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Biomedical subjects

J R Lee

Publications and source records attributed to J R Lee.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted-3'-phenyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel nicotinic antagonist.

A series of 2'-substituted-3'-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3'-position exerted a profound influence on both receptor binding and antinociceptive effects. Substitution of different groups at the 2'-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different.

Analgesics↗
PubMed2001

Structural relaxation, self-diffusion, and kinetic heterogeneity in the two-dimensional lattice Coulomb gas.

We present Monte Carlo simulation results on the equilibrium relaxation dynamics in the two-dimensional lattice Coulomb gas, where finite fractions f of the lattice sites are occupied by positive charges. In the case of high-order rational values of f close to the irrational number 1-g [g identical with (square root of 5-1)/2 is the golden mean], we find that the system exhibits, for a wide range of temperatures above the first-order transition, a glassy behavior resembling the primary relaxation of supercooled liquids. Single-particle diffusion and structural relaxation show that there exists a breakdown of proportionality between the time scale of diffusion and that of structural relaxation analogous to the violation of the Stokes-Einstein relation in supercooled liquids. Suitably defined dynamic cooperativity is calculated to exhibit the characteristic nature of dynamic heterogeneity present in the system.

Journal Article↗
PubMed2001

Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases.

The polytopic membrane protein Rhomboid-1 promotes the cleavage of the membrane-anchored TGFalpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Until now, the mechanism of this key signaling regulator has been obscure, but our analysis suggests that Rhomboid-1 is a novel intramembrane serine protease that directly cleaves Spitz. In accordance with the putative Rhomboid active site being in the membrane bilayer, Spitz is cleaved within its transmembrane domain, and thus is, to our knowledge, the first example of a growth factor activated by regulated intramembrane proteolysis. Rhomboid-1 is conserved throughout evolution from archaea to humans, and our results show that a human Rhomboid promotes Spitz cleavage by a similar mechanism. This growth factor activation mechanism may therefore be widespread.

Amino Acid Sequence↗
PubMed2001

Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila.

The membrane proteins Star and Rhomboid-1 have been genetically defined as the primary regulators of EGF receptor activation in Drosophila, but their molecular mechanisms have been elusive. Both Star and Rhomboid-1 have been assumed to work at the cell surface to control ligand activation. Here, we demonstrate that they control receptor signaling by regulating intracellular trafficking and proteolysis of the ligand Spitz. Star is present throughout the secretory pathway and is required to export Spitz from the endoplasmic reticulum to the Golgi apparatus. Rhomboid-1 is localized in the Golgi, where it promotes the cleavage of Spitz. This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface.

Animals↗
PubMed2001

Role integration and perceived health in Asian American women caregivers.

In this study, role involvement, role integration (including role stress and role satisfaction), and perceived health were examined in 50 Asian American women who were caregivers of aging parents in addition to being wives, mothers, and employees. Their mean age was 47.8 years. Twenty-nine of the participants were Chinese and 21 Filipino, with an average length of caregiving for each group of 11 years. All participants were born outside the United States. Instruments used in the study were translated and back-translated into Chinese and Tagalog and tested for validity and reliability. The association of role involvement, role integration, role stress, and role satisfaction with perceived physical and psychological health in the combined and separate groups was examined. Role involvement was not associated with health in the combined group of caregivers but was associated with overall health in the sample of Chinese women. Role integration was positively associated with all three perceived health measures in the Filipino group but not in the Chinese group. Role satisfaction was consistently high in both groups. Role satisfaction and psychological well-being were significantly correlated for the combined group and for the Filipino caregivers. Total role stress was significantly correlated with overall health and current health only in the combined group. Thus, support that helps to decrease role stress and to increase role satisfaction may be more effective than efforts to decrease the extent of role involvement.

Acculturation↗
PubMed2001

Modified Lecompte procedure for the anomalies of ventriculoarterial connection.

