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Biomedical subjects

Daniel Lee

Publications and source records attributed to Daniel Lee.

At least 19 recordsLinked to original sources
PubMed2006

Cytoplasmic domain of human myelin protein zero likely folded as beta-structure in compact myelin.

Myelin protein zero (P0 or P0 glycoprotein), the major integral membrane protein in peripheral nervous system myelin, plays a key role in myelin membrane compaction and stability. While the structure of P0 extracellular domain was determined by crystallography, the paucity of any structural data on the highly positive-charged P0 cytoplasmic domain (P0-cyt) has greatly limited our understanding of the mechanism of P0 function. Here, using circular dichroism and intrinsic fluorescence spectroscopy, we attempted to elucidate the structure of human P0-cyt (hP0-cyt) in membrane mimetic environments composed of detergents or lipid vesicles. We found that the secondary structure of P0-cyt was polymorphic-at the lipid/protein ratio corresponding to that of mature peripheral myelin ( approximately 50:1), hP0-cyt mainly adopted a beta-conformation, whereas when the proportion of lipid increased, the structure underwent a beta-->alpha transition. By contrast, the secondary structure of the major isoform of myelin basic protein, another myelin protein with a very large positive charge, remained unchanged across a wide range of lipid/protein ratios. We propose that when hP0-cyt is bound at sufficient concentration to lamellar lipid bilayers such as myelin, it folds into a beta-conformation; before this threshold lipid/protein ratio is reached, the domain is alpha-helical. We suggest that the cytoplasmic apposition (major dense line) in compact myelin may be stabilized via the hydrogen-bonding of beta-strands formed as a result of local P0-P0 aggregation.

Amino Acid Sequence↗
PubMed2006

Body image in women with HIV: a cross-sectional evaluation.

BACKGROUND: HIV lipodystrophy syndrome is a recognized complication of potent antiretroviral therapy and is characterized by often dramatic changes in various body fat stores, both central and peripheral. Given prior findings of heightened body image dysphoria among HIV-infected men with lipodystrophy as compared to HIV-infected men without lipodystrophy, we sought to determine body image among HIV-infected and HIV-negative women and to determine the relationship of HIV and lipodystrophy with body image. Our a priori hypothesis was that women with HIV and lipodystrophy would have significantly poorer body image as compared to women without HIV and to women with HIV without lipodystrophy. RESULTS: 116 women responded to two previously validated self-report instruments (Body Image Quality of Life Index (BIQLI) and the Situational Inventory of Body-Image Dysphoria-Short Form (SIBID-S)) on body image. 62 (53% subjects) HIV-infected women were recruited at the university-based HIV clinic. 54 (47% subjects) HIV-negative female controls were recruited from another study evaluating bone density in otherwise healthy controls. 96% identified their sexual orientation as women having sex with men. Among the HIV-infected group, 36 reported the presence of lipodystrophic characteristics and 26 reported no lipodystrophic changes. Agreement regarding the presence of lipodystrophy between physician and subject was 0.67 as measured by the kappa coefficient of agreement. Compared to HIV-negative women, HIV-positive women demonstrated poor body image as measured by BIQLI (p = 0.0009). Compared with HIV-infected women who denied lipodystrophy, HIV-infected women with self-reported lipodystrophy demonstrated poor body image as measured by BIQLI (p = 0.02) and SIBID-S scales (p = 0.001). CONCLUSION: We demonstrate that HIV and lipodystrophy status among women is associated with poor body image. Universal efforts should be made in the HIV medical community to recognize body image issues particularly among persons affected by lipodystrophy so that appropriate intervention and support may be provided.

Journal Article↗
PubMed2006

Stereochemical analysis of the functional significance of the conserved inverted CCAAT and TATA elements in the rat bone sialoprotein gene promoter.

