposed the vertical hand velocity profiles into bell-shaped velocity pulses according to the minimum-jerk model. The number of submovements was roughly proportional to the movement time, resulting in a relatively constant submovement frequency (approximately 2.5 Hz). On the other hand, the submovement onset asynchrony showed significantly more variability than the intersubmovement interval, indicating that the submovement onset was delayed more following a submovement with a longer duration. Examination of submovement amplitude and its relation to target motion revealed that the subjects achieved interception mainly by producing a series of submovements that would keep the displacement of the hand proportional to the first-order estimate of target position at the end of each submovement along the axis of hand movement. Finally, we did not find any evidence that information regarding target acceleration is properly utilized in the production of submovements.

Adult↗
PubMed1997

Fatal reaction from inadvertent intrathecal entry of ionic contrast medium during a nephrogram.

A fatal case of inadvertent intrathecal entry of an ionic contrast medium during a nephrogram is reported. The patient developed seizures and failed to regain consciousness following the event. Computerized tomography revealed extensive intraventricular and subarachnoid hyperdensity and cerebrospinal fluid analysis revealed markedly elevated protein content. At autopsy a traumatic communication between the kidney and thecal sac was identified. Histopathological examination revealed cytoplasmic shrinkage and eosinophilia, nuclear pyknosis and karyorrhexis in neocortical neurons. Central chromatolysis was seen in brain stem motor nuclei and anterior horn cell neurons. The neuropathological findings appear to be on the basis of direct neurotoxicity from the contrast medium and excitotoxic injury secondary to seizure activity. Inadvertent intrathecal administration of ionic contrast media is a rare occurrence with often fatal consequences despite aggressive medical management.

Brain↗
PubMed1997

Chronic use of apraclonidine decreases its moderation of post-laser intraocular pressure spikes.

OBJECTIVE: The purpose of the study is to investigate the efficacy of 1.0% apraclonidine in preventing intraocular pressure (IOP) spike after argon laser trabeculoplasty (ALT) in patients on chronic apraclonidine therapy compared with patients not on chronic apraclonidine use. DESIGN: The study design was a prospective study. PARTICIPANTS: This study consisted of 231 consecutive eyes of patients with primary open-angle glaucoma undergoing ALT: 70 eyes (30%) were started on a regimen including chronic apraclonidine 0.5% use (group A) and 161 eyes (70%) were started on a regimen without chronic apraclonidine 0.5% use (group B). INTERVENTION: Both groups received one drop of apraclonidine 1.0% 15 minutes before ALT to 180 degrees of previously untreated trabecular meshwork. Intraocular pressure was measured before the procedure and at 5 minutes, 1 hour, and 24 hours after the laser treatment. MAIN OUTCOME MEASURES: Incidences of an IOP spike and mean IOPs at 5 minutes, 1 hour, and 24 hours after the laser treatment were compared between the two groups. Multivariate logistic regression analysis also was carried out to identify the significant risk factors for post-ALT IOP spikes despite prophylactic apraclonidine 1.0% treatment. RESULTS: The incidences of IOP spikes greater than 0 mmHg, greater than 2 mmHg, and greater than 5 mmHg at 1 hour after ALT were 32.9%, 22.9%, and 12.9%, respectively, in group A versus 13.7%, 11%, and 3.1%, respectively, in group B (P = 0.0007, P = 0.009, and P = 0.004). Chronic apraclonidine 0.5% use was found to be the only significant risk factor for IOP spikes at 1 hour after ALT by multivariate logistic regression analysis. CONCLUSIONS: The incidences of IOP spikes in group A were significantly greater than in group B and approached the reported incidences of IOP spikes without perilaser apraclonidine prophylaxis. This indicates that peri-ALT apraclonidine is relatively ineffective in patients with chronic apraclonidine 0.5% use (group A) compared with patients without chronic apraclonidine use (group B), presumably because of saturation of the ocular alpha-2 receptors with apraclonidine in patients with chronic apraclonidine use. Therefore, in patients receiving chronic apraclonidine therapy, it is especially important to monitor their post-ALT IOPs and to be prepared to treat postlaser IOP spikes using agents other than apraclonidine.