BACKGROUND: The Lecompte procedure for correcting transposition of the great arteries has an advantage because it obviates the need for an extracardiac conduit for the reconstruction of the pulmonary outflow tract. In this study, we evaluated the effectiveness and the application of the Lecompte procedure based on our experiences. METHODS: A retrospective review was conducted of the records of 45 patients who underwent the Lecompte procedure during the past 11 years to achieve direct right ventricle to pulmonary artery continuity. Mean age at operation was 2.4+/-1.7 years (range 3.5 months to 6.9 years). The diagnoses involved anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction, such as transposition of the great arteries, double-outlet right ventricle, and double-outlet left ventricle. RESULTS: Early mortality was 4.4% (2 of 45 patients) and late mortality was 4.7% (2 of 43). The mean follow-up was 4.9+/-3.1 years. Fourteen patients (34.1% of survivors, n = 41) had pulmonary stenosis (pressure gradient above 30 mm Hg), the main reason for which was a calcified monocusp valve (n = 10, 71.4%). Eight of 45 patients (17.8%) underwent reoperation: 2 for residual ventricular septal defect, 1 for recurrent septic vegetation, and 5 for pulmonary stenosis. The cumulative survival rates were 91.1%+/-4.2% at 10 years. The actuarial probabilities of freedom from reoperation for pulmonary stenosis were 93.8%+/-4.3% and 71.4%+/-11.8% at 5 and 10 years, respectively. CONCLUSIONS: Our review suggests that the Lecompte procedure is an effective treatment modality for anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction. Repair in early age is possible with acceptable morbidity and mortality, but recurrent right ventricular outflow tract obstruction caused by degeneration of the monocusp valve is a problem that needs resolution.

Actuarial Analysis↗
PubMed2001

A new guaianolide as apoptosis inhibitor from Chrysanthemum boreale.

The 8-O-acetyl-3,10-dihydroxy-4(15),11(13)-guaiadien-12,6-olide, named borenolide, was isolated from Chrysanthemum boreale M. Borenolide inhibits the etoposide-induced apoptosis in U937 cell with an IC(50) value of 6.2 microg/ml. Structural assignment was based on NMR-spectroscopic methods and X-ray crystallographic analysis.

Apoptosis↗
PubMed2001

Gastrointestinal autonomic nerve tumor: immunohistochemical and molecular identity with gastrointestinal stromal tumor.

Gastrointestinal autonomic nerve tumor (GANT) is a gastrointestinal neoplasm that ultrastructurally recapitulates the enteric neural plexus. This study identifies and defines the features of 10 cases of this rare mesenchymal tumor and compares its clinicopathologic and molecular genetic features with the data on gastrointestinal stromal tumor (GIST). The majority of patients in this series presented at an older age (mean 64 years). Tumors arose from the stomach (6), small intestine (2), and retroperitoneum (2). Mean tumor size was 14 cm; however, four neoplasms were <6 cm. Histologically, tumors were spindled or epithelioid; one epithelioid tumor demonstrated a previously undescribed rhabdoid histologic phenotype. All tumors were positive for CD117 (KIT), while eight of 10 were positive for CD34. In contrast, only two were positive for S-100, and all were negative for actin and desmin. Five GANTs demonstrated GIST-specific gain-of-function mutations in the juxtamembrane domain of the c-kit gene (50%). Three of 10 patients died of disease in 22-30 months, one patient died in the postoperative period, and one patient died of complications of CML. The clinicopathologic, histologic, immunohistologic, and molecular features of GANT are similar to GIST, indicating that GANT merely represents a phenotypic variant of GIST.

Adult↗
PubMed2001

Development of a new epitope tag recognized by a monoclonal antibody to Rickettsia typhi.