Basal transcription of the bone sialoprotein gene is mediated by highly conserved inverted CCAAT (ICE; ATTGG) and TATA elements (TTTATA) separated by precisely 21 nucleotides. Here we studied the importance of the relative position and orientation of the CCAAT and TATA elements in the proximal promoter by measuring the transcriptional activity of a series of mutated reporter constructs in transient transfection assays. Whereas inverting the TTTATA (wild type) to a TATAAA (consensus TATA) sequence increased transcription slightly, transcription was reduced when the flanking dinucleotides were also inverted. In contrast, reversing the ATTGG (wild type; ICE) to a CCAAT (RICE) sequence caused a marked reduction in transcription, whereas both transcription and NF-Y binding were progressively increased with the simultaneous inversion of flanking nucleotides (f-RICE-f). Reducing the distance between the ICE and TATA elements produced cyclical changes in transcriptional activity that correlated with progressive alterations in the relative positions of the CCAAT and TATA elements on the face of the DNA helix. Minimal transcription was observed after 5 nucleotides were deleted (equivalent to approximately one half turn of the helix), whereas transcription was fully restored after deleting 10 nucleotides (approximately one full turn of the DNA helix), transcriptional activity being progressively lost with deletions beyond 10 nucleotides. In comparison, when deletions were made with the ICE in the reversed (f-RICE-f) orientation transcriptional activity was progressively lost with no recovery. These results show that, although transcription can still occur when the CCAAT box is reversed and/or displaced relative to the TATA box, the activity is dependent upon the flexibility of the intervening DNA helix needed to align the NF-Y complex on the CCAAT box with preinitiation complex proteins that bind to the TATA box. Thus, the precise location and orientation of the CCAAT element is necessary for optimizing basal transcription of the bone sialoprotein gene.

Animals↗
PubMed2006

Intracellular uptake and release of poly(ethyleneimine)-co-poly(methyl methacrylate) nanoparticle/pDNA complexes for gene delivery.

Our previous studies demonstrated that cationic nanoparticles composed of well-defined poly(methyl methacrylate) (PMMA) cores surrounded by a hairly poly(ethyleneimine) (PEI) shells have comparative advantages over the PEI system for gene delivery. In this study, we focused on the intracellular uptake and release of PEI-PMMA nanoparticle/pDNA complexes. The behavior of the nanoparticle/pDNA complexes in recipient cells was monitored by using confocal laser scanning microscopy. We found that the nanoparticle/pDNA complexes were internalized very effectively by endocytosis. In the recipient cells the nanoparticles were found localized in the cytoplasm. At the same time, the pDNA carried by the nanoparticles successfully detached from the nanoparticles and localized in the nucleus of the HeLa cells.

Active Transport, Cell Nucleus↗
PubMed2006

Psychometric properties of a lipodystrophy scale.

Prior HIV lipodystrophy (LD) scales have been unidimensional, often combining changes of fat loss with fat accumulation with retinoid changes. Our objective was to determine the psychometric properties of a LD scale used in an outpatient LD subspecialty clinic at a university hospital HIV clinic. A patient and clinician self-administered LD scale was used to evaluate 107 patients referred to the Owen LD Clinic from March of 1999 to August of 2002. Sixteen measures of the LD syndrome were assessed on a severity scale ranging from 0 (none) to 3 (severe). SPSS was used to perform a reliability and factor analysis. A total of 150 paired patient and clinician assessments were performed. Thirty-one patients had repeat assessments. Reliability analysis of the patient and clinician self-administered LD scale revealed an alpha of 0.76 and 0.73, respectively. Factor analysis of patient self-assessment of LD identified 3 factors, which clustered in the following order: fat loss, fat accumulation, and retinoid changes. Factor analysis of clinician self-assessment of LD identified 4 factors. The first factor clustered around items of fat loss. A second cluster consisted of retinoid changes. The final 2 factors clustered around items consistent with fat accumulation. The patient and clinician self-administered Owen Clinic LD scale was found to be highly reliable and useful in the assessment of LD. Our analysis confirms clinical intuition that the evaluation of LD is a multidimensional construct and that 3 subscales may be used to evaluate dimensions of fat loss, fat accumulation, and retinoid changes.