Adrenergic alpha-Agonists↗
PubMed1997

The effect of adjunctive mitomycin C in Molteno implant surgery.

PURPOSE: The purpose of the study is to assess the effect of adjunctive intraoperative mitomycin C (MMC) in Molteno drainage device implantation for patients with recalcitrant glaucomas. METHOD: Forty-nine eyes of 49 patients who underwent one-stage, single-plate Molteno device implantation with adjunctive intraoperative MMC (0.5 mg/ml) for 3 to 5 minutes (MMC group) were compared to a historic control group of 51 eyes of 51 patients (control group) who received one-stage, single-plate Molteno device implantation without MMC. Success (survival) was defined as an intraocular pressure (IOP) between 6 and 21 mmHg, inclusive, with (qualified success) or without (complete success) glaucoma medications and with no additional glaucoma surgery, phthisis, implant removal, or loss of light perception. RESULTS: Preoperative conditions were similar between the two groups. There was no significant difference in surgical survival rate between the two groups (P = 0.13, log-rank test). There also were no significant differences in the postoperative IOP levels and numbers of antiglaucoma medications between the two groups at all times (P > 0.05). Visual acuity was improved or remained within one line of preoperative visual acuity in 76.1% of the MMC group and 78.7% of the control group at 1 year after surgery (P = 0.76, chi-square test). Complications and reoperation for complications were similar in both groups (P > 0.05, chi-square test) except for the incidence of early postoperative hypotony and the total number of eyes with complications not requiring reoperation, which were more common in the MMC group (P = 0.027, 0.005, respectively, chi-square test). The most common complications included hypotony with or without a flat anterior chamber or choroidal detachment, followed by hyphema and tube plugging. CONCLUSION: Molteno device implantation with adjunctive intraoperative MMC in patients with complicated glaucoma may not offer a better chance of surgical success compared with Molteno implantation without MMC.

Adult↗
PubMed1997

Analysis of reliability indices from Humphrey visual field tests in an urban glaucoma population.

PURPOSE: Visual field assessment is extremely important in glaucoma management, but interpretation is affected by the quality of the patient's performance. The authors have investigated the reliability of visual field performance by a randomly selected sample of the chronic glaucoma population at an urban tertiary care practice. METHODS: Patient reliability in Humphrey automated visual field testing was studied in 106 randomly selected chronic open-angle glaucoma patient charts, which provided 768 tests (mean, 7.2 +/- 4.8 fields; range, 2-18 fields). Reliability criteria were established as less than 20% fixation losses, less than 33% false-negative error, and less than 33% false-positive error, as recommended by Humphrey Instruments, Inc (San Leandro, CA). RESULTS: Patients performed reliably in 61% of right eye fields, 58% of left eye fields, and 59.5% overall. Of the 106 patients, only 35 (33%) were always reliable in both eyes, whereas 8 (7.5%) were always unreliable in both eyes. The most common cause of unreliability was fixation loss (39%), whereas false-positive error (5%) and false-negative error (9%) were less frequent. A more severely depressed mean deviation correlated significantly with poorer performance on the three reliability indices, with false-negative error having the greatest correlation, followed by fixation loss and false-positive error. Corrected pattern standard deviation correlated closely only with false-negative error. Prolonged test time also correlated with all three reliability indices. Age was a significant factor for fixation loss but not for false-negative or false-positive error. CONCLUSIONS: The authors conclude that fewer than two thirds of the Humphrey visual fields were reliable with the authors' urban tertiary care population of patients with glaucoma. Relaxing the fixation loss criterion to less than 33% improved the rate of reliability to approximately 75%. The severity of glaucomatous visual field defects, test time, and age were identified as factors influencing the reliability of the Humphrey visual fields.

Aged↗
PubMed1997

Identification of sequence requirement for the origin of DNA replication in human papillomavirus type 18.