The epitope recognized by a mouse monoclonal antibody (MAb) to the crystalline surface layer protein of Rickettsia typhi, SRT10, was mapped to 10 amino acid residues (SRTag TFIGAIATDT). The oligonucleotide sequence covering the epitope recognized by SRT10 was inserted into a mammalian expression vector together with multiple cloning sites. When the SRTag was fused in frame to the coding region of the NCC27/CLIC1 gene and expressed in mammalian cells, the MAb SRT10 could detect the tagged protein by immunoblotting, immunocytochemistry, and immunoprecipitation. In addition to the SRT-NCC27/CLIC1, SRT10 could detect N-terminal-tagged MEF2D and C-terminal-tagged CD4 by immunocytochemistry. We suggest that this specific recognition of the SRTag by SRT10 is generally applicable to cellular and molecular biology research that requires the expression and detection of fusion proteins.

Amino Acid Sequence↗
PubMed2001

Expression of NF-kappaB and cytokines in chronic rejection of transplanted murine heart.

The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure.

Animals↗
PubMed2001

Solitary fibrous tumors arising in abdominal wall hernia sacs.

Solitary fibrous tumor (SFT) of the peritoneum is an unusual spindle-cell neoplasm. SFT was originally described in the pleura; however it is now diagnosed in multiple extrathoracic sites. Most believe that the tumor is of mesenchymal origin and should be classified as a variant of fibroma. SFT of the pleura and peritoneum have also been called fibrous mesothelioma, and the cell of origin is felt to be a pluripotential submesothelial mesenchymal cell. Primary tumors arising in hernia sacs are rare, and we report on two patients with hernia SFT. The first is a 67-year-old man who had a diffusely thickened distal left inguinal hernia sac. Within the sac was copious myxoid material mimicking pseudomyxoma peritonei. Herniorrhaphy and orchiectomy were performed. The second is a 44-year-old woman with a midepigastric mass attached to a ventral hernia. Wide local excision was performed. Both tumors demonstrated plump spindle cells, one with myxoid background and the other with keloidal collagen. Calretinin immunostaining was positive in both tumors, whereas CD34 was negative. This suggests tumor origin from a submesothial pluripotential cell that maintains potential for mesothelial differentiation. Surgical excision is the treatment of choice with the degree of resectability being a powerful predictor of outcome.

Abdominal Muscles↗
PubMed2001

Anal melanoma: an aggressive malignancy masquerading as hemorrhoids.

Anal melanoma is a devastating malignancy easily confused with benign hemorrhoids. Physician unfamiliarity with this bleeding rectal lesion can lead to delays in diagnosis and therapy. Four cases of anal melanoma, all initially mistaken for hemorrhoids, have been documented in the past 4 years at our institution. Despite surgical intervention and chemoimmunotherapy, each patient succumbed to widely metastatic disease. Average survival was 15.2 months. The clinical, pathologic, surgical, and oncologic features of anal melanoma are reviewed to enhance physician recognition of this unusual anorectal disorder.

Adult↗
PubMed2001

Circling mouse: possible animal model for deafness.

Mutant mice with abnormalities are potentially useful as models for studying human defects. Here we report a group of mice with abnormal behavioral patterns. A new spontaneous mutant mouse exhibited hyperactive behavior at about seven days of age, followed by tight circling behavior. Breeding studies suggest that this mutation is caused by a single gene defect inherited in an autosomal recessive manner. Consequently, this mutation is referred to as a circling (cir) mouse mutation with the gene symbol cir. Auditory test results identified clearly the hearing loss of the cir, compared with wild-type mice. Pathologic studies confirmed developmental defects in cochlea and spiral ganglions that were correlated to the abnormal behavior observed in the cir mice. Thus, cir mice may be useful as a model for studying inner ear abnormalities and deafness in humans.

Animals↗
PubMed2000

Rice 1Cys-peroxiredoxin over-expressed in transgenic tobacco does not maintain dormancy but enhances antioxidant activity.