Adult↗
PubMed2006

Body image in men with HIV.

OBJECTIVE: To determine body image among HIV-infected men and to determine the relationship of lipodystrophy on body image. METHODOLOGY: Self-report questionnaires on body image were distributed to HIV-infected men at the university-based HIV clinic. Two previously validated instruments, the Body Image Quality of Life (BIQLI) scale and the Situational Inventory of Body Image Dysphoria Short Form (SIBID-S) were used to measure body image effects. The presence of lipodystrophy was determined by both self-report and physician examination. Demographic characteristics, disease stage, health status, and quality of life were also ascertained. Analysis of responses was performed via both group comparisons and linear regression analyses. RESULTS: One hundred ten men responded. Seventy-one percent identified their sexual orientation as men having sex with men (MSM). Forty-eight reported the presence of lipodystrophic characteristics; 62 reported no lipodystrophic changes. Agreement regarding the presence of lipodystrophy between physician and subject was 0.80 as measured by the kappa coefficient of agreement. Compared to HIV-infected men who denied lipodystrophy, HIV-infected men with self-reported lipodystrophy demonstrated poor body image as measured by BIQLI (p < 0.0001) and SIBID-S scales (p = 0.0001). Similarly, physician rated lipodystrophy was significantly associated with both body image subscale scores. CONCLUSIONS: We demonstrate that lipodystrophy among HIV-infected men is associated with poor body image.

Adult↗
PubMed2006

Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes.

OBJECTIVE: Stereotactic radiosurgery is an established, effective treatment for brain arteriovenous malformations. The mechanisms of vessel occlusion in arteriovenous malformations has not been extensively evaluated. To better understand these mechanisms, we report histopathological changes in the swine rete mirabile after stereotactic radiosurgery. METHODS: Thirty-five swine were used, 15 as nonradiated controls and 20 as radiated. Two in the control group and five in the radiated group were sacrificed before the study endpoint. Tissue was obtained from 13 nonradiated (4 at 3 mo, 5 at 6 mo, 4 at 9 mo) and 15 radiated swine (2 at 3 mo, 3 at 6 mo, 10 at 9 mo) for histological, immunohistochemical, and morphometric analysis. RESULTS: Radiated vessels showed increasing intimal hyperplasia over the follow-up period. Histometrical analysis confirmed this with evidence of progressive luminal narrowing over the follow-up period. Immunohistochemical analysis showed intimal cells to be proliferating smooth muscle cells with surrounding extracellular collagen Type IV. Adventitial fibrosis composed of collagen Type IV was also seen with smooth muscle cells interspersed within the collagen matrix. The nonradiated animals showed no intimal hyperplasia or change in the appearance or size of the vessels over the same follow-up period. Adventitial fibrosis was minimal in the nonradiated animals. CONCLUSION: The vessels show an intimal response to radiation with progressive occlusion caused by migrating, proliferating smooth muscle cells, a likely source of the extracellular collagen in the intima. Cytokine mediated pathways likely produce these morphological changes. Future studies will be directed toward elucidating these underlying molecular mechanisms.

Animals↗
PubMed2005

Use of bipolar power source for transurethral resection of bladder tumor in patient with implanted pacemaker.

Patients with implanted electrical devices such as cardiac pacemakers and cochlear implants typically must have the device inactivated before surgical procedures in which the use of electrocautery is possible. In situations in which the patient cannot tolerate inactivation of the device even for a short while, the use of a bipolar energy source may allow performance of the procedure without inactivating the device. We report the case of a patient who underwent transurethral resection of a bladder tumor using a bipolar energy source uneventfully despite the presence of an implanted cardioverter defibrillator that was not deactivated before resection.

Electrosurgery↗
PubMed2005

Clinical experience with a circumferential clip-based vascular closure device in diagnostic catheterization.

BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular Devices, Redwood City, California) utilizes a small, flexible nitinol clip to complete a circumferential, extravascular closure of the femoral arteriotomy site. The StarClose is an investigational device in the United States, limited by Federal law to investigational use. The StarClose is CE Mark approved. METHODS: The CLIP study was a prospective, randomized, multicenter trial utilizing a noninferiority design to compare the rate of major vascular complications and time-to-hemostasis using the StarClose system versus manual compression. A total of 596 subjects were enrolled, 208 of whom underwent diagnostic angiography. This diagnostic subset is the focus of this report. The primary safety endpoint was major vascular complications and the primary efficacy endpoint was time-to-hemostasis. All patients were followed at 30 days with a clinical exam. RESULTS: Subjects were randomized 2:1 to the StarClose (n = 136) or manual compression (n = 72). There were no major vascular complications in either group. Minor vascular complications occurred in 3 StarClose patients (2.2%), and 1 manual compression patient (1.4%) (p = 1.00). Use of the StarClose device reduced mean time-to-hemostasis from 15.47 +/- 11.4 to 1.46 +/- 4.5 minutes (p < 0.001) when compared to manual compression, and reduced the average time-to-ambulation from 269 +/- 135 to 163 +/- 105 minutes (p < or = 0.001). Device success was 94.1% (127/135), and procedural success was 100% (136/136). CONCLUSION: The clinical results of this study concluded that the StarClose Vascular Closure System is noninferior to standard compression with respect to the the primary safety endpoint of closing arteriotomies in patients who undergo percutaneous diagnostic procedures.

Alloys↗
PubMed2004

Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury.

The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro. Transgenic or viral blockade of NgR function allows axonal sprouting in vivo. Here, we administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats. Purified NgR(310)ecto-Fc protein was delivered intrathecally after midthoracic dorsal over-hemisection. Axonal sprouting of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved spinal cord electrical conduction and improved locomotion. The ability of soluble NgR(310)ecto to promote axon growth and locomotor recovery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.

Animals↗
PubMed2004

Hypopnea in pediatric patients with obesity hypertension.

Obesity is associated with the development of hypertension but it is still not clear why hypertension is not observed in all obese patients. Obesity is a risk factor for the development of obstructive sleep apnea syndrome (OSAS) in children. OSAS has been linked to the development of hypertension in adults and children. The purpose of this study was to test the hypothesis that OSAS is one of the reasons that some obese children are hypertensive and some are not. The overnight polysomnography records of 90 patients (aged 4.2-18.8 years) were reviewed. BMI(score) [body mass index (BMI)/95th percentile BMI for age, sex, and race] was used to express the degree of obesity. The severity of systolic hypertension and diastolic hypertension were expressed as SBP(score) (systolic BP/the 95th percentile systolic BP for age, sex, and height) and DBP(score) (diastolic BP/the 95th percentile diastolic BP for age, sex, and height), respectively. OSAS was defined as more than one episodes of apnea per hour (AI) or an O(2) saturation associated with obstructive apnea of less than 90%. There were 56 obese patients; 42 were hypertensive and 40 patients were diagnosed with OSAS. The incidence of hypertension (68% vs. 30%) and obesity (75% vs. 52%) was higher in OSAS patients than those without OSAS. Compared with the non-obese patients, obese patients had a higher incidence of hypertension or OSAS, a higher BMI(score), SBP(score), DBP(score), AI, hypopnea index (HI), and apnea-hypopnea index (AHI). In obese patients, both SBP(score) and DBP(score) correlated positively with BMI(score), arousal index, and HI. DBP(score) also correlated positively with AHI. Multiple regression analysis showed that HI and BMI(score) were significant independent predictors of SBP(score) or DBP(score). Obese and hypertensive patients had a higher HI, AHI, and incidence of OSAS (64% vs. 29%) than the obese and normotensive patients. In conclusion, HI had a significant correlation with the degree of hypertension in obese patients, which could not be attributed to the degree of obesity. These findings are consistent with the hypothesis that OSAS is one of the reasons why some obese children are hypertensive and some are not.