DNA replication of human papillomavirus type 18 is dependent on viral proteins E1 and E2 and the subsequent interaction of these proteins with the viral origin of replication. Using a site-directed mutagenesis analysis, we examined the sequence requirement for the DNA replication of the human papillomavirus type 18. We showed that both the E1BS palindrome and E2BS are the major determinants of the HPV replication efficiency. In particular, abolishing E2 binding sites demonstrated that E2BS makes a significant contribution towards HPV-18 DNA replication. Each part of the 18-bp inverted repeat sequence of the E1BS motif showed a clear functional difference between two regions: nt 13-21 (3' half segment) is evidently more important for replication than nt 4-12 (5' half segment). Besides E1BS and E2BS, cis-acting elements such as the poly-A6 track, perhaps the YY1 binding site, and the TATA box sequence within the origin region exhibited some contributions to optimum replication. In addition, inserting an enhancer region to the minimum origin DNA derivatives increased replication approximately 2-fold compared with the wild type levels and showed some compensational effects on loss of the cis-element within the HPV-18 minimum origin, suggesting that an enhancer region is required for efficient replication of the papillomavirus origin. These results suggest that the formation of an E1-E2-ori complex is important for replication, and other sequences near the E1 and E2 binding sites assist E1-E2-ori-mediated DNA replication in vivo.

Base Sequence↗
PubMed1997

Adenoid bacteriology and sinonasal symptoms in children.

OBJECTIVE: To study the correlation between sinonasal symptoms in children and the prevalence of bacterial pathogens in the adenoid core. DESIGN: Prospective cross-sectional survey. SETTING: Tertiary referral center. PATIENTS: Consecutive sample of 84 children, aged 2 to 12 years, scheduled for adenoidectomy between July 1995 and November 1995. A blocked recruitment scheme was used to ensure a balanced distribution of sinonasal symptoms in the study sample. METHODS: A caregiver-completed quality-of-life survey was used to measure the frequency and severity of baseline sinonasal, ear, obstructive, and behavioral symptoms. Standard microbiologic techniques were used for qualitative and quantitative adenoid bacteriology. OUTCOME MEASURES: Pathogenic and nonpathogenic bacteria isolated, percentage of specimens with no growth, colony-forming units of pathogens per gram of adenoid tissue, dominant bacterial organism, and number of pathogenic species per adenoid with concentration greater than 10(5) colony-forming units. RESULTS: One or more bacterial pathogens were recovered from core samples of all adenoids, with a concentration greater than 10(5) colony-forming units in 31 specimens (26%). Haemophilus influenzae, group A beta-hemolytic streptococcus, and Staphylococcus aureus were encountered most often. Multivariate analysis revealed a significant correlation of sinonasal infection symptom scores with colony-forming units of adenoid core pathogens (R2 = 0.48, p < 0.0001), adjusted for the confounding effects of nasal obstructive symptoms and adenoid size (specimen weight). CONCLUSIONS: Sinonasal infectious symptoms explain 48% of the variability in quantitative bacteriology of the adenoid core, independent of adenoid size. Although longitudinal studies are required, our results support a potential role for adenoidectomy in the management of refractory pediatric sinusitis.

Adenoidectomy↗
PubMed1997

Low-velocity gunshot wounds to the paranasal sinuses.

There are more than 200 million private firearms in the United States today. Firearm-associated deaths are the second leading cause of mortality for men 1 to 38 years of age. There are many studies in the literature concerning the management of high-velocity gunshot injuries to the head and neck. However, there are no studies in the English language literature concerning the management of isolated low-velocity gunshot wounds to the paranasal sinuses. We retrospectively reviewed 35 patients treated for low-velocity gunshot wounds of the paranasal sinuses between 1985 and 1994 at Kings County Hospital Center. The injuries sustained by these patients were less severe than previously reported for high-velocity missile or shotgun injuries. The management of these injuries is outlined with emphasis on (1) indications for angiographic studies, (2) airway management, and (3) indications for operative removal of bullet fragments.

Adolescent↗
PubMed1997

Fixed-dose combination therapy with trandolapril and verapamil SR is effective in primary hypertension. Trandolapril Study Group.