Possible functions that have been proposed for the plant 1Cys-peroxiredoxin, include activity as a dormancy regulator and as an antioxidant. The transcript level of rice 1Cys-peroxiredoxin (R1C-Prx) rapidly decreased after imbibition of rice seeds, but the protein was detected for 15 days after imbibition. To investigate the function of this protein, we generated transgenic tobacco plants constitutively expressing the R1C-Prx gene. The transgenic R1C-Prx plants showed a germination frequency similar to control plants. However, the transgenic lines exhibited higher resistance against oxidative stress, suggesting that antioxidant activity may be its primary function.

Animals↗
PubMed2000

Functional neuroimaging studies of reading and reading disability (developmental dyslexia).

Converging evidence from a number of neuroimaging studies, including our own, suggest that fluent word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system is functionally disrupted in developmental dyslexia. Reading disabled readers, relative to nonimpaired readers, demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers the dorsal circuit predominates at first, and is associated with analytic processing necessary for learning to integrate orthographic features with phonological and lexical-semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word identification system which underlies fluent word recognition in skilled readers.

Cerebral Cortex↗
PubMed2000

Correlation between ICAM-1 and functional recovery of piglet myocardium with leukocyte-depleted reperfusion.

BACKGROUND: Reperfusion injury involves leukocyte-endothelial interaction mediated by cell adhesion molecules. This study was designed to determine the time course of intercellular adhesion molecule-1 (ICAM-1) expression and the functional recovery of myocardium when reperfused with leukocyte depleted whole blood. METHODS: Sixteen neonatal piglet hearts were harvested and stored with 4 degrees C cold University of Wisconsin Solution (UWS) for 12 hours. An ex vivo model consisting of an isolated working heart perfusion circuit, roller pumps, and a membrane oxygenator, was used for reperfusion. Atrial tissues were taken for staining ICAM-1. The stroke work index (SWI) was calculated during 4 hours of reperfusion. Two groups (group 1: reperfused with whole blood, group 2: with leukocyte depleted blood) were compared. RESULTS: The differences of ICAM-1 expression between group 1 and 2 were significant at 3 and 4 hours of reperfusion (p < 0.05). The differences of the mean stroke work indices were significant at 2, 3, and 4 hours after reperfusion (p < 0.05). CONCLUSIONS: Leukocyte-depleted reperfusion attenuates the expression of ICAM-1 and reduces the time-dependent functional deterioration of the myocardium. These results suggest that adhesion molecule like ICAM-1 plays a major role in deteriorating myocardial function during the reperfusion, possibly by leukocyte-mediated inflammatory process.

Animals↗
PubMed2000

Catastrophic outcomes of noncardiac surgery soon after coronary stenting.

OBJECTIVES: To assess the clinical course of patients who have undergone coronary stent placement less than six weeks before noncardiac surgery. BACKGROUND: Surgical and percutaneous transluminal coronary angioplasty revascularization performed before high-risk noncardiac surgery is expected to reduce perioperative cardiac morbidity and mortality. Perioperative and postoperative complications in patients who have undergone coronary stenting before a noncardiac surgery have not been studied. METHODS: Forty patients who underwent coronary stent placement less than six weeks before noncardiac surgery requiring a general anesthesia were included in the study (1-39 days, average: 13 days). The records were screened for the occurrence of adverse clinical events, including myocardial infarction, stent thrombosis, peri- and postoperative bleeding and death. RESULTS: In 40 consecutive patients meeting the study criteria, there were seven myocardial infarctions (MIs), 11 major bleeding episodes and eight deaths. All deaths and MIs, as well as 8/11 bleeding episodes, occurred in patients subjected to surgery fewer than 14 days from stenting. Four patients expired after undergoing surgery one day after stenting. Based on electrocardiogram, enzymatic and angiographic evidence, stent thrombosis accounted for most of the fatal events. The time between stenting and surgery appeared to be the main determinant of outcome. CONCLUSIONS: Postponing elective noncardiac surgery for two to four weeks after coronary stenting should permit completion of the mandatory antiplatelet regimen, thereby reducing the risk of stent thrombosis and bleeding complications.

Aged↗