Adolescent↗
PubMed2004

The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes.

The ubiquitous bacterium Pseudomonas aeruginosa is the quintessential opportunistic pathogen. Certain isolates infect a broad range of host organisms, from plants to humans. The pathogenic promiscuity of particular variants may reflect an increased virulence gene repertoire beyond the core P. aeruginosa genome. We have identified and characterized two P. aeruginosa pathogenicity islands (PAPI-1 and PAPI-2) in the genome of PA14, a highly virulent clinical isolate. The 108-kb PAPI-1 and 11-kb PAPI-2, which are absent from the less virulent reference strain PAO1, exhibit highly modular structures, revealing their complex derivations from a wide array of bacterial species and mobile elements. Most of the genes within these islands that are homologous to known genes occur in other human and plant bacterial pathogens. For example, PAPI-1 carries a complete gene cluster predicted to encode a type IV group B pilus, a well known adhesin absent from strain PAO1. However, >80% of the PAPI-1 DNA sequence is unique, and 75 of its 115 predicted ORF products are unrelated to any known proteins or functional domains. Significantly, many PAPI-1 ORFs also occur in several P. aeruginosa cystic fibrosis isolates. Twenty-three PAPI ORFs were mutated, and 19 were found to be necessary for full plant or animal virulence, with 11 required for both. The large set of "extra" virulence functions encoded by both PAPIs may contribute to the increased promiscuity of highly virulent P. aeruginosa strains, by directing additional pathogenic functions.

Animals↗
PubMed2004

Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study.

Restless legs syndrome (RLS) is a neurological condition with significant impact on sleep and quality of life (QoL). This double-blind, randomized, 12-week, multinational study compared the efficacy and safety of ropinirole and placebo in RLS. In total, 267 outpatients with moderate-to-severe RLS were randomly assigned to ropinirole (0.25-4.0 mg/day) or placebo, 1 to 3 hours before bedtime. The primary endpoint was the change in International Restless Legs Scale (IRLS) score at week 12. Key secondary endpoints were the percentage of patients showing significant improvement on the Clinical Global Impression-Improvement (CGI-I) scale at week 12 and changes in IRLS and CGI-I scale scores at week 1. Other measures included the Medical Outcomes Study sleep scale and Restless Legs Syndrome Quality of Life questionnaire. Improvements were significantly greater for ropinirole than placebo for change in IRLS score at week 12 (-11.2 [SE 0.76] vs. -8.7 [0.75], respectively; adjusted treatment difference -2.5 [95% confidence interval [CI], -4.6, -0.4], P = 0.0197); all key secondary endpoints; sleep and QoL parameters. Adverse events were typical for dopamine agonists; disease augmentation, although not directly assessed, was not reported during treatment. Ropinirole improves symptoms, associated sleep disturbance, and QoL of RLS patients and is generally well tolerated.

Adolescent↗
PubMed2003

The evolving etiology of bilateral vocal fold immobility.

In the past, bilateral vocal fold immobility (BVFI) occurred most commonly after thyroidectomy. However, no large series documenting the etiology of adult BVFI has been published within the past fifteen years. This study reviews the etiologic patterns of BVFI at our institutions. We compare BVFI from before and after 1980. We also review combined studies of unilateral vocal fold immobility (UVFI) to compare and unilateral versus bilateral etiologic trends. In comparison with previously published series, fewer cases of BVFI present today as a complication of thyroid surgery and more as the result of malignancies and nonsurgical trauma. Unfortunately, BVFI caused by malignancy is not usually an initial sign of local disease, but an ominous sign of recurrence or metastases. In comparing UVFI and BVFI we found that thyroidectomy causes a higher percentage of BVFI than of UVFI. Over one-third of UVFI cases were caused by neoplasm which further underscores the potential seriousness of immobile vocal folds and the need for careful investigation.

Adolescent↗
PubMed2003

Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection.

Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.

Anti-HIV Agents↗