We assessed the efficacy of monotherapy with trandolapril, an angiotensin converting enzyme (ACE) inhibitor, and of verapamil slow-release (SR), a calcium antagonist, each in a range of three doses as monotherapy, and in the nine possible combinations of therapy in patients with stage I to III diastolic hypertension. After 4 weeks of single-blind placebo, 746 patients in 39 study centers were randomized to one of the 16 double-blind treatments for 6 weeks (placebo; verapamil SR monotherapy 120, 180, or 240 mg; trandolapril monotherapy 0.5, 2, or 8 mg; and trandolapril/verapamil SR combinations 0.5/120, 0.5/180, 0.5/240, 2/120, 2/180, 2/240, 8/120, 8/180, or 8/240 mg. Both mono- and combination therapies achieved the primary efficacy parameters: lowered supine diastolic blood pressure (at trough) more than placebo, P < .01 (except 0.5 mg trandolapril, 0.5/180 and 2/120 combinations, P < .05, and the 120 mg verapamil SR, P = NS). The therapies yielded a trough to peak ratio of >0.52 and had higher percentages of responders as compared with placebo (P < .01, < .05). Supine systolic blood pressures were lowered more by combination therapy than the respective monotherapies, P < .05, P < .01, except the 8/120 combination. Combination therapy was more effective than monotherapy for sitting diastolic blood pressure, P < .05. The percentage of patients with adverse reactions were similar for mono- and combination therapy. Trandolapril had a greater "apparent" incremental effect on the systolic blood pressure reductions than verapamil SR.

Adult↗
PubMed1997

Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase.

Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

An invitational workshop on collaboration between quality improvement organizations and business coalitions.

BACKGROUND: The center for Clinical Quality Evaluation, in conjunction with The American Health Quality Association, Midwest Business Group on Health, National Business Coalition on Health, and the funder, the Agency for Health Care Policy and Research, conducted an invitational workshop January 14-15, 1997, in Washington, DC. A select group of federally designated peer review/quality improvement organizations (QIOs)--organizations that work at the local level to improve and promote the health status of Medicaid and Medicare beneficiaries--and business coalitions from nine states met to discuss public/private collaboration on community-based quality improvement projects. WORKSHOP AGENDA: The 1 1/2-day sessions included a keynote address by Chris Queram, MA, chief executive officer of the Employer Health Care Alliance, Madison, Wisconsin, who provided background and context on the principles of community-based collaboration; a presentation on an advanced QIO/business coalition collaborative case study by HealthInsight, Inc (the Utah QIO), and Business/Health Partnership (the Salt Lake City business coalition); a case study on a beginning QIO/business coalition collaborated by the Health Accountability Foundation, a partnership between IPRO (the New York State QIO) and the New York Business Group on Health (the New York City business coalition); small group breakout sessions, where participants from each state/local community and Washington, DC-based health associations and specialty societies met to identify common goals and opportunities to collaborate; report on the progress made by each small group; and discuss future plans for collaborating on quality improvement projects. CONCLUSIONS: Many of the participating QIOs and business coalitions have already begun collaborating on quality improvement projects.

Cooperative Behavior↗
PubMed1997

Isolation and structure determination of sulfonoquinovosyl dipalmitoyl glyceride, a P-selectin receptor inhibitor from the alga Dictyochloris fragrans.

Bioassay-guided fractionation of the marine alga Dictyochloris fragrans led to the isolation and identification of sulfonoquinovosyl dipalmitoyl glyceride (1). The structure of 1 was determined by a combination of spectroscopic methods. On the basis of P-selectin inhibition assays (i.e., P-selectin-IgG ELISA, cell binding assay of receptor globulin, and platelet:HL60 adhesion, it was demonstrated that 1 selectively blocks the P-selectin-ligand interaction in vitro and could be considered a lead compound for synthetic modification in order to design more potent inhibitors of cell adhesion processes that play important roles in development of inflammatory-mediated disease states.

Cell Adhesion